Subsequent breast and high grade serous carcinomas after risk-reducing salpingo-oophorectomy in BRCA mutation carriers and patients with history of breast 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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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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BRCA mutation carriers undergoing combined mastectomy with immediate reconstruction and gynecologic risk-reducing surgery: An analysis of outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13004 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13004-e13004

Author(s):

Olga Ivanov ◽

Nicole Centers ◽

Karen Wiercinski ◽

Eva Reina ◽

Cynthia Buffington ◽

...

Keyword(s):

Breast Cancer ◽

Minimally Invasive ◽

Operative Time ◽

Brca Mutation ◽

Immediate Reconstruction ◽

Postoperative Wound ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

Multidisciplinary Model ◽

Risk Reducing

e13004 Background: The aim of this study was to assess outcomes of a multidisciplinary model for combined prophylactic and/or therapeutic mastectomy with immediate reconstruction and gynecologic risk-reducing surgery in patients with hereditary breast cancer syndromes. Methods: Between 2012 and 2016, 12 patients with documented BRCA1 and BRCA2 mutations underwent combined surgery at our facility. Procedures included bilateral mastectomy, axillary lymph node staging, immediate expander based reconstruction and minimally invasive salpingo-oophorectomy with added hysterectomy when indicated. All procedures were performed in a single operating room setting by rotating subspecialty teams. Results: Patient characteristics included a mean (+SD) BMI of 32.1±6.7 (23-44) kg/m2 and ASA of 2.2±0.4 (2-3). Fifty-eight percent (7/12) were premenopausal. Patient’s average age was 45.8+10.8 (30-73). Therapeutic mastectomy for breast cancer was performed in 4/12 patients. Of the 4 affected patients 2 had neo-adjuvant chemotherapy for locally advanced cancer. The remaining 8/12 had prophylactic mastectomies. Risk-reducing salpingo-oophorectomy was performed in 12/12 patients. Seventy-five percent (9/12) underwent concurrent minimally invasive hysterectomy for suspected gynecologic malignancy, leiomyoma, complex endometrial hyperplasia, dysmenorrhea and menorrhagia. Two gynecologic specimens required mini-laparotomy for removal. Mean total operative time was 283.3±66.5 (206-447) minutes and estimated blood loss (EBL) was 209.2±139.2 (50-500) ml. Hospital length of stay (LOS) was 1.4±0.7 (1-3) days. There were no significant differences (p > 0.05) in operative time, EBL, or LOS in comparing therapeutic to prophylactic mastectomies. Follow-up revealed no postoperative wound infections. Conclusions: Combined mastectomy with immediate reconstruction and gynecologic risk reducing surgery had no untoward surgical complications with a zero postoperative wound infection rate. Although a small study population, results indicate this approach is a prudent and feasible multidisciplinary model that can be offered to BRCA mutation carriers.

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Risk-reducing salpingo-oophorectomy and breast cancer incidence among BRCA-mutation carriers.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10548 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10548-10548

Author(s):

Tamar Perri ◽

Shani Naor-Ravel ◽

Perry Eliassi-Revivo ◽

Dror Lifshitz ◽

Eitan Friedman ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Incidence ◽

Brca Mutation ◽

Brca2 Mutation ◽

Breast Cancer Incidence ◽

Mutation Carriers ◽

Age At Surgery ◽

Significant Difference ◽

Brca Mutation Carriers ◽

Risk Reducing

10548 Background: Uncertainty exists with regard to the role of bilateral salpingo-oophorectomy in altering the risk of breast cancer in BRCA-mutation carriers. Methods: Included were 1645 healthy Jewish Israeli BRCA1/2 -mutation carriers from a single center without prophylactic mastectomy. Carriers with and without risk-reducing bilateral salpingo-oophorectomy (RRBSO) were matched according to BRCA-mutation type (BRCA1 vs. BRCA2) and year of birth (±1 year). Hormonal and reproductive variables were compared and incidence of breast cancer recorded. Association between RRBSO and breast cancer was studied. Results: Seventy-seven and 50 matched-pairs had BRCA1 and BRCA2 mutation respectively. Fifty-two carriers had breast cancer, 21 in RRBSO-group and 31 in no- RRBSO group, with no statistically significant difference. When analysing each mutation group separately, stratified by age at surgery, no association between RRBSO and breast cancer incidence was found among BRCA1-mutation carriers. However, in BRCA2 mutation carriers, RRBSO was associated with a statistically significant decreased overall incidence of breast cancer, HR = 0.2 (confidence interval 0.44-0.913, p = 0.038). Breast cancer incidence was lower after 5, 10,15 and 20 years in BRCA2-mutation carriers with RRBSO compared to no-RRBSO. Age at menarche, age at surgery, parity and oral contraceptive use were not significant risk factors for breast cancer. Hormone replacement therapy was used by 62 mutation carriers, 52 in the RRBSO group and 10 in the no-RRBSO group, and its use did not alter breast cancer risk (p = 0.463). Conclusions: According to our findings, RRBSO is associated with a reduced risk of breast cancer only in BRCA2 mutation carriers, regardless of HRT use.

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Risk-Reducing Bilateral Salpingo-Oophorectomy for BRCA Mutation Carriers and Hormonal Replacement Therapy: If It Should Rain, Better a Drizzle than a Storm

Medicina ◽

10.3390/medicina55080415 ◽

2019 ◽

Vol 55 (8) ◽

pp. 415

Author(s):

Maria Luisa Gasparri ◽

Katayoun Taghavi ◽

Enrico Fiacco ◽

Veronica Zuber ◽

Rosa Di Micco ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Replacement Therapy ◽

Brca Mutation ◽

Brca1 Mutation ◽

Effective Strategy ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

Risk Reducing

Women carrying a BRCA mutation have an increased risk of developing breast and ovarian cancer. The most effective strategy to reduce this risk is the bilateral salpingo-oophorectomy, with or without additional risk-reducing mastectomy. Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is recommended between age 35 and 40 and between age 40 and 45 years for women carriers of BRCA1 and BRCA2 mutations, respectively. Consequently, most BRCA mutation carriers undergo this procedure prior to a natural menopause and develop an anticipated lack of hormones. This condition has a detrimental impact on various systems, affecting both the quality of life and longevity; in particular, women carrying BRCA1 mutation, who are likely to have surgery earlier as compared to BRCA2. Hormonal replacement therapy (HRT) is the only effective strategy able to significantly compensate the hormonal deprivation and counteract menopausal symptoms, both in spontaneous and surgical menopause. Although recent evidence suggests that HRT does not diminish the protective effect of RRBSO in BRCA mutation carriers, concerns regarding the safety of estrogen and progesterone intake reduce the use in this setting. Furthermore, there is strong data demonstrating that the use of estrogen alone after RRBSO does not increase the risk of breast cancer among women with a BRCA1 mutation. The additional progesterone intake, mandatory for the protection of the endometrium during HRT, warrants further studies. However, when hysterectomy is performed at the time of RRBSO, the indication of progesterone addition decays and consequently its potential effect on breast cancer risk. Similarly, in patients conserving the uterus but undergoing risk-reducing mastectomy, the addition of progesterone should not raise significant concerns for breast cancer risk anymore. Therefore, BRCA mutation carriers require careful counselling about the scenarios following their RRBSO, menopausal symptoms or the fear associated with HRT use.

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