Microscopic and early-stage ovarian cancers in brca1/2 mutation carriers: Building a model for early BRCA-associated tumorigenesis

Risk-reducing salpingo-oophorectomy (RRSO) is the cornerstone of ovarian cancer prevention in BRCA1/ 2 mutation carriers. Occult fallopian tube and ovarian cancers have been reported in a small percentage of BRCA1/2 mutation carriers undergoing RRSO. Here, we review our single-institution experience with RRSO in BRCA1/2 mutation carriers to characterize cases of microscopic cancers in these patients. At the time of RRSO, 7.9% of BRCA1 mutation carriers were diagnosed with microscopic fallopian tube or ovarian cancers and no cases were diagnosed in BRCA2 mutation carriers. The majority of the microscopic cancers include cases that were confined to the fallopian tubes, although there were also cases involving ovaries only or peritoneal washings only. This suggests that the site of origin may be in the ovary, fallopian tube, or peritoneum for BRCA-associated serous cancers. However, an analysis of early-stage (stages I and II) ovarian and fallopian tube cancers diagnosed in BRCA1/2 mutation carriers confirms that the ovary is a preferred site for tumor growth with 11 of 14 early-stage cancers having a dominant ovarian mass. Overall, these data suggest that cancer initiation may occur in the ovary, fallopian tube, or peritoneum, but tumor growth and progression are favored in the ovary. We present an updated model for BRCA1/2 mutation-associated ovarian and fallopian tube carcinogenesis, which may aid in identifying improved prevention strategies for high-risk women who delay or decline RRSO.