Erin Roesch, MD

roesch_erin_headshot_1_0_0_0_0.jpg

A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.^[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.

Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.^[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further to understand the differences within this subtype itself.

Additional References

1. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source 
2. Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): a multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X  Source
3. Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
4. Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
5. Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
6. style="font-family:Calibri,sans-serif">Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source

roesch_erin_headshot_1_0_0_0_0.jpg

A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.^[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.

Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.^[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further to understand the differences within this subtype itself.

Additional References

1. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source 
2. Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): a multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X  Source
3. Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
4. Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
5. Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
6. style="font-family:Calibri,sans-serif">Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source

roesch_erin_headshot_1_0_0_0_0.jpg

A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.^[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.

Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.^[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further to understand the differences within this subtype itself.

Additional References

1. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source 
2. Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): a multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X  Source
3. Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
4. Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
5. Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
6. style="font-family:Calibri,sans-serif">Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source

roesch_erin_headshot_1_0_0_0_0.jpg

The benefit of immunotherapy in combination with chemotherapy for programmed death–ligand 1–positive (PD-L1+) metastatic triple-negative breast cancer (mTNBC) has been shown in both the IMpassion130 and KEYNOTE-355 trials.^[2,3] However, the IMpassion131 trial, which evaluated atezolizumab plus paclitaxel, did not show a progression-free survival (PFS) or overall survival (OS) benefit vs paclitaxel alone in PD-L1+ mTNBC.^[4] Various explanations for these divergent results have been proposed, including the inherent properties of the chemotherapy backbone, patient populations, and the heterogenous nature of TNBC, which can affect response to immunotherapy. Of present, the various KEYNOTE-355 regimens (pembrolizumab plus investigator's choice chemotherapy [nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin]) are US Food and Drug Administration approved for PD-L1+ mTNBC in the first-line setting. The phase 2 randomized TBCRC 043 trial investigated the effect of atezolizumab with carboplatin in patients with mTNBC and further looked at clinical and molecular correlates of response (Lehmann et al). A total of 106 patients were randomly assigned to carboplatin or carboplatin plus atezolizumab; the combination improved PFS (median PFS, 4.1 vs 2.2 mo; hazard ratio [HR] 0.66; P = .05) and OS (12.6 vs 8.6 mo; HR 0.60; P = .03). Grade 3/4 serious adverse events were more common with carboplatin-atezolizumab vs carboplatin alone (41% vs 8%). In addition, an association of better responses with PD-L1 immunotherapy was seen in patients with obesity, uncontrolled blood glucose levels, high tumor mutation burden, and increased tumor infiltrating lymphocytes. These data support the role of immunotherapy in mTNBC, highlight tumor heterogeneity within this subtype and encourage correlative studies to better define which patients benefit from immunotherapy.

Various studies have demonstrated the favorable impact of physical activity on breast cancer risk in postmenopausal women.^[5] However, data in premenopausal women is less clear. Various mechanisms connecting physical activity to premenopausal breast cancer risk have been proposed including the effect of exercise on sex steroid hormones, fasting insulin levels, and inflammation.^[6] A pooled analysis from 19 cohort studies including 547,601 premenopausal women, with 10,231 incident cases of breast cancer, aimed to examine the relationship between leisure-time physical activity (sports, exercise, recreational walking) and breast cancer risk in young women (Timmins et al). Higher (90th percentile) vs lower (10th percentile) levels of leisure-time physical activity were associated with a 10% reduction in breast cancer risk after adjustment for body mass index (BMI; adjusted HR 0.90; 95% CI 0.85-0.95; P < .001). They also found a significant reduction in risk: 32% (HR 0.68; P = .01) and 9% (HR 0.91; P = .005) for women with underweight (BMI < 18.5) and with average weight (BMI 18.5-24.9), respectively. Further, the effect of physical activity was most pronounced in the human epidermal growth factor receptor 2 (HER2)–enriched breast cancer subtype, wherein higher vs lower levels of activity were associated with an estimated 45% reduction in breast cancer risk (adjusted HR 0.55; 95% CI 0.37-0.82). These findings support the beneficial role of aerobic exercise and healthy body weight on breast cancer risk among premenopausal women and highlight the value of incorporating this information into counseling for our patients.

