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Breast cancer is the most common cancer diagnosed in women worldwide, with approximately 5-10% of cases attributed to high penetrance hereditary breast cancer (HBC) genes. The tremendous advances in precision oncology have broadened indications for germline genetic testing to guide both systemic and surgical treatment, with increasing demand for cancer genetic services. The HBC continuum of care includes (1) identification, access, and uptake of genetic counseling and testing; (2) the delivery of genetic counseling and testing services; and (3) initiation of guideline-adherent follow-up care and family communication of results. Challenges to delivering care on the HBC care continuum include factors such as access to services, cost, discrimination and bias, and lack of education and awareness, which can be mitigated through implementing a multi-level approach. This includes strategies such as increasing awareness and utilization of genetic counseling and testing, developing new methods to meet the growing demand for genetic services, and improving the uptake of follow-up care by increasing patient and provider awareness of the management recommendations.

This case series study examines differences in surgical treatment among adult females with invasive breast cancer who have pathogenic or likely pathogenic variants in genes with high vs moderate breast cancer penetrance.

Background Despite lower cancer incidence rates, cancer mortality is higher among rural compared to urban dwellers. Patient, provider, and institutional level factors contribute to these disparities. The overarching objective of this study is to leverage the multidisciplinary, multispecialty oncology team from an academic cancer center in order to provide comprehensive cancer care at both the patient and provider levels in rural healthcare centers. Our specific aims are to: 1) evaluate the clinical effectiveness of a multi-level telehealth-based intervention consisting of provider access to molecular tumor board expertise along with patient access to a supportive care intervention to improve cancer care delivery; and 2) identify the facilitators and barriers to future larger scale dissemination and implementation of the multi-level intervention. Methods Coordinated by a National Cancer Institute-designated comprehensive cancer center, this study will include providers and patients across several clinics in two large healthcare systems serving rural communities. Using a telehealth-based molecular tumor board, sequencing results are reviewed, predictive and prognostic markers are discussed, and treatment plans are formulated between expert oncologists and rural providers. Simultaneously, the rural patients will be randomized to receive an evidence-based 6-week self-management supportive care program, Cancer Thriving and Surviving, versus an education attention control. Primary outcomes will be provider uptake of the molecular tumor board recommendation and patient treatment adherence. A mixed methods approach guided by the Consolidated Framework for Implementation Research that combines qualitative key informant interviews and quantitative surveys will be collected from both the patient and provider in order to identify facilitators and barriers to implementing the multi-level intervention. Discussion The proposed study will leverage information technology-enabled, team-based care delivery models in order to deliver comprehensive, coordinated, and high-quality cancer care to rural and/or underserved populations. Simultaneous attention to institutional, provider, and patient level barriers to quality care will afford the opportunity for us to broadly share oncology expertise and develop dissemination and implementation strategies that will enhance the cancer care delivered to patients residing within underserved rural communities. Trial registration Clinicaltrials.gov, NCT04758338. Registered 17 February 2021 – Retrospectively registered, http://www.clinicaltrials.gov/

Purpose: All women diagnosed with breast cancer (BC) ≤ age 50 should be referred for genetic counseling (GC) and testing. We sought to compare differences in provider practices and access across a racially and ethnically diverse population of young BC survivors. Methods: A registry-based sample of women diagnosed with invasive BC ≤ age 50 from 2009 to 2012 was recruited through the Florida Cancer Registry, and completed a questionnaire and medical record release. Differences were compared across those tested with or without the involvement of a board-certified or credentialed genetics health professional (GHP) in 1) clinical and demographic variables; and 2) pre-test GC elements. Results: Of 1622 participants, there were 440 Blacks, 285 Hispanics, and 897 Non-Hispanic Whites. Of 831 participants with medical record verification of testing provider, 170 (20%) had documentation of GHP involvement. Among the 613 who recalled a pre-test discussion and had GC elements collected, those with GHP involvement were significantly more likely to recall the seven recognized GC elements. Conclusion: GHP involvement was associated with adherence to nationally recommended best practices. With the expanding importance of identifying inherited cancers, it is critical to ensure equitable access to best practices across all populations.

