I have known that hormonal therapy would be part of my treatment since the day I got my diagnosis. The biopsy indicated that my tumor was positive for estrogen and progesterone receptors (ER/PR Positive). As I received more information about my diagnosis and it became clear that my treatment would also include surgery, chemotherapy, and radiation, I knew that this hormonal therapy would be the last step in this process. I also assumed it would be the easiest of all of this. Get a prescription; pick up the bottle of pills at the pharmacy; take this pill every day for the next 5-10 years. But it turns out that nothing is really that simple.
The first anti-estrogen therapy has been around longer than I have. Tamoxifen was first developed in 1962. Tamoxifen works by competing for the estrogen receptor and blocking it so that estrogen can not bind to the receptor. This is important because ER/PR positive tumors are stimulated to grow if estrogen binds to the estrogen receptor. Ultimately this drug has been incredibly beneficial in preventing recurrence of breast cancer in patients with ER/PR positive breast cancer.
However, more recently a new class of drugs has been made available to treat ER/PR positive breast cancer. These drugs are in the class called aromatase inhibitors (AI). As you could probably figure out because of their name, these drugs inhibit an enzyme called aromatase. Aromatase converts androgens (another hormone) into estrogen. So the ultimate goal is that after taking an AI, the estrogen floating around in the body is decreased so there is less opportunity for it to bind to any tumor cells that may have an estrogen receptor. The really important thing though is that in order for this to be effective, the patient must be post-menopausal. This is because in pre-menopausal women, AIs will still do a fine job of inhibiting aromatase and preventing the conversion of androgens to estrogen, but this low estrogen sends alarms out indicating that the estrogen levels in the body are low and since the ovaries in pre-menopausal women are still functioning, they respond to this alarm by sending more estrogen into the system.
So with all of this, you might think, this still seems pretty simple. Pre-menopausal women with ER/PR breast cancer should be treated with tamoxifen and post-menopausal women should be treated with AIs. Although this is a reasonable and acceptable approach, this has become a little more interesting because of a number of clinical trials that have compared tamoxifen to AIs.
First, several clinical trials that have compared tamoxifen to AIs in post-menopausal women with ER/PR positive breast cancer have shown that AIs do a better job of preventing breast cancer recurrence. Given these results, the question was entertained: can we suppress ovarian function of pre-menopausal women such that AIs may be an option? The answer is yes, and the results showed that pre-menopausal woman who underwent ovarian suppression + AI had lower breast cancer recurrence compared to these pre-menopausal women who were treated with tamoxifen alone.
Back to me. I assumed that I was a slam dunk post-menopausal. I had not had a period for a year at the time I was diagnosed and my pre-chemo hormonal levels were in the post-menopausal range. But my very wise medical oncologist recommended that we check my hormonal levels again since in early menopause, hormone levels can fluctuate. It turns out that my ovaries are “not dead yet”. My hormonal levels were no longer in the post-menopausal range. So now what? This is no longer a quick trip to CVS to pick up a bottle of pills. I now have a somewhat complicated decision to make which includes the following options:
1. Tamoxifen for a few years and then switch to an AI when we are sure that I am in menopause.
2. Suppress ovarian function with a shot called Lupron and then add AI.
3. Go for the ultimate ovarian suppression and have the ovaries surgically removed and then go on AI.
Every decision has risks and benefits. These are the things I thought about when considering this decision:
Option 1: Benefits include simple pill each day, just that the pill changes in a few years. Tamoxifen is less likely to cause osteoporosis and lower incidence of heart problems. Downsides of tamoxifen include more blood clots and endometrial cancer. The most important downside for me are numerous studies showing that tamoxifen is not as effective at preventing the recurrence of breast cancer compared to AIs.
Option 2: Benefits include starting on the most effective anti-hormonal therapy now rather than wait a few years. Downsides include getting into a clinic every month for a shot in addition to taking a pill every day. Specific to AIs are risk of osteoporosis. I should mention that I just had a Dexa scan and despite years of running and weight training, I discovered that I have osteopenia. So this is a downside I need to really pay attention to.
Option 3: Benefits are similar to #2, starting the most effective anti-hormonal therapy now. Bonus: no ovaries, no chance for ovarian cancer. Downsides include the normal risks with anesthesia, pain and downtime after surgery.
My decision was to use a hybrid of option #2 and #3. I received my first Lupron shot on November 15 and will I continue this shot each month until I have surgery to remove my ovaries. I will have surgery to remove my ovaries sometime in the New Year. I will ultimately start an AI when my oncologist is satisfied that my ovaries are suppressed. In the meantime, I am also adding more calcium and vitamin D to my life in attempts to strengthen my bones.
Tamoxifen vs AIs in post-menapausal women
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Dowsett M et. al. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341. Epub 2015 Jul 23.
Ovarian Suppression + AI studies in pre-menaposal women
Francis PA et. al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436. Epub 2014 Dec 11.
Francis PA e.t al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med. 2018;379(2):122. Epub 2018 Jun 4.
Pagani O et. al.Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT.
J Clin Oncol. 2019 https://doi.org/10. 1200/JCO.18.01967