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Purpose:Prognostic value of Oncotype DX Breast Recurrence Score (RS) in male patients with breast cancer is understudied. We evaluated associations of RS with overall mortality in male patients with breast cancer and compared it with female counterparts.Experimental Design:With a cohort of 848 male and 110,898 female patients with breast cancer identified from the National Cancer Database (2010–2014), we estimated HRs and 95% confidence intervals (CI) for overall mortality associated with RS using Cox regression models. RS was evaluated continuously, as well as by categorization following respective traditional (≤17, 18–30, and ≥31) and TAILORx (≤10, 11–25, and ≥26) cutoffs.Results:RS was positively associated with mortality in male patients (HR = 1.13; 95% CI, 1.02–1.26 per unit RS increment) up to RS > 21, after which the risk plateaued. Among female patients, mortality began to increase with RS only when RS > 23 (HR = 1.02; 95% CI, 1.01–1.02 per unit of RS increment). The intermediate- (HR = 5.37; 95% CI, 1.79–16.11) and high-risk diseases (HR = 4.28; 95% CI, 1.22–14.97) defined by TAILORx, but not traditional cutoffs established for female patients, were associated with elevated mortality risk in men even after adjustment for demographic, clinical characteristics, and treatments, except chemotherapy.Conclusions:RS is associated with mortality in male patients with breast cancer at a much lower threshold than that for female patients. Studies are needed to establish specific guidelines for RS thresholds for male patients with breast cancer.

Supplementary Table S1. Characteristics of male breast cancer patients by receipt of Oncotype DX Recurrence Score (RS) testing Supplementary Table S2. HRs (95% CI) for total mortality associated with the Recurrence Score categories among patients {less than or equal to} 50 years Supplementary Table S3. HRs (95% CI) for total mortality associated with the Recurrence Score categories among patients > 50 years Supplementary Table S4. HRs (95% CI) for total mortality associated with chemotherapy status among intermediate-risk patients by age Supplementary Table S5. HRs (95% CI) for total mortality associated with Recurrence Score categories (sensitivity analysis)

Background: Oncotype DX recurrence score (ODX RS) is a prognostic biomarker for early-stage, node-negative, estrogen receptor–positive (ER+) breast cancer. Whether test uptake, associated factors, and the test's prognostic values differ by race/ethnicity is unknown. Methods: From the National Cancer Database, 2010–2014, we identified 227,259 early-stage ER+, node-negative breast cancer cases. Logistic regression was used to examine ODX RS uptake and associated factors among non-Hispanic White (White), non-Hispanic Black (Black), Hispanic, and Asian American patients. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for overall mortality with ODX RS by race/ethnicity. Results: White patients were more likely to receive an ODX RS test compared with Black, Hispanic, and Asian American patients (36.7%, 32.8%, 31.6%, and 35.5%, respectively; P < 0.001). Disparities persisted after adjustments for demographics, clinical characteristics, and access-to-care, with rate ratios of 0.87 (95% CI, 0.85–0.88), 0.82 (95% CI, 0.80–0.85), and 0.89 (95% CI, 0.87–0.92), respectively, for Black, Hispanic, and Asian American compared with White patients. Black patients had higher proportions of high-risk scores (≥26) compared with White, Hispanic, and Asian American patients (19.1%, 14.0%, 14.2%, and 15.6%, respectively; P < 0.0001). ODX RS was predictive for total mortality across all races/ethnicities, particularly younger patients ( Conclusions: Although ODX RS uptake and risk distribution varied by race/ethnicity, ODX RS was prognostic for mortality across groups. Impact: These findings emphasize the importance of developing strategies to increase ODX RS uptake among racial/ethnic minorities and call for more investigations on potential racial/ethnic differences in breast cancer biology. See related commentary by Wang et al., p. 704

Background:Factors contributing to breast cancer survival disparities in underrepresented racial and ethnic groups and low-income populations are poorly understood as few clinical trials and population based studies have included these underserved populations. The Southern Community Cohort Study (SCCS), a prospective cohort of underserved, low-income adults with high representation of Black participants, provides a unique opportunity to evaluate such disparities in cancer outcomes. A previous study utilizing SCCS data found no evidence of increased breast cancer risk among women with diabetes in this population. The purpose of this study was to evaluate the association of diabetes with overall survival in women with breast cancer in the SCCS. Methods:The SCCS enrolled approximately 86,000 participants aged 40-79 from 12 southeastern states between 2002-2009, 86% of whom were enrolled at Community Health Centers. This analysis includes women diagnosed with incident localized breast cancers identified through annual cohort linkage with 12 state cancer registries. Demographic data including participant age at breast cancer diagnosis, self-reported history of diabetes (patient answered yes to “has a doctor ever told you that you have diabetes”), body mass index (BMI), race, household income, and insurance coverage were obtained from baseline surveys, cancer type and stage data from state cancer registries, and survival data from death registries. Survival time was defined as the number of months between initial breast cancer diagnosis and death from any cause. Descriptive characteristics including mean (standard deviation) or number (%) were used to summarize demographics. We used Pearson Chi-squared analysis to examine the association between diabetes and overall survival. Multivariable Cox proportional hazards regression was used to evaluate overall survival and diabetes, adjusting for covariates including age (continuous), race, BMI (categorical by WHO classifications), household income (binary – annual income =$25,000), insurance coverage, cancer subtype, and cancer stage). Results:We identified a total of 1,347 women diagnosed with breast cancer. Of these, 1,016 were diagnosed with localized disease (stage 1-3) and comprised our analytic sample. Difference in denominators reflects missing data. The women were predominantly Black (667/1,016, 65.6%), low income (719/1,016 annual income less than $25,000, 70.8%), and insured (Private insurance 220/763, 28.8%; Medicare 331/763, 43.4%; Medicaid 178/763, 23.3%). Average age at diagnosis was 60.7 years (SD 9.1, IQR 41-88). Approximately one quarter of the patients (258/994, 26.0%) self-reported diabetes and 59.6% (605/1,016) were obese (BMI >=30). The breast cancer immunohistochemistry subtypes in this cohort of women included HR+HER2- (392/564, 69.5%), HR+,HER2+ (55/564, 9.8%), HR-,HER2+ (31/564, 5.5%), and HR-HER2- (86/564, 15.3%). Women with diabetes had lower overall survival (174/258, 67.4%) than women without diabetes (587/746, 79.8%) (p Conclusion: In a low-income, predominantly Black population with incident localized breast cancer, decreased overall survival was observed among women diabetes compared to those without diabetes. Future studies should explore additional biological, societal, and socio-economic factors affecting survival among women with breast cancer in medically underserved minority populations. Citation Format: Lucy B. Spalluto, Sonya Reid, Diane Haddad, Tuya Pal, Ingrid A. Mayer, Xiao-ou Shu, Maureen Sanderson, Wei Zheng, William J. Blot, Loren Lipworth. Diabetes decreases overall survival in women with breast cancer in the southern community cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD11-05.