Background: The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case–control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer. Methods: A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer. Results: In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34–0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87–1.70; P = 0.26). Conclusions: The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk. Impact: Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.

Background: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75years of age with a BRCA1 or BRCA2 pathogenic variant. Methods: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50years. Participants completed a baseline questionnaire and follow-up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow-up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan-Meier method. Results: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n=186) and ovarian (n=45) were the most frequent cancers observed. For women who had both risk-reducing mastectomy and bilateral salpingo-oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. Conclusion: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75years and should be counselled appropriately.

OBJECTIVE To examine the patterns and covariates of benefit finding over time among young Black breast cancer (BC) survivors. METHODS Black women (N = 305) with invasive BC diagnosed ≤50 years were recruited an average of 1.9 years post-BC diagnosis. Participants completed self-report questionnaires of benefit finding, social support, and illness intrusions at three time points (M time since BC diagnosis: T2 = 3.1 years, T3 = 4.0 years). Relationships between posttraumatic growth constructs (social support, illness intrusions) and benefit finding over time were examined using mixed models. Models controlled for cultural variables (religiosity, time orientation, and collectivism), receipt of chemotherapy, general health status, and partner status. RESULTS Participants reported high levels of benefit finding (M = 2.99, SE = 0.04 on a 0-4 scale). When accounting for covariates, benefit finding did not change over time since BC diagnosis (P = .21). Benefit finding scores at BC diagnosis were associated with more illness intrusions, greater religiosity, and having received chemotherapy (all Ps

IMPORTANCE: Survival differences between male and female patients with breast cancer have been reported, but the underlying factors associated with the disparity have not been fully studied. This understanding is fundamental to developing strategies for cancer treatment and survivorship care. OBJECTIVE: To compare mortality between male and female patients with breast cancer and quantitatively evaluate the factors associated with sex-based disparity in mortality. DESIGN, SETTING, AND PARTICIPANTS: This large, nationwide, registry-based cohort study used the National Cancer Database to identify and obtain data on patients who received a breast cancer diagnosis between January 1, 2004, and December 31, 2014. After exclusions, the final study population comprised 1 816 733 patients. Statistical analyses were conducted from September 1, 2018, to January 15, 2019. MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival. Secondary outcomes were 3-year and 5-year mortality. Mortality differences were evaluated by Kaplan-Meier analysis. The roles of race/ethnicity, clinical characteristics, treatments, and access-to-care factors in the association between sex and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age. RESULTS: In total, 16 025 male (mean [SD] age, 63.3 [13.0] years) and 1 800 708 female (mean [SD] age, 59.9 [13.3] years) patients with breast cancer were included in the study. Compared with female patients, male patients had higher mortality across all stages. For men, the overall survival rate was 45.8% (95% CI, 49.5-54.0; P

Objective Breast cancer (BC) survivors with a genetic mutation are at higher risk for subsequent cancer; knowing genetic risk status could help survivors make decisions about follow-up screening. Uptake of genetic counseling and testing (GC/GT) to determine BRCA status is low among high risk BC survivors. This study assessed feasibility, acceptability, and preliminary efficacy of a newly developed psychoeducational intervention (PEI) for GC/GT. Methods High risk BC survivors (N = 119) completed a baseline questionnaire and were randomized to the intervention (PEI video/booklet) or control (factsheet) group. Follow-up questionnaires were completed 2 weeks after baseline (T2), and 4 months after T2 (T3). We analyzed recruitment, retention (feasibility), whether the participant viewed study materials (acceptability), intent to get GC/GT (efficacy), and psychosocial outcomes (eg, perceived risk, Impact of Events Scale [IES]). t tests or chi-square tests identified differences between intervention groups at baseline. Mixed models examined main effects of group, time, and group-by-time interactions. Results Groups were similar on demographic characteristics (P ≥ .05). Of participants who completed the baseline questionnaire, 91% followed through to study completion and 92% viewed study materials. A higher percentage of participants in the intervention group moved toward GC/GT (28% vs 8%; P = .027). Mixed models demonstrated significant group-by-time interactions for perceived risk (P = .029), IES (P = .027), and IES avoidance subscale (P = .012). Conclusions The PEI was feasible, acceptable, and efficacious. Women in the intervention group reported greater intentions to pursue GC, greater perceived risk, and decreased avoidance. Future studies should seek to first identify system-level barriers and facilitators before aiming to address individual-level barriers.

