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Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Supplementary Table 1 - PDF file 57K, Supplementary Table 1. Details of platinum sensitivity and best response to olaparib and post-PARPi chemotherapy of the six patients whose tumor samples were analyzed by massively parallel sequencing. (NE: not evaluable)

Purpose: Preclinical data suggest that exposure to PARP inhibitors (PARPi) may compromise benefit to subsequent chemotherapy, particularly platinum-based regimens, in patients with BRCA1/2 mutation carrier ovarian cancer (PBMCOC), possibly through the acquisition of secondary BRCA1/2 mutations. The efficacy of chemotherapy in the PARPi-resistant setting was therefore investigated.Experimental Design: We conducted a retrospective review of PBMCOC who received chemotherapy following disease progression on olaparib, administered at ≥200 mg twice daily for one month or more. Tumor samples were obtained in the post-olaparib setting where feasible and analyzed by massively parallel sequencing.Results: Data were collected from 89 patients who received a median of 3 (range 1–11) lines of pre-olaparib chemotherapy. The overall objective response rate (ORR) to post-olaparib chemotherapy was 36% (24 of 67 patients) by Response Evaluation Criteria in Solid Tumors (RECIST) and 45% (35 of 78) by RECIST and/or Gynecologic Cancer InterGroup (GCIG) CA125 criteria with median progression-free survival (PFS) and overall survival (OS) of 17 weeks [95% confidence interval (CI), 13–21] and 34 weeks (95% CI, 26–42), respectively. For patients receiving platinum-based chemotherapy, ORRs were 40% (19 of 48) and 49% (26/53), respectively, with a median PFS of 22 weeks (95% CI, 15–29) and OS of 45 weeks (95% CI, 15–75). An increased platinum-to-platinum interval was associated with an increased OS and likelihood of response following post-olaparib platinum. No evidence of secondary BRCA1/2 mutation was detected in tumor samples of six PARPi-resistant patients [estimated frequency of such mutations adjusted for sample size: 0.125 (95%-CI: 0–0.375)].Conclusions: Heavily pretreated PBMCOC who are PARPi-resistant retain the potential to respond to subsequent chemotherapy, including platinum-based agents. These data support the further development of PARPi in PBMCOC. Clin Cancer Res; 19(19); 5485–93. ©2013 AACR.

Family history screening to identify individuals at increased risk for hereditary cancers could be a powerful strategy to prevent cancer but is used inconsistently in primary care. The objective was to improve identification of women with at-risk family histories using a point-of-care family history screening tool administered on an electronic tablet device during well-woman appointments. A total of 288 women were invited to participate and 136 women (47.2%) completed the electronic family history screening tool. Significantly more women were identified and referred to the genetics department with the electronic family history screening tool than the standard-of-care paper questionnaire (11.8% versus 0.8%, P < 0.001). There were no statistically significant differences in the proportion of referred women who were evaluated by the genetic counselors, and no pathogenic variants were found with either family history screening method. Implementing innovative self-reporting tools may improve inherited cancer risk detection.

To describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing.Examination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California.A total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p0.001, 5.3% (p0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p0.001) and for unknown risk 0.4% (p0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV.Surgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.

Objective To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Methods Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. Results A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). Conclusion A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies.A retrospective study of endometrial cancer (EC) cases from 2 regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified.During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among womenage 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and1% were possible LS. In the universal group, 87% of women age60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (60: 3% vs. 3.6%, p=0.62; ≥60:1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04-0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18-0.80).Universal IHC screening did not result in increased LS detection in EC.

Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testing within 12 months after a new cancer diagnosed between August 1, 2013 and December 31, 2018. For patients meeting institutional criteria for HBOC testing, 60.6% were referred for genetic counseling, 88% of whom underwent germline testing; at least one pathogenic variant was found in 15.3%. Referral rates for patients with breast (69%) or ovarian cancer (65.7%) were much higher than for metastatic prostate (11.1%, p 0.0001) or pancreatic cancer (22.3%, p 0.0001); referral criteria were implemented more recently for the latter two cancers. Younger age, family history, and chemotherapy were associated with referral. Higher Elixhauser comorbidity score and prior cancer were associated with non-referral. No other factors were associated with genetic referral for all eligible cancers combined, although differences were seen in specific cancers. Race was a significant factor only for breast cancer, with fewer Asians than Whites referred. Health disparities in referral to genetics for HBOC cancers are mitigated in a comprehensive integrated health care system.

Highlights • Rate of breast cancer diagnosis after ovarian cancer in women with BRCA pathogenic mutations was 14.5%. • The majority of breast cancers, 87%, were diagnosed at stage 0-II. • Median times from ovarian cancer to breast cancer diagnosis was 80 months., Objective Evaluate the incidence and characteristics of breast cancers (BC) diagnosed following an epithelial ovarian cancer (EOC) diagnosis in women with pathogenic BRCA mutations. Methods Retrospective cohort study of all women in an integrated healthcare system with BRCA mutations diagnosed with EOC from 1/1/1997–12/31/2018. Primary outcome was rate of subsequent BC diagnosis. Secondary outcomes included risk factors associated with development of BC, median time to detection following EOC, and method of detection. Results There were 284 women with BRCA-associated EOC identified. Fifty-two women had risk-reducing mastectomy and were excluded. Of the 232 eligible women with a median follow-up of 5.6 years, 33 (14%) women were diagnosed with BC following EOC: 27 (11%) new cases and 6 (3%) recurrences. Twelve (36%) cases of BC were detected on screening mammogram, 4 (12%) on screening MRI, and 9 (27%) on work-up after presenting with a palpable lump. Twenty-nine (87%) were early stage (0-II) disease. Median interval from EOC to BC diagnosis was 80 months (IQR 32, 134) for new and 63 months (IQR 21, 94) for recurrent BCs. There was one death from breast cancer while 12 women died of ovarian cancer. Conclusions Most BC following BRCA-associated EOC is early stage and not associated with mortality. Given BC rate similar to general population and median diagnosis at 6.6 years following ovarian cancer, increased BC screening may not be warranted in the early years after EOC diagnosis.

