Prognosis and Expanded Definition of Pregnancy-associated Breast Cancer: A Dose-Response Meta-Analysis
Abstract Background Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or postpartum period. Definitions of the duration in the postpartum have controversial and this variability may led to diverse results on the prognosis. Moreover, evidence on the dose-response association between the time from last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized. Methods We systematically searched PubMed, Embase, and the Cochrane Database for observational studies about the prognosis of PABC published up to June 1, 2019. We estimated summary adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosed time, PABC definition, geographic region, year of publication and the way of HR estimate were performed. Additionally, the dose–response analysis was conducted by using the variance weighted least-squares regression (vwls) trend estimation. Results A total of 54 articles (76 studies) were included in our study. PABC is associated with poor prognosis on overall survival (OS), disease-free survival (DFS) and cause-special survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30-1.63), 1.39 (1.25-1.54) and 1.40 (1.17-1.68), respectively. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a non-linear association between the time from last pregnancy to breast cancer diagnosis and overall mortality ( P <0.001). Compared with nulliparous women, PABC had a HR for all cause death that peaked at 1.62 (95% CI, 1.46-1.80) at 28 months since last pregnancy, starting from 78 months since last pregnancy became insignificant 1.07(95%CI, 0.99-1.26). It suggested that the definition of PABC should be extended to include cases diagnosed up to about six-years postpartum (78 months since last pregnancy) in order to capture this ongoing increased risk. Conclusion This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include cases diagnosed up to about six-years postpartum.