26 December 2016
Approximately 75% of breast cancers express the estrogen receptor – we term these breast cancers ER positive (ER+) or hormone-sensitive. Endocrine therapy refers to using medications to exploit this cancer cell property. Tamoxifen is used in premenopausal women and it blocks the estrogen receptor. In post-menopausal women, aromatase inhibitors (AI) are used which prevent estrogen from being produced (primarily in the fat cells after menopause).
In June, a study was presented which suggested that 10 years of endocrine therapy in post-menopausal women might be superior to 5 years of treatment, which had been the standard. The study noted that disease free survival was improved and development of new breast cancers were reduced in the extended therapy patients, but there were more side effects. A conclusion was that extended therapy might be appropriate for higher risk patients – those who based on certain tumor factors we suspect might have a higher risk of recurrence. A challenge has been that we do not have good tests to tell us with certainty which patients will truly benefit from a longer course of therapy.
At the 2016 San Antonio Breast Cancer Symposium, 3 studies were presented which addressed the issue of extended endocrine therapy in post-menopausal women. In all 3 studies, extended endocrine therapy with an AI did not improve disease free survival, in contrast to the study presented in June. A lack of survival benefit does not mean that extended therapy is not worthwhile, as noted in this ASCO Post article, and one of the studies did show improvements in distant metastases and contralateral (other side) breast cancers. Dr. Michael Gnant, who discussed the studies at the meeting, noted that “The trials did not reach the necessary statistical levels to demonstrate a clear benefit for aromatase inhibition extension. Extending aromatase inhibitor therapy may be a good idea for many patients after 2 to 5 years of tamoxifen, but after initial treatment with an aromatase inhibitor, the benefits and risks must be carefully balanced on an individual basis. We are going to need the ‘art of medicine’ here.”
While ER+ breast cancers tend to be “better behaved”, we know that these patients are at risk for relapse many years after initial treatment. This knowledge has to be balanced with the real side effects women experience from taking the medications. Common side effects of the AIs include joint and bone pains, vaginal dryness, hot flashes, and bone loss. Deciding whether or not to continue on the medications in the setting of significant side effects is also difficult for patients, who then have concerns about “not doing enough” to reduce the risk of cancer recurrence. More research is needed to develop both tests to help predict which patients will actually benefit from extended therapy, and treatments with fewer side effects,