Ovarian Cancer Risk-Reduction and Screening in BRCA1/2 Mutation Carriers.

Objective: To determine the utilization of risk-reducing strategies and screening protocols for ovarian cancer in female BRCA1/2 carriers. Methods: This study was a sub-analysis of female participants from a larger multicenter, cross-sectional survey of BRCA1/2 mutation carriers unaffected by cancer. The questionnaire was administered electronically via email at four institutions located in the northeast United States. Data were analyzed with Fisher's exact test. Results: The survey was completed by 104 female BRCA mutation carriers. BRCA subtypes included 54.3% BRCA2, 41.0% BRCA1, and 2.9% both. The age at which patients underwent genetic testing varied 21.2% were 18-24 years, 25.0% were 25-34 years, 29.8% were 35-44 years, and 24.0% were 45 years or older. Nearly, all respondents (97.1%) reported that a provider had discussed risk-reducing surgeries. Of the 79 females who underwent genetic testing before 45 years of age, 53.2% reported that a health care provider recommended taking combined oral contraceptive pills (COCs) to reduce their risk of ovarian cancer, and, of these women, 88.1% chose to use them. COCs were offered at higher rates among women who were younger at the age of genetic testing (18-24: 86%, 25-34: 62%, 35-44: 23%; p < 0.0001). Approximately half (55.8%) of the respondents reported having been offered increased screening for possible early detection of ovarian cancer, of which 81.0% chose to undergo screening. The majority utilized a combination of transvaginal ultrasound and serum CA125 measurements. There were no differences observed in screening utilization based on BRCA mutation type. Conclusion: In our cohort of female BRCA mutation carriers, risk-reducing surgery was offered to almost all women, whereas only half were offered risk-reducing medication and/or increased screening. Further investigation is needed to identify barriers to the utilization of risk-reducing strategies among this high-risk population.

The impact of converting to telehealth for cancer genetic counseling and testing during the COVID-19 pandemic.

The COVID-19 outbreak in March 2020 resulted in a shift to telemedicine for cancer genetic counseling (GC). The objective of this study was to determine the effect of telehealth (TH) services on patient acceptance of recommended genetic testing, time to test completion, and follow-up test-disclosure GC appointment, as well as compliance with National Comprehensive Cancer Network (NCCN) recommendations for medical screenings when testing positive for a genetic variant. Data for this retrospective cohort study were collected at a tertiary-care academic health center using the electronic medical record and laboratory portal. Patients with traditional in-person visits (the 2019 control group) and date-matched TH visits (2020) were compared. In total, 206 new GC appointments occurred in the in-person group and 184 new appointments occurred in the TH group. The in-person group was more likely to consent to testing than the TH cohort (92.6% vs. 82.1%, p = 0.003) and had increased rates of sample submission (99.5% vs. 93.75%, p < 0.01), as well as a shorter turn-around time between their initial appointment and laboratory result reporting (34.24 vs. 20.32 days, p < 0.01). There was no increase in time from initial to follow-up GC appointments (67.87 days for control, 62.39 days for THs, p = 0.37). With >2.5 years of follow-up for all study participants, there were no statistically significant differences in pathogenic variant (PV) carrier compliance with screening recommendations. During the COVID-19 pandemic, use of TH allowed patients to access GC with no significant differences in time between initial consultation and follow-up. However, in-person visits were associated with increased patient willingness to consent to and complete genetic testing. This work offers a nuanced look at the success of TH GC during the pandemic and follow-up with screening recommendations, while offering future opportunities to address the acceptance of testing as GC is practiced in a virtual or hybrid model.

Barriers to hormone therapy following prophylactic bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers.

OBJECTIVE: This study aimed to identify barriers to hormone therapy (HT) use among women with BRCA1/2 mutations after prophylactic bilateral salpingo-oophorectomy (BSO). METHODS: A cross-sectional, electronic survey was conducted of BRCA1/2 mutation carriers at Women and Infants Hospital, Yale Medical Center, Hartford Healthcare, and Maine Medical Center. This study was a subanalysis of a subset of female BRCA1/2 mutation carriers who had undergone a prophylactic BSO. Data were analyzed using the Fisher's exact test or t test. RESULTS: We performed a subanalysis of 60 BRCA mutation carriers who underwent a prophylactic BSO. Only 24 women (40%) reported ever using HT. HT use was higher in women who underwent their prophylactic BSO at age younger than 45 years (51% vs. 25%, P = 0.06). Among all women who had a prophylactic BSO, the majority (73%) reported that a provider talked to them about using HT. Two thirds reported having seen contradictory information in the media about long-term consequences of HT. Seventy percent listed their provider as the primary influence in their decision to start HT. The most common reasons for not starting HT included it not being recommended by their physician (46%) and that it was not necessary (37%). CONCLUSIONS: BRCA mutation carriers frequently undergo prophylactic BSO at young ages, and less than half report using HT. This study highlights barriers to HT use, such as patient fears and physician discouragement, and identifies potential areas to improve educational efforts.