Additional References

1. Figueroa JD, Gierach GL, Duggan MA, et al. Risk factors for breast cancer development by tumor characteristics among women with benign breast disease. Breast Cancer Res. 2021;23:34. doi: 10.1186/s13058-021-01410-1 Source
2. Schmid P, Adams S, Rugo HS, et al, for the IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121. doi: 10.1056/nejmoa1809615 Source
3. Cortes J, Rugo HS, Cescon DW, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226. doi: 10.1056/NEJMoa2202809 Source
4. Miles D, Gligorov J, André F, et al, on behalf of the IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32:994-1004. doi: 10.1016/j.annonc.2021.05.801 Source
5. Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 2010;170:1758-1764. doi: 10.1001/archinternmed.2010.363 Source
6. Swain CTV, Drummond AE, Boing L, et al. Linking physical activity to breast cancer via sex hormones, part 1: The effect of physical activity on sex steroid hormones. Cancer Epidemiol Biomarkers Prev. 2022;31:16-27. doi: 10.1158/1055-9965.EPI-21-0437 Source

roesch_erin_headshot_1_0_0_0_0.jpg

The benefit of immunotherapy in combination with chemotherapy for programmed death–ligand 1–positive (PD-L1+) metastatic triple-negative breast cancer (mTNBC) has been shown in both the IMpassion130 and KEYNOTE-355 trials.^[2,3] However, the IMpassion131 trial, which evaluated atezolizumab plus paclitaxel, did not show a progression-free survival (PFS) or overall survival (OS) benefit vs paclitaxel alone in PD-L1+ mTNBC.^[4] Various explanations for these divergent results have been proposed, including the inherent properties of the chemotherapy backbone, patient populations, and the heterogenous nature of TNBC, which can affect response to immunotherapy. Of present, the various KEYNOTE-355 regimens (pembrolizumab plus investigator's choice chemotherapy [nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin]) are US Food and Drug Administration approved for PD-L1+ mTNBC in the first-line setting. The phase 2 randomized TBCRC 043 trial investigated the effect of atezolizumab with carboplatin in patients with mTNBC and further looked at clinical and molecular correlates of response (Lehmann et al). A total of 106 patients were randomly assigned to carboplatin or carboplatin plus atezolizumab; the combination improved PFS (median PFS, 4.1 vs 2.2 mo; hazard ratio [HR] 0.66; P = .05) and OS (12.6 vs 8.6 mo; HR 0.60; P = .03). Grade 3/4 serious adverse events were more common with carboplatin-atezolizumab vs carboplatin alone (41% vs 8%). In addition, an association of better responses with PD-L1 immunotherapy was seen in patients with obesity, uncontrolled blood glucose levels, high tumor mutation burden, and increased tumor infiltrating lymphocytes. These data support the role of immunotherapy in mTNBC, highlight tumor heterogeneity within this subtype and encourage correlative studies to better define which patients benefit from immunotherapy.

Various studies have demonstrated the favorable impact of physical activity on breast cancer risk in postmenopausal women.^[5] However, data in premenopausal women is less clear. Various mechanisms connecting physical activity to premenopausal breast cancer risk have been proposed including the effect of exercise on sex steroid hormones, fasting insulin levels, and inflammation.^[6] A pooled analysis from 19 cohort studies including 547,601 premenopausal women, with 10,231 incident cases of breast cancer, aimed to examine the relationship between leisure-time physical activity (sports, exercise, recreational walking) and breast cancer risk in young women (Timmins et al). Higher (90th percentile) vs lower (10th percentile) levels of leisure-time physical activity were associated with a 10% reduction in breast cancer risk after adjustment for body mass index (BMI; adjusted HR 0.90; 95% CI 0.85-0.95; P < .001). They also found a significant reduction in risk: 32% (HR 0.68; P = .01) and 9% (HR 0.91; P = .005) for women with underweight (BMI < 18.5) and with average weight (BMI 18.5-24.9), respectively. Further, the effect of physical activity was most pronounced in the human epidermal growth factor receptor 2 (HER2)–enriched breast cancer subtype, wherein higher vs lower levels of activity were associated with an estimated 45% reduction in breast cancer risk (adjusted HR 0.55; 95% CI 0.37-0.82). These findings support the beneficial role of aerobic exercise and healthy body weight on breast cancer risk among premenopausal women and highlight the value of incorporating this information into counseling for our patients.

