Breast cancer remains the most common cancer among women. In the last two decades, the treatment of breast cancers has been personalized. This has been possible due to the subtype of breast cancers. Breast cancers have been subtyped based on breast cancer cell receptors. The most clinically significant receptors, those with targeted therapies, are the estrogen and progesterone receptors and the human epidermal growth factor (HER2) receptor 2. Cancers that have estrogen and progesterone receptors are called 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 give up chemotherapy. The development of genomic assays, tests that analyze genes expressed in cancer, have helped doctors and women decide who will get the best benefits from chemotherapy.
How do genomic testing help personalize breast cancer treatment?
An increasingly detailed knowledge of breast cancers has led to the development of personalized therapy. In addition to knowing the type and stage of cancer, genomic testing has further perfected the way to assess the risk of breast cancer recurrence. A genomic test, the Oncotype Dx, is a useful tool that can help predict the likelihood of benefiting 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 is not enough. Oncotype Dx analyzes the expression of 21 genes in HR-positive and HER2-negative breast cancer and assigns a recurrence score (RS) based on the risk of recurrence. The Oncotype Dx test places women in 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 with a high recurrence score benefit more from chemotherapy. Besides a hormone therapy.
There is new research to help women make decisions about chemotherapy
Until recently, it was unclear how much women benefit from an intermediate risk score obtained from chemotherapy. A randomized controlled trial, the Rx tailor test, answered this question. The trial randomized women with lymph node-negative breast cancer (cancer that has not yet spread to the lymph nodes), HR-positive, and HER2-negative with an intermediate risk score only to hormone therapy or additional chemotherapy. hormone therapy. The results showed that most women with an intermediate risk of invasive cancer did not gain any added benefit from chemotherapy. However, the subgroup of women who did premenopausal women under the age of 50 benefited from chemotherapy.
Although the results of the Tailor Rx trial changed practice, it led to questions about the benefit of chemotherapy in women whose cancer has spread to the lymph nodes and who had HR-positive and HER2-negative breast cancer. . The RxPonder trial answered that question.
The RxPonder trial randomized 5,015 women with HR-positive, HER2-negative phase II / III 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 reappear invasive breast cancer while following them.
There were many ways to compare the women in the study, but the main features chosen for the comparison were: menopausal status, RS, and the type of axillary surgery they received. At a mean 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 entire population. However, an association between the benefit of chemotherapy and menopausal status was observed. This trial provided evidence that even women with lymph node cancer, 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. Subsequent 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 the risk of invasive disease was reduced by 46%. For this subgroup of women, five-year survival rates without invasive disease 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 chemotherapy and hormone therapy had an additional benefit of about 5%. It is unclear 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 decision making about breast cancer treatment?
Breast cancer treatment has been really personalized. It has always been important to know the stage of your cane, but now it is 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 are a premenopausal woman with HR-positive and lymph node-positive breast cancer, chemotherapy and hormone therapy can give you the best chance of lowering your risk of cancer returning. However, for a postmenopausal woman with HR-positive breast cancer, chemotherapy may not add many benefits of treatment to hormone therapy and carries 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.