PURPOSE: Uptake of genetic counseling among breast cancer survivors is low. We used the Health Belief Model (HBM) to explore factors associated with readiness for genetic counseling among breast cancer survivors. METHODS: Breast cancer survivors meeting NCCN genetic counseling referral criteria were recruited through clinics and community settings. Participants completed questionnaires capturing demographic and clinical information and factors guided by the HBM, including health beliefs, psychosocial variables, and cues to action. Using logistic regression, we examined whether the above variables differed based on readiness group (pre-contemplators, who did not plan to make a genetic counseling appointment, and contemplators, who planned to make a genetic counseling appointment in the next 1– 6 months). RESULTS: Of 111 participants, 57% were pre-contemplators and 43% were contemplators. In the multivariable model, higher cancer worry was associated with increased odds of being a contemplator (OR=2.99; 95% CI=1.37–6.54) and higher perceived barriers to genetic counseling were associated with decreased odds of being a contemplator (OR=0.31; 95% CI= 0.11–0.85). Those who reported a family member encouraged them to get tested were more likely to be contemplators (OR=3.57; 95% CI=1.19– 10.70). CONCLUSIONS: Our results suggest key factors for predicting genetic counseling readiness include cancer worry, perceived barriers, and family influence. IMPLICATIONS FOR CANCER SURVIVORS: Ideally genetic counseling occurs prior to treatment, but significant advantages exist for survivors. There is need for increased genetic counseling awareness. Better understanding of factors related to survivors’ decisions about counseling can inform tailored interventions to improve uptake and ultimately reduce cancer recurrence risk.

PurposeBlack women are more likely to develop early-onset (≤50years) breast cancer (BC) and have the lowest five-year, cause-specific survival rate of any United States (U.S.) racial or ethnic group. These disparities can be attributed partially to the higher rate of triple-negative BC (TNBC) in Blacks. Yet, little is known about health-related quality of life (HRQOL) among Black women with TNBC.MethodsBlack women with invasive BC≤50years were recruited via the Florida Cancer Data System as part of a population-based case-only study of etiology and outcomes of early-onset invasive BC. Of 460 consented participants, a subset of 355 self-reported sociodemographic, clinical, and psychosocial variables. Descriptive analyses included participants with known TNBC (n=85) or non-TNBC (n=245) disease. Univariable and multivariable analyses were conducted to examine differences in factors associated with HRQOL.ResultsIn unadjusted analyses, TNBC participants had significantly lower FACT-B total scores (90.1±27.9) compared to non-TNBC (98.5±27.6) participants (p&nbsp

Anthracycline-based cardiotoxicity is concerning for women with breast cancer and portends a dose-dependent risk of developing left ventricular dysfunction. Overall, the prevalence of heart failure (HF) is ≈2% of the total US population; however, BRCA-deficient mice have shown increased HF. We evaluated for the inherent risk of HF in women with BRCA mutations to determine whether treatment with anthracycline-based therapy increased this risk. We obtained results on BRCA mutation carriers regarding cancer treatment and HF, identified through the BRCA patient advocacy organization Facing Our Risk for Cancer Empowered (FORCE) and the Moffittbased Inherited Cancer Registry. In our patient group (232 BRCA1 and 159 BRCA2 patients; 10 with both mutations), 7.7% reported HF, with similar proportions in BRCA1 versus BRCA2 carriers (7.4% and 8.2%, respectively). These proportions are significantly higher than published rates (p < 0.001). There was no statistically significant difference in HF rates comparing anthracycline-treated versus anthracycline-naïve patients however (7.1% vs. 8.3%; p = 0.67). In addition, 9.1% of BRCA1 carriers and 8.2% of BRCA2 carriers reported arrhythmias. BRCA mutation carriers showed increased risk of cardiotoxicity versus the general population and an overall increased risk of cardiotoxicity from anthracycline-based therapy. Our study supports data that BRCA carriers have increased noncancer mortality from cardiotoxicity. A prospective trial to determine HF and conduction abnormalities in this population is warranted.