Additional References

1. Figueroa JD, Gierach GL, Duggan MA, et al. Risk factors for breast cancer development by tumor characteristics among women with benign breast disease. Breast Cancer Res. 2021;23:34. doi: 10.1186/s13058-021-01410-1 Source
2. Schmid P, Adams S, Rugo HS, et al, for the IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121. doi: 10.1056/nejmoa1809615 Source
3. Cortes J, Rugo HS, Cescon DW, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226. doi: 10.1056/NEJMoa2202809 Source
4. Miles D, Gligorov J, André F, et al, on behalf of the IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32:994-1004. doi: 10.1016/j.annonc.2021.05.801 Source
5. Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 2010;170:1758-1764. doi: 10.1001/archinternmed.2010.363 Source
6. Swain CTV, Drummond AE, Boing L, et al. Linking physical activity to breast cancer via sex hormones, part 1: The effect of physical activity on sex steroid hormones. Cancer Epidemiol Biomarkers Prev. 2022;31:16-27. doi: 10.1158/1055-9965.EPI-21-0437 Source

roesch_erin_headshot_1_0_0_0_0.jpg

The benefit of immunotherapy in combination with chemotherapy for programmed death–ligand 1–positive (PD-L1+) metastatic triple-negative breast cancer (mTNBC) has been shown in both the IMpassion130 and KEYNOTE-355 trials.^[2,3] However, the IMpassion131 trial, which evaluated atezolizumab plus paclitaxel, did not show a progression-free survival (PFS) or overall survival (OS) benefit vs paclitaxel alone in PD-L1+ mTNBC.^[4] Various explanations for these divergent results have been proposed, including the inherent properties of the chemotherapy backbone, patient populations, and the heterogenous nature of TNBC, which can affect response to immunotherapy. Of present, the various KEYNOTE-355 regimens (pembrolizumab plus investigator's choice chemotherapy [nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin]) are US Food and Drug Administration approved for PD-L1+ mTNBC in the first-line setting. The phase 2 randomized TBCRC 043 trial investigated the effect of atezolizumab with carboplatin in patients with mTNBC and further looked at clinical and molecular correlates of response (Lehmann et al). A total of 106 patients were randomly assigned to carboplatin or carboplatin plus atezolizumab; the combination improved PFS (median PFS, 4.1 vs 2.2 mo; hazard ratio [HR] 0.66; P = .05) and OS (12.6 vs 8.6 mo; HR 0.60; P = .03). Grade 3/4 serious adverse events were more common with carboplatin-atezolizumab vs carboplatin alone (41% vs 8%). In addition, an association of better responses with PD-L1 immunotherapy was seen in patients with obesity, uncontrolled blood glucose levels, high tumor mutation burden, and increased tumor infiltrating lymphocytes. These data support the role of immunotherapy in mTNBC, highlight tumor heterogeneity within this subtype and encourage correlative studies to better define which patients benefit from immunotherapy.

Various studies have demonstrated the favorable impact of physical activity on breast cancer risk in postmenopausal women.^[5] However, data in premenopausal women is less clear. Various mechanisms connecting physical activity to premenopausal breast cancer risk have been proposed including the effect of exercise on sex steroid hormones, fasting insulin levels, and inflammation.^[6] A pooled analysis from 19 cohort studies including 547,601 premenopausal women, with 10,231 incident cases of breast cancer, aimed to examine the relationship between leisure-time physical activity (sports, exercise, recreational walking) and breast cancer risk in young women (Timmins et al). Higher (90th percentile) vs lower (10th percentile) levels of leisure-time physical activity were associated with a 10% reduction in breast cancer risk after adjustment for body mass index (BMI; adjusted HR 0.90; 95% CI 0.85-0.95; P < .001). They also found a significant reduction in risk: 32% (HR 0.68; P = .01) and 9% (HR 0.91; P = .005) for women with underweight (BMI < 18.5) and with average weight (BMI 18.5-24.9), respectively. Further, the effect of physical activity was most pronounced in the human epidermal growth factor receptor 2 (HER2)–enriched breast cancer subtype, wherein higher vs lower levels of activity were associated with an estimated 45% reduction in breast cancer risk (adjusted HR 0.55; 95% CI 0.37-0.82). These findings support the beneficial role of aerobic exercise and healthy body weight on breast cancer risk among premenopausal women and highlight the value of incorporating this information into counseling for our patients.

