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Women who are at high risk of developing breast cancer may be failing to take the preventive anti-cancer drug tamoxifen because they are confusing naturally-occurring symptoms with side effects from the medicine, according to a study of nearly 4,000 women led by Queen Mary University of London (QMUL).

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The researchers reported their findings have important implications about how to communicate with women, because getting it right could improve adherence to medication, thereby helping women reduce their risk of developing breast cancer. Tamoxifen has been shown to reduce the incidence of breast cancer by at least 30 percent if it is given before disease develops in women who are at high risk of developing it due to factors such as a family history of breast cancer.


The International Breast Cancer Intervention Study (IBIS-1), which has been running since 1992, has shown that the preventive effects of tamoxifen last at least 20 years. However, only one in six high-risk women opt to take the drug when it is offered and not all of them manage to take it consistently for at least 5 years.


Treatment Adherence Statistics

In the study published in the Journal of Clinical Oncology, researchers at QMUL, University of Leeds, University of Manchester in the U.K., and Calvary Mater Newcastle Hospital in Australia analyzed data on 3,823 U.K. women taking part in IBIS-1 who had been randomized to receive placebo or tamoxifen for 5 years (J Clin Oncol 2017; doi:10.1200/JCO.2016.71.7439).


Overall, 69.7 percent of women managed to adhere to their treatment for at least 4.5 years (74% taking placebo and 65.2% taking tamoxifen). Symptoms that were reported included nausea or vomiting, headaches, hot flashes, and gynecological symptoms, such as irregular bleeding, vaginal dryness, and vaginal discharge. Dropout rates were highest in the first 12-18 months of follow-up (7.4% on placebo vs. 12.2% on tamoxifen).


At 6 months among women who reported symptoms of nausea or vomiting, just over 40 percent failed to adhere to their treatment, regardless of whether they were receiving placebo or tamoxifen.


Medication or Menopause?

"We found that the association between nausea, vomiting, headaches, hot flashes, and gynecological symptoms, and non-adherence to treatment was largely similar between women taking placebo or tamoxifen: the greater the severity the less likely the women were to adhere to their treatment, with the exception of headaches, which were associated with increased non-adherence of 38 percent only in the placebo group," explained Ivana Sestak, PhD, Lecturer in the Center for Cancer Prevention, QMUL, and coauthor of the study. "Therefore, this suggests that women may be attributing normally-occurring, age-related symptoms, such as those experienced around the time of menopause, to their medication instead."


Samuel Smith, MSc, PhD, co-author of the research and a Cancer Research UK Fellow and University Academic Fellow at the University of Leeds, noted: "The fact that there was a relationship between reporting symptoms and non-adherence among women in the placebo group shows that behavior is being affected by the symptoms, but these symptoms clearly could not have been caused by the drug because it was a placebo."


Better communication with women is important, noted the researchers. "Communicating accurate information on side effects to patients, and highlighting that some naturally-occurring symptoms may occur during the course of therapy, could be a useful approach in encouraging adherence. This is particularly important for women who are expected to experience the menopause while taking preventive therapy," said Sestak. "These discussions may encourage more realistic expectations of the likelihood of experiencing side effects."


"Intervention strategies that help to communicate effectively the harms and benefits of preventive therapy to patients need to be developed. At present, interventions that help to improve adherence to medications are few and far between. So we are considering ways to intervene with these patients to ensure the safe and appropriate use of preventive therapy. We are also planning a secondary analysis of the IBIS-II trial, which looked at another anti-cancer drug, anastrozole, versus placebo, to see if the same effects are observed in a separate group of women," Smith concluded.