Objective Black women have a higher rate of BRCA1 and BRCA2 (BRCA) mutations, compared with other populations, that increases their risk for hereditary breast and ovarian cancer (HBOC). However, Black women are less likely to know about HBOC and genetic testing. Based on a request from a community advisory panel of breast cancer survivors, community leaders and healthcare providers in the Black community, our team developed a culturally targeted educational brochure to promote awareness of HBOC among Black women.

This article introduces the identification, prevention, and treatment of hereditary cancer as an important public health concern. Hereditary cancer research and educational outreach activities are used to illustrate how public health functions can help to achieve health benefits of genetic and genomic medicine. First, we evaluate genetic service delivery through triangulating patient and provider survey results which reveal variability among providers in hereditary cancer knowledge and genetic service provision. Second, we describe efforts we have made to assure competency among healthcare providers and to inform, educate and empower patients with regard to the rapidly evolving field of genomics and hereditary cancer. Lastly, key policy-issues raised by our experiences are discussed in the context of how they may help us to more effectively translate future genomic technologies into practice in order to attain population health benefits from genetic and genomic medicine.

Given that Black women remain underrepresented in clinical research studies, we sought to recruit a population-based sample of young Black women with breast cancer through a state cancer registry. Demographic and clinical information on all Black women diagnosed with invasive breast cancer at or below age 50 between 2009 and 2012 in Florida was obtained through the state cancer registry. Survivors were invited to participate in the study through state-mandated recruitment methods. Participant demographic and clinical characteristics were compared using Chi-squared tests for categorical variables and the two sample t-test for continuous variables to identify differences between: (i) consented participants versus all other eligible; and (ii) living versus deceased. Of the 1,647 young Black women with breast cancer, mean age at diagnosis was 42.5, with the majority having localized or regional disease, unmarried, privately insured, and employed. There were no significant differences in demographic and clinical variables between the 456 consented study participants versus the remaining 1,191 presumed eligible individuals. Compared to potential participants, women determined to be deceased prior to recruitment (n = 182) were significantly more likely to have distant disease and a triple-negative phenotype. They were also significantly more likely to be unemployed, and uninsured or have public insurance (i.e., Medicaid or Medicare). Our results demonstrate that recruitment of a population-based sample of breast cancer survivors through a state cancer registry is a feasible strategy in this underserved and underrepresented population. However, survival bias, which was observed due to the lag time between diagnosis and recruitment, is important to adjust for when generalizing findings to all young Black breast cancer patients.

Qualitative comparative analysis (QCA) was developed over 25 years ago to bridge the qualitative and quantitative research gap. On searching PubMed and the Journal of Mixed Methods Research, this review identified 30 original research studies that used QCA. Perceptions that QCA is complex and provides few relative advantages over other methods may be limiting QCA adoption. Thus, to overcome these perceptions, this article demonstrates how to perform QCA using data from 15 institutions that implemented universal tumor screening programs to identify patients at high risk for hereditary colorectal cancer. In this example, QCA revealed a combination of conditions unique to effective universal tumor screening programs. Results informed additional research and provided a model for improving patient follow-through after a positive screen.

There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone.

Institutions have increasingly begun to adopt universal tumor screening (UTS) programs whereby tumors from all newly diagnosed patients with colorectal cancer (CRC) are screened to identify who should be offered germline testing for Lynch syndrome (the most common cause of hereditary CRC). Given limited information about the impact of universal screening programs to detect hereditary disease in adults, we apply criteria used to evaluate public health screening programs and compares and contrasts UTS with universal newborn screening (NBS) for the purpose of examining ethical implications and anticipating potential outcomes of UTS. Both UTS and a core set of NBS conditions clearly meet most of the Wilson and Jungner screening criteria. However, many state NBS panels include additional conditions that do not meet several of these criteria, and there is currently insufficient data to confirm that UTS meets some of these criteria. Comparing UTS and NBS with regard to newer screening criteria raises additional issues that require attention for both UTS and NBS. Comparisons also highlight the importance of evaluating the implementation of genomic tests to ensure or improve their effectiveness at reducing morbidity and mortality while minimizing potential harms.

