Should breast conservation be offered to young women with breast cancer?

Abstract

A growing body of literature suggests that younger women with breast cancer have poorer outcomes including higher rates of local relapse compared to older women with similar disease features and treatment. This has been attributed to several factors including genetics, tumor biology, hormonal factors, and differences in competing risks and leads to questions and reservations regarding optimal management given the lack of randomized trial data explicitly focused on breast cancer treatment of younger women. Numerous randomized trials comparing breast conserving therapy (BCT; lumpectomy and radiation) to mastectomy for early stage breast cancer have convincingly demonstrated no detriment in overall survival to BCT [1–7]. Unfortunately, however, the relatively small number of young women on these trials and the lack of and/or conflicting subset analyses of the local relapse outcomes for young women treated on many of these trials makes it difficult to extrapolate these data to specifically address the efficacy of BCT for younger women. Such information would be of value because numerous retrospective reports have suggested that young women have high local recurrence rates after BCT compared to older women treated with BCT [2, 8–16]. To further complicate the existing analyses, reported local relapse rates are decreasing over time [17, 18] likely because the indications for effective systemic therapies are expanding, and understanding of the prognostic importance of factors not previously accounted for like tumor subtype is increasing. Both issues make it extremely difficult to interpret retrospective analyses regarding BCT for younger women treated today. With an age cut-off for younger generally being 35–40 years of age, numerous retrospective studies have attempted to shed light on this question and suggest that younger women experience local relapse rates of 20–40% after BCT for breast cancer [2, 8–16]. The question remains whether mastectomy with or without radiation would reduce these rates and increase overall survival in stage matched patients. In this issue, van der Sangen et al. report local relapse rates among 1,451 women under 40 treated with BCT or mastectomy ± post-mastectomy radiation for early stage breast cancer (refer this issue). They find that although systemic therapy significantly reduces local relapse rates, the annual recurrence risk remains *1% per year up to 15 years after treatment versus *1% per year for the first 5 years after mastectomy without further increase on longer follow up. These are compelling data from a large national database characterized by thorough follow up and standard management, but still fraught with the inherent biases of retrospective research: hidden confounders and imbalances between the groups related to biology, staging, treatment, and treatment era. Indeed, the authors note the local relapse rates decrease over the study period likely related to increased use of chemotherapy. Taking the results at face value, one might expect the reported differences in local relapse in this young cohort to translate into worse distant relapse free survival based on the results from the Early Breast Cancer Trialists’ Collaborative Group relating prevention of local relapse to outcome with long follow up [19]. However, multivariate analysis for factors related to distant metastasis revealed only the expected influences. Stage, use of systemic This is an invited commentary to article doi: 10.1007/s10549-010-1110-x.