Objective To assess CA 125 and transvaginal ultrasound surveillance in women with BRCA1 or BRCA2 pathogenic variants in a pragmatic clinical setting with>1 year follow up. Methods Retrospective cohort study in a large integrated health care system of women identified from 1/1/2003 to 12/31/2017 with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Demographic and clinical data were collected from date of genetic testing until oophorectomy, an ovarian cancer diagnosis, or 7/1/2019. Primary outcome was frequency and findings of CA 125 tests and ultrasounds performed; secondary outcome was epithelial ovarian cancers diagnosed. Results There were 1418 women, age ≥ 30 years with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Of the total of 1683 ultrasounds and 2437 CA 125 tests done, 1022 ultrasounds and 1709 CA 125 tests were performed for surveillance in 771 women followed >1 year. Of these women 241 (31%) women had no surveillance, and 530 (69%) women underwent any surveillance. Only 108 (20%) underwent regular surveillance. The number who underwent regular surveillance declined each year. Twenty-one women underwent surveillance indicated surgery with only 2 ovarian cancers found by surveillance. Conclusions Many women with BRCA1 or BRCA2 pathogenic variants undergo ultrasound and CA 125 surveillance testing but abnormal surveillance testing led to diagnosis of ovarian cancer in only two cases. These findings question the use of CA 125 and ultrasound surveillance in the clinical setting for ovarian cancer detection in women with BRCA1 or BRCA2 pathogenic variants.

Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing.A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system.Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process.Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.

Objective Estimate the prevalence and identify risk factors for bone loss in women with BRCA mutations. Methods Women, age 40 and older, with BRCA mutations identified from the Breast Cancer Surveillance database at Kaiser Permanente Northern California were invited to participate and undergo a dual-energy x-ray absorptiometry scan to assess for bone loss (osteopenia or osteoporosis). Multivariable logistic regression analysis was performed to assess clinical factors associated with bone loss. Results Of the 238 women in the final cohort, 20 women had intact ovaries (median age 54.5years) and 218 had undergone risk reducing salpingo-oophorectomy (RRSO) (median age 57). The prevalence of bone loss was 55% in the no RRSO group and 72.5% in the RRSO group (P=0.10). In multivariable analysis, only higher body mass index (OR 0.6 per 5kg/m 2 , 95% CI: 0.4–0.7) and nonwhite race compared to white (OR 0.5, 95% CI: 0.2–0.9) were protective for bone loss while older age (OR 1.5 per 10years, 95% CI: 1.1–2.1) and selective estrogen receptor modulator use (3.1, 95% CI: 1.2–10.1) were associated with increased odds of bone loss. Among women with RRSO, bone loss was more frequent in women who had postmenopausal (n=106) compared to women who had premenopausal RRSO (n=112), (82.1% and 63.4% respectively, P=0.002). In multivariable analysis, only BMI was protective of bone loss (OR 0.5, 95%, CI: 0.4–0.7) but neither age nor menopausal status at RRSO were associated with bone loss. Conclusion Bone loss is common in women with BRCA mutations who undergo RRSO.

To determine the association between resident involvement and operative time for minimally invasive surgery (MIS) for endometrial cancer.A retrospective cohort study (Canadian Task Force classification II-2).An integrated health care system in Northern California.A total of 1433 women who underwent MIS for endometrial cancer and endometrial intraepithelial neoplasia from January 2009 to January 2014.Resident participation in 430 of 688 laparoscopic cases (62%) and 341 of 745 robotic cases (46%).The primary outcome was the impact of resident involvement on surgical time. When residents were involved in laparoscopic and robotic surgery, there was an increase of 61 minutes (median operative time, 186 vs 125 minutes; p .001) and 31 minutes (median operative time, 165 vs 134 minutes; p .001), respectively. Resident participation was associated with increased operative times in all levels of surgical complexity from hysterectomy alone to hysterectomy with pelvic and para-aortic lymph node dissection. Resident participation was also associated with increased major intraoperative complications (3.4% vs 1.8%, p = .02) as well as major postoperative complications (6.4% vs 3.8%, p = .003).The presence of a resident was associated with a 32% increase in operative time for minimally invasive cases in gynecologic oncology for endometrial cancer. Because of the retrospective nature, we cannot infer causality of operative outcomes because residents were also involved in more high-risk patients and complex cases. For health care systems using surgical metrics, there may be a need to allocate more time for resident involvement.

Background: Research on the effect of body mass index (BMI) on ovarian cancer survival is inconsistent, but previous studies did not consider the possible impact of ascites, bowel obstruction, or cachexia, which commonly occur in late-stage disease. Methods: We evaluated the association of BMI, before and around the time of diagnosis, with overall and disease-specific survival in a cohort study of primary invasive epithelial ovarian cancers diagnosed from 2000 to 2013 in Kaiser Permanente Northern California (KPNC) (n=1184). Deaths were identified through December 2014, with a median follow-up of 37 months. Proportional hazards regression was used to estimate overall and ovarian cancer-specific mortality, accounting for prognostic variables including age at diagnosis, race, stage, grade, histology, comorbidities, treatment, post-treatment CA125 levels, ascites, and bowel obstruction. Results: There was no evidence of an association between BMI and overall or ovarian cancer-specific survival. However, we found strong effect modification by stage (Pinteraction