Additional References

1. Figueroa JD, Gierach GL, Duggan MA, et al. Risk factors for breast cancer development by tumor characteristics among women with benign breast disease. Breast Cancer Res. 2021;23:34. doi: 10.1186/s13058-021-01410-1 Source
2. Schmid P, Adams S, Rugo HS, et al, for the IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121. doi: 10.1056/nejmoa1809615 Source
3. Cortes J, Rugo HS, Cescon DW, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226. doi: 10.1056/NEJMoa2202809 Source
4. Miles D, Gligorov J, André F, et al, on behalf of the IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32:994-1004. doi: 10.1016/j.annonc.2021.05.801 Source
5. Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 2010;170:1758-1764. doi: 10.1001/archinternmed.2010.363 Source
6. Swain CTV, Drummond AE, Boing L, et al. Linking physical activity to breast cancer via sex hormones, part 1: The effect of physical activity on sex steroid hormones. Cancer Epidemiol Biomarkers Prev. 2022;31:16-27. doi: 10.1158/1055-9965.EPI-21-0437 Source

roesch_erin_headshot_1_0_0_0_0.jpg

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.³ Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.⁴ A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.⁵ This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m²), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.⁶ Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source

roesch_erin_headshot_1_0_0_0_0.jpg

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.³ Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.⁴ A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.⁵ This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m²), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.⁶ Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source

roesch_erin_headshot_1_0_0_0_0.jpg

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.³ Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.⁴ A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.⁵ This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m²), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.⁶ Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source

roesch_erin_headshot_1_0_0_0_0.jpg

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308

roesch_erin_headshot_1_0_0_0_0.jpg

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308

roesch_erin_headshot_1_0_0_0_0.jpg

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308

roesch_erin_headshot_1_0_0_0_0.jpg

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308

roesch_erin_headshot_1_0_0_0_0.jpg

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308

roesch_erin_headshot_1_0_0_0_0.jpg

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308

roesch_erin_headshot_1_0_0_0_0.jpg

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

roesch_erin_headshot_1_0_0_0_0.jpg

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

roesch_erin_headshot_1_0_0_0_0.jpg

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

roesch_erin_headshot_1_0_0_0_0.jpg

Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.² In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.³ These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.

Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.⁴ A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.

Additional References

1. Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586  
2. Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X  
3. Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
4. Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797

roesch_erin_headshot_1_0_0_0_0.jpg

Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.² In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.³ These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.

Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.⁴ A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.

Additional References

1. Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586  
2. Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X  
3. Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
4. Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797

roesch_erin_headshot_1_0_0_0_0.jpg

Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.² In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.³ These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.

Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.⁴ A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.

Additional References

1. Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586  
2. Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X  
3. Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
4. Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797

roesch_erin_headshot_1_0_0_0_0.jpg

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

roesch_erin_headshot_1_0_0_0_0.jpg

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

roesch_erin_headshot_1_0_0_0_0.jpg

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

roesch_erin_headshot_1_0_0_0_0.jpg

The addition of pertuzumab to trastuzumab plus chemotherapy has demonstrated improvement in pathologic complete response (pCR) rates compared with trastuzumab plus chemotherapy in early-stage HER2-positive breast cancer.³ The framework of oncology is built on clinical trials through their rigorous design, enrollment, and synthesis of data; however, real-world studies are an integral component of cancer research because they provide a more representative sample of the general population treated in routine clinical practice. Neopearl was a retrospective, observational, real-world study that evaluated the efficacy and safety of trastuzumab plus chemotherapy with or without pertuzumab among 271 patients with stage II-III HER2-positive breast cancer (Fabbri et al). The addition of pertuzumab led to an increase in pCR rate (49% vs 62%; odds ratio 1.74; P = .032) and improvement in 5-year event-free survival (81% vs 93%; hazard ratio 2.22; P = .041), and the benefit on univariate analysis was restricted to patients with positive axillary nodes. Furthermore, there were no significant differences in adverse events, including cardiac, between the two groups. These results serve to strengthen the available data regarding the clinical efficacy and favorable safety profile of dual HER2-targeted therapy combined with neoadjuvant chemotherapy.

