So what are the experts saying about anti-estrogen therapy for pre-menopausal patients diagnosed with breast cancer?
Late last year, three dynamic oncologists from the University of Wisconsin, Madison – Amye Tevaarwerk, MD; Kari Wisinski, MD; and Ruth O’Regan, MD – collaborated to publish a review about the history and current state of anti-estrogen treatment. for pre-menopausal women diagnosed with early-stage, hormone receptor-positive (HR+) breast cancer. The trio agreed that even though therapy has evolved in the past 5 years, there are still unanswered questions.
Let’s start with “How things have changed, and how they’ve stayed the same”
As background, tamoxifen has been established as the drug of choice for nearly 20 years for the vast majority of pre-menopausal women who have been diagnosed with breast cancer that (according to lab tests) is HR+. This means estrogen in the body can promote growth of the tumor, and therefore physicians prescribe drugs that block the effects of estrogen. Tamoxifen works by occupying estrogen receptors in breast cancer cells, effectively blocking the ability of estrogen to cause tumor growth.1 Studies have shown that tamoxifen may reduce the risk of breast cancer coming back by 30-50% in pre-menopausal women and until a few years ago, patients were typically treated for 5 years.2 But within the past 5 years, two large studies showed that extending tamoxifen therapy out to 10 years was more beneficial than only 5 years for a small portion women. Following these studies, the standard of care shifted to longer treatment for younger women.3 So it’s fair to say that tamoxifen remains the most common treatment option for younger women. One question each breast cancer survivor along with her oncologist has about her treatment is, “How long is right for me?” and “Is longer therapy right for all patients?” We’ll take a look at this in more detail later in this blog post.
A lot has been happening in the past 5 years
While the extended anti-estrogen trials were ongoing, researchers were studying the effects of suppressing estrogen release by shutting down the ovaries of pre-menopausal breast cancer patients (called ovarian function suppression or “OFS” for short) using either an injectable drug, radiation or surgical removal. Soon, clinical trials were providing information on whether the combination of ovarian suppression plus tamoxifen might be better than tamoxifen alone in preventing breast cancer from coming back. Results from these studies showed that the addition of OFS to tamoxifen was no better than tamoxifen alone at preventing breast cancer recurrence. In one study, researchers did note that patients who received chemotherapy (due to higher risk cancers), showed more benefit from the combination of OFS plus tamoxifen. These studies also reported that a large percentage of women taking tamoxifen and OFS had a lower quality of life as a result of menopausal symptoms compared to those taking tamoxifen alone.3
Additional clinical trials were investigating whether the combination of OFS and a different class of anti-estrogen drugs called aromatase inhibitors might demonstrate superior results over tamoxifen alone in pre-menopausal breast cancer patients.
Aromatase inhibitors (AIs) work by preventing production of estrogen from places other than the ovaries (like the adrenal glands, fat, muscle and liver) by blocking the enzyme aromatase from converting androgen to estrogen.4 In post-menopausal patients (in whom the ovaries are no longer producing estrogen), AIs are better at preventing breast cancer recurrence than tamoxifen.
For this reason, researchers thought that complete estrogen suppression could be achieved in pre-menopausal women through OFS (to remove ovary sources of estrogen) and AI treatment (to prevent estrogen production from other sources). They were correct. In fact, clinical studies showed that pre-menopausal patients who received complete estrogen suppression through combination OFS and AI therapy had a lower risk of breast cancer relapse than women on tamoxifen alone or tamoxifen plus OFS.
What else you need to know about ovarian function suppression
An important note is that when added to tamoxifen alone, OFS was associated with more sexual dysfunction and menopausal symptoms like hot flashes, loss of libido, and vaginal dryness and over 20% of women in one study discontinued therapy based on side effects. There has been little long-term follow-up for breast cancer survivors who have been treated with OFS and AI therapy. Bone loss may become an issue for young patients treated with combination OFS therapy3 (see previous blog post for impact of AI therapy on bone). As you discuss options with your own doctor, be sure to evaluate the promise as well as the practical for this therapy and be sure to visit these videos of ours (https://www.youtube.com/watch?v=w9JRTcVYBJs, https://www.youtube.com/watch?v=lg_dihcrHCE) as well as our educational partners’ websites for information on how to manage the side effects of anti-estrogen treatment (http://www.breastcancer.org/tips/menopausal/treat/hot-flashes, https://www.lbbc.org/learn/living-breast-cancer/sex-and-intimacy/sexual-side-effects).
Now for many women and their oncologists, shared decision-making doesn’t take place just at the beginning of treatment, but is revisited at several time points.
Is OFS and AI therapy right for everyone?
The medical oncologists referenced above suggest that tests available today (like the Breast Cancer IndexSM) might help physicians select patients with HR+ early stage breast cancer who might be at increased risk of breast cancer coming back – an important issue to understand since the treatment can be quite difficult. Testing may also help physicians select those women at lowest risk who may be able to avoid OFS and AI therapy and opt for 5 years of tamoxifen alone.3
Is a longer duration of anti-estrogen therapy right for everyone?
As we touched on earlier in this post, based on studies that demonstrated a small, but significant benefit, many pre-menopausal breast cancer survivors are offered up to 10 years of anti-estrogen therapy to prevent the cancer from coming back. In these studies, 3 to 5 out of 100 women benefited from taking a daily anti-estrogen for another 5 years.3 The conversation with your physician about the option of continuing anti-estrogen therapy will likely include information about your tumor from pathology reports, your current physical health and quality of life, your willingness to continue treatment and any side effects that you may be experiencing. To help with decision making for you as an individual, your doctor may order the Breast Cancer Index test to provide an assessment of the risk of the cancer returning and likelihood of that you will benefit from another 5 years of anti-estrogen therapy. To understand more about personalizing your breast cancer treatment plan with your physician, watch this video. For women in whom the risk of cancer returning is low and the likelihood of benefit from additional anti-estrogen therapy is low, your physician may recommend completing therapy after the first 5 years. For patients who have a higher risk of cancer recurrence and a high likelihood of benefit from 10 years of anti-estrogen therapy, your physician may recommend continuing anti-estrogen therapy. Your physician will make the decision to end or extend treatment is based on all clinical factors.
What is the best combination or sequence of anti-estrogen medicines for pre-menopausal patients?
This question has not been fully addressed and is still under investigation with the addition of newer medicines. An important thing to remember is that early-stage, estrogen receptor positive breast cancer is treated very successfully today and your oncologist has a lot of experience in helping other women make the right decisions for them.
- Tevaarwerk, A. et al. Journal of Oncology Practice Volume 12 / Issue 11 / November 2016
This material was created or sponsored by Biotheranostics, Inc. The content, products and services discussed are offered to educate consumers on health care and medical issues that may affect their daily lives and should not be considered, or used as a substitute for, medical advice, diagnosis or treatment. You should always talk to your health care provider for diagnosis and treatment information, including your specific medical needs, and to answer any questions regarding personal health or medical conditions.
For Breast Cancer Index Intended Use and Limitations, visit www.answersbeyond5.com.