Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus).

BACKGROUND Several studies have evaluated the clinical effectiveness of endocrine therapy alone in women aged 70 years or over with operable breast cancer and who are fit for surgery. OBJECTIVES To systematically review the evidence for the clinical effectiveness of surgery (with or without adjuvant endocrine therapy) in comparison to primary endocrine therapy in the treatment of operable breast cancer in women aged 70 years and over, both in terms of local progression and mortality. SEARCH METHODS We conducted an updated search of the Cochrane Breast Cancer Group's Specialised Register (27th March 2013) and new searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 3), MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and www. CLINICALTRIALS gov, using the search terms 'early breast cancer', 'endocrine therapy', 'psychosocial' or 'surgery'. SELECTION CRITERIA Randomised trials comparing surgery, with or without adjuvant endocrine therapy, to primary endocrine therapy in the management of women aged 70 years or over with early breast cancer and who were fit for surgery. DATA COLLECTION AND ANALYSIS We assessed studies for eligibility and quality, and two review authors independently extracted data from published trials. We derived hazard ratios for time-to-event outcomes, where possible, and used a fixed-effect model for meta-analysis. We extracted toxicity and quality-of-life data, where present. Where outcome data were not available, we contacted trialists and requested unpublished data. MAIN RESULTS We identified seven eligible trials, of which six had published time-to-event data and one was published only in abstract form with no usable data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen. Data, based on an estimated 1081 deaths in 1571 women, did not show a statistically significant difference in favour of either surgery or primary endocrine therapy in respect of overall survival. However, there was a statistically significant difference in terms of progression-free survival, which favoured surgery with (474 participants) or without endocrine therapy (164 participants). The hazard ratios (HRs) for overall survival were: HR 0.98 (95% confidence interval (CI) 0.81 to 1.20, P = 0.85; 3 trials, 495 participants) for surgery alone versus primary endocrine therapy; HR 0.86 (95% CI 0.73 to 1.00, P = 0.06; 3 trials, 1076 participants) for surgery plus endocrine therapy versus primary endocrine therapy. The HRs for progression-free survival were: HR 0.55 (95% CI 0.39 to 0.77, P = 0.0006) for surgery alone versus primary endocrine therapy; HR 0.65 (95% CI 0.53 to 0.81, P = 0.0001) for surgery plus endocrine therapy versus primary endocrine therapy (each comparison based on only one trial). Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included paraesthesia on the ipsilateral arm and lateral thoracic wall in those who had axillary clearance. One study suggested that those undergoing surgery suffered more psychosocial morbidity at three months post-surgery, although this difference had disappeared by two years. AUTHORS' CONCLUSIONS Primary endocrine therapy should only be offered to women with oestrogen receptor (ER)-positive tumours who are unfit for surgery, at increased risk of serious surgical or anaesthetic complications if subjected to surgery, or who refuse surgery. In a cohort of women with significant co-morbid disease and ER-positive tumours it is possible that primary endocrine therapy may be a superior option to surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for an infirm older population with ER-positive tumours.