Findings from the study were reported at the 12th European Breast Cancer Conference.
Dr. Lynda Wyld
“Primary endocrine therapy is usually reserved for older, less fit, and frail women. Rates of use vary widely,” noted investigator Lynda Wyld, MBChB, PhD, of the University of Sheffield (England).
“Although there is no set threshold for who is suitable, some women are undoubtedly over- and undertreated for their breast cancer,” she added.
Dr. Wyld and colleagues undertook the Age Gap study among women older than 70 years with breast cancer recruited from 56 U.K. breast units during 2013-2018.
The main goals were to determine which women can be safely offered primary endocrine therapy as nonstandard care and to develop and test a tool to help women in this age group make treatment decisions.
The first component of the study was a multicenter, prospective cohort study of women with ER+ disease who were eligible for surgery. Results showed that breast cancer–specific mortality was greater with primary endocrine therapy than with surgery in the entire cohort. However, breast cancer–specific mortality was lower with primary endocrine therapy than with surgery in a cohort matched with propensity scores to achieve similar age, fitness, and frailty.
The second component of the study was a cluster-randomized controlled trial of women with operable breast cancer, most of whom had ER+ disease. Results showed that a decision support tool increased awareness of treatment options and readiness to decide. The tool also altered treatment choices, prompting a larger share of patients with ER+ disease to choose primary endocrine therapy.
Prospective cohort study
The prospective observational study was conducted in 2,854 women with ER+ disease who were eligible for surgery and treated in usual practice. Most women (n = 2,354) were treated with surgery (followed by antiestrogen therapy), while the rest received primary endocrine therapy (n = 500).
In the entire cohort, patients undergoing surgery were younger, had a lower level of comorbidity, and were less often frail. But these characteristics were generally similar in a propensity-matched cohort of 672 patients.
At a median follow-up of 52 months, overall and breast cancer–specific survival were significantly poorer with primary endocrine therapy versus surgery in the entire cohort but not in the propensity-matched cohort.
In the entire cohort, the breast cancer–specific mortality was 9.5% with primary endocrine therapy and 4.9% with surgery. In the propensity-matched cohort, breast cancer–specific mortality was 3.1% and 6.6%, respectively.
The overall mortality was 41.8% with primary endocrine therapy and 14.6% with surgery in the entire cohort, but the gap narrowed to 34.5% and 25.6%, respectively, in the propensity-matched cohort.
In the latter, “although there is a slight divergence in overall survival and it’s likely that with longer-term follow-up this will become significant, at the moment, it isn’t,” Dr. Wyld commented.
Curves for breast cancer–specific survival basically overlapped until 5 years, when surgery started to show an advantage. The rate of locoregional recurrence or progression was low and not significantly different by treatment.
None of the women in the entire cohort died from surgery. “But it’s worth bearing in mind that these were all women selected for surgery, who were thought to be fit for it by their surgeons. The least fit women in this cohort will have obviously been offered primary endocrine therapy,” Dr. Wyld cautioned.
Although 19% of patients had a surgical complication, only 2.1% had a systemic surgical complication.