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NON-COMPLIANCE WITH HORMONAL THERAPY FOR BREAST CANCER AND RISK OF DEATH
The management of breast cancer today bears little resemblance to the way that we managed this most common cancer among women when I entered medical school in the early 1980s. Back then, both early-stage and advanced breast cancers were managed with a standard “one-size-fits-all” approach that included removal of the entire breast (mastectomy) and most of the lymph nodes in the armpit area (axillary lymph node dissection). Twenty-five years ago, most women with breast cancer also received chemotherapy, while “hormonal therapy” for many premenopausal women with breast cancer consisted of the surgical removal of both ovaries (oopherectomy).
In 2010, 85 to 90 percent of women are eligible to undergo breast-conserving surgery (“lumpectomy”). Radical removal of the armpit lymph nodes has also become unnecessary for the majority of women with newly diagnosed breast cancer, as approximately two-thirds of women will be found to have normal armpit lymph nodes using a high-tech lymph node mapping procedure known as sentinel lymph node biopsy. (Sentinel lymph node biopsy is associated with one-tenth the incidence of the risks associated with more radical lymph node dissections.) Using a recently validated genetic test (Oncotype DX), many women with early-stage, favorable breast cancers can also safely choose to avoid chemotherapy, based upon the results of individualized “molecular” testing of their breast tumors.
Instead of undergoing surgery to remove their ovaries, premenopausal women with hormone-sensitive breast cancers can now opt to take one of several different hormone-blocking medications (selective estrogen receptor modulators, or “SERMs”) for 5 years, to further reduce their risk of developing either a recurrence of their breast cancer or a new breast cancer. For postmenopausal women with hormone-sensitive cancers, a different class of hormone blocking medications, the aromatase inhibitors (“AIs”), are often prescribed, also for 5 years. These medications have been shown to reduce the risk of both recurrent breast cancer and new breast cancers by as much as 50 percent, and so they have become powerful clinical tools in our breast cancer prevention and treatment armamentarium. However, as with almost all medications, SERMs and AIs are associated with some rather significant side effects. In the case of SERMs, these side effects can include bone pain, hot flashes, nausea, mood swings, decreased libido, and constipation, among others. Tamoxifen, the most commonly prescribed SERM, is also associated with a small but significant increase in the risk of uterine cancer. (Raloxifene, the newest SERM to be approved for breast cancer prevention and treatment, appears not to significantly increase the risk of uterine cancer.) Both of these SERMS are also associated with an increased risk of blood clots in the body, as well. On the other hand, in addition to their potent ability to reduce the risk of both recurrent and new breast cancers, tamoxifen and raloxifene also decrease the risk of osteoporosis and osteoporosis-related bone fractures.
AIs are also associated with significant side effects in some patients, including hot flashes, bone and joint pain, mood changes, rash, headache, insomnia, and a small but significant increase in the risk of osteoporosis and osteoporosis-related bone fractures, among other symptoms and complications.
In view of the side effects profiles of SERMs and AIs, it is not surprising that patient compliance with these medications is an ongoing problem in the management of breast cancer (and, especially, among premenopausal women). A newly published clinical research study in the journal Breast Cancer Research & Treatment reveals just how serious the issue of patient compliance with hormonal therapy is among breast cancer patients, as well as the significant impact of such noncompliance on the subsequent risk of death.
In this clinical study, performed by my Northern California Kaiser Permanente colleagues, 8,769 women diagnosed with hormone-sensitive breast cancer between 1996 and 2007 were evaluated. One of the most powerful clinical assets of Kaiser Permanente is its comprehensive electronic health records system (“Health Connect”), which allows any Kaiser Permanente health care provider to access any individual patient’s detailed medical history, including diagnoses, past and current treatments (including surgeries and medications), lab results, radiology results, and other important clinical information. This rich source of clinical information not only improves the quality and efficiency of care provided to patients, but it also serves as a powerful tool to conduct meaningful clinical research on large numbers of patients in an effort to further improve the delivery of high-quality health care. (Indeed, Kaiser Permanente’s computerized medical records system is often held up as an example of what the future of electronic medical records should look like in the United States.)
The results of this study revealed the true potential costs of noncompliance with hormonal therapy among patients diagnosed with relatively early-stage hormone-sensitive breast cancers. Among the nearly 9,000 women who filled at least an initial prescription for their breast cancer hormonal therapy medications, 31 percent subsequently discontinued their SERMs or AIs, and an additional 28 percent continued with hormonal therapy, but were not fully compliant in taking their SERMs or AIs. (This combined 59 percent incidence of overall noncompliance is consistent with the 50 to 60 percent incidence of noncompliance with hormonal therapy that has been identified in previous clinical research studies.)
During an average follow-up period of 4.4 years, 831 of these 8,769 patients died. Based upon the observed survival data collected in this study, the women who were compliant with their SERMs or AIs had a statistically predicted 10-year survival rate of 81 percent, while the women who prematurely discontinued their hormonal therapy had a predicted 10-year survival rate of 74 percent. (The women who continued with their hormonal therapy, but who were not compliant with their daily doses, were projected to have an intermediate 10-year survival rate of 78 percent.)
In the final analysis of their data, the authors of this study found that early discontinuation of hormonal therapy or continuing with hormonal therapy in a noncompliant manner were associated with a significant reduction in survival among patients with hormone-sensitive breast cancers.
The results of this study say two important things, in my mind. The first is that SERMs and AIs significantly reduce the risk of death in patients with hormone-sensitive breast cancer (as has already clearly been shown by multiple prospective, randomized, blinded, placebo-controlled clinical research studies). As with all medications, discontinuing hormonal therapies prematurely, or taking these important breast cancer medications in a haphazard manner, deprives breast cancer patients of the full potential benefits of SERMs and AIs. The second important observation to be derived from this study is that we need to continue to search for new hormonal therapies with improved side effect profiles, to encourage better patient compliance with this important aspect of breast cancer prevention and treatment.
If you are a breast cancer survivor who has been prescribed hormonal therapy (or a woman who is at very high risk of developing breast cancer, and who been prescribed a SERM or AI for breast cancer prevention purposes), then you should make every effort to work together with your Oncologist to help you to remain compliant with your SERM or AI prescription, including the aggressive management of any unpleasant treatment side effects that you might be experiencing.
To learn more about an evidence-based approach to breast cancer prevention, watch for the publication of my new landmark book, “A Cancer Prevention Guide for the Human Race,” in September of this year.
Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity
Dr. Wascher is an oncologic surgeon, a professor of surgery, a cancer researcher, an oncology consultant, and a widely published author
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