Objective: In epithelial ovarian cancer, concordance between results of microsatellite instability (MSI) and immunohistochemical (IHC) testing has not been demonstrated. This study evaluated the association of MSI-high (MSI-H) status with loss of expression (LoE) of mismatch repair (MMR) proteins on IHC and assessed for potential factors affecting the strength of the association. Methods: Tumor specimens from three population-based studies of epithelial ovarian cancer were stained for MMR proteins through manual or automated methods, and results were interpreted by one of two pathologists. Tumor and germline DNA was extracted and MSI testing performed. Multivariable logistic regression models were fitted to predict loss of IHC expression based on MSI status after adjusting for staining method and reading pathologist. Results: Of 834 cases, 564 (67.6%) were concordant; 41 were classified as MSI-H with LoE and 523 as microsatellite stable (MSS) with no LoE. Of the 270 discordant cases, 83 were MSI-H with no LoE and 187 were MSS with LoE. Both IHC staining method and reading pathologist were strongly associated with discordant results. Conclusions: Lack of concordance in the current study may be related to inconsistencies in IHC testing methods and interpretation. Results support the need for validation studies before routine screening of ovarian tumors is implemented in clinical practice for the purpose of identifying Lynch syndrome.

Familial cases of carcinoid tumours that are not associated with any known syndrome or disease are extremely rare. All cases reported in the world literature have involved carcinoid tumours of the gastrointestinal tract. Two cases of carcinoid tumours of the small intestine in a father and daughter are presented. Laboratory analyses did not support the hypothesis that the occurrence of carcinoid tumours in this family is a variant of the multiple endocrine neoplasia type 1 syndrome. A review of the literature on familial occurrence of intestinal carcinoid tumours in the absence of any other known carcinoid tumour-predisposing genetic syndrome is provided.

Recognizing the importance of identifying patients at high risk for inherited cancer predisposition, the United States Preventive Services Task Force (USPSTF) has outlined specific family history patterns associated with an increased risk for BRCA mutations. However, national data indicate a need to facilitate the ability of primary care providers to appropriately identify high risk patients. Once a patient is identified as high risk, it is necessary for the patient to undergo a detailed genetics evaluation to generate a differential diagnosis, determine a cost-effective genetic testing strategy, and interpret results of testing. With identification of inherited predisposition, risk management strategies in line with national guidelines can be implemented to improve patient outcomes through cancer risk reduction and early detection. As use of genetic testing increasingly impacts patient outcomes, the role of primary care providers in the identification and care of individuals at high risk for hereditary cancer becomes even more important. Nevertheless it should be acknowledged that primary care providers face many competing demands and challenges to identify high risk patients. Therefore initiatives which promote multidisciplinary and coordinated care, potentially through academic-community partnerships, may provide an opportunity to enhance care of these patients.

Low levels of awareness about hereditary breast cancer and ovarian cancer and underutilization of genetic services combined with the high incidence of early onset breast cancer in the black community underscore the urgent need to provide information about hereditary breast and ovarian cancer to black women. The primary goal of the present study was to develop a culturally targeted brochure designed to increase awareness about inherited breast cancer among black women using the principles of Learner Verification. Three focus groups were conducted with black women, including those with or without a history of breast cancer (n = 46), to evaluate the brochure. Data were analyzed through hand coding using a simple classification system placing participants' responses in the predetermined Learner Verification categories. On the basis of the feedback obtained, the brochure has been modified to improve cultural-targeting, relevance, and clarity and has been made available for dissemination. Our study illustrates the importance of obtaining feedback from the target audience when developing a culturally targeted informational brochure for black women. Further, the complexity of our subject matter (i.e., inherited breast and ovarian cancer) underscores the importance of using inviting visuals and personal vignettes, while maintaining a simple and clear message.