摘要：

11506 Background: Very limited data are available on the safety of pregnancy and reproductive outcomes in mBRCA pts with prior BC history. We report the results of the largest study to date addressing these questions. Methods: This international, multicenter, hospital-based, retrospective cohort study included consecutive pts with invasive early BC (stage I-III) diagnosed between Jan-2000 and Dec-2012 at the age of ≤40 years and carrying a deleterious germline mBRCA. Primary endpoints were pregnancy rate and disease-free survival (DFS); overall survival (OS) and pregnancy outcomes were secondary endpoints. To account for guarantee-time bias, we performed two survival analyses: 1) Case-control approach matching pregnant and non-pregnant (1:3) pts for classic prognostic factors (each non-pregnant control had a disease-free interval ≥ than the time elapsing between BC diagnosis and date of pregnancy of the matched pregnant case); 2) Extended Cox model with time-varying covariates including all pts. Results: 1,252 mBRCA BC pts (811 mBRCA1, 430 mBRCA2, 11 mBRCA1&2) were included from 30 centers worldwide, of whom 195 pts had a pregnancy (pregnancy rate = 16% [95% CI 14-18]) after a median 4.5 years (range 3.1-6.7 years) following BC diagnosis. Pregnant pts were younger and had more ER-negative tumors (all p < 0.01). 16 (8.2%) and 20 (10.3%) pts had an induced and spontaneous abortion, respectively. Among the 150 (76.9%) pts who conceived (n = 170 babies), pregnancy complications and congenital anomalies were described in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up was 8.3 years (range 8.1-8.7 years). In the case-control analysis, pregnant pts had better DFS (HR 0.71; 95% CI 0.51-0.99; p = 0.045), with no difference in OS (HR 0.86; 95% CI 0.44-1.67; p = 0.65). Subgroup analysis suggested that the superior outcome was restricted to mBRCA1 pregnant pts (p-interaction < 0.01). Similar results were obtained in the second supportive analysis. Conclusions: Pregnancy following BC is safe in mBRCA pts, particularly mBRCA1, with no detrimental impact on maternal prognosis or fetal outcomes . These findings are of paramount importance for fertility counseling in young mBRCA BC pts.

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