Endocrine therapy is anti-estrogen treatment used to prevent and treat hormone receptor positive breast cancer. Tamoxifen, which interferes with a tumor's ability to use estrogen, is prescribed for both premenopausal and postmenopausal women. Aromatase inhibitors, including Femara (letrozole), Arimidex (anastrozole), and Aromasin (exemestane), block the production of estrogen within the body.
Aromatase inhibitors normally are not used to treat breast cancer in premenopausal women unless accompanied by ovarian function suppression since inhibiting aromatase does not effect the production of estrogen by the ovaries (the most abundant source of estrogen in premenopausal women). Blocking the effects of estrogen or decreasing its production in the body is designed to prevent breast cancer or suppress recurrence since the growth of hormone receptor positive breast cancer is promoted by estrogen. Please also see our articles on what to eat if you are taking an aromatase inhibitor or tamoxifen.
Women who complete their anti-estrogen treatments have been found to have better recurrence and survival profiles than women who do not. However, many women do not finish their prescribed schedule of treatment. This is for the most part because of side effects, which can reduce quality of life or result in new medical conditions. However, having vasomotor (hot flashes, night sweats), genitourinary (vaginal dryness, frequent urinary tract infections, urinary incontinence, sexual dysfunction), or musculoskeletal (joint pain, fractures) symptoms is associated with improved survival compared to not having such side effects while on treatment.
Effectiveness of aromatase inhibitors compared to tamoxifen
Based on the most current published data, postmenopausal women taking aromatase inhibitors for five years have better survival outcomes than women taking tamoxifen for five years. The second most favorable schedule is to take an aromatase inhibitor for two or three years, followed by tamoxifen. However any combination of endocrine treatment is far superior to none at all for estrogen positive breast cancer patients. Recent evidence suggests that 10 years of tamoxifen treatment is superior to five years since it reduces the rate of late recurrence among women with early-stage ER+ breast cancer. One 2016 study reported that positive lymph node status was associated with late recurrence among women who had completed only five years of tamoxifen. It is not known whether 10 years of aromatase inhibitor treatment would have similar results.
One 2014 study reported that, compared to no use of oral contraceptives, birth control pill use at any age was associated with significantly lower risk of breast cancer recurrence among women diagnosed at age at least 50 who were treated with aromatase inhibitors. No such reduction in risk was observed for ever users of the pill who were treated with tamoxifen. This suggests that women with ER+ postmenopausal breast cancer who have used the pill at any point in their lives may be better off using an aromatase inhibitor rather than tamoxifen.
Arimidex appears to be somewhat more effective than Femara, but Arimidex tends to be less well tolerated. Leaving aside individual factors that can influence the choice of treatment, the implications of these findings is that women undergoing endocrine treatment should start with Arimidex and switch to Femara if the side effects of Arimidex are intolerable, do not improve over time, and cannot be relieved. Tamoxifen is an acceptable option for women who cannot use an aromatase inhibitor.
Use of bisphosphonates during endocrine treatment
Bisphosphonates like Actonel, Boniva, Fosamax, Zometa are used to treat osteoporosis and may be prescribed for women on endocrine therapy who start with suboptimal bone density or develop it during treatment. Bisphosphonates are also given to breast cancer patients to protect against the effects of bone metastases once they have developed. Some studies have reported that using bisphosphonates may protect women from developing breast cancer.
Reports are inconsistent as to whether bisphosphonate use prevents disease progression once a women has developed early stage breast cancer, in particular, whether bisphosphonate use prevents metastasis to the bone. Bisphosphonates can also cause rare but potentially serious jaw bone death (osteonecrosis of the jaw). Women should take bisphosphonates as appropriate to maintain bone health during endocrine treatment, if indicated. Of the bisphosphonates studied, Zometa and Boniva appear to have the most beneficial effects with respect to breast cancer.
Tamoxifen and antidepressants
Premenopausal and perimenopausal women taking tamoxifen are sometimes prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants to reduce hot flashes associated with the treatment. Prozac (fluoxetine), Paxil (paroxetine), and Zoloft (sertraline) all have been suspected of increasing breast cancer risk, although this is far from established. Such antidepressants might also interfere with tamoxifen's effectiveness. For example, Paxil use during tamoxifen treatment has been found to be associated with an increased risk of death from breast cancer — Paxil appears to reduce or extinguish the benefit of tamoxifen. Therefore, tamoxifen users are normally prescribed Effexor (venlafaxine, a serotonin-norepinephrine reuptake inhibitor) to relieve hot flashes, which appears to be safe.
Tamoxifen and aspirin
Factors influencing effectiveness of aromatase inhibitors
High body mass index (BMI) appears to reduce the effectiveness of aromatase inhibitor treatment. One study found that the relative efficacy of Arimidex compared to tamoxifen was greater in thin women. The authors hypothesized that higher doses or more complete inhibitors might be needed for overweight women, but this has not been confirmed. However, another study reported that Femara and tamoxifen had similar outcomes for obese women.
African-American women appear to receive less benefit from aromatase inhibitor treatment than Caucasians. Women with lobular breast cancer also appear to receive less benefit than those with ductal tumors. The reasons for these differences have not been established.
Vitamin D influences aromatase activity (in which androgens are converted to estrogens in the body). A study presented at the June 2011 American Society of Clinical Oncology (ASCO) Meeting reported that high circulating vitamin D levels were associated with higher estrogen levels among aromatase inhibitor users (but not among women using tamoxifen or not using any anti-estrogen treatment). If replicated, this finding has implications for breast cancer survivors receiving aromatase inhibitors. In the mean time, we suggest that breast cancer survivors have their circulating vitamin D levels checked and use vitamin D supplementation only as required in combination with exposure to sunlight and consumption of vitamin D-rich foods to bring their levels to normal (please see our article on vitamin D).
Weight gain should be avoided during endocrine treatment
Weight gain during endocrine treatment is common. However, such weight gain should be avoided since it has been found to be associated with less favorable prognosis (including among initially normal weight women).
Specific statistics concerning endocrine treatment-related survival, which varies depending on numerous factors, can be found in the studies below.