Lifestyle factors, including physical activity and diet, are becoming increasingly recognized as important determinants of various cancer-specific outcomes and overall health. Furthermore, because these are modifiable, there is often motivation on behalf of an individual to change behaviors that can affect their outcome. Adherence to the Mediterranean diet (MD) has been associated with reduced risk for breast cancer development and lower mortality among women with breast cancer.^4,5 Data from a prospective multicenter European cohort including 13,270 breast cancer survivors demonstrated that low compared with medium adherence to a MD before a breast cancer diagnosis was associated with a 13% higher risk for all-cause mortality (hazard ratio 1.13; 95% CI 1.01-1.26). A three-unit increase in the adapted relative MD score was associated with an 8% reduced risk for overall mortality (hazard ratio_3-unit 0.92; 95% CI 0.87-0.97); this result was sustained in the postmenopausal population and strengthened in metastatic disease (Castro-Espin et al). The connection between diet and cancer outcomes is complex, and future research evaluating specific dietary interventions and the underlying biologic pathways by which nutrition exerts its effects will be important to inform our counseling for patients with breast cancer in the survivorship setting.

Additional References

1. Whelan TJ, Olivotto IA, Parulekar WR, et al, for the MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-16. doi:10.1056/NEJMoa1415340
2. ClinicalTrials.gov. Regional radiotherapy in biomarker low-risk node positive and T3N0 breast cancer (TAILOR RT). National Library of Medicine. Last updated November 23, 2022. https://www.clinicaltrials.gov/study/NCT03488693
3. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32. doi:10.1016/S1470-2045(11)70336-9
4. Buckland G, Travier N, Cottet V, et al. Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2013;132:2918-27. doi:10.1002/ijc.27958
5. Haslam DE, John EM, Knight JA, et al. Diet quality and all-cause mortality in women with breast cancer from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2023;32:678-686. doi:10.1158/1055-9965.EPI-22-1198

roesch_erin_headshot_1_0_0_0_0.jpg

The addition of pertuzumab to trastuzumab plus chemotherapy has demonstrated improvement in pathologic complete response (pCR) rates compared with trastuzumab plus chemotherapy in early-stage HER2-positive breast cancer.³ The framework of oncology is built on clinical trials through their rigorous design, enrollment, and synthesis of data; however, real-world studies are an integral component of cancer research because they provide a more representative sample of the general population treated in routine clinical practice. Neopearl was a retrospective, observational, real-world study that evaluated the efficacy and safety of trastuzumab plus chemotherapy with or without pertuzumab among 271 patients with stage II-III HER2-positive breast cancer (Fabbri et al). The addition of pertuzumab led to an increase in pCR rate (49% vs 62%; odds ratio 1.74; P = .032) and improvement in 5-year event-free survival (81% vs 93%; hazard ratio 2.22; P = .041), and the benefit on univariate analysis was restricted to patients with positive axillary nodes. Furthermore, there were no significant differences in adverse events, including cardiac, between the two groups. These results serve to strengthen the available data regarding the clinical efficacy and favorable safety profile of dual HER2-targeted therapy combined with neoadjuvant chemotherapy.

Lifestyle factors, including physical activity and diet, are becoming increasingly recognized as important determinants of various cancer-specific outcomes and overall health. Furthermore, because these are modifiable, there is often motivation on behalf of an individual to change behaviors that can affect their outcome. Adherence to the Mediterranean diet (MD) has been associated with reduced risk for breast cancer development and lower mortality among women with breast cancer.^4,5 Data from a prospective multicenter European cohort including 13,270 breast cancer survivors demonstrated that low compared with medium adherence to a MD before a breast cancer diagnosis was associated with a 13% higher risk for all-cause mortality (hazard ratio 1.13; 95% CI 1.01-1.26). A three-unit increase in the adapted relative MD score was associated with an 8% reduced risk for overall mortality (hazard ratio_3-unit 0.92; 95% CI 0.87-0.97); this result was sustained in the postmenopausal population and strengthened in metastatic disease (Castro-Espin et al). The connection between diet and cancer outcomes is complex, and future research evaluating specific dietary interventions and the underlying biologic pathways by which nutrition exerts its effects will be important to inform our counseling for patients with breast cancer in the survivorship setting.

