Breast cancer remains the most common type of cancer in women. Over the past two decades, breast cancer treatment has been personalized. This was possible because of the subtyping of breast cancer. Breast cancer was 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 with estrogen and progesterone receptors are known as hormone receptor (HR) positive cancers.
Developing 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 genome assays, tests to analyze genes expressed in cancer, has helped doctors and women decide who will get the most benefit from chemotherapy.
How does 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, genome tests have further refined assessments of the risk of breast cancer recurring. A genomic test, Oncotype Dx, is a useful tool that can help predict the likelihood of chemotherapy benefits and the risk of recurrence in invasive breast cancer.
Not all women need chemotherapy, but hormone therapy alone is not enough for some women. Oncotype Dx analyzes the expression of 21 genes in HR-positive, HER2-negative breast cancer and assigns a relapse score (RS) based on the risk of relapse. The Oncotype Dx test divides women into three groups: low, medium, or medium, and high risk of relapse. Women with a low score do not need chemotherapy and benefit most from hormone therapy, while women with a high relapse score benefit most from chemotherapy in addition to Hormone therapy.
There is new research aimed at helping women make decisions about chemotherapy
Until recently, it was unclear what benefit women at moderate risk get from chemotherapy. A randomized, clinically controlled study, the Tailor Rx study, answered this question. The study randomized women with node-negative (cancer that has not yet spread to the lymph nodes), HR-positive, HER2-negative breast cancer at a moderate risk for hormone therapy alone or chemotherapy in addition to hormone therapy. The results showed that most women at moderate risk of invasive cancer could not get any additional benefit from chemotherapy. However, the subgroup of women is who did Pre-menopausal women under the age of 50 benefited from chemotherapy.
While the results of the Tailor Rx study changed practice, it led 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 study answered this question.
In the RxPonder study, 5,015 women with HR-positive, HER2-negative stage II / III breast cancer with one to three positive lymph nodes and a mean RS (≤ 25) were randomized. Patients were randomized to receive hormone therapy alone or hormone therapy with chemotherapy. The main aim of the study was to determine how many women did not receive recurrence of invasive breast cancer during observation.
There were many ways to compare the women in the study, but the main characteristics selected for comparison were: menopausal status, RS, and the type of axillary surgery they received. With a mean follow-up time of 5.1 years, there was no association between the benefit of chemotherapy and the RS value between zero and 25 for the entire population. However, an association between the benefit of chemotherapy and menopausal status was found. This study provided evidence that even women with cancer in their lymph nodes, if they had low or moderate RS, could avoid chemotherapy.
Pre-menopausal women responded better to hormone therapy and chemotherapy
Of the women who participated in the RxPonder study, 3,350 were postmenopausal and 1,665 were premenopausal. Another analysis of menopausal status found that there was no difference in five-year survival for postmenopausal women treated with hormone therapy only compared to hormone therapy with chemotherapy.
However, in pre-menopausal women, the risk of invasive disease was reduced by 46%. For this subgroup of women, the five-year invasive disease-free survival rate for women treated with hormone therapy and chemotherapy was 94.2%, compared with 89% for women treated with hormone therapy only. The pre-menopausal women who received both chemotherapy and hormone therapy had an additional benefit of about 5%. It is unclear whether the survival benefit in pre-menopausal women is mainly due to the effects of chemotherapy or indirectly to ovarian suppression due to chemotherapy
What does this mean for breast cancer treatment decision making?
Treatment for breast cancer has become truly personalized. Knowing the stage of your cancer has always been important, but now it’s also important to know the type of cancer. With this information, women can have an informed discussion with their oncologist about the risks and benefits of chemotherapy.
If you’re a pre-menopausal woman with HR-positive, node-positive breast cancer, chemotherapy and hormone therapy may be your greatest chance of reducing the risk of the cancer returning. For a postmenopausal woman with HR-positive breast cancer, chemotherapy may not offer many treatment benefits than hormone therapy and it carries risks that can affect your quality of life. Studies like the TailorRx and RxPonder studies have provided additional information to help you make an informed decision.