Background:Breast cancer outcomes in minority and low socioeconomic status populations are not clearly defined due to underrepresentation of these underserved populations in breast cancer clinical trials and population-based studies. The Southern Community Cohort Study (SCCS), a prospective cohort of underserved, predominantly Black participants, provides a unique opportunity to evaluate disparities in breast cancer outcomes. We sought to examine the association between race and socioeconomic status (SES) and overall survival (OS) in women with localized breast cancer in the SCCS. Methods:The SCCS enrolled approximately 86,000 participants aged 40-79 from 12 Southeastern states between 2002-2009, 86% of whom were enrolled at Community Health Centers. This analysis includes women diagnosed with incident localized breast cancer (stage I-III) identified through annual cohort linkage with 12 state cancer registries through December 20, 2017. Demographic data including participant age, self-reported history of diagnosed diabetes, body mass index (BMI), race, annual household income, and insurance coverage were obtained from baseline surveys. Tumor grade and stage were obtained from state cancer registries, and survival data were obtained from death registry records. Immunohistochemical (IHC) subtype was determined from tumor estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status obtained from cancer registry records and pathology reports. Survival time was defined as the number of months between initial breast cancer diagnosis and death from any cause. Descriptive analyses including mean (standard deviation) and number (%) were used to summarize clinical and sociodemographic characteristics by race. Multivariable Cox survival analysis was used to evaluate OS by race and annual household income, adjusting for age, insurance, stage, IHC subtype, diabetes, and BMI. Results:Of the 1347 women diagnosed with incident breast cancer, 1016 had localized disease (stage I-III) and comprised our analytic sample. Compared to White women, Black women were more likely to have lower income, higher prevalence of triple negative breast cancer (TNBC), grade III tumors and stage III breast cancer (Table 1). After adjusting for clinical and sociodemographic factors, Black women had similar OS compared to White women (HR 0.67; 95% CI 0.42-1.07). However, after adjusting for race, women with a household income ≥ $25,000 had an improved OS compared to those with annual household income < $25,000 (HR 0.53; 95% CI 0.30-0.93). Conclusion: In a low-income, medically underserved population, Black women with localized breast cancer had similar OS compared to White women. However, socioeconomic disparities were observed, with worse OS for women with low annual household income. Future studies focused on minority, underserved groups are imperative to better understand the non-biological and biological factors contributing to disparities in survival among women with breast cancer. Table 1. Patient characteristics overall and by racePatient CharacteristicsTotal(N=1016)Black(N=667)White(N=349)P-value*Age at diagnosis, years (Mean, SD)61 (9)60 (9)63 (9)Income, annual household (N, %) < $25,000 ≥ $25,000719 (71)297 (29)503 (75)164 (25)216(62)133 (38) Citation Format: Sonya Reid, Lucy B Spalluto, Diane Haddad, Tuya Pal, Ingrid Mayer, Xiao-ou Shu, Wei Zheng, Maureen Sanderson, William Blot, Loren Lipworth. The association of race and socioeconomic status with overall survival in women with breast cancer in the southern community cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-34.

Background: There have been renewed calls for greater inclusivity of populations most prominently affected by cancer health inequities across the cancer research enterprise, particularly Black and African American populations. In cancer health services research there are myriad methodologies and data sources to study cancer treatment outcomes including medical records, cancer registries, and primary data collection. These different methodologies have varying levels of resource intensity that may affect the recruitment of marginalized populations. Little is known about how much concordance between data sources may exist among marginalized populations with cancer, which has substantial implications for cancer inequities research. Objective: To evaluate the data concordance between medical records, cancer registries, and self-reported survey data among an underrepresented population in cancer population sciences research. Methods: This investigation used a population-based sample of self-identified Black women recruited through the Tennessee and Florida Cancer registries who were diagnosed with invasive breast cancer at or below the age of 50. Participants completed medical records release forms and questionnaires about their cancer treatment trajectories. Comparing data contained in the cancer registries, medical records, and self-reported data, we quantitatively assessed the concordance between data sources for receipt of surgery, chemotherapy, and radiation, using medical records as the gold standard. Results: In total, 558 Black women at or below 50 with invasive breast cancer had available registry data and also completed a medical records release. In terms of missing data for receipt of surgery, chemotherapy, and radiation, self-report was the most complete, followed by the registry and then the medical records. Among those with complete data, comparing the medical records to the cancer registry, accuracy was high for surgery (94.6% ; 95% CI 92.2, 96.4) and chemotherapy (89.7%; 95% CI: 85.7, 92.8) , but low for radiation (55.4%, 95% CI: 48.5, 62.2) with the cancer registry missing the receipt of radiation that was noted in the medical records. Comparing medical records to self-report data, accuracy was >90% for surgery, chemotherapy, and radiation. Comparing the cancer registry to self-report, accuracy was high for surgery (94.5%; 95% CI: 92.0, 96.4), moderate for chemotherapy (88.2; 95% CI: 85.1,90.9), and low for radiation (67.2%; 95% CI 62.9, 71.3). Conclusion: For receipt of surgery and chemotherapy, there was high concordance between medical records, cancer registries, and self-reported data. The receipt of radiation was inconsistently reported in the cancer registry and medical records. When considering inclusivity in the study of cancer services delivery among marginalized populations, tradeoffs of data validity and resource intensity must be weighed. Citation Format: Mya L. Roberson, Lindsay Venton, Anne Weidner, Sonya Reid, Tuya Pal. Evaluating treatment data concordance among young Black women diagnosed with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1939.