Additional References

1. Whelan TJ, Olivotto IA, Parulekar WR, et al, for the MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-16. doi:10.1056/NEJMoa1415340
2. ClinicalTrials.gov. Regional radiotherapy in biomarker low-risk node positive and T3N0 breast cancer (TAILOR RT). National Library of Medicine. Last updated November 23, 2022. https://www.clinicaltrials.gov/study/NCT03488693
3. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32. doi:10.1016/S1470-2045(11)70336-9
4. Buckland G, Travier N, Cottet V, et al. Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2013;132:2918-27. doi:10.1002/ijc.27958
5. Haslam DE, John EM, Knight JA, et al. Diet quality and all-cause mortality in women with breast cancer from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2023;32:678-686. doi:10.1158/1055-9965.EPI-22-1198

roesch_erin_headshot_1_0_0_0_0.jpg

The addition of pertuzumab to trastuzumab plus chemotherapy has demonstrated improvement in pathologic complete response (pCR) rates compared with trastuzumab plus chemotherapy in early-stage HER2-positive breast cancer.³ The framework of oncology is built on clinical trials through their rigorous design, enrollment, and synthesis of data; however, real-world studies are an integral component of cancer research because they provide a more representative sample of the general population treated in routine clinical practice. Neopearl was a retrospective, observational, real-world study that evaluated the efficacy and safety of trastuzumab plus chemotherapy with or without pertuzumab among 271 patients with stage II-III HER2-positive breast cancer (Fabbri et al). The addition of pertuzumab led to an increase in pCR rate (49% vs 62%; odds ratio 1.74; P = .032) and improvement in 5-year event-free survival (81% vs 93%; hazard ratio 2.22; P = .041), and the benefit on univariate analysis was restricted to patients with positive axillary nodes. Furthermore, there were no significant differences in adverse events, including cardiac, between the two groups. These results serve to strengthen the available data regarding the clinical efficacy and favorable safety profile of dual HER2-targeted therapy combined with neoadjuvant chemotherapy.

Lifestyle factors, including physical activity and diet, are becoming increasingly recognized as important determinants of various cancer-specific outcomes and overall health. Furthermore, because these are modifiable, there is often motivation on behalf of an individual to change behaviors that can affect their outcome. Adherence to the Mediterranean diet (MD) has been associated with reduced risk for breast cancer development and lower mortality among women with breast cancer.^4,5 Data from a prospective multicenter European cohort including 13,270 breast cancer survivors demonstrated that low compared with medium adherence to a MD before a breast cancer diagnosis was associated with a 13% higher risk for all-cause mortality (hazard ratio 1.13; 95% CI 1.01-1.26). A three-unit increase in the adapted relative MD score was associated with an 8% reduced risk for overall mortality (hazard ratio_3-unit 0.92; 95% CI 0.87-0.97); this result was sustained in the postmenopausal population and strengthened in metastatic disease (Castro-Espin et al). The connection between diet and cancer outcomes is complex, and future research evaluating specific dietary interventions and the underlying biologic pathways by which nutrition exerts its effects will be important to inform our counseling for patients with breast cancer in the survivorship setting.

Additional References

1. Whelan TJ, Olivotto IA, Parulekar WR, et al, for the MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-16. doi:10.1056/NEJMoa1415340
2. ClinicalTrials.gov. Regional radiotherapy in biomarker low-risk node positive and T3N0 breast cancer (TAILOR RT). National Library of Medicine. Last updated November 23, 2022. https://www.clinicaltrials.gov/study/NCT03488693
3. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32. doi:10.1016/S1470-2045(11)70336-9
4. Buckland G, Travier N, Cottet V, et al. Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2013;132:2918-27. doi:10.1002/ijc.27958
5. Haslam DE, John EM, Knight JA, et al. Diet quality and all-cause mortality in women with breast cancer from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2023;32:678-686. doi:10.1158/1055-9965.EPI-22-1198

