Risk of second non-breast primary cancer in Chinese breast cancer patients with germline BRCA1/2 pathogenic variants

Abstract

Purpose: The risk of second non-breast primary cancer in Chinese women with breast cancer who carry germline BRCA1/2 pathogenic variants (PVs) is largely unknown.

Methods: From October 2003 to February 2023, 11,212 women with breast cancer were recruited. BRCA1/2 mutation status of these patients was determined; the age-specific cumulative risk of second non-breast primary cancer was estimated.

Results: Of the 11,212 breast cancer patients, 284 carried BRCA1 PVs, 433 carried BRCA2 PVs, and 10,495 were non-carriers. After a median follow-up of 8.4 years, 10.9% of BRCA1 carriers, 7.2% of BRCA2 carriers, and 3.6% of non-carriers developed second non-breast primary cancers; and 6.7% of BRCA1 carriers, 1.4% of BRCA2 carriers, and 0.1% of non-carriers developed ovarian cancer. Cumulative risks of second primary cancer to age 70 years were 28.4% for BRCA1 carriers, 17.3% for BRCA2 carriers, and 6.2% for non-carriers. Cumulative risks of ovarian cancer to age 70 years were 19.8% for BRCA1 carriers, 3.9% for BRCA2 carriers, and 0.4% for non-carriers. No BRCA1 and BRCA2 carriers developed ovarian cancer before the ages of 40 and 45 years, respectively. BRCA2 carriers had higher risks of thyroid cancer (relative risk [RR] 2.16; 95% CI, 1.04-4.51; P = 0.039) and endometrial adenocarcinoma (RR 3.90; 95% CI, 1.47-10.32; P = 0.006) than non-carriers.

Conclusions: BRCA1/2 carriers exhibit a 2- to 3-fold higher risk of second primary cancer than non-carriers. Ovarian cancer represents the majority of second primary cancers in BRCA1 carriers, while BRCA2 carriers have a wider spectrum of second primary cancers.

Keywords: BRCA1/2 pathogenic variant; Cumulative risk; Ovarian cancer; Second primary cancer.