Can some postmenopausal women with breast cancer skip chemotherapy?

Breast cancer remains the most common cancer in women. Over the past two decades, breast cancer treatment has become personalized. This was possible due to the subtyping of breast cancers. Breast cancers have been subtyped based on breast cancer cell receptors. The most clinically significant receptors – those with targeted therapies – are estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2). Cancers that have both estrogen and progesterone receptors are called hormone receptor positive (HR) cancers.

The development of hormone therapy for HR-positive breast cancers means that some women, for whom the risks of chemotherapy outweigh the benefits, may be able to forgo chemotherapy. The development of genomic assays, tests that analyze genes expressed in cancer, has provided a way to help doctors and women decide who will benefit most from chemotherapy.

How do genomic testing help personalize breast cancer treatment?

Increasingly detailed knowledge of breast cancer has led to the development of personalized therapy. In addition to knowing the type and stage of your cancer, genomic testing has further refined how we assess your risk of breast cancer recurrence. A genomic test, Oncotype Dx, is a useful tool that can help predict the likelihood of benefit from chemotherapy, as well as the risk of recurrence of invasive breast cancer.

Not all women will need chemotherapy, but for some women hormone therapy alone is not enough. Oncotype Dx analyzes the expression of 21 genes in HR-positive, HER2-negative breast cancer and assigns a recurrence score (RS) based on the risk of recurrence. The Oncotype Dx test classifies women into three groups: low, intermediate or moderate risk of recurrence, and high. Women with a low recurrence score do not need chemotherapy and benefit the most from hormone therapy, while women with a high recurrence score benefit the most from chemotherapy more at hormonal therapy.

There is new research to help women make decisions about chemotherapy

Until recently, it was not known what benefit women with an intermediate risk score obtained from chemotherapy. A randomized controlled clinical trial, the Tailor Rx trial, answered this question. The trial randomized women with lymph node negative (cancer that has not yet spread to the lymph nodes), HR-positive, HER2-negative breast cancer with an intermediate risk score on hormone therapy alone or chemotherapy in addition to hormone therapy. The results showed that most women at intermediate risk for invasive cancer did not get any additional benefit from chemotherapy. However, the subgroup of women who did benefit of chemotherapy were premenopausal women under 50 years of age.

Although the results of the Tailor Rx trial changed practice, it led to questions about the benefits of chemotherapy in women whose cancer has spread to their lymph nodes and who had HR- breast cancer. positive, HER2-negative. The RxPonder trial answered this question.

The RxPonder trial randomized 5,015 women with HR-positive, HER2-negative stage II / III breast cancer with one to three lymph nodes positive and an intermediate RS (≤ 25). Patients were randomized to receive hormone therapy alone or hormone therapy combined with chemotherapy. The main objective of the study was to find out how many women did not have a recurrence of invasive breast cancer while they were being followed.

There were many ways to compare the women in the study, but the main characteristics chosen for comparison were: menopausal status, RS, and type of axillary surgery they received. At a median follow-up of 5.1 years, there was no association between the benefit of chemotherapy and the RS value between zero and 25 for the general population. However, an association has been observed between the benefits of chemotherapy and menopausal status. This trial provided evidence that even women with lymph node cancer, if they had low or intermediate RS, could avoid chemotherapy.

Premenopausal women responded better to hormone therapy and chemotherapy

Of the women enrolled in the RxPonder trial, 3,350 were postmenopausal and 1,665 were premenopausal. Further analysis of menopausal status revealed that there was no difference in five-year survival for postmenopausal women treated with hormone therapy alone compared to hormone therapy with chemotherapy.

However, for premenopausal women, there was a 46% reduction in the risk of invasive disease. For this subgroup of women, the five-year invasive disease-free survival rates were 94.2% in women treated with hormone therapy and chemotherapy, compared with 89% in women treated with hormone therapy alone. Premenopausal women who received both chemotherapy and hormone therapy had an additional benefit of about 5%. It is not known whether the survival benefit observed in premenopausal women is primarily due to the effect of chemotherapy, or indirectly to ovarian suppression due to chemotherapy.

What does this mean for breast cancer treatment decision making?

Breast cancer treatment is truly personalized. Knowing the stage of your canerosis has always been important, but now it’s also important to know the type of your cancer. With this information, women can have an informed discussion with their oncologist about the risks and benefits of chemotherapy.

If you are a premenopausal woman with HR-positive, lymph node positive breast cancer, chemotherapy and hormone therapy may give you the greatest chance of reducing your risk of the cancer coming back. However, for a postmenopausal woman with HR-positive breast cancer, chemotherapy may not add many of the benefits of hormone therapy, and it comes with risks that can affect your quality of life. Studies such as the TailorRx and RxPonder trials have provided more information to help you make an informed decision.

The Job Can Some Postmenopausal Women With Breast Cancer Avoid Chemotherapy? first appeared on the Harvard Health Blog.

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Jothi Venkat

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