roesch_erin_headshot_1_0_0_0_0.jpg

The neoadjuvant setting provides a favorable environment to study de-escalation approaches as treatment response (via pathologic complete response [pCR] assessment) can be used as a surrogate marker for outcome. Studies have shown the effect of HER2-enriched subtype and high ERBB2 expression on pCR rates after receipt of a chemotherapy-free, dual HER2-targeted regimen.² The prospective, multicenter, neoadjuvant phase 2 WSG-TP-II trial randomly assigned 207 patients with HR+/HER2+ early breast cancer to 12 weeks of endocrine therapy (ET)–trastuzumab-pertuzumab vs paclitaxel-trastuzumab-pertuzumab. The pCR rate was inferior in the ET arm compared with the paclitaxel arm (23.7% vs 56.4%; odds ratio 0.24; 95% CI 0.12-0.46; P < .001). In addition, an immunohistochemistry ERBB2 score of 3 or higher and ERBB2-enriched subtype were predictors of higher pCR rates in both arms (Gluz et al). This study not only supports a deescalated chemotherapy neoadjuvant strategy of paclitaxel + dual HER2 blockade but also suggests that a portion of patients may potentially be spared chemotherapy with very good results. The role of biomarkers is integral to patient selection for these approaches, and the evaluation of response in real-time will allow for the tailoring of therapy to achieve the best outcome.

Systemic staging for locally advanced breast cancer (LABC) is important for informing prognosis as well as aiding in development of an appropriate treatment plan for patients. The PETABC study included 369 patients with LABC (TNM stage III or IIB [T3N0]) with random assignment to ¹⁸F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of chest/abdomen/pelvis), and was designed to assess the rate of upstaging with each imaging modality and effect on treatment (Dayes et al). In the PET-CT group, 23% (N = 43) of patients were upstaged to stage IV compared with 11% (N = 21) in the conventional-staging group (absolute difference 12.3%; 95% CI 3.9-19.9; P = .002). Fewer patients in the PET-CT group received combined modality treatment vs those patients in the conventional staging group (81% vs 89.2%; P = .03). These results support the consideration of PET-CT as a staging tool for LABC, and this is reflected in various clinical guidelines. Furthermore, the evolving role of other imaging techniques such as ¹⁸F-fluoroestradiol (18F-FES) PET-CT in detection of metastatic lesions related to estrogen receptor–positive breast cancer³ will continue to advance the field of imaging.

Additional References

1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22:489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum in: Lancet Oncol. 2021;22(5):e184. doi: 10.1016/S1470-2045(21)00194-7
2. Prat A, Pascual T, De Angelis C, et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. J Natl Cancer Inst. 2020;112:46-54. doi: 10.1093/jnci/djz042
3. Ulaner GA, Jhaveri K, Chandarlapaty S, et al. Head-to-head evaluation of ¹⁸F-FES and ¹⁸F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med. 2021;62:326-331. doi: 10.2967/jnumed.120.247882

roesch_erin_headshot_1_0_0_0_0.jpg

The neoadjuvant setting provides a favorable environment to study de-escalation approaches as treatment response (via pathologic complete response [pCR] assessment) can be used as a surrogate marker for outcome. Studies have shown the effect of HER2-enriched subtype and high ERBB2 expression on pCR rates after receipt of a chemotherapy-free, dual HER2-targeted regimen.² The prospective, multicenter, neoadjuvant phase 2 WSG-TP-II trial randomly assigned 207 patients with HR+/HER2+ early breast cancer to 12 weeks of endocrine therapy (ET)–trastuzumab-pertuzumab vs paclitaxel-trastuzumab-pertuzumab. The pCR rate was inferior in the ET arm compared with the paclitaxel arm (23.7% vs 56.4%; odds ratio 0.24; 95% CI 0.12-0.46; P < .001). In addition, an immunohistochemistry ERBB2 score of 3 or higher and ERBB2-enriched subtype were predictors of higher pCR rates in both arms (Gluz et al). This study not only supports a deescalated chemotherapy neoadjuvant strategy of paclitaxel + dual HER2 blockade but also suggests that a portion of patients may potentially be spared chemotherapy with very good results. The role of biomarkers is integral to patient selection for these approaches, and the evaluation of response in real-time will allow for the tailoring of therapy to achieve the best outcome.

