Conference Coverage

Misconceptions remain on gene signature use in breast cancer


 

AT ESMO BCC 2022

BERLIN – Some breast cancer specialists still have misconceptions about the appropriate use of multigene signatures in making prognostic and treatment decisions in early-stage disease, a European survey suggests.

The authors found, for instance, that while most specialists agreed that molecular intrinsic subtypes had clinical utility for understanding prognosis in early-stage hormone receptor (HR)–positive disease and for identifying patients for whom chemotherapy could be safely avoided, about 1 in 4 experts either disagreed or felt neutral about the use of signatures in these settings.

Similarly, almost 75% of respondents felt that these signatures were not useful in the triple-negative or metastatic setting, but a small percentage believed they were, and about 10% were neutral.

“Considering that breast cancer multigene signatures were developed in the post menopausal HR+/HER2- early breast cancer setting, the fact that some experts consider [them] useful in triple-negative, HER2+ breast cancer or in the metastatic setting corroborates a misunderstanding on how to interpret the results,” study author Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, and colleagues wrote.

Dr. Curigliano, who is also head of the Division of Early Drug Development at the European Institute of Oncology, presented the survey findings on May 4 at the European Society for Medical Oncology (ESMO BCC) Breast Cancer Congress.

Although several breast cancer multigene signatures are available to profile early breast cancer, little information exists on how these signatures should be used in clinical practice.

To investigate, Dr. Curigliano and colleagues convened a scientific committee of eight breast cancer experts to develop a Delphi questionnaire to examine respondents’ opinions and uses of these signatures.

The questionnaire asked about the clinical utility of multigene signatures in breast cancer and recommendations for their use in clinical practice.

In all, 133 breast cancer specialists from 11 European countries completed the questionnaire. Respondents were about 49 years old on average, and most (86.5%) worked in a teaching hospital. More than 72% were medical oncologists; 12% were pathologists.

Consensus was considered to be reached when 70% or more of the respondents were in agreement on a topic.

Participants had “extensive experience in the management of breast cancer patients and have been using breast cancer multigene signatures in clinical practice,” Dr. Curigliano said.

Almost all respondents (93.6%) reported using breast cancer multigene signatures routinely or in selected patients, and 73.4% had more than 5 years of experience with them.

Overall, more than 70% of respondents agreed that identifying tumor intrinsic subtype via gene expression profiling was important in making prognostic and treatment decisions; however, a consensus was not reached on the use of immunohistochemistry.

In addition, most respondents (76%) agreed that identifying breast cancer molecular intrinsic subtypes had clinical utility for prognosis in early-stage HR-positive disease and for identifying patients for whom chemotherapy can be safely avoided (75%). However, in both cases, about one-quarter of respondents either disagreed or felt neutral.

No consensus was reached on the clinical utility of these subtypes for selecting the most appropriate chemotherapy treatment – two-thirds disagreed, while 13% agreed and 17% felt neutral.

When deciding on the use of chemotherapy in the adjuvant setting in early node-negative breast cancer, 88% of respondents felt that breast cancer multigene signatures were important. Moreover, 75% considered such signatures important when deciding whether to use chemotherapy in the adjuvant setting for patients with one to three positive lymph nodes. However, no consensus was reached on the utility of signatures for deciding whether to extend endocrine therapy in either setting.

When examining the usefulness of signatures in more special settings, the authors found that the vast majority (90%) of respondents believed that multigene signatures had clinical utility for postmenopausal early breast cancer patients, and 82% did not consider signatures clinically useful in the early-stage HER2-overexpressed setting.

In addition, 74% thought that breast cancer multigene signatures were not useful in triple-negative disease or in the metastatic setting.

Respondents did not reach a consensus on the clinical utility of multigene signatures in the neoadjuvant setting – only 27% considered them useful, and almost half did not.

The “low percentage” of respondents using the signatures in the neoadjuvant setting and the “misconception regarding the predictive value of these tests on chemotherapy benefits suggest there is still room for training on results interpretation [for breast cancer multigene signatures],” the authors write.

The study was sponsored by Veracyte. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, and Veracyte. No other relevant financial relationships were disclosed.

A version of this article first appeared on Medscape.com.

This article was updated 5/9/22.

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