Purpose: Prognostic value of Oncotype DX Breast Recurrence Score (RS) in male patients with breast cancer is understudied. We evaluated associations of RS with overall mortality in male patients with breast cancer and compared it with female counterparts. Experimental Design: With a cohort of 848 male and 110,898 female patients with breast cancer identified from the National Cancer Database (2010–2014), we estimated HRs and 95% confidence intervals (CI) for overall mortality associated with RS using Cox regression models. RS was evaluated continuously, as well as by categorization following respective traditional (≤17, 18–30, and ≥31) and TAILORx (≤10, 11–25, and ≥26) cutoffs. Results: RS was positively associated with mortality in male patients (HR = 1.13; 95% CI, 1.02–1.26 per unit RS increment) up to RS > 21, after which the risk plateaued. Among female patients, mortality began to increase with RS only when RS > 23 (HR = 1.02; 95% CI, 1.01–1.02 per unit of RS increment). The intermediate- (HR = 5.37; 95% CI, 1.79–16.11) and high-risk diseases (HR = 4.28; 95% CI, 1.22–14.97) defined by TAILORx, but not traditional cutoffs established for female patients, were associated with elevated mortality risk in men even after adjustment for demographic, clinical characteristics, and treatments, except chemotherapy. Conclusions: RS is associated with mortality in male patients with breast cancer at a much lower threshold than that for female patients. Studies are needed to establish specific guidelines for RS thresholds for male patients with breast cancer.

Background: Young-onset breast cancer is associated with higher mortality due to multiple factors including tumor biology and delayed presentation. Young women with breast cancer with longer treatment delays have decreased survival time, with the impact on survival being more prominent in Black women. The factors contributing to the racial survival disparity are complex and are likely an interplay between tumor biology, genomics, patterns of care and socioeconomic factors. This study looked at socioeconomic and clinical factors that may affect timely access to care for breast cancer in young Black women, and thus impact survival. Methods: Data from the Black Women Etiology and Survival of Triple-negative Breast Cancers (BEST) Study, a population-based cohort of Black women diagnosed with breast cancer ≤ 50 years old between 2009 and 2015 from the Florida and Tennessee State Cancer Registries was used. The time to treatment (in days) was used as the exposure variable and defined as the time from breast cancer diagnosis to the date of first treatment. The primary outcome was determined by distant or local recurrence or death. Pearson chi-square test was conducted to assess the association between clinical and socioeconomic factors with time to treatment. The socioeconomic variables studied were insurance, income and education. Clinical factors evaluated were the stage of breast cancer at diagnosis, hormone subtype, neoadjuvant chemotherapy and type of surgery. Survival analysis and Cox proportional hazard model were performed to analyze the 10-year overall survival and recurrence rate while adjusting for income, breast cancer stage and hormone subtype. Results: There was a statistically significant association between time to treatment and hormone receptor subtype (p=0.04). More than 60% of women with triple-negative breast cancer (TNBC), and 57% of women with HER2+ breast cancer received treatment within a month of their breast cancer diagnosis. There was also a significant association between the time to treatment and type of surgery received (p=0.03). 64% of patients who had lumpectomies received treatment in ≤30 days, compared to 54% of patients who had a mastectomy. Survival analysis showed the highest mortality in patients with time to treatment >90 days, followed by patients who received treatment in ≤30 days. The study did not find a statistically significant association between insurance, income, or education on the timeliness of treatment for breast cancer. Conclusion: In our study of young Black women, delayed breast cancer treatment resulted in lower survival. While those with TNBC and HER2+ disease were more likely to receive treatment ≤30 days, i.e. neoadjuvant chemotherapy to assess response to chemotherapy and the amount of residual disease at the time of the surgery, the enrichment for aggressive disease is likely the reason for the low survival observed in this group. Timely access to treatment for breast cancer impacts survival and strategies to decrease treatment delays are crucial to reducing breast cancer mortality. Citation Format: Kikelola Oyeleye, Rebecca Lee, Sonya Reid, Tuya Pal, Anne Weidner, Lindsay Venton. Association between socioeconomic and clinical factors on timely access to care among young Black women with breast cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A070.

