Preventive Tamoxifen Side Effects May Be Partly Explained by Menopausal Symptoms

Misinterpreting menopausal symptoms during preventive tamoxifen therapy may impact adherence to treatment

medwireNews: Women using prophylactic tamoxifen wrongly attribute some symptoms of aging to the medication, warn IBIS I investigators who found this misunderstanding of side effects reduces adherence to treatment.

“Our data have implications for communicating with prospective users of preventive therapy, particularly with regard to encouraging accurate symptom expectations and correcting potential misattributions”, say Samuel George Smith, from the University of Leeds in the UK, and co-workers.

“Intervention strategies are needed to promote adherence, as well as to effectively communicate the harms and benefits of preventive therapy to participants”, they recommend.

The team examined adherence among 3823 women with an increased risk of breast cancer who were randomly assigned to receive tamoxifen 20 mg/day (n=1890) or placebo (n=1933).

The majority of patients continued with treatment for at least 4.5 years, but the rate was significantly lower in tamoxifen users than controls, at 66.8% versus 75.2% and a hazard ratio of 1.43.

The highest rates of drop out occurred between 12 and 18 months, with 12.2% of tamoxifen users and 7.4% of placebo-treated patients discontinuing their treatment; by 12 months there was a significant difference in adherence between the groups and this discrepancy continued to widen until month 54.

Women using tamoxifen and women with menopausal symptoms at baseline were significantly less likely to continue treatment than placebo-treated patients and those without symptoms, respectively, with odds ratios (ORs) of 0.67 and 0.73, after adjusting for factors such as age, body mass index, history of hysterectomy and number of relatives affected by breast cancer.

Current smokers were also significantly less likely to adhere to treatment than never smokers (OR=0.57), as were users or former users of hormone replacement therapy at baseline than never users (OR=0.81 and 0.67, respectively).

By contrast, patients were more likely to adhere to treatment if they were premenopausal (OR=1.29), older (OR=1.03 per year), or if they had a higher Tyrer-Cuzick 10-year breast cancer risk score (OR=1.03 per 1% increase).

At 6 months, the tamoxifen and placebo groups had comparable rates of nausea or vomiting (5.6 vs 4.5%) and headache (7.3 vs 6.8%), but tamoxifen users had significantly higher rates of gynaecological symptoms (28.9 vs 14.2%) and hot flashes (44.2 vs 20.5%).

Further analysis revealed that 53% of nonadherence to treatment could be explained by the assigned treatment and 22% by prior reporting of symptoms experienced at 6 months, say Samuel George Smith et al.

They note that women who experienced nausea or vomiting were less likely to be adherent than those who did not, regardless of whether they were using tamoxifen or placebo (OR=0.57 and 0.58, respectively).

Headache was significantly linked to adherence only in the placebo arm (OR=0.62) whereas gynaecological symptoms were associated with adherence only in the tamoxifen users (OR=0.77) and hot flash symptoms were not associated with adherence in either group.

Although most patients said their symptoms at 6 months were mild or moderate, adherence reduced with increasing severity of each symptom and these were significant relationships except for headache, the team adds.

Discussing their findings in the Journal of Clinical Oncology, the authors emphasize the importance of addressing patient concerns about medication symptoms before preventive tamoxifen is initiated, as well as ensuring patients understand the prevalence and natural history of normal bodily changes with age and menopause.

“These discussions may encourage more realistic expectations of the likelihood of experiencing adverse effects, which have been shown to be powerful drivers of subsequent experience and adherence in the adjuvant setting”, they conclude.


Smith SG, Sestak I, Howell A, Forbes J, Cuzick J. Participant-reported symptoms and their effect on long-term adherence in the International Breast Cancer Intervention Study I (IBIS I). J Clin Oncol; Advance online publication 29 June 2017. DOI: 10.1200/JCO.2016.71.7439

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