Endocrine therapy in early-stage breast cancer
March 07, 2022
Outcomes4Me sat down with Dr. Karen Smith, a medical oncologist specializing in breast cancer at Johns Hopkins Sidney Kimmel Cancer Center, to discuss endocrine therapy in early-stage breast cancer. We have included the entire webinar video above for anyone who missed it and wants to watch it in full.
Here is a recap of the key takeaways from the discussion with Dr. Smith:
Who is this session relevant to?
- Patients with hormone positive early stage breast cancer.
What is endocrine therapy and why is it prescribed to early-stage breast cancer patients?
- The majority of breast cancer patients are diagnosed with early-stage breast cancer (90% of breast cancer diagnoses are early-stage), which is curable. The goal of recommended treatments provided in early-stage breast cancer is to help patients achieve cure and reduce the risk of a cancer recurrence. Part of the recommended treatment for those diagnosed with hormone receptor positive breast cancer (at least 75% of breast cancer cases are hormone positive) is endocrine therapy, which is a form of treatment that targets estrogen and progesterone in the female body and blocks the effects of the hormones.
How effective is endocrine therapy at preventing a recurrence?
- While we know that endocrine therapy reduces the risk of breast cancer recurrence in hormone positive breast cancers, and improves overall survival, it can be difficult to measure the benefits from endocrine therapy. Generally speaking, endocrine therapy can decrease the risk of a recurrence by half. The absolute risk reduction of a recurrence depends on an individual’s risk to start with, which is determined by the pathology (size of the tumor, lymph node involvement, aggressive nature).
Does taking endocrine therapy for 10 years instead of 5 years significantly decrease a person’s chance of recurrence?
- Historically, endocrine therapy was recommended for 5 years based on how clinical studies were performed many years ago. However, the risk of recurrence for hormone positive breast cancer persists for a very long time, even over 10 years. Due to the longer risk for recurrence, we have started to look at continuing endocrine therapy for over 5 years. Data shows that there is benefit in continuing Tamoxifen for 10 years versus 5 years. Further data shows benefit in those women that start with Tamoxifen for 5 years and then continue with an Aromatase Inhibitor for 5 more years. There have been studies looking at whether staying on an Aromatase Inhibitor for 10 years has provided increased benefit, and the findings have been mixed.
In the past year, many patients had to start endocrine therapy prior to surgery rather than after surgery due to COVID-19 related cancellations, does that impact outcomes?
- No, occasionally we need to start endocrine therapy prior to surgery for other reasons and there does not seem to be any impact on the overall benefit.
How do we know if endocrine therapy is working?
- Unfortunately, this is difficult to know. In most cases, endocrine therapy is given to patients whose cancer has been completely removed. We recommend endocrine therapy due to the concern for a possible recurrence, as there may be micro metastatic disease (disease that is too small to detect), that is not seen at the time of surgery or on imaging studies. The only way to know that it is working currently is that the cancer does not return. There are studies looking at possible testing to give us better information, but this is not yet available and is not the standard of care at this point.
- What are the latest treatment advances? Any new drugs on the horizon?
- Yes, and this is very exciting! A new class of drugs is being evaluated (they have not yet been approved), called oral SERD (estrogen receptor degrader), in women with metastatic breast cancer and in early-stage breast cancer. Another great advance is CDK4/6 inhibitors, which have been found to be very effective in metastatic hormone positive breast cancer and are now being evaluated in combination with hormonal therapy for those diagnosed with early-stage breast cancer. Abemaciclib is one of these medications, and has shown that when given for the first few years along with hormonal therapy there is a further reduction in the risk of a recurrence. However, these inhibitors are recommended for only those women that have a particularly high risk of recurrence, and should be carefully considered by your oncologist.
Are there any alternative and/or holistic options to Tamoxifen?
- There are no alternatives that replace tamoxifen, but holistic treatments can aid in decreasing the bothersome side effects of hormone treatment.
What are your recommendations for managing side effects of hormone therapy?
- There is a range of evidence-based management options for treatment related side effects which could include taking another medication, holistic treatments such as acupuncture, or lifestyle changes such as reducing alcohol or caffeine intake. Talking to your doctor about any side effects is very important.
What are your thoughts on decreased doses of endocrine therapy due to side effects?
- Taking endocrine therapy in ways other than what is prescribed is a big problem and absolutely not recommended. There is data that shows women who do not take endocrine therapy as prescribed have a higher chance of recurrence and a lower overall chance of curing their breast cancer. I am not aware of any data regarding lowering the dose of aromatase inhibitors. There is one study that looked at lowering the dose of tamoxifen given over 3 years, however this study was not done in women with invasive breast cancer and was used in the setting of prevention. We occasionally give aromatase inhibitors or tamoxifen to women that have NOT been diagnosed with an invasive breast cancer, but are at increased risk for getting breast cancer, and this was the setting that the study was performed in.
Are the toxicity profiles of aromatase inhibitors (letrozole, exemestane, anastrozole) different?
- Efficacy is equivalent in these medications, as is the side effect profile. Joint pain, risk of osteoporosis, and vaginal dryness are the most common side effects found in aromatase inhibitors. Individual women can, however, tolerate these medications differently and up to 40% of the time find that the side effects are manageable after switching medications. For example, if a woman is having difficulty with letrozole they may be able to change to either exemestane or anastrozole and tolerate it much better.
Should endocrine therapy be discontinued or avoided if a woman wants to have children?
- Hormone treatment such as tamoxifen is not thought to directly impact fertility, however, getting pregnant while on tamoxifen should be avoided. Since hormonal therapy is recommended for 5-10 years depending on patient diagnosis, and a woman’s fertility declines with age, it is very important to discuss fertility options prior to starting any medications for breast cancer. Typically, if there is any interest in family planning, we recommend that women meet with a Reproductive Endocrinologist to discuss the possibility of either freezing eggs or freezing embryos prior to the start of treatment.
Another decision that is discussed among younger women with breast cancer is whether taking a break from hormonal treatment in order to get pregnant is recommended. Unfortunately, there is not any great data that is currently available that has looked directly at this. We do however have data that shows women who have gotten pregnant after having gone through treatment for breast cancer do not seem to have a higher risk of cancer recurrence. There is a trial that is currently taking place looking at women who have had at least 1.5 years of hormone treatment that are taking a break from treatment to try to conceive. They are encouraged to continue with treatment after they give birth. We are looking at the data coming in to see if the rate of recurrence remains low for these patients and will be better able to give recommendations on the risk of pausing hormone therapy for pregnancy once the study has been completed.
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