Introduction Genetic testing is an increasingly important part of cancer treatment for women with breast cancer diagnosed under age 45. There has been evidence about low testing uptake and barriers to genetic testing for eligible Black women but less is known about motivations for testing. The objective of this study was to assess reasons for pursuing genetic testing among young Black women with breast cancer. Methods Study participants were a population-based sample of self-identified Black women diagnosed with invasive breast cancer at or below age 50, recruited through the Florida and Tennessee state cancer registries. Participants were categorized into tested and not tested groups. Among the tested, participants were asked why they pursued testing and response options included to guide surgical decisions, chemotherapeutic decisions, radiation decisions, or to benefit family. Respondents were categorized into 4 groups: no motivation specified; treatment motivation only; family benefit motivation only; both treatment and family motivation. Logistic regression was used to estimate factors associated with type of motivation. Results In total, 175 women were eligible for inclusion, 135 women had received genetic testing, and 40 had not. Median age of breast cancer diagnosis was 43. Among tested women, 30 (22%) endorsed treatment motivation only, 69 (51%) endorsed family motivation only, and 31 (23%) endorsed both treatment and family motivation. Women who had daughters had higher odds of endorsing being motivated by family benefit (OR 3.87, 95% CI 1.98, 7.57). This relationship was not seen for having sons (OR 0.84, 0.49, 1.83), sisters (OR 0.78, 95% CI 0.34, 1.77) or brothers (0.87, 0.43, 1.73). Among the 40 women who did not receive genetic testing, 24 (60%) indicated a lack of testing recommendation. Conclusions In our investigation, we found that a greater number of Black women were motivated to pursue genetic testing because of the potential benefit to family members rather than to guide treatment decisions. This finding was especially pronounced among women who had daughters. The null relationship between having sons or either gender sibling and motivation driven by family benefit may reflect greater awareness of BRCA associations with female breast cancer and low awareness of male breast and other BRCA associated cancers. Our findings suggest that conversations around the importance of genetic testing may need to go beyond the importance of guiding treatment decisions and include discussions around the potential benefit for family members. Citation Format: Mya L. Roberson, Sonya Reid, Tuya Pal. Reasons for pursuing genetic testing among young Black women with breast cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C007.

Introduction: Identification of inherited breast cancer (BC) risk through genetic testing (GT) may guide button. Abstracts received without a properly medical care, which can be amplified by sharing test results with relatives. Among women with a completed Disclosure Declaration will not be pathogenic/likely pathogenic (P/LP) variant in an inherited BC gene, we sought to compare cancer risk considered. The size limit for the abstract (including management (CRM), as well as family sharing (FS) practices and family testing (FT) rates across genes. Methods: Female participants with a P/LP variant in BRCA, PALB2, CHEK2, or ATM were surveyed about CRM and FS/FT practices Frequencies of CRM (i.e., screening and/or risk-reducing surgery), and FS/FT rates were compiled and compared. Descriptive statistics, bivariate analyses, and non-parametric tests were performed to assess for associations. Results: The 238 participants with P/LP variants were as follows: 186 BRCA, 28 PALB2, 15 CHEK2, and 9 ATM. Median age of participants was 54 and most were non-Hispanic white (89%) with a prior cancer diagnosis (59%). Rates of risk-reducing mastectomy (RRM; defined as at least one breast removed prophylactically regardless of a prior BC diagnosis) was 65.1% among BRCA carriers, with lower rates among PALB2, CHEK2, and ATM carriers (32.1%, 33.3%, and 33.3%, respectively). Rates of risk-reducing salpingo- oophorectomy (RRSO) were appropriately higher among BRCA carriers (89.8%), but were also relatively common among PALB2, CHEK2, and ATM carriers (32.1%, 33.3%, and 66.7%, respectively). Rates of FS and FT were significantly higher in relatives of BRCA carriers compared to others (p=.003; p0.05). Conclusion: Our results suggest that adherence to CRM for BRCA carriers is appropriately high. However, RRM among those with PALB2, CHEK2, and ATM P/LP variants are also frequently observed, despite the lack of practice guidelines to recommend RRM. Even more concerning is the appreciable RRSO rates in the absence of practice guidelines or data to confirm high ovarian cancer risk. Thus, our data suggest that many patients with P/LP variants in genes other than BRCA receive surgeries for which guidelines are lacking. These efforts highlight the tremendous need to promote risk appropriate care and reduce over-treatment among these individuals. Furthermore, reasons for lower FS and FT rates among women with P/LP variants in genes other than BRCA should be evaluated in future studies. Ultimately, as more data to refine cancer risks and management are generated across these other inherited BC genes, strategies are needed to improve FS and FT among at-risk relatives and amplify testing benefits. Table 1: Average percent of FS and FT rates among relatives across genes BRCA PALB2 CHEK2 ATM N = 186 N = 28 N = 15 N = 9 Aware Tested Aware Tested Aware Tested Aware Tested First-degree 81.0% 38.9% 74.5% 27.7% 71.6% 26.8% 78.3% 23.3% Second-degree 56.4% 11.5% 35.2% 6.3% 41.1% 7.3% 26.2% 3.2% Third-degree 60.7% 13.3% 46.2% 5.8% 58.2% 5.1% 39.3% 6.6% Female 69.9% 30.6% 63.3% 22.6% 57.6% 13.7% 44.6% 13.6% Male 60.3% 10.8% 43.9% 6.1% 52.2% 9.9% 47.4% 7.6% Citation Format: Tuya Pal, Anne Weidner, Ann Tezak, Kate Clouse, Deborah Cragun. Cancer risk management and family sharing of genetic test results among women with inherited breast cancer genes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-20.