Objective To assess the feasibility of a novel hysteroscopic catheter to collect fallopian tube cytologic samples and to correlate cytologic findings with histopathology. Methods This was a prospective, multicenter, single-arm pilot study. Women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or for prevention of cancer for BRCA mutation carriers were recruited from 3 gynecologic oncology centers (October 2016–August 2017). Cytologic samples were collected from the fallopian tube using a novel FDA-cleared hysteroscopic catheter and evaluated by a pathologist blinded to surgical or pathologic findings. The correlation between cytologic results and final surgical pathology was assessed. Results Of the 50 patients enrolled, 42 were eligible. Hysteroscopies were completed in 40 patients with 78 fallopian tubes, of which 65 ostia (83%) were identified. Of these, 61 (72%) were successfully catheterized resulting in 44 (68%) cytology samples adequate for further evaluation: 5 were classified as positive (3 neoplastic and 2 malignant) and 39 as negative (34 benign and 5 reactive/atypical). A comparison of cytology results with fallopian tube histopathology showed a concordance rate of 95% (42/44). Of the two samples with discordant results, both had positive cytology but negative tubal pathology, and both were stage I ovarian cancers with malignant ovary histology. Conclusions Deployment of the device yielded an evaluable cytologic sample in 68% of cases with a high rate of concordance with histopathology. Further evaluation of the device's ability to detect malignancy in high risk populations is warranted.

We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months.Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale.There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034).This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

OBJECTIVES Assess sexual function, menopausal symptoms, and depression in women with BRCA mutations associated with oophorectomy and menopause status. METHODS Women age 40 and older with BRCA mutations completed a questionnaire with validated measures of sexual activity, menopausal symptoms, depression, and cancer worry. These measures were compared between those with intact ovaries and those who had undergone pre- or post-menopausal risk-reducing salpingo-oophorectomy (RRSO). RESULTS Of the 244 women, 21 had intact ovaries and 223 had undergone RRSO. Women with intact ovaries had less menopausal symptoms (Menopausal Symptom Checklist (MSCL) score 14 versus 23, P = .01) but more cancer worry than women who had undergone RRSO (median Cancer Worry Scale (CWS) score 5 versus 4, P < .0001) with no significant difference in sexual activity or function. Compared with women with postmenopausal RRSO, women with premenopausal RRSO were more likely to be sexually active (56.3% versus 42.0%, P =.04) but had similar sexual functioning, including frequency, pleasure and discomfort. Women with premenopausal RRSO were also more likely to report menopausal symptoms (MSCL score 26 versus 19, P = .04) and depression (PHQ-8 score 4 versus 2, P < .001). Factors associated with sexual activity included younger age, lower BMI, living with a partner, and lower depression scores. Higher current depression score was associated with history of depression and more menopausal symptoms. CONCLUSIONS Risk-reducing surgery decreases cancer risk and worry in women with BRCA mutations. Among women undergoing oophorectomy, factors such as age and history of depression were related to reduced sexual activity and increased depression, but menopausal status was not related.

Objectives: To identify racial and health factors associated with referral, assessment and genetic testing patterns for women with ovarian cancer. Methods: Women were identified with a new diagnosis of ovarian cancer in a large integrated health care system in Northern California between 8/1/2013 and 12/31/2018. Women were excluded if they had undergone genetic testing prior to the diagnosis of ovarian cancer. Standardized guidelines of the health system at the time of diagnosis were used for genetics referral criteria: from 8/2013 until 4/2015, the guidelines limited referral to ovarian cancer diagnosed under age ≤70 years and non-mucinous histology; from 4/2015-4/2017, ovarian cancer diagnoses of all ages became eligible; and starting in 4/2017, all ovarian cancer histologies were eligible for referral. Demographic variables including race, ethnicity, primary language and personal cancer history were retrieved from the electronic medical record. The primary outcome was referral to genetics for assessment within 12 months of ovarian cancer diagnosis. Secondary outcomes were completion of genetics contact and testing, as well as testing result. Results: We identified 1,414 women, newly diagnosed with ovarian cancer between 8/1/2013 and 12/31/2018, who were eligible for testing based on the health system criteria. Most of these women, 941 (66.5%) were referred to genetics in the first 12 months after diagnosis with a mean time from diagnosis to referral of 2.3 months. Referral rates varied by race and ethnicity: White 65.9%, Hispanic 69.7%, Black 58.2%, Asian 70.3%. Overall rates of referral to Genetics, seen by a genetic counselor, and tested for genetic mutations were lower for Black women compared to non-Black women although the difference was not significant (p-value = 0.07, 0.06, 0.07, respectively). Over the three time periods of genetics referral criteria, referrals for all races increased, the rate in Blacks increased from 45.8 % to 67.6% from the first period to the last (p-value = 0.09). Overall, 919/941 (65%) were seen by Genetics and 842 (59.5%) completed genetic testing, 796 had a multigene panel test, and the remainder had BRCA or single gene testing, with 161 (20%) with a positive test and 228 with variants of unknown significance. Only 6% (6/98) of Black women had a pathogenic mutation. Download : Download high-res image (335KB) Download : Download full-size image Conclusions: In a large integrated health system with comprehensive health services, access to medical records for all tests and care, and a uniform cost structure for genetic services, Black women had lower referral and genetic testing rates than women of other races but the difference was not significant. While academic centers have shown significant differences in referral to genetic services of ovarian cancer patients by race, primary language and insurance types, these differences may be mitigated in systems with universal cost structures, integrated referrals and systemwide access for counseling, but more work still needs to be done to reach Black women.

