Evaluation of screening and risk-reducing surgery for women followed in a high-risk breast/ovarian cancer clinic: it is all about the tubes in BRCA mutation carriers

1518 Background: We prospectively evaluated the timing and uptake of risk-reducing surgery in a cohort of female BRCA mutation carriers that have no personal cancer history (“previvors”). Methods: Patients at high risk of breast and ovarian cancer were enrolled between 2007 and 2011 and followed in a high-risk ovarian cancer screening clinic. Women were offered risk-reducing salpingo-oophorectomy (RRSO) and/or prophylactic mastectomy (PM) per guidelines. Their clinical data were recorded and analyzed using descriptive statistics. Results: Of 260 BRCA mutation carriers enrolled, 73 have no personal history of cancer and are “previvors.” Patients have been followed for a median of 26.5 months (1-50 months). The median age is 38 years, 81.1% are white, 16.2% are Ashkenazi Jewish, and 79.7% are premenopausal. BRCA1 carriers account for 43.2% of participants and 55.4% have a BRCA2 mutation. The majority of patients (77.6%) presented for ovarian cancer screening <1 year after their BRCA testing. In all, 60.8% of women underwent prophylactic surgery: 28.4% chose RRSO, 18.9% chose PM, and 13.5% chose both procedures. Postmenopausal women were more likely to choose RRSO, while uptake for both procedures was common for premenopausal women (Table, p=0.04). RRSO was also more likely in parous than nulliparous premenopausal women (35.2% vs 9% p=0.001). PM was not associated with parity (p=0.79). Of women that had both surgeries, 20% had them concurrently and 20% had PM first. Of the 60% that underwent RRSO first, all had their second surgery within 14 months. Conclusions: BRCA mutation “previvors” have a high overall uptake of prophylactic surgery. Premenopausal women are more likely to choose PM than postmenopausal women; reasons for this are unclear. “Previvors” that choose RRSO and PM typically have both surgeries within a fairly short timeframe. With the growing population of “previvors” in the US, further study of patient preferences regarding preventative surgery and long-term consequences is needed. [Table: see text]

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Comparison of risk-reducing surgery in women with BRCA and non-BRCA ovarian cancer susceptibility genes.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.1547 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 1547-1547

Author(s):

Zachary Phillip Schwartz ◽

Mae Zakhour ◽

Andrew John Li ◽

Christine S. Walsh ◽

Bj Rimel ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Susceptibility ◽

Brca Mutation ◽

Susceptibility Genes ◽

Brca Mutations ◽

Cancer Susceptibility Genes ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

History Of ◽

Risk Reducing

1547 Background: Risk reducing gynecologic surgery (RRSO) is standard of care for women with BRCA mutations. The optimal management for women with non-BRCA ovarian cancer susceptibility mutations remains unclear. We sought to characterize the practice patterns for these women at our two institutions. Methods: Women with germline ovarian cancer susceptibility genes who had a RRSO were identified from 1/2000-1/2019 in an IRB approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. Continuous variables were analyzed with Kruskal-Wallis and categorical variables analyzed with chi square and t-tests. Results: 152 BRCA1, 95 BRCA2, and 63 Non-BRCA mutation carriers were identified—50 Lynch (22 MLH1, 13 MSH2, 13 MSH6, 2 PMS2) and 13 Other (6 BRIP1, 2 RAD51C, 5 RAD51D). There was no difference between age at testing, age at RRSO, and interval between testing and RRSO between groups. Genetic counseling was higher in Non-BRCA patients. Family history of ovarian cancer was more common in women with BRCA1 and Other germline mutations compared to BRCA2 and Lynch. Family and personal history of breast cancer was high in all groups except Lynch carriers. Prophylactic mastectomy was seen mostly in BRCA mutation carriers. Concomitant hysterectomy was performed in the majority of women (BRCA1 59%, BRCA2 57%, and Other 62%), with the highest frequency in Lynch carriers (86%, p<.01). Occult cancer was only seen in BRCA mutation carriers: BRCA1 (7%), BRCA2 (2%), Lynch (0%), Other (0%). Conclusions: In this cohort, women with Non-BRCA mutations are managed similarly to women with BRCA mutations. We observed no occult cancers in Non-BRCA patients. The optimal role of surgery as a risk reducing strategy in this group requires further study. [Table: see text]

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Pathologic findings at risk-reducing salpingo-oophorectomy among women at increased ovarian cancer risk: Results from GOG-199.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1519 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1519-1519 ◽

Cited By ~ 3

Author(s):

Phuong L. Mai ◽

Mark E Sherman ◽

Marion Piedmonte ◽

Olga B. Ioffe ◽

Brigitte M. Ronnett ◽

...

Keyword(s):

Ovarian Cancer ◽

Family History ◽

Brca Mutation ◽

Brca2 Mutation ◽

Ovarian Cancer Risk ◽

Strong Family History ◽

Mutation Carriers ◽

Pelvic Cancer ◽

Brca Mutation Carriers ◽

Risk Reducing

1519 Background: Although risk-reducing salpingo-oophorectomy (RRSO) is a standard management option for women with BRCA1/2 mutations, the lack of large, prospective cohort studies makes estimating the prevalence of cancer at RRSO problematic. Methods: GOG-199 is a large, non-randomized multi-center trial which enrolled women at high-risk (due to BRCA mutations or strong family history) of ovarian cancer, comparing surgery at enrollment with serial transvaginal ultrasound and CA-125 screening. RRSO specimens were processed according to a standardized tissue processing protocol including 2-3mm sectioning of both ovaries and tubes. Results: 2,605 participants were accrued to GOG-199. Of the 1 030 enrolled in the baseline RRSO cohort, 28 were ineligible and 36 declined surgery after enrollment, resulting in 966 baseline RRSO. Pathology review demonstrated 4 tubal intraepithelial carcinoma and 20 serous pelvic cancers, of which 12 were identified only microscopically. Among the 20 serous cancers, the predominant or exclusive site of involvement was ovary in 10, fallopian tube in 5, and peritoneum in 5 cases. In addition, 6 endometrial cancers (among the 515 undergoing concomitant hysterectomy) and 3 adenocarcinomas suggestive of metastasis were identified. The serous pelvic cancer prevalence was: entire cohort=2.1% (20/966), all BRCA mutation carriers=3.2 (18/558), BRCA1 mutation carriers=3.7% (12/325), BRCA2 mutation carriers=2.6% (6/231), and mutation-negative=0.5% (2/402). Compared to those without cancer, women with serous pelvic cancer were older at surgery (p< .001), and more often menopausal (vs pre-menopausal, p= .002), nulliparous (vs parous, p=.04) and never users of tamoxifen (vs ever users, p= .04). Serous pelvic cancers were more frequent in BRCA mutation carriers (vs no mutation, p= .004), and among carriers, more common in those with BRCA1 mutations (vs BRCA2 mutation, p= .02). Conclusions: The prevalence of serous pelvic cancers in this cohort was 3.2% among carriers vs 0.5% among the mutation-negative but with a strong family history. Our data will be useful when counseling women at increased ovarian cancer risk who are contemplating risk-reducing surgery.

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