Introduction Haitians diagnosed with breast cancer in Haiti experience a significantly worse outcome than immigrants in Miami that appears to be related to 1) more advanced stage, 2) younger age, 3) more ER-negative tumors, and 4) lack of timely effective treatments including restricted access to trastuzumab and radiation. The objective of the study was to evaluate the epigenetic differences by DNA methylation between women of African descent who have breast cancer and are native to Haiti, the USA or who have emigrated from Haiti to the USA. Methods The study was IRB approved and conducted between 2017-2019 at University of Miami (n=50), Ministry of Health Haiti and Innovating Health International (n=35) and Moffit Cancer Center (n=14). DNA were extracted from saliva (DNAGenotek PrepIT-LP), FFPE breast tumor and normal adjacent breast epithelia (QIAmp DNA FFEP kit) when available. Reduced representation bisulfite sequencing was performed by BGI Inc (Cambridge MA) with EZ DNA metylation gold kit (Zymo) and followed by directional BS-sequence library preparation on HISeq x Ten, PE150. Data was processed in methylKit package and analyzed in a two-step filtering process to 1) include 200bp tiled regions to maximize CpG coverage, > 10 read coverage, 3 shared CpGs per group or all samples if the number of samples was less than 3 in the group, q Citation Format: Vincent DeGennaro, Kaliyah Brown, Danielle A Cerbon, Daniel Karl, Sofia Palacio, Jennifer Garcia, Camille Ragin, Tuya Pal, Susan Vadaparampil, Carmen Gomez, Judith Hurley, Sophia HL George. Short-term effects of immigration on the development of breast cancer in women of African descent [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B086.

Although non-Hispanic White and non-Hispanic Black women have similar breast cancer incidence rates, Black women are more likely to be diagnosed with aggressive or late-stage disease and have higher mortality rates compared to White women. Clinical studies have demonstrated that tumors lacking estrogen receptor (ER), progesterone receptor (PR) and/or human epidermal growth factor receptor 2 (HER2) (referred to as “triple negative breast cancers” or TNBC), are associated with an aggressive pathology and poor prognosis and distinct risk factor profiles, compared to those with receptor positivity. Through the current study, we examined the effect of obesity in the development of breast cancer subtypes; specifically, ER- tumors and TNBC. To examine the association between body mass index (BMI) and breast cancer subtype, we utilized a pooled dataset of Black women with breast cancer from four studies: Black Women Etiology and Survival of Triple-negative Breast Cancers Study, Southern Community Cohort Study, Nashville Breast Health Study and the Tri-State Breast Study. For all four studies, information on tumor ER, PR and HER2 status was abstracted from state cancer registry records and supplemented by available pathology reports and medical records. We calculated BMI as kg/m2, based on self-reported weight and height, and classified it as normal (18.5- Citation Format: Jaleesa Moore, Maureen Sanderson, Tuya Pal, Mary Kay Fadden, Steffie-Ann Dujon, Sonya Reid, Anne Tezak, Loren Lipworth. Association of obesity with breast cancer subtypes among non-Hispanic Black women [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C075.

Introduction: Practice guidelines put forth through the American Society of Clinical Oncology (ASCO) evolved to encompass a new method of testing whereby multiple genes are tested in parallel (i.e., multi-gene panel testing) and racial disparities in genetic testing rates persist. To measure and compare knowledge of inherited cancer predisposition and multi-gene panel testing across racially diverse patient groups, we administered a newly developed and validated knowledge scale aligned with the 2016 ASCO guidelines. Methods: Online survey data inclusive of 14 knowledge questions was collected among Black women diagnosed with breast cancer at or below age 50 recruited through the Tennessee and Florida state cancer registries (“Registry group”; N=39) and an insured, predominately non-Hispanic White patient population referred for cancer genetic risk assessment at the Vanderbilt Hereditary Cancer Clinic (“Clinic group”; N= 55). Demographic and clinical information were compared using Chi-Square and Fisher’s Exact tests. Mean knowledge scores were calculated and compared using multiple regression analysis. Results: Rates of cancer among the Registry and Clinic groups were 100% and 49% (p Citation Format: Sydney Cadiz, Sonya Reid, Brenda Zuniga, Ann Tezak, Anne Weidner, Tuya Pal. Assessing knowledge of genetic testing for inherited cancer among registry-based young black breast cancer survivors and predominantly non-Hispanic white clinic-based patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B056.