Objectives: Investigate the clinical presentation and diagnosis of ovarian cancer in women with BRCA mutations. Methods: Retrospective cohort study of all women in an integrated healthcare system with pathogenic mutations identified between 1/1/2003-12/31/2018 who were diagnosed with ovarian cancer (OC). Primary outcome was stage of OC; secondary outcomes included method of diagnosis in women with genetic testing before OC diagnosis, interval to diagnosis, and age at genetic testing and ovarian cancer diagnosis. Results: Of the 299 women with OC and a BRCA mutation, 41 women were diagnosed with OC after BRCA testing, with 26 (63%) diagnosed on risk-reducing salpingo-oophorectomy (RRSO), 4 (10%) diagnosed by abnormal surveillance testing, and 11 (27%) diagnosed with symptoms. Median age at OC diagnosis was 55, 54, and 58 years for the RRSO, surveillance and symptom groups respectively. Women with a known BRCA mutation status at the time of their OC diagnosis were more likely to have earlier stage OC compared to those who underwent genetic testing after their OC diagnosis (54% vs 15%, p Download : Download high-res image (170KB) Download : Download full-size image Conclusions: In women with a known BRCA mutation, most OC is diagnosed in older women and at the time of RRSO. Women with a known BRCA mutation at the time of their OC diagnosis were more likely to have earlier stage disease compared to those who underwent genetic testing after their OC diagnosis. The late age at genetic testing of these patients, as well as the earlier stage disease seen in those with a known BRCA mutation, highlights the need for earlier genetic testing and RRSO. Cancers diagnosed on RRSO are more likely to be early stage. Few cancers are detected by surveillance.

Objective To determine the rate of venous thromboembolism (VTE) among women undergoing minimally invasive surgery (MIS) for endometrial cancer. Methods Women undergoing robotic or laparoscopic hysterectomy for endometrial carcinoma or complex hyperplasia with atypia were identified between January 2009 and 2014 in a community based health care system. Patient data including age, race, cancer stage, grade, procedure type, length of hospital stay, use of prophylaxis, and diagnosis of VTE were collected retrospectively. The primary outcome was the rate of VTE within 30days following surgery. Fischer's exact tests were performed to evaluate factors associated with VTE. Results During the study period, 1433 patients underwent MIS for endometrial cancer, with 20 excluded due to known thrombophilia, VTE history, or long-term anticoagulation. A total of 1413 patients were included (739 robotic and 674 laparoscopic cases). All women received mechanical prophylaxis per hospital policy and 61% had additional pharmacologic prophylaxis. The rate of VTE was 0.35% (5/1413), which did not differ among those who received pharmacologic compared to mechanical prophylaxis (0.23% [2/865] versus 0.55% [3/548] respectively, p =0.38). No factors were associated with increased risk of VTE due to the low event rate. Conclusion VTE in patients undergoing MIS for endometrial cancer was very low irrespective of the mode of prophylaxis received in this large cohort. National guidelines for VTE prophylaxis need to differentiate the low risk associated with MIS surgery from the risk associated with laparotomy for endometrial cancer. We recommend mechanical prophylaxis is sufficient for these women undergoing MIS.

Estimate the prevalence of cardiovascular disease risk factors and endpoints in women with BRCA mutations.Women, age 40 and older, with BRCA mutations identified in Kaiser Permanente Northern California completed a questionnaire and underwent a lipid and fasting glucose panel. Bivariable analysis of clinical and demographic factors was performed. The Atherosclerotic Cardiovascular Disease (ASCVD) calculator was used to predict 10-year risk of a cardiovascular event.Of the 233 women, 19 women had intact ovaries (median age 56.0) and 214 had undergone risk-reducing salpingo-oophorectomy (RRSO). Among the 108 women with RRSO under age 50 (median age 51.0), compared to the 106 women who had RRSO at or over age 50 (median age 63.5) 6.5% vs 10.4% reported diabetes (p = 0.30), 23.2% versus 28.3% had elevated fasting blood glucose (p = 0.39), 21.3% versus 34.0% reported hypertension (p = 0.04) with median systolic blood pressure of 118 mmHg versus 125.5 mmHg (p 0.009), 25% versus 32% reported hyperlipidemia (p = 0.40), and 42% versus 49% had any abnormal lipid test (p = 0.28). An elevated 10-year ASCVD risk of over 10% was seen in 6.1% versus 24.8% respectively (p = 0.0001).Women who underwent RRSO at age of 50 and over, had higher ASCVD 10-year risk than women who underwent RRSO at younger ages most likely owing to older age at study entry. The ASCVD risks for women with BRCA mutation who had RRSO did not suggest increased risk associated with being a BRCA mutation carrier.

ObjectiveThe aim was to identify clinical parameters and immunohistochemical markers predictive of recurrence and overall survival (OS) in a community cohort of patients with primary uterine leiomyosarcoma (ULMS).Methods/MaterialsAll patients with new diagnosis of ULMS from 1999 to 2007 were identified from the Kaiser Permanente Northern California pathology database. A retrospective chart review was performed to gather demographic and clinical data. The primary outcomes were recurrence-free survival and OS. In addition, a subset of tumor samples was available to analyze 3 immunohistochemical markers using tissue microarray techniques; these are as follows: estrogen receptor (ER) alpha, epidermal growth factor receptor (EGFR), and Ki-67.ResultsSeventy-five patients with ULMS were identified, of which 63 had adequate tumor tissue available for immunohistochemical evaluation. The median follow-up for all stages was 28 months. The rate of recurrence or progressive disease was 76% for stage I patients compared with 85% for stage II to IV patients. At 3 years, 37% of stage I patients were recurrence free compared with 27% of stage II to IV patients. Overall survival for stage I patients declined from 64% to 38% between 3 and 5 years while remaining stable at 30% for stage II to IV patients. In multivariable analysis, increasing mitotic counts were associated with increased risk of recurrence (hazards ratio [HR], 3.2; P = 0.013) and a trend toward decreased OS (HR, 2.2; P = 0.10). Expression of ER (HR, 1.0), EGFR expression (HR, 1.0), and Ki-67 expression (HR, 1.0) were not predictive of recurrence or OS.ConclusionsRecurrence rate of 76% for patients with stage I ULMS was higher than previously published cohorts. Mitotic counts were associated with increased recurrence and decreased OS. Expressions of ER, EGFR, and Ki-67 were not useful for predicting overall recurrence or survival.

Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high-grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer.

Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast & Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk of ovarian, tubal, and peritoneal cancers. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancers as well as a 9-12% lifetime risk of ovarian cancer. Mutations in other genes including TP53, PTEN, and STK11 are responsible for hereditary syndromes associated with gynecologic, breast, and other cancers. Evaluation of the likelihood of a patient having one of these gynecologic cancer predisposition syndromes enables physicians to provide individualized assessments of cancer risk, as well as the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Evaluation for the presence of a hereditary cancer syndrome is a process that includes assessment of clinical and tumor characteristics, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from assessment for the presence of a hereditary breast and/or gynecologic cancer syndrome.

OBJECTIVE To evaluate the utilization rate of salpingectomy for cesarean deliveries and postpartum and interval tubal sterilization procedures. METHODS This is a retrospective cohort study using the electronic medical record to identify women older than 18 years of age undergoing surgical sterilization from June 2011 to May 2016 in an integrated health care system. The primary objective is to describe the change in utilization rate of salpingectomy for tubal sterilization procedures over time and after a systemwide practice recommendation was issued in 2013. Rates of salpingectomy and tubal occlusion were calculated for each of the five 1-year intervals in the study. Secondary outcomes included blood loss, operating time, length of stay, readmission, and emergency department visits. RESULTS A total of 10,741 tubal sterilization procedures were identified. There was an increase in salpingectomies from 0.4% (8/1,938; 95% CI 0.2-0.8) to 35.5% (902/2,538; 95% CI 33.7-37.4) of tubal sterilization procedures performed over the study period (test for trend, P

Objective To assess current practice, advise minimum standards, and identify educational gaps relevant to genetic screening, counseling, and testing of women affected by gynecologic cancers. Methods The Society of Gynecologic Oncology (SGO) organized a multidisciplinary summit that included representatives from the American College of Obstetricians and Gynecologists (ACOG), the American Society Clinical Oncology (ASCO), the National Society of Genetic Counselors (NSGC), and patient advocacy groups, BrightPink and Facing our Risk of Cancer Empowered (FORCE). Three subject areas were discussed: care delivery models for genetic testing, barriers to genetic testing, and educational opportunities for providers of genetic testing. Results The group endorsed current SGO, National Comprehensive Cancer Network (NCCN), and NSGC genetic testing guidelines for women affected with ovarian, tubal, peritoneal cancers, or DNA mismatch repair deficient endometrial cancer. Three main areas of unmet need were identified: timely and universal genetic testing for women with ovarian, fallopian tube, and peritoneal cancers; education regarding minimum standards for genetic counseling and testing; and barriers to implementation of testing of both affected individuals as well as cascade testing of family members. Consensus building among all stakeholders resulted in an action plan to address gaps in education of gynecologic oncology providers and delivery of cancer genetics care.

Objective Describe clinical characteristics and risk reducing strategies utilized among women with a BRCA mutation who lived to age 75 and above. Methods A retrospective study of women with BRCA mutations identified from 1995 to 2015 in a California health care system. From a database of 1189 women, 69 participants were identified who lived to age 75 or older. Demographic and clinical characteristics were recorded, as well as cancer history and risk-reducing strategies utilized. Descriptive and bivariate analyses were used to analyze the cohort. Results The median age of the cohort at study entry was 78 (IQR: 76–84) and the median age at time of genetic testing was 73 (IQR 68–79). Fifty (72%) women had a prior history of breast cancer and 27 (39%) had a history of ovarian cancer. Three of 19 (16%) women with no history of breast cancer elected to undergo a risk-reducing mastectomy (RRM) after their positive genetic test. Among 30 women with ovaries still in place, 14 (47%) underwent a risk-reducing salpingo-oophorectomy (RRSO); six were age 70 or older at the time of surgery. Four (6%) women in the cohort developed BRCA-related cancer after testing, one developed breast cancer and three developed pancreatic cancer. Conclusions Most women with BRCA mutations surviving beyond age 75 received their genetic test result at an older age and had a history of BRCA-related cancer. Women continued surveillance and risk reducing surgeries at an older age. Pancreatic cancer was the most common new cancer diagnosed in older BRCA mutation carriers.

Purpose: Preclinical data suggest that exposure to PARP inhibitors (PARPi) may compromise benefit to subsequent chemotherapy, particularly platinum-based regimens, in patients with BRCA1/2 mutation carrier ovarian cancer (PBMCOC), possibly through the acquisition of secondary BRCA1/2 mutations. The efficacy of chemotherapy in the PARPi-resistant setting was therefore investigated. Experimental Design: We conducted a retrospective review of PBMCOC who received chemotherapy following disease progression on olaparib, administered at ≥200 mg twice daily for one month or more. Tumor samples were obtained in the post-olaparib setting where feasible and analyzed by massively parallel sequencing. Results: Data were collected from 89 patients who received a median of 3 (range 1–11) lines of pre-olaparib chemotherapy. The overall objective response rate (ORR) to post-olaparib chemotherapy was 36% (24 of 67 patients) by Response Evaluation Criteria in Solid Tumors (RECIST) and 45% (35 of 78) by RECIST and/or Gynecologic Cancer InterGroup (GCIG) CA125 criteria with median progression-free survival (PFS) and overall survival (OS) of 17 weeks [95% confidence interval (CI), 13–21] and 34 weeks (95% CI, 26–42), respectively. For patients receiving platinum-based chemotherapy, ORRs were 40% (19 of 48) and 49% (26/53), respectively, with a median PFS of 22 weeks (95% CI, 15–29) and OS of 45 weeks (95% CI, 15–75). An increased platinum-to-platinum interval was associated with an increased OS and likelihood of response following post-olaparib platinum. No evidence of secondary BRCA1/2 mutation was detected in tumor samples of six PARPi-resistant patients [estimated frequency of such mutations adjusted for sample size: 0.125 (95%-CI: 0–0.375)]. Conclusions: Heavily pretreated PBMCOC who are PARPi-resistant retain the potential to respond to subsequent chemotherapy, including platinum-based agents. These data support the further development of PARPi in PBMCOC. Clin Cancer Res; 19(19); 5485–93. ©2013 AACR.

ObjectiveKaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated cancers for genetic counseling. This study assesses adherence to genetic counseling referral guidelines within this health system.MethodsChart review was performed to identify patients with cancer who met the following pathology-based Kaiser Permanente Northern California guidelines for referral for genetic counseling: invasive breast cancer, younger than age 40; nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer, younger than age 60; women with synchronous or metachronous primary cancers of the breast and ovaries; and male breast cancer. We assessed compliance with referral guidelines. An electronic notice was sent to the managing physician of patients with newly diagnosed cancer to assess the feasibility of this intervention.ResultsA total of 340 patients were identified with breast cancer at younger than age 40 or with ovarian, peritoneal, or tubal cancer between January and June, 2008. Upon chart review, 105 of these patients met pathology-based criteria for referral to genetic counseling, of whom 47 (45%) were referred within the 2-year study period. Of the 67 subjects with breast cancer, 40 subjects (60%) were referred. In contrast, only 7 (21%) of 33 patients with ovarian cancer were referred (P < 0.001). A pilot study was performed to test the feasibility of notifying managing oncologists with an electronic letter alerting them of eligibility for genetic referral of patients with new diagnosis (n = 21). In the 3 to 6 months after this notification, 12 of these 21 patients were referred for counseling including 5 of 7 patients with a diagnosis of ovarian cancer.ConclusionThere is a missed opportunity for referring patients to genetic counseling, especially among patients with ovarian cancer. A pilot study suggests that alerting treating physicians is a feasible strategy to increase appropriate referral.

To compare intraoperative and postoperative surgical complications and outcomes between robotic-assisted and laparoscopic surgical management of endometrial cancer using a standardized classification system.A retrospective cohort study (Canadian Task Force classification II-2).An integrated health care system in Northern California.One thousand four hundred thirty-three women with a diagnosis of complex atypical hyperplasia and endometrial cancer managed by minimally invasive hysterectomy and surgical staging from January 2009 to January 2014.Seven hundred forty-five robotic-assisted and 688 laparoscopic hysterectomies were evaluated.The primary outcome was intraoperative and postoperative complications within 30 days. All complications were categorized using the Clavien-Dindo classification system. Secondary outcomes included total operative time, estimated blood loss, transfusion rates, length of stay, conversion to laparotomy, and number of pelvic and para-aortic lymph nodes retrieved. The modality of hysterectomy was not associated with either overall intraoperative complications or major postoperative complications (p .1). However, there were significantly fewer minor postoperative complications with robotic surgery (16.6% vs 25.6%, p .01). Statistically significant differences were also noted in the following outcomes: decreased median operative time, length of stay, estimated blood loss, conversion to laparotomy, and median number of lymph nodes retrieved in the robotic group when compared with the laparoscopic group.There was no difference in the rate of major complication between robotic and laparoscopic surgery using the Clavien-Dindo system of categorizing surgical complications; however, there were clinically significant differences favoring the robotic approach, including a lower rate of minor complications and conversion rate to laparotomy.

OBJECTIVE To evaluate the trend in uptake of salpingectomy at the time of hysterectomy and assess physicians' attitudes toward the practice. METHODS This was a retrospective cohort study using the electronic medical record to identify women 18 years of age or older undergoing hysterectomy from June 2011 to May 2014 in a large integrated health care delivery system. The primary outcome was the change in rate of opportunistic salpingectomy over time and after a systemwide practice recommendation was issued in May 2013. Secondary outcomes included data on blood loss, operating time, and length of stay. RESULTS Of the 12,143 hysterectomies performed over the 3-year study period, 7,498 were performed without oophorectomy. There was a statistically significant rise in rate of salpingectomy over time from 14.7% for June 2011 to May 2012 to 44.6% from June 2012 to May 2013 and to 72.7% from June 2013 to May 2014 (P

Purpose: Among patients with ovarian cancer, African American (AA) women experience poorer survival compared with other race/ethnicity groups. This has been attributed to differences in access to health care. Experimental Design: We evaluated racial/ethnic differences in chemotherapy dosing and survival in a cohort study among members of Kaiser Permanente Northern California, and thus with equivalent access to health care. Analyses included epithelial-invasive ovarian cancer cases (n = 793) receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent, with median follow-up of 50 months. Relative dose intensity (RDI) was computed for carboplatin and paclitaxel separately as dose administered per week divided by expected dose per week, and average RDI (ARDI) was then calculated for the regimen. Proportional hazards regression was used to calculate HRs and 95% confidence intervals (CIs) after adjusting for relevant covariates. Results: Compared with whites, AAs were more likely to have dose reduction (ARDI < 85%), treatment delay, and early discontinuation. Hispanics were also more likely to have dose reduction, but less likely to have early discontinuation or treatment delay. After controlling for prognostic factors including ARDI, AA women had the worst survival. Compared with whites, adjusted HRs (95% CI) for overall mortality were 1.56 (1.01–2.39) for AAs; 0.89 (0.61–1.31) for Asians; and 1.41 (0.98–2.04) for Hispanics. Findings for ovarian cancer–specific mortality were similar. Conclusions: Disparities in ovarian cancer treatment and survival in AA persisted among women with equal access to care. These findings warrant further evaluation of biological, personal, and social factors that may be responsible for these differences. Clin Cancer Res; 22(23); 5909–14. ©2016 AACR.

