Anticipation of Side Effects Makes Them Worse for Breast Cancer Patients

Negative expectations increase both the severity and number of side effects experienced by breast cancer patients undergoing hormone therapy, according to a study published in Annals of Oncology.

In a prospective cohort of 111 patients receiving adjuvant endocrine therapy, pretreatment expectations tended to match patient-reported 2-year outcomes and quality of life.

Patients received either 2 years of tamoxifen or an aromatase inhibitor such as exemestane.

Women who anticipated moderate to severe side effects had almost twice the number of side effects compared with patients who had relatively positive expectations for treatment: the ‘nocebo’-related effects accounted for a risk reduction of 45%.

The expectation of negative side effects prior to the start of treatment was also associated with adherence at 2 years (r = -0.25, P = .006). According to the study authors, the results show anticipation to be an important factor in maintaining adherence to endocrine therapy, which contributes to the effectiveness of treatment and outcomes, including survival.

“This finding is of high clinical relevance since nonadherence to adjuvant endocrine therapy predicts lower survival,” wrote Yvonne Nestoriuc, PhD, of the department of Psychosomatic Medicine and Psychotherapy at the University Medical Centre in Hamburg, Germany, and coauthors. “Expectation-modification interventions might be especially promising for patients with negative expectations who initially report high side effects.”

Prior to starting adjuvant therapy, 8.1% of patients expected no side effects, 63.1% of patients expected mild side effects, and 28.8% had expectations of moderate to severe side effects from their long-term treatment. The relative risk (RR) of side effects after 2 years of therapy was higher in patients with high negative expectations prior to the start of therapy compared to those with low negative expectations (RR, 1.833; CI 95%, 1.032–3.256). At 2 years, 71.3% of patients experienced arthralgia, 53.4% had weight gain, and 46.5% had hot flashes.

Besides known side effects of endocrine therapy, 31% of patients also reported back pain, 24.7% reported breathing problems, and 20.7% reported palpitations, none of which are directly attributable to treatment. “This substantiates the conclusion that psychological mechanisms such as negative expectations about the treatment play a significant role in the side effects breast cancer patients experience,” said Nestoriuc in a statement.

A limitation of the study, noted by the authors, is that almost 40% of patients who were eligible to participate did not, suggesting that these patients may already have had negative expectations about their course of hormone therapy.

The study authors are currently conducting a randomized and controlled trial to understand what, if any, strategies may be effective to improve breast cancer patients’ expectations about endocrine therapy.