Context Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival.Objective To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. Design and SettingRetrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PatientsThe study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison.Main Outcome Measures Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advancedstage (III and IV) cases. ResultsHereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1-vs BRCA2-linked patients (54 vs 62 years; P= .04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (PϽ.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P = .03). ConclusionsAlthough BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advancedstage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

Objectives Our primary objective was to assess the detection rate of sentinel lymph nodes (SLNs) using indocyanine green (ICG) and near-infrared (NIR) fluorescence imaging for uterine and cervical malignancies. Methods NIR fluorescence imaging for the robotic platform was obtained at our institution in 12/2011. We identified all cases planned for SLN mapping using fluorescence imaging from 12/2011-4/2013. Intracervical ICG was the fluorophobe in all cases. Four cc (1.25 mg/mL) of ICG was injected into the cervix alone divided into the 3- and 9-o'clock positions, with 1 cc deep into the stroma and 1cc submucosally before initiating laparoscopic entry. Blue dye was concurrently injected in some cases. Results Two hundred twenty-seven cases were performed. Median age was 60 years (range, 28-90). Median BMI was 30.2 kg/m2 (range, 18-60). The median SLN count was 3 (range, 1-23). An SLN was identified in 216 cases (95%), with bilateral pelvic mapping in 179 (79%). An aortic SLN was identified in 21 (10%) of the 216 mapped cases. When ICG alone was used to map cases, 188/197 patients mapped, for a 95% detection rate compared to 93% (28/30) in cases in which both dyes were used (P=NS). Bilateral mapping was seen in 156/197 (79%) ICG-only cases and 23/30 (77%) ICG and blue dye cases (P=NS). Conclusions NIR fluorescence imaging with intracervical ICG injection using the robotic platform has a high bilateral SLN detection rate and appears favorable to using blue dye alone and/or other modalities. Combined use of ICG and blue dye appears unnecessary.

Importance The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. Objective To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. Design, Setting, and Participants This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0–8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. Main Outcomes and Measures Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. Results Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 – 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8–3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1–56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2–35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. Conclusions and Relevance Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.

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