Endometrial cancer (EC) is the most common gynecologic cancer in women. Although the prognosis of this neoplasm is generally good, with a 5-year survival rate around 81%, significant differences exist according to the histological classification of the disease. Indeed, patients diagnosed with the variant uterine papillary serous carcinoma (UPSC) have a halved 5-year survival (40%). UPSC may clinically mimic the high-grade serous ovarian cancer since both are characterized by a widespread disease, poor prognosis and similar standard-of-care (i.e., surgery followed by platinum-based chemotherapy). Given that approximately 15%-20% of patients with serous ovarian cancer carries a genetic mutation in breast cancer susceptibility genes type 1 or type 2 (BRCA1 or BRCA2), it has been supposed that UPSC could be part of the same hereditary syndrome. Previous authors have been shown around 25% of BRCA germline mutations in UPSC. The aim of the current study is to clarify the role of BRCA mutations in UPSC in large sample size, focusing on the prognostic effect of BRCA status.
UPSC is a rare cancer; however, even if it represents less than 10% of uterine cancers, it accounts for more than 50% of relapses and deaths attributed to endometrial carcinoma [Hendrickson M et al. 1982, Slomovitz BM et al. 2003, Nicklin JL et al. 1996].
Demonstrating that UPSC is an expression of hereditary breast/ovarian cancer syndrome, associated with a genetic mutation, could have at least two critical implications. Firstly, considering that the introduction of PARP-inhibitors has improved the prognosis of patients affected by ovarian cancer carrying a BRCA mutation, [Ledermann et al. 2012], a similar therapeutic approach could be tested in UPSC patients. Secondly, the strategy for cancer prevention in BRCA mutation carriers could change: from the screening to the prophylactic surgery.