Family planning in carriers of BRCA1 and BRCA2 pathogenic variants.

BRCA1 and BRCA2 pathogenic variant carriers have a high lifetime risk of developing breast and ovarian malignancies. Given the risks and significant ramifications of undergoing risk-reducing surgeries, many pathogenic variant carriers unaffected by cancer (previvors) struggle with family planning and reproductive decision making. The objective of this study was to determine the attitudes and practices of BRCA1 and BRCA2 pathogenic variant carriers with respect to family planning decision making. A cross-sectional survey was conducted of BRCA1 and BRCA2 previvors at four Northeastern medical centers. The survey was administered electronically via email using REDCap. The survey included demographic information as well as questions about genetic testing, prophylactic surgeries, family planning, and partnering. Data were analyzed with Fisher's exact tests and t tests. The survey was completed by 139 of 422 BRCA1 and BRCA2 pathogenic variant carriers (response rate 33%). Thirteen were excluded from analysis due to self-reported cancer history. Of the remaining 126, 21 (16.7%) were male and 105 (83.3%) were female. Female participants <35 years old at the time of genetic testing were significantly more likely than those 35 or greater to report feeling urgency to have a family after finding out about their BRCA1 and BRCA2 pathogenic variant (p < 0.0001). Younger women also reported their genetic status had a stronger impact on their romantic relationships (p = 0.029). Men were significantly more likely to report that they felt no urgency to have a family compared to women (p < 0.0001). Our study reflects the complex decision making for previvors and the intricacies of family planning in this population. Providers can use this knowledge as a guide to counsel patients about reproductive options.

Choosing high-risk screening vs. surgery and the effect of treatment modality on anxiety and breast-specific sensuality in BRCA mutation carriers.

BACKGROUND: We have previously shown that breast cancer surgery affects breast specific sensuality, and that women who undergo mastectomy may have worse sexual function outcomes than those who undergo lumpectomy. It is less clear if patients who undergo prophylactic mastectomy are equally as affected as those with a cancer diagnosis. We sought to compare sexual function outcomes and their relationship to depression and anxiety between BRCA mutation carriers (mBRCA) with and without cancer in order to guide surgical counseling and improve survivorship outcomes. METHODS: A confidential, cross-sectional survey was distributed electronically to mBRCA at least 18 years of age. The survey included investigator-generated questions, the Female Sexual Function Index (FSFI), and the Hospital Anxiety and Depression Scale (HADS) surveys. Responses were analyzed in total and divided into two subgroups: those with and without breast cancer. RESULTS: Sixty-three mBRCA responded (37%) of 170 email addresses were identified, and 77% were postmenopausal. Although more than half of all mBRCA reported that the role of the breast in intimacy was important, most patients without cancer and all of those with cancer experienced an impressive decline in certain breast-specific sensuality parameters postoperatively. Among those without cancer, anxiety scores were not different between those choosing prophylactic mastectomy and high-risk screening (HRS). Sexual function as measured by the FSFI was negatively correlated with depression and anxiety in mBRCA. FSFI scores were not significantly different between those with and without cancer. However, the median FSFI of mBRCA with cancer, those undergoing HRS, and those who underwent prophylactic mastectomy indicated sexual dysfunction. CONCLUSIONS: As the availability of genetic testing increases, more women are found to harbor BRCA mutations and must choose between HRS and prophylactic surgery. Women with BRCA mutations, both with and without breast cancer, are susceptible to derangements in sexual function during the course of both screening or treatment, and this appears to be negatively correlated to depression and anxiety.

Adherence Patterns to National Comprehensive Cancer Network Guidelines for Referral of Women With Breast Cancer to Genetics Professionals.