Germline mutations in several cancer predisposition genes included in hereditary multigene testing panels have been associated with increased breast cancer risk. However, estimates of breast cancer risks for each gene have in large part been derived from studies of high-risk populations enriched for family history of breast and ovarian cancer, young age of breast cancer diagnosis, or founder mutations. The breast cancer risks associated with mutations in many of these genes in the general population remain to be clearly defined. As clinical hereditary cancer genetic testing is already provided to many women at increased risk and may soon be offered to all breast cancer patients, population-based risk estimates associated with predisposition gene mutations will be needed for appropriate clinical management of mutation carriers. The “CAnceR RIsk Estimates Related to Susceptibility” (CARRIERS) consortium of 17 cohort-based case-control, population-based case-control, and family studies focused on estimation of population-based breast cancer risks and penetrance analysis for mutations in known and candidate breast cancer predisposition genes. Germline DNA from 39486 breast cancer cases and 35868 matched controls was subjected to dual bar-coded QIAseq multiplex amplification of 1733 target regions in 37 predisposition genes. Products from sets of 768 samples were pooled and sequenced in each lane of a HiSeq 4000 system. Mutations were called by GATK Haplotype Caller and Verdict. High quality sequence data was obtained for 99.3% of target regions. Here we report on results from 34741 population-based breast cancer cases and 32728 matched unaffected controls. The mean age of breast cancer diagnosis for cases was 61.2 years and mean age for controls was 61.1 years. Overall, 20.9% of cases and 14.3% of controls had a family history of breast cancer. Furthermore, 74.3% of cases and 75.8% of controls were non-Hispanic white, whereas 13.3% of cases and 15.3% of controls were African American. Among cases with tumor information available, 81.7% were ER-positive and 7.7% were triple negative breast cancers (TNBC). We assessed mutation frequencies in 24 genes including 12 established breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, andTP53). The overall mutation frequency was 6.2% in cases and 2.7% in controls. Case-control association analysis after adjusting for study, age, family history of breast cancer, and race/ethnicity showed that BRCA1(OR=7.45; 95%CI:5.24-10.95) and BRCA2(OR=5.31; 95%CI:4.15-6.88) were associated with high risks of breast cancer in the general population. However, PALB2mutations were only associated with moderate risks (OR=3.63; 95%CI:2.57-5.26). ATMmutations conferred attenuated risks (OR=1.83; 95%CI:1.47-2.28) relative to studies of high-risk families or young onset breast cancers. NBNmutations were not associated with increased breast cancer risk. Mutations in BARD1, RAD51C, RAD51Dand XRCC2were specifically significantly associated with moderate risks of ER-negative breast cancer and TNBC, whereas mutations in ATM, CDH1and CHEK2were specifically significantly associated with ER-positive disease. On the basis of these findings age-related absolute breast cancer risks for commonly mutated genes were estimated. Overall, results from the CARRIERS study establish that mutations in predisposition genes are associated with lower risks of breast cancer in the general population than in enriched populations including high-risk families and young onset, bilateral, or multiple primary cases. We anticipate that the results from this study will inform cancer screening and other risk management strategies for women in the general population with mutations in predisposition genes. Citation Format: Fergus J Couch, Chunling Hu, Steven N Hart, Rohan Gnanaolivu, Kun Y Lee, Jie Na, Chi Gao, Nicholas J Boddicker, Bruce Eckloff, Raed Samara, Josh Klebba, Christine B Ambrosone, Hoda Anton-Culver, Paul Auer, Leslie Bernstein, Mia M Gaudet, Christopher Haiman, Esther M John, Susan Neuhausen, Janet E Olson, Tuya Pal, Julie R Palmer, Dale P Sandler, Jack A Taylor, Amy Trentham-Dietz, Celine M Vachon, Clarice Weinberg, Song Yao, Jeffrey N Weitzel, David E Goldgar, Susan M Domchek, Katherine L Nathanson, Peter Kraft, Eric C Polley. Population-based breast cancer risk estimates for predisposition gene mutations: Results from the CARRIERS study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-01.

Introduction: Per national practice guidelines, pre-test genetic counseling through a provider experienced and proficient in genetics (such as a genetics health professional (GHP)) is recommended prior to genetic testing for hereditary cancer. We sought to determine if there are differences in clinical and demographic variables between young breast cancer (BC) survivors who saw a GHP prior to genetic testing compared to those tested without involvement of a GHP. Methods: A population-based sample of Black, Hispanic and non-Hispanic white (NHW) women diagnosed with invasive BC < age 50 in 2009-2012 was recruited through the Florida State Cancer Registry. Participants were asked to complete a questionnaire and medical records release to verify clinical information and genetic test results. Women tested through a GHP were compared to those tested through a non-GHP based on the following variables: 1) Socioeconomic status (SES) (income, college education and private insurance); 2) Racial group (Black, Hispanic and NHW); and 3) Clinical factors (age at diagnosis, family history (FH) of breast or ovarian cancer and triple negative breast cancer (TNBC) status) using Pearson chi-squared analyses. Results: Of 1618 study participants, 1080 reported genetic counseling and/or testing, of which provider information was verified on 981 based on documentation in medical record and/or genetic test result report. GHP involvement (either through consultation and/or test ordering) was reported in 193 women (19.7%) whereas the remaining 788 women (80.3%) had no documentation of GHP involvement. There was a significantly higher rate of GHP involvement among women with TNBC compared to those without TNBC (26.1% vs. 19.1%; p=0.05); and non-significant increases in those with and without a FH of BC (21.1% vs. 17.6%; p=0.17); and ovarian cancer (22.8% vs. 19.2%; p=0.34). GHP involvement did not vary among: 1) women diagnosed < or > age 45 (19.6% vs. 19.8%; p=0.96); 2) Blacks (20.1% vs. 19.6%; p=0.88); 3) Hispanics (23.5% vs. 18.8%; p=0.15); and 4) NHW (18.5% vs. 22%; p=0.19). Regarding SES-related indicators, GHP involvement was lower among women with private insurance versus those without (18.3% vs. 29.3%; p=0.002), annual household income > $25,000 versus those < $25,000 (18.8% vs. 30.8%; p=0.004) and a college education (55.4% vs. 60.9%; p=0.17). Conclusions: Our results demonstrate that TNBC status was associated with testing through a GHP, while other clinical and demographic variables were not associated with GHP involvement. This finding may be due to widespread recognition of a more aggressive disease phenotype and association of TNBC with hereditary disease. Furthermore, the inverse relationship between higher SES-related indicators and GHP involvement suggests that those with higher SES are less likely to receive care through a GHP, as recommended per national guidelines. Citation Format: Sonya Reid, Deborah Cragun, Ann Tezak, Anne Weidner, Ingrid Mayer, Xiao-ou Shu, Susan Vadaparampil, Tuya Pal. Patterns of BRCA testing by provider type based on biological and non-biological factors among a diverse sample of young breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2427.

