| Summary: | Background: Old age is associated with increased co-morbidities, resulting in reduced life expectancy. Primary endocrine therapy is an alternative to primary surgical therapy for patients with breast cancer and increased co-morbidities. The aim was to review outcomes of primary endocrine therapy versus primary surgical therapy in older women with breast cancer. Methods: PubMed, Embase (Ovid), Scopus, and the Cochrane Library were searched systematically from January 2000 to May 2022. Single-arm studies were excluded. Primary outcomes were overall survival and breast cancer-specific survival. Secondary outcomes were local and regional failure of primary endocrine therapy, recurrence after primary surgical therapy, and health-related quality of life. Results: There were 14 studies including 14 254 patients (primary endocrine therapy 2829, 19.8 per cent; primary surgical therapy 11 425, 80.2 per cent), with the addition of four major studies (9538 patients) compared with the latest review in 2014. Seven studies defined primary surgical therapy as surgery plus adjuvant endocrine therapy, and six studies included patients with oestrogen receptor-positive tumours only. Patients in the primary endocrine therapy group were older than the primary surgical therapy group (mean difference 2.43 (95 per cent c.i. 0.73 to 4.13) years). Primary endocrine therapy led to worse overall survival than primary surgical therapy (HR 1.42, 95 per cent c.i. 1.06 to 1.91). Subgroup analysis of RCTs and prospective studies, however, showed comparable overall survival. Breast cancer-specific survival was also comparable (HR 1.28, 95 per cent c.i. 0.87 to 1.87). At 6 weeks, operated patients had significant arm symptoms and illness burden following major breast surgery compared with patients receiving primary endocrine therapy. Health-related quality of life, measured by the European Organization for Research and Treatment of Cancer QLQ-C30 and EuroQol EQ-5D-5L™, was comparable in the two treatment groups. Conclusion: Overall survival was worse among older women receiving primary endocrine therapy in an analysis including all studies, but comparable in RCTs and prospective studies. This may be due to confounding by age and co-morbidities in retrospective cohort studies of primary endocrine therapy.
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