OBJECTIVE: Genetic predisposition is responsible for 5% to 10% of breast cancer. The National Comprehensive Cancer Network (NCCN) established guidelines delineating appropriate candidates for genetic counseling. This study aims to determine referral patterns for genetic counseling in women who met such guidelines. MATERIALS AND METHODS: Utilizing an institutional tumor registry, patients from an academic oncology program who met a subset of NCCN guidelines for genetic referrals between 2004 and 2010 were identified (breast cancer diagnosis ≤50 y without a known BRCA mutation). A retrospective chart review was conducted. Statistics were analyzed using SAS version 9.2. RESULTS: A total of 314 patients were identified and 107 (34.1%) were referred for genetic counseling. Median age at diagnosis was younger for those referred versus not referred (43 and 46 y; P<0.0001). Women were more likely referred with a family history suspicious for an inherited cancer syndrome (67.3% vs. 36.2%; P<0.0001). There was no difference in stage at diagnosis, insurance, or race among women referred. Those patients who choose prophylactic contralateral mastectomy were likely to have been referred for genetic counseling (63.6% vs. 36.4%, P<0.0001). Among patients referred, 77.6% consulted with a genetics counselor, 95.2% underwent genetic testing, and 16.5% had a BRCA mutation. CONCLUSIONS: Genetic counseling and testing is being underutilized in women who meet NCCN referral guidelines. Age and family history were noted to be predictive of referral for genetic evaluation. Further research is needed to determine additional factors that may impact not only referral rates but subsequent care for women with possible genetic predispositions to cancer.

Adherence patterns to National Comprehensive Cancer Network (NCCN) guidelines for referral to cancer genetic professionals.

OBJECTIVE: Genetic predisposition is responsible for 5-10% of breast cancer, 10% of ovarian cancer and 2-5% of uterine cancer. The study objective was to compare genetic counseling and testing referral rates among women with breast cancer that met NCCN referral guidelines to the referral rates among women with gynecologic cancers and determine predictors of referral. METHODS: Utilizing an institutional tumor registry database, patients from an academic women's oncology program were identified who met a subset of NCCN guidelines for genetic referral between 2004 and 2010. Patients diagnosed with ovarian cancer, breast cancer ≤50years of age, or uterine cancer <50years of age were included. A retrospective electronic chart review was conducted to evaluate for a genetic referral and uptake of genetic testing. RESULTS: 820 women were included (216 uterine, 314 breast, and 290 ovarian cancer). The overall genetic referral rate was 21.7%. 34% of eligible breast cancer patients were referred compared to 13.4% of uterine cancer and 14.5% of ovarian cancer patients (p<0.0001). Younger age, breast cancer diagnosis, family history and earlier stage were all significant referral predictors. The odds of being referred increased with the number of affected family members. 70.8% of referred patients, consulted with genetics. Among those who consulted with genetics, 95.2% underwent testing. CONCLUSIONS: Although increasing, genetic counseling remains underutilized across cancer diagnosis. Women with breast cancer are more likely to be referred than women with gynecologic cancers. Younger age, earlier stage and positive family history appear to be predictive of referral for genetic evaluation.

Preoperative genetic testing affects surgical decision making in breast cancer patients.

OBJECTIVES: Our aim was to determine if BRCA mutation status changes surgical decision making in women who undergo genetic testing after the diagnosis of breast cancer. METHODS: This is a retrospective cohort study of breast cancer patients who had BRCA mutation testing performed prior to surgery. We compared surgical choice and change in surgical choice in women who tested positive for a BRCA mutation with those who tested negative. Surgery was considered the most definitive surgery within a year of diagnosis. Other data collected included age, race, stage, histology, receptor status, adjuvant treatment, gravity, parity, and family history. Variables were compared by BRCA status using Fisher's exact test and logistic regression. RESULTS: Three hundred and two women were included. Thirty-two (10.6%) were identified as carrying a BRCA mutation. Most women had early stage disease (55.6% T1 lesions, 72.8% node negative); 55.6% had breast-conserving surgery, and the remaining had unilateral or bilateral mastectomy. BRCA mutation carriers were more likely to have both a personal history of breast cancer (RR 2.74, 95% CI=1.08-6.98) and hormone receptor-negative tumors (56.0% vs. 26.2%, p=0.002). BRCA mutation carriers were more likely to choose bilateral mastectomy with reconstruction (56.3% vs. 15.9%, p<0.0001); 71.9% of BRCA mutation carriers opted for a different surgery than what was initially planned by their surgeon as compared to 29% of mutation-negative patients (p<0.0001). CONCLUSIONS: BRCA mutation testing strongly influences surgical decision making in newly diagnosed breast cancer patients. For women who meet NCCN referral guidelines, genetic evaluation should be performed prior to surgical intervention.