Can some postmenopausal women with breast cancer skip chemotherapy?

Breast cancer remains the most common cancer among women. In the last two decades, the treatment of breast cancers has become personalized. This has been possible due to the subtyping of breast cancers. Breast cancers have been subtyped based on the receptors on the breast cancer cell. The most clinically significant receptors — those that have targeted therapies — are the estrogen and progesterone receptors and the human epidermal growth factor receptor 2 (HER2). Cancers that have the estrogen and progesterone receptors are termed hormone receptor (HR)-positive 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 forego chemotherapy. The development of genomic assays, tests that analyze genes expressed in cancer, have provided a way to help doctors and women decide who will obtain the most benefit from chemotherapy.

How does genomic testing help to personalize breast cancer treatment?

Increasingly detailed knowledge about breast cancers 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 the risk of recurrence for breast cancer. One 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 for invasive breast cancer.

Not all women will require 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 risk of recurrence. The Oncotype Dx test places women into three groups: low, intermediate or moderate, and high risk of recurrence. Women with a low score do not need chemotherapy and benefit the most from hormone therapy, while women who have a high recurrence score benefit the most from chemotherapy in addition to hormone therapy.

There is new research to help women make decisions about chemotherapy

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

While the results of the Tailor Rx trial were practice-changing, it did lead to questions about the benefit of chemotherapy in women whose cancer has spread to their lymph nodes and who had HR-positive, HER2-negative breast cancer. The RxPonder trial answered this question.

The RxPonder trial randomized 5,015 women with stage II/III HR-positive, HER2-negative breast cancer, with one to three positive lymph nodes, and an intermediate RS (≤ 25). Patients were randomized to receive hormone therapy alone, or hormone therapy with chemotherapy. The main goal of the study was to determine how many women did not get a recurrence of the 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 the kind of axillary surgery they received. At a median follow up of 5.1 years, there was no association between chemotherapy benefit and RS value between zero and 25 for the entire population. However, there was an association seen between chemotherapy benefit and menopausal status. This trial provided evidence that even women with cancer in their lymph nodes, if they had a 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 by menopausal status revealed that there was no difference in five-year survival for postmenopausal women treated with hormone therapy alone versus 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 to 89% in women treated with hormone therapy alone. The premenopausal women who received both chemotherapy and hormone therapy had an additional benefit of around 5%. It is unclear if the survival benefit seen in premenopausal women is primarily due to chemotherapy’s effect, or indirectly by ovarian suppression due to chemotherapy

What does this mean for breast cancer treatment decision-making?

The treatment of breast cancer has truly become personalized. It has always been important to know the stage of your caner, but now it is also important to know the type of your cancer. With this information, women can make an informed discussion with their oncologist about the risks and benefits of chemotherapy.

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

(T. Salewa Oseni, M.D., is a contributor to Harvard Health Publications.)