Introduction: Tissue microarrays (TMA) enable rapid analysis of biomarkers in large-scale studies involving archival tumor specimens, however, their utility in heterogeneous tumors such as ovarian cancer is limited. Methods: In this study, immunohistochemical analysis was done on TMAs comprised of epithelial ovarian cancer (EOC) to estimate the prevalence of loss of expression of three mismatch repair proteins. TMAs were initially created using cores sampled from the center of donor tissue blocks from 59 EOC cases. Full sections were subsequently created and levels of expression were compared between tissues sampled from the central portion versus the periphery. Follow-up analyses were done by obtaining cores from the periphery of up to five additional donor blocks per case. A linear mixed model for each protein was used to investigate differences between results from the initial and follow-up blocks. Results: In the original TMAs created using centrally sampled cores, loss of mismatch repair expression was noted in 17 (29%) of the 59 cases. By comparison, analyses from peripherally sampled cores revealed loss of expression in only 6 of these 17 cases. For each protein, significant differences (P < 0.05) were detected between results from the initial donor block and the majority of the follow-up blocks. Conclusions: Our investigations, based on EOC, suggest that sampling variability in protein expression may result when TMAs are used. Thus, at least for EOC, it is important to preferentially sample from the periphery of tumor blocks where exposure to tissue fixatives is optimal. (Cancer Epidemiol Biomarkers Prev 2009;18(1):28–34)

Women with germ-line mutations in the mismatch repair genes (responsible for hereditary nonpolyposis colorectal cancer) face an increased risk of colonic and endometrial cancer. However, these germ-line mutations are rare and are responsible for fewer than 1% of endometrial cancers. Therefore, we examined whether or not common variants of the hereditary nonpolyposis colorectal cancer–associated genes might also be associated with an increased risk of endometrial cancer. Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2 mismatch repair genes. All the various 672 women with endometrial cancer and 880 controls were genotyped. Each of these three single-nucleotide polymorphisms was associated with an increased risk of endometrial cancer. Carriers of the MLH1 nt-93 A allele were at a 1.5-fold increased risk of developing endometrial cancer compared with controls [95% confidence interval (95% CI), 1.2-2.0; P = 0.001]. The risk was higher for homozygote carriers [odds ratio (OR), 1.9; 95% CI, 1.2-3.2; P = 0.009]. For carriers of the MSH2 rs2303428 C allele, the OR was 1.4 (95% CI, 1.0-1.9; P = 0.05), and for carriers of the MSH2 rs2059520 G allele, the OR was 1.3 (95% CI, 1.0-1.7; P = 0.03). More than 9% of endometrial cancer cases carried a variant allele in both MLH1 and MSH2. For these women, the risk of endometrial cancer was particularly high (OR, 2.1; 95% CI, 1.2-3.6; P = 0.005). For patients younger than 50 years at diagnosis who carried both variants, the risk was even higher (OR, 3.4; 95% CI, 1.7-6.6; P = 0.0005). In summary, two common variant alleles of the MLH1 and MSH2 genes make a substantial contribution to endometrial cancer incidence in Ontario. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1636–40)

The spectrum of mutations in BRCA1 and BRCA2 among African Americans has not been well characterized because most studies to date have been done in Caucasian families. According to Myriad Genetic Laboratories, Inc., only ∼3% of individuals undergoing BRCA1/BRCA2 testing reported African American ancestry. Data from previous studies show that among African American women a greater proportion of breast cancer cases are diagnosed at age We conducted a hospital-based study of African American breast cancer patients with early age at diagnosis (≤45 years) or family history of breast or ovarian cancer. We identified four deleterious mutations in BRCA1 or BRCA2 among the 10 families tested, of which two were novel BRCA2 mutations, one was the west African founder mutation (BRCA1 943ins10), and one was a recurrent mutation that may be a candidate for a second African American founder mutation (BRCA1 IVS13+1G>A). Our results support previous data in demonstrating that (a) the spectrum of mutations among African Americans is unique, (b) family history of breast cancer is an important predictor of hereditary cancer susceptibility among African Americans, and (c) empirical data may be useful in estimating mutation risk among African Americans.

Purpose: Black women are more likely to develop early onset (age ≤50 years) breast cancer and have the lowest five year cause specific survival rate of any U.S. racial or ethnic group. The disparity in incidence and survival can be attributed partially to the higher rate of triple negative breast cancer (TNBC) in Blacks. Yet, little is known about health-related quality of life (HRQOL) among Black women with TNBC. Guided by the Contextual Model of HRQOL, the purpose of these analyses is to examine factors associated with HRQOL in patients with TNBC and non-TNBC. Methods: Black women with invasive breast cancer at age ≤50 years and diagnosed between 2009-2012 were recruited through the Florida State Cancer Registry as part of a population-based case-only study to investigate etiology and outcomes of early-onset invasive breast cancer (n=456). A subset of participants (n=355) consented to complete additional study questions assessing those sociodemographic, clinical, and psychosocial variables selected based on the Contextual Model. The Functional Assessment of Cancer Treatment-Breast (FACT-G) was used to assess HRQOL. Descriptive analyses included those participants confirmed to have either TN or non-TN disease (n=330); univariable and multivariable analyses included participants who met the aforementioned criteria and completed baseline HRQOL data (n=299). Results: Participants in the TNBC and non-TNBC group were similar (p>0.05) with respect to age (TNBC: 41.4 ±5.9 years; non-TNBC: 42.2 ±6.5) and time since diagnosis (TNBC: 18.5 ±7.0 months; non-TNBC: 19.8±10.1). TNBC participants had lower mean FACT-G total scores (71 ± 22.3) compared to non-TNBC (77 ± 21.6) participants (p Conclusions: The Contextual Model of HRQOL provides a useful framework for evaluating HRQOL in Black breast cancer patients; differences based on triple negative disease status suggest possible intervention targets to improve HRQOL in these women. Effective interventions should focus on reducing anxiety at the individual level, with additional consideration for depressed affect, cancer worry, and social support in the non-TNBC group. For patients with TNBC, interventions may include addressing fatalistic cognitions and collectivist attitudes that may adversely affect HRQOL. Citation Format: Susan T. Vadaparampil, Juliette Christie, Kristine Donovan, Jongphil Kim, Bianca Augusto, Cheryl Holt, Kimlin Ashing, Chanita Hughes Halbert, Tuya Pal. Health-related quality of life in black breast cancer patients with Triple Negative Breast Cancer (TNBC). [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B26.