Systemic staging for locally advanced breast cancer (LABC) is important for informing prognosis as well as aiding in development of an appropriate treatment plan for patients. The PETABC study included 369 patients with LABC (TNM stage III or IIB [T3N0]) with random assignment to ¹⁸F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of chest/abdomen/pelvis), and was designed to assess the rate of upstaging with each imaging modality and effect on treatment (Dayes et al). In the PET-CT group, 23% (N = 43) of patients were upstaged to stage IV compared with 11% (N = 21) in the conventional-staging group (absolute difference 12.3%; 95% CI 3.9-19.9; P = .002). Fewer patients in the PET-CT group received combined modality treatment vs those patients in the conventional staging group (81% vs 89.2%; P = .03). These results support the consideration of PET-CT as a staging tool for LABC, and this is reflected in various clinical guidelines. Furthermore, the evolving role of other imaging techniques such as ¹⁸F-fluoroestradiol (18F-FES) PET-CT in detection of metastatic lesions related to estrogen receptor–positive breast cancer³ will continue to advance the field of imaging.

Additional References

1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22:489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum in: Lancet Oncol. 2021;22(5):e184. doi: 10.1016/S1470-2045(21)00194-7
2. Prat A, Pascual T, De Angelis C, et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. J Natl Cancer Inst. 2020;112:46-54. doi: 10.1093/jnci/djz042
3. Ulaner GA, Jhaveri K, Chandarlapaty S, et al. Head-to-head evaluation of ¹⁸F-FES and ¹⁸F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med. 2021;62:326-331. doi: 10.2967/jnumed.120.247882

roesch_erin_headshot_1_0_0_0_0.jpg

The neoadjuvant setting provides a favorable environment to study de-escalation approaches as treatment response (via pathologic complete response [pCR] assessment) can be used as a surrogate marker for outcome. Studies have shown the effect of HER2-enriched subtype and high ERBB2 expression on pCR rates after receipt of a chemotherapy-free, dual HER2-targeted regimen.² The prospective, multicenter, neoadjuvant phase 2 WSG-TP-II trial randomly assigned 207 patients with HR+/HER2+ early breast cancer to 12 weeks of endocrine therapy (ET)–trastuzumab-pertuzumab vs paclitaxel-trastuzumab-pertuzumab. The pCR rate was inferior in the ET arm compared with the paclitaxel arm (23.7% vs 56.4%; odds ratio 0.24; 95% CI 0.12-0.46; P < .001). In addition, an immunohistochemistry ERBB2 score of 3 or higher and ERBB2-enriched subtype were predictors of higher pCR rates in both arms (Gluz et al). This study not only supports a deescalated chemotherapy neoadjuvant strategy of paclitaxel + dual HER2 blockade but also suggests that a portion of patients may potentially be spared chemotherapy with very good results. The role of biomarkers is integral to patient selection for these approaches, and the evaluation of response in real-time will allow for the tailoring of therapy to achieve the best outcome.

Systemic staging for locally advanced breast cancer (LABC) is important for informing prognosis as well as aiding in development of an appropriate treatment plan for patients. The PETABC study included 369 patients with LABC (TNM stage III or IIB [T3N0]) with random assignment to ¹⁸F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of chest/abdomen/pelvis), and was designed to assess the rate of upstaging with each imaging modality and effect on treatment (Dayes et al). In the PET-CT group, 23% (N = 43) of patients were upstaged to stage IV compared with 11% (N = 21) in the conventional-staging group (absolute difference 12.3%; 95% CI 3.9-19.9; P = .002). Fewer patients in the PET-CT group received combined modality treatment vs those patients in the conventional staging group (81% vs 89.2%; P = .03). These results support the consideration of PET-CT as a staging tool for LABC, and this is reflected in various clinical guidelines. Furthermore, the evolving role of other imaging techniques such as ¹⁸F-fluoroestradiol (18F-FES) PET-CT in detection of metastatic lesions related to estrogen receptor–positive breast cancer³ will continue to advance the field of imaging.

Additional References

1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22:489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum in: Lancet Oncol. 2021;22(5):e184. doi: 10.1016/S1470-2045(21)00194-7
2. Prat A, Pascual T, De Angelis C, et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. J Natl Cancer Inst. 2020;112:46-54. doi: 10.1093/jnci/djz042
3. Ulaner GA, Jhaveri K, Chandarlapaty S, et al. Head-to-head evaluation of ¹⁸F-FES and ¹⁸F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med. 2021;62:326-331. doi: 10.2967/jnumed.120.247882