Objectives To characterize the post-operative care of BRCA1 and BRCA2 mutation carriers who undergo risk-reducing salpingo-oophorectomy (RRSO). Methods BRCA1 and BRCA2 mutation carriers from our Cancer Risk Program who elected RRSO were sent questionnaires regarding their post-surgical surveillance and treatment for menopause symptoms, primary peritoneal cancer and bone loss. Results In 51 mutation carriers who were surveyed a median of 6years after RRSO, 24 (47%) received dual-energy X-ray absorptiometry (DXA) testing, yearly CA-125 serum testing and yearly pelvic examination. Three women received none of these examinations in follow-up. Respondents reported an average of 3.5 menopausal symptoms (range 0–9). The mean number of menopausal symptoms reported by respondents using HRT was 2.8, compared to 3.9 symptoms reported by women not using HRT (p=0.06). Six of 10 (60%) subjects who reported no history of DXA bone scan, and 10 of 15 (67%) subjects who reported no post-surgical CA-125 serum monitoring noted that their physicians "did not recommend" testing. Two out of six symptomatic women who were younger than 50 (33%) who had no other contraindication to the use of HRT reported their non-use was because their care providers "advised against" HRT use. Conclusion We believe that the lack of post-RRSO health care guidelines has resulted in inconsistent care for this cohort of patients. We proposed that national guidelines be developed to standardize care with the goal of optimizing long term survival in this unique cohort of young cancer previvors.

Objective A minority of risk-reducing salpingo-oophorectomy (RRSO) specimens from BRCA mutation carriers will contain clinically occult carcinoma that is detectable only using a specialized pathologic evaluation protocol. Although intraoperative detection of cancer may alter immediate surgical management, technical complications impairing pathologic diagnosis may result if fresh tissue dissection and frozen sections are performed on unselected RRSO specimens. We hypothesize that macroscopic specimen findings may predict which RRSO specimens contain cancer and therefore may guide selection of specimens for intraoperative pathologic evaluation. The aim of this study was to correlate the macroscopic and microscopic pathologic findings in RRSO. Methods RRSO specimens from 134 women with a BRCA mutation were retrospectively classified by their grossly visible findings (cysts and/or nodules versus grossly unremarkable). Correlation of the gross findings with the microscopic finding of occult tubal and/or ovarian carcinoma was performed by re-examination of all pathology slides. Results While 46% of RRSO had visible ovarian cysts and 34% had visible tubal/paratubal cysts, no cyst contained cancer on microscopic examination. Carcinoma was detected in 2/22 (9%) visible ovarian nodules and in 2/8 (25%) visible tubal nodules. Conversely, among all 11 RRSO specimens containing cancer, 7 (64%) had no corresponding visible abnormality. Conclusion Frozen section evaluation of a solid nodule may be valuable in patients consented for immediate surgical staging. Otherwise it is best to avoid intraoperative dissection or frozen section of RRSO that are macroscopically normal or contain only cysts; such specimens should remain undissected for immediate formalin-fixation as the first step of the specialized pathology evaluation protocol.

Objective To assess the uptake of risk-reducing options for the management of ovarian and breast cancer risk in BRCA mutation carriers in a large community based integrated health system in Northern California. Methods A retrospective cohort of deleterious BRCA mutation carriers (1995–2012) was evaluated for consistency with NCCN guidelines for risk reducing salpingo-oophorectomy (RRSO) by age of 35–40, risk reducing mastectomy (RRM), as well as surveillance practices, including pelvic ultrasound, CA 125, mammogram, and breast MRI. Secondary outcomes included the use of chemoprevention and hormone replacement. Results Of the 305 eligible women, 170 were BRCA 1 positive, and 135 were BRCA 2 positive. Seventy four percent underwent RRSO with only 17% under age 40, while 44% underwent RRM. The median time from the test to both RRSO and RRM was 6months. In the first year after BRCA diagnosis, 45% underwent a pelvic ultrasound, dropping to 2.3% by year 5. In year 1, 47% had a CA 125, dropping to 2% by year 5. The number of women undergoing annual MRI and mammogram fell similarly over time. Sixteen percent of BRCA carriers used oral contraceptives (OCPs) and only one patient used tamoxifen for chemoprevention. Conclusion Uptake of RRSO in BRCA carriers in a population based health system is high, however the majority of women do not have RRSO by the NCCN recommended age. Compliance with surveillance is low and rapidly declines even 1year out from testing. Attention needs to be focused on the earlier identification of BRCA mutation carriers with consolidated and standardized care to improve risk reduction.

Our aim was to compare perioperative patient controlled epidural analgesia (PCEA) versus patient controlled intravenous analgesia (PCA) after gynecologic oncology laparotomy.This was a prospective cohort study where perioperative pain management was decided through patient-centered discussion by anesthesia and surgical teams. The study was designed to accrue 224 patients, to test for equivalence in pain control on postoperative day 1, defined as less than a 10% difference in the proportion of patients with a visual analog scale pain score of2 (0-10 scale).Two hundred forty patients were enrolled, with 205 patients evaluable for outcomes: 98 received PCA, while 107 received a thoracic level PCEA. Utilization of PCEA was associated with longer anesthesia time pre-op (means: 60 vs. 44 min, p0.0001), as well as more likely use of pressors during surgery (78% vs. 57%, p=0.002). Pain control was comparable between groups on postoperative day 1 (mean VAS: 2.4 vs. 2.5, p=0.56), but patients with PCEA tended to require more supplemental pain medications. Time to first ambulation was longer in the PCEA patients (means: 49 vs. 36 h post-op, p=0.03), with no difference in time to tolerating regular diet (means: 89 vs. 77 h post-op, 0.17) and no difference in readiness for discharge (means: 144 vs. 145 h post-op, p=0.95).In this nonrandomized prospective study, selection of a PCEA for perioperative pain management did not improve pain management for patients undergoing gynecologic oncology surgery.

Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast/Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk ovarian cancer. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2 or MSH6, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancer as well as a 9-12% lifetime risk of ovarian cancer. Genetic risk assessment enables physicians to provide individualized evaluation of the likelihood of having one of these gynecologic cancer predisposition syndromes, as well the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Hereditary cancer risk assessment is a process that includes assessment of risk, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from hereditary cancer risk assessment for Hereditary Breast/Ovarian Cancer and the Lynch/Hereditary Non-Polyposis Colorectal Cancer syndrome.

Optimal chemotherapy dosing in obese patients remains uncertain, with variation in practice. Dose reduction strategies are often used to avoid chemotoxicity, but recent American Society of Clinical Oncology guidelines recommend full dose.To evaluate the impact of body mass index (BMI) on chemotherapy dosing and of dose reduction on ovarian cancer survival.Cohort study in Kaiser Permanente Northern California (KPNC) health care setting of patients with primary invasive epithelial ovarian cancers diagnosed from January 2000 through March 2013. Analyses focused on 806 patients receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent.Overall and ovarian cancer-specific mortality. Deaths were identified through the KPNC Mortality Linkage System, with median follow-up of 52.5 months. Hazard ratios (HRs) and 95% CIs were estimated from proportional hazards regression, accounting for prognostic variables including age at diagnosis, race, stage, grade, histologic type, chemotoxic effects, comorbidities, cancer antigen 125 levels, and BMI at diagnosis.The strongest predictor of dose reduction was a high BMI. Compared with normal-weight women, obese class III women received 38% and 45% lower doses in milligrams per kilogram of body weight of paclitaxel and carboplatin, respectively (P .001 for each agent). They also received lower relative dose intensity (RDI) for each agent and the combined regimen, calculated as average RDI (ARDI). Mean ARDI was 73.7% for obese class III women and 88.2% for normal-weight women (P .001). Lower ARDI (70%) was associated with worse overall (HR, 1.62 [95% CI, 1.10-2.37]) and ovarian cancer-specific survival (HR, 1.69 [95% CI, 1.12-2.55]). Women who were obese at diagnosis appeared to have better survival. In multivariable-adjusted analyses considering joint effects by BMI and ARDI, compared with women with normal weight and no dose reduction, normal-weight women with dose reduction (ARDI 85%) experienced worse survival (HR, 1.50 [95% CI, 1.02-2.21]). For each BMI category, those with ARDI less than 85% had worse survival than those without dose reduction. The improved survival among obese women was no longer apparent with dose reduction.Lower RDI was an independent predictor of ovarian cancer mortality. This finding was strongest among normal-weight women but seen at all levels of BMI. Our results suggest that body size should not be a major factor influencing dose reduction decisions in women with ovarian cancer.

Objective Characterize current management of osteoporosis risk in BRCA carriers following risk-reducing salpingo-oophorectomy (RRSO). Methods Women with a BRCA1 or BRCA2 mutation who underwent RRSO were identified from a community-based health system in Northern California from 1995 to 2012. Retrospective chart review using the electronic medical record was performed. The primary outcome was the number of women who had a dual-energy X-ray absorptiometry scan post-RRSO. Secondary outcomes included new diagnoses of osteopenia, osteoporosis, and fracture. Information on the following risk factors was also recorded: calcium and vitamin D use, history of breast cancer, chemotherapy, use of aromatase inhibitors, and use of hormone replacement therapy. Results Two hundred and twenty five women tested positive for a BRCA1 or BRCA2 mutation and underwent RRSO. Median follow-up was 41months from testing. Ninety-nine (44.0%) had at least one DXA scan following testing. The median time from RRSO to a diagnosis of bone disease was 29months (range 1–170). Seventy-two percent had only one DXA scan (range 1–7) following testing. Thirty-two percent had normal results, 55.6% had osteopenia and 12.1% had osteoporosis. Four percent of women had an atraumatic fracture after surgery. Age, breast cancer history, prior chemotherapy, and tamoxifen or aromatase inhibitor (AI) use were not associated with having osteoporosis or osteopenia. Conclusions Women with BRCA mutations who undergo RRSO have many risk factors for bone loss. The majority of these women are not being screened for bone loss. A clear guideline for screening needs to be established to improve detection of post-RRSO bone disease.

Purpose Women who carry deleterious mutations of BRCA1 or BRCA2 genes have up to a 54% lifetime risk of developing ovarian cancer. After childbearing, women at high risk increasingly choose bilateral risk-reducing salpingo-oophorectomy (RRSO). Two recent studies of BRCA mutation carriers reported occult malignancy in 2.5% of women undergoing RRSO. This study aimed to increase this detection rate using a protocol. Methods In 1996, the University of California San Francisco Gynecologic Oncology Program instituted a surgical-pathologic RRSO protocol that was composed of complete removal and serial sectioning of both ovaries and fallopian tubes, peritoneal and omental biopsies, and collection of peritoneal washings for cytology. We report the pathologic findings in 67 BRCA mutation carriers according to the degree of adherence to this protocol. Results Of the 67 procedures, the protocol was followed completely or partially in 41 (61%). Seven occult malignancies were discovered, four in the fallopian tube and three in the ovaries. Six of these were microscopic, and all seven (17%) were found in specimens from complete or partial protocol procedures as opposed to standard procedures (P = .026). Other variables such as age, parity, BRCA1 or BRCA2 mutation, or type of surgery did not alter the strong effect of protocol procedure on the cancer detection rate. Conclusion A rigorous operative and pathologic protocol for RRSO increases the detection rate of occult ovarian malignancy in BRCA mutation carriers nearly seven-fold. If confirmed, this finding will alter postoperative management because additional staging, chemotherapy, and follow-up may be necessary in affected women.