Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer

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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Efficacy of risk-reducing mastectomy (RRM) on overall survival (OS) in BRCA1/2-associated breast cancer (BC) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1502 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1502-1502 ◽

Cited By ~ 2

Author(s):

Bernadette Anna Maria Heemskerk-Gerritsen ◽

Maartje Hooning ◽

Christi J van Asperen ◽

Margreet GEM Ausems ◽

Margriet Collée ◽

...

Keyword(s):

Brca Mutation ◽

Incidence Rates ◽

Dna Diagnosis ◽

Multicenter Cohort ◽

Mutation Carriers ◽

Time Period ◽

Brca Mutation Carriers ◽

Status Differentiation ◽

History Of ◽

Risk Reducing

1502 Background: RRM in BRCA1/2 mutation carriers with a history of unilateral BC significantly reduces the risk of developing contralateral BC (CBC). However, the outcome regarding OS is insufficiently known. Methods: The efficacy of RRM on CBC incidence and OS was studied in a Dutch multicenter cohort consisting of 515 BRCA-associated BC patients (399 BRCA1, 116 BRCA2) of whom 177 BRCA1 and 48 BRCA2 carriers underwent RRM. Data on patient, tumor and treatment characteristics were collected up to June 30, 2012. Women contributed person-years of observation (PYO) to the Non-RRM group from the date of primary BC (PBC) diagnosis or DNA diagnosis (whichever came last) to the date of death, RRM, or last contact. Contribution of PYO to the RRM group started at the date of RRM until similar endpoints as described for the Non-RRM group. Results: Regarding PBC, no significant differences in size, nodal status, differentiation grade, hormone and Her2Neu receptor, and endocrine therapy were observed between the Non-RRM and RRM group. Median age of PBC diagnosis was 42 years for Non-RRM and 38 for RRM women (p<0.001). Median time period between PBC and RRM was 2.3 years (range 0.02-20.1). PBC treatment included radiotherapy for 68% of Non-RRM versus 50% of RRM women (p< 0.001). Compared to Non-RRM, chemotherapy was more often given to RRM women (66% versus 49%; p<0.001), and more RRM women underwent risk-reducing salpingo-oophorectomy (81% versus 67%; p<0.001), while ovarian cancer incidence was not different. With a median FU of 11.7 years after PBC diagnosis, 58 CBC cases were observed in Non-RRM women, while 4 CBC cases occurred after RRM, yielding incidence rates (per 1000 PYO) of 30.6 and 2.5, respectively (adjusted HR 0.09, 95% CI 0.03-0.24). In the Non-RRM group 45 women died during 2408 PYO versus 17 women in the RRM group during 1756 PYO, yielding mortality rates (per 1000 PYO) of 18.9 and 9.7, respectively (adjusted HR 0.56, 95% CI 0.32-0.99). 10 year OS was 80% for the Non-RRM and 90% for the RRM group (p=0.008). Conclusions: RRM in BRCA mutation carriers with unilateral BC reduces CBC incidence and is associated with improved OS. Further research is needed to identify potential prognostic factors for this survival benefit.

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Risk‐Reducing Strategies for Ovarian Cancer in BRCA Mutation Carriers: A Balancing Act

The Oncologist ◽

10.1634/theoncologist.2016-0444 ◽

2017 ◽

Vol 22 (4) ◽

pp. 450-459 ◽

Cited By ~ 11

Author(s):

Roi Tschernichovsky ◽

Annekathryn Goodman

Keyword(s):

Ovarian Cancer ◽

Brca Mutation ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

Risk Reducing

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Practical assessment of psychosocial concerns associated with genetic testing in ovarian cancer patients using the MICRA questionnaire.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9569 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9569-9569

Author(s):

Merete Bjørnslett ◽

Alv A. Dahl ◽

Øystein Sørebø ◽

Anne Dørum

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Patients ◽

Brca Mutation ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

History Of ◽

Positive Experiences ◽

Explained Variance

9569 Background: Ten to 15% of ovarian cancer patients are BRCA mutation carriers. By offering genetic testing, families at risk and healthy female mutation carriers will be identified and offered clinical follow-up. The MICRA questionnaire was developed as a brief, practical, and targeted assessment of concerns and psychosocial issues associated with genetic testing. This study evaluates the practical and psychometric properties of the MICRA (Norwegian translation) in tested ovarian cancer patient. Methods: Since 2002, ovarian cancer patients at Oslo University Hospital, Norwegian Radium Hospital are offered genetic counseling and testing. By the end of 2009, 1,032 were included. The 530 (51%) patients still alive, were mailed the MICRA and three other instruments relevant for mental distress. 354 (67%) patients responded. Among them 9% were BRCA mutation carriers, 7% had a personal history of breast cancer, 29% had a family history of breast and/or ovarian cancer, and 55% had no such family history. Results: In the BRCA mutation carrier group, the total MICRA score and its subscale scores of distress, uncertainty, and positive experiences were all significantly higher than in the other groups. Confirmatory factor analyses of the three subscales of MICRA showed inadequate fit indices, while a four factors solution including the new factor of Support from family (items #18 and #19), showed adequate fit. The Positive Experiences subscale showed a maximum of 4% explained variance in relation to the Hospital Anxiety and Depression Scale total score, the Impact of Event Avoidance and Intrusion scores, and the Eysenck’s Neuroticism score. The subscales of Distress and Uncertainty showed maximum 12% and 41% explained variance, respectively, while the total MICRA score showed 22% explained variance. Conclusions: Our study supports the feasibility of the MICRA in ovarian cancer patients. Frail women may be identified for closer follow-up by using MICRA. Discrimant, content and construct validities of the MICRA were supported, while the factor structure still is open to further investigation.

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