Samuel G. Smith, PhD
Women who are experiencing symptoms of menopause are less likely to adhere to treatment, according to findings presented at the 2016 San Antonio Breast Cancer Symposium.1
Better addressing patient concerns prior to treatment may help prevent the misattribution of menopausal symptoms to side effects from treatment, said lead investigator Samuel G. Smith, PhD.
“Communicating the likelihood of experiencing those symptoms is important,” said Smith, a Cancer Research UK postdoctoral fellow and university academic fellow at the University of Leeds. “What would be particularly interesting would be to look at all of the symptoms that were reported in trial arms [of this and similar trials] compared with placebo arms of each trial to look at what were naturally occurring symptoms and what were actually triggered by those particular therapies, and that way you can communicate more accurate information to patients so they can make an informed decision about whether or not they want to participate.”
Nine randomized trials have studied the effect of selective estrogen receptor modulators on the prevention of breast cancer, and have shown a reduction in the incidence of breast cancer by at least 30%, said Smith. In the IBIS-1 trial, extended analysis showed that 5 years of tamoxifen treatment can reduce the incidence of breast cancer for at least 20 years.2
This analysis of patients enrolled in the IBIS-1 explored whether women experiencing menopausal symptoms were likely to adhere to their assigned treatment of tamoxifen or placebo for a period of 4.5 years.
Across both arms of the trial, 66.8% of women adhered to treatment, meaning that they remained on either tamoxifen therapy or placebo for 4.5 years (odds ratio, 1.53; 95% CI, 1.34-1.75; P
<.0001). Women receiving tamoxifen (n = 1987) were less likely to adhere to treatment than women in the placebo arm (n = 2000) at a rate of 62.1% versus 71.5%, respectively.
Among women aged 35 to 70 at an increased risk of developing breast cancer in the United Kingdom, women experiencing menopausal symptoms including nausea/vomiting; gynecologic symptoms, such as irregular bleeding, vaginal dryness, or vaginal discharge; headaches; and hot flashes were included in the analysis. Symptoms were assessed prior to trial entry and at 6 months.
Characteristics were well matched across the 2 arms at baseline. The median age of the patients was 49 and a majority of patients had a family history of at least 2 family members affected by breast cancer. In each arm, patients had a median Tyrer-Cuzick risk of 5.7% of developing breast cancer (P
Overall, symptoms of nausea/vomiting were experienced by 5% of patients, headaches by 7%, hot flashes by 31.5%, and gynecologic symptoms by 20.9%. Most of these symptoms were mild, yet hot flashes at moderate levels were noted in 8.7% and at severe levels in 5.1%.
Of the women who reported nausea/vomiting, 53.7% adhered to either treatment (P
<.001) and 58.6% of women reporting headaches adhered to treatment (P
= .01). Smith indicated that there was no relationship between hot flashes or gynecologic symptoms and adherence.
When stratified by trial arm, it was demonstrated that patients reporting nausea/vomiting in either arm of the trial were less likely to adhere to their assigned treatment, whereas patients reporting headaches who were receiving placebo were less likely to adhere to treatment, but this was not noted in the tamoxifen arm. Patients with gynecologic symptoms were less likely to be adherent in the tamoxifen arm, but not in the placebo arm.
“Tests of heterogeneity revealed that these effects of symptoms on adherence were comparable between the trial arms,” noted Smith.
Smith noted that increased interventions are needed to manage menopausal symptoms for women on these trials.
“Dropout rates were fastest within the first 6 to 12 months, indicating that this is an optimal time in which to deliver such interventions,” Smith said.
Moderator Kent Osborne, MD, director of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, noted that while many methods now exist to ease these menopausal symptoms, most of these options—including venlafaxine HCI (Effexor) or other antidepressants to reduce hot flashes or acupuncture—were not known when the IBIS-1 trial was started over 20 years ago.
Perhaps recommending these methods for women experiencing menopausal symptoms could reduce the level of nonadherence to breast cancer prevention treatments.
- Smith SG, Sestak I, Howell A, Forbes J, Cuzick J. Menopausal symptoms as predictors of long-term adherence in the International Breast Cancer Intervention Study (IBIS-1). Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract S5-03.
- Cuzick J, Sestak I, Cawthorn S, et al; IBIS-1 Investigators. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-1 breast cancer prevention trial. Lancet. 2015;16:67-75. doi: 10.1016/S1470-2045(14)71171-4.