San Antonio, TX—Endocrine therapy is known to reduce breast cancer risk by 30% when used as primary prevention in women at risk for the disease, and the reduction lasts for at least 20 years. Despite this proven benefit, many women prescribed these drugs do not take them. The results of a new study found that specific menopausal symptoms, such as nausea/vomiting and headaches, made women significantly less likely to be adherent to endocrine therapy.
The study results also found that women randomized to receive placebo reported menopausal symptoms at a frequency similar to those assigned to tamoxifen, suggesting that women may attribute naturally occurring menopausal symptoms to hormonal agents they are taking.
The study was an analysis of the older, large, IBIS-1 placebo-controlled trial that randomized women at risk for developing breast cancer to receive 5 years of tamoxifen or placebo. Results of the current analysis were reported at the recent San Antonio Breast Cancer Symposium.
“Tamoxifen is effective only if you take the drug. Tamoxifen is known to increase the rate of thromboembolic events, endometrial cancer, and menopausal side effects. Our analysis of IBIS-1 sought to assess the role of menopausal symptoms on adherence in the IBIS-1 trial,” said lead investigator Samuel G. Smith, PhD, Cancer Research UK Postdoctoral Fellow and Yorkshire Cancer Research University Academic Fellow, Leeds Institute of Health Sciences, University of Leeds, United Kingdom.
The study enrolled 3987 women in the United Kingdom aged 35 to 70 years who were at increased risk for breast cancer. The following menopausal symptoms were assessed before trial entry, and again at 6 months after starting therapy: nausea/vomiting, gynecologic symptoms (ie, irregular bleeding, vaginal dryness, and vaginal discharge), headaches, and hot flashes. Symptoms were graded as mild, moderate, and severe.
Baseline characteristics of the tamoxifen group (n = 1987) and placebo group (n = 2000) were similar; median age was 49 years, and median body mass index was 25.8. Approximately 40% of patients had 1 relative with breast cancer, and 60% had ≥2 family members with breast cancer.
Overall adherence for the whole group was 66.8%. In the placebo group, overall adherence was significantly better at 4.5 years (71.5% vs 62.1% for tamoxifen; P <.0001). Women continued taking placebo for significantly longer than tamoxifen (4.3 years vs 3.9 years, respectively; P <.0001).
Among all women in the trial, 31.5% reported hot flashes (17.7% mild, 8.7% moderate, 5.1% severe); 20.9% reported gynecologic symptoms (16.8% mild, 3.1% moderate, 1% severe); 7% reported headache (4.3% mild, 1.5% moderate, 1.2% severe); and 5% reported nausea/vomiting (4% mild, 0.8% moderate, 0.3% severe). The frequency of symptoms was similar in the placebo and tamoxifen treatment arms.
The association between these self-reported symptoms and adherence was analyzed and adjusted for age, risk status, smoking status, use of hormone replacement therapy, menopausal status, baseline symptoms, and treatment arm.
Nausea/vomiting was significantly associated with adherence (P <.001); 53.7% of women were adherent, whereas 71.3% were not. Headache was also significantly associated with adherence (P = .01); 58.6% of those with headache were adherent, whereas 71.3% were not. No significant relationship was found between hot flashes or gynecologic symptoms and adherence, but women with these symptoms trended toward poorer adherence.
“We were surprised to find that while menopausal symptoms do play a role in adherence to medication, the strength of the association between menopausal symptoms and adherence was similar among those women assigned placebo and those assigned tamoxifen. This suggests that women may be attributing naturally occurring menopausal symptoms as caused by the medications they are taking. Therefore, we need to find new and innovative ways of supporting women who experience these symptoms,” Dr Smith said.
The researchers found that dropout rates from treatment peaked within the first 12 months, suggesting that oncologists and primary care physicians who treat high-risk women should address medication concerns before treatment initiation, inform women about what to expect in terms of adverse effects, and target interventions for managing menopausal symptoms during the first 6 to 12 months of treatment. If adverse effects develop, there are effective interventions, Dr Smith said, including cognitive behavioral therapy, which has been helpful in managing endocrine-related side effects in the breast cancer setting.
Dr Smith noted that tamoxifen was the endocrine therapy of choice when IBIS-1 was initiated, but today many women are treated with aromatase inhibitors, which have a different adverse effect profile (eg, joint pain, bone loss).
The take-home message would apply to aromatase inhibitors as well. Because the rate of nonadherence to aromatase inhibitors is high, healthcare providers must educate women and present information about adverse effects. Healthy women without breast cancer (but at increased risk for the disease) may not want to take a drug associated with side effects unless they are at very high risk.
“There are things we can do to ameliorate symptoms associated with hormonal therapy. We did not know about acupuncture, Effexor, and other antidepressants when this study was conducted. The discussion about side effects should be up-front, and we can tell women we have tools to manage them,” said Kent Osborne, MD, Director, Baylor College of Medicine, Houston, TX, who moderated the press conference where these findings were presented.