Abstract
To assess clinical and surgical factors affecting local recurrence and survival in young breast cancer patients in the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH). Emerging data suggest young age is a predictor of increased local recurrence. POSH is a prospective cohort of 3024 women of 18 to 40 years with breast cancer. Cohort characteristics were grouped by mastectomy or BCS. Endpoints were local-recurrence interval (LRI), distant disease-free interval (DDFI), and overall survival (OS); described using cumulative-hazard and Kaplan-Meier plots and multivariable analyses by Flexible Parametric and Cox regression models. Mastectomy was performed in 1464 patients and breast-conserving surgery (BCS) in 1395. Patients undergoing mastectomy had larger tumors and higher proportions of positive family history, estrogen receptor+, progesterone receptor+, and/or human epidermal growth factor receptor 2+ tumors. Local events accounted for 15% of recurrences. LRI by surgical type varied over time with LRI similar at 18 months (1.0% vs 1.0%, P = 0.348) but higher for BCS at 5 and 10 years (5.3% vs 2.6%, P < 0.001; and 11.7% vs 4.9%, P < 0.001, respectively). Similar results were found in the adjusted model. Conversely, distant-metastases and deaths were lower for BCS but not after adjusting for prognostic factors. After mastectomy chest-wall radiotherapy was associated with improved LRI (hazard ratio, HR = 0.46, P = 0.015). Positive surgical margins, and development of local recurrence predicted for reduced DDFI (HR = 0.50, P < 0.001; and HR = 0.29, P = 0.001, respectively). Surgical extent appears less important for DDFI than completeness of excision or, where appropriate, chest-wall radiotherapy. Despite higher local-recurrence rates for BCS, surgical type does not influence DDFI or OS after adjusting for known prognostic factors in young breast cancer patients.
Highlights
Surgical extent appears less important for distant disease-free interval (DDFI) than completeness of excision or, where appropriate, chest-wall radiotherapy
Young women have been found to develop more aggressive tumors coupled with lower survival and higher local-recurrence rates (LRR) than older women,[2,3,4,5,6,7,8,9] and this may be a particular issue in the developing world where a greater proportion of breast cancer appears in women of young age.[7,8]
Randomized controlled trials (RCTs) suggest equivalent survival for mastectomy and breast-conserving surgery (BCS), very few young patients were included in these analyses.[6,14]
Summary
Study Population POSH (MREC: 00/06/69) is a multicenter prospective observational cohort study of 3000 young women diagnosed with breast cancer in the UK between 2000 and 2008 (http://www.southampton.ac.uk/medicine/research/posh.page). All patients received treatment according to local protocols. The detailed study protocol was published in 2007,22 and the cohort previously described.[23]. For this analysis, type of surgery was defined as the final oncological surgery to the breast for example, if a patient had BCS followed by mastectomy 3 months; this was classed as a mastectomy. Margin status was the final surgical margin after oncological operation(s), and a positive margin was defined according to American Society for Clinical Oncology (ASCO) guidance as tumor at the margin (ie, tumor on ink).[24] This article presents analyses conducted on follow-up data from the POSH cohort received until June 26, 2015
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