Purpose: Of an estimated 3 million breast cancer survivors in the U.S, the median age at diagnosis is 61 years for all racial/ethnic groups combined. Although the overall incidence of breast cancer is lower in Black women compared to White women, they are more likely to develop and die from early onset (age 50 years or younger) aggressive disease. As a result, young Black women with invasive breast cancer may experience poorer quality of life after breast cancer diagnosis; yet, few studies have focused on this subset of younger Black breast cancer survivors. As part of an ongoing population-based case-only study to investigate etiology and outcomes of early-onset breast cancer in Black women, we sought to evaluate baseline predictors of health-related quality of life (HRQOL) at time of study entry. Methods: Black women with invasive breast cancer at age 50 or younger diagnosed between 2009-2012 were recruited through the Florida State Cancer Registry utilizing state-mandated recruitment methods. Participants completed a comprehensive baseline questionnaire which included sociodemographic, clinical, and psychosocial characteristics. In the current study, we used multiple regression analysis to examine predictors of HRQOL measured with the FACT-G instrument. Predictors were selected based on the Contextual Model of HRQOL and included individual clinical (e.g., age at diagnosis) and psychosocial (e.g., anxiety) as well as macro/systemic (e.g., social support) level variables. Results: This report includes the first 206 women who completed the baseline questionnaires. The mean age at diagnosis was 42.5 years (SD=6.2; range=21-50). The mean HRQOL score was 74.4 (SD=21.6; range= 25-108), which is lower than ranges reported in normative samples of both healthy females (mean: 79.6, SD=18.6; range=25-108) and cancer patients (mean: 82.1, SD=16.3; range=15-108). In bivariate analyses, HRQOL was significantly associated with 19 predictor variables (p < .05). In multiple regression, these variables accounted for about 78% of the variance in HRQOL. Adjusting for other model variables, self-reported current general health (beta=.15); role limitations for moderate activities (.12) and climbing stairs (.15); and social support (.14) were significantly associated with higher HRQOL, whereas life stress (-.37) was inversely associated with HRQOL. Conclusions: Individual-level factors such as better self-reported general health, more social support, and less stress were associated with higher HRQOL. Conversely, women with moderate role limitations reported higher HRQOL. These findings document baseline characteristics among a sample of younger Black breast cancer survivors and provide an important benchmark by which to compare subsequent changes in HRQOL in this cohort. Citation Format: Susan T. Vadaparampil, Teri L. Malo, Chanita Hughes-Halbert, Cheryl L. Holt, Shalanda A. Bynum, Jongphil Kim, Devon Bonner, Linda Bomboka, Courtney Scherr, Kimlin Ashing, Tuya Pal. Health-related quality of life among younger black breast cancer survivors. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C43. doi:10.1158/1538-7755.DISP13-C43

Background: Black women have a higher incidence of and mortality from early-onset breast cancer than White women. This may partly be attributed to mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2 (BRCA), as well as a greater proportion of the aggressive triple negative breast cancer subtype (TN). Recruitment of Black women with early onset breast cancer into etiologic studies is an important step toward identifying factors contributing to this health disparity and developing appropriate risk reduction and treatment strategies to reduce mortality in this underserved population. Objective: Within a registry-based sample of Black women diagnosed with breast cancer ≤ 50 years between 2009-2011, the purpose of this analysis was to examine differences in clinical characteristics between those 1) in whom contact was versus was not established and 2) among those contacted, those who indicated interest versus declined participation to a study investigating the etiology of breast cancer. Methods: The state-wide cancer registry, Florida Cancer Data System (FCDS) provided contact information and clinical characteristics (i.e. age at diagnosis, stage, grade, histology, TN status, nodes positive, primary site, and treatment [dates and types]) on eligible cases. Potential participants were approached using state-mandated recruitment methods consisting of two mailings sent three weeks apart followed by phone to discuss interest in participation. Study participation included completion of a risk-factor questionnaire, phone genetic counseling, and donation of a biological sample for BRCA testing. Bivariate analyses were used to analyze differences in contact and interest in participation. Results: Among 912 eligible women identified by FCDS, the average age at diagnosis was 42.6 ± 6.2 years and the majority of diagnoses were unilateral (96.4%), ductal (78.9%), stage1/2 (51.6%), and lymph node negative (58.6%). Furthermore, 13.2% were TN and 85.6%, 62.1%, and 23.7% had surgery, chemotherapy, and radiation therapy, respectively. Contact was established with 481 (52.7%) potential participants. Those in whom contact was not established were similar on all clinical and treatment characteristics other than a slightly younger age at diagnosis [42.1 ± 6.4 years versus 43.0 ± 5.9 years; p=0.03]. Of those contacted, 284 (59%) were interested, 100 (20.8%) declined participation, and 97 (20.2%) neither indicated interest nor declined or were deemed ineligible at first contact. Potential participants who indicated interest and those who declined participation at first contact were comparable based on all clinical and treatment factors. Conclusions: Our results suggest state-wide cancer registries are a feasible recruitment source to establish contact with a clinically representative population-based sample of Black women diagnosed with early-onset invasive breast cancer. Furthermore, contrary to prior reports, clinical features did not appear to affect interest in participation, highlighting the need to investigate the effects of socioeconomic, cultural, and behavioral factors on recruitment of minority populations. Citation Format: Devon Bonner, Tuya Pal, Christine Tallo, Susan T. Vadaparampil. The ut\ility of a state-wide cancer registry in recruiting a clinically representative population-based sample of young black women diagnosed with early-onset breast cancer. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A33.

Background: Young Black women are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. Deleterious mutations in the BRCA genes include those identified by sequencing technology as well as large genomic rearrangements that are found with different technologies (i.e., multiplex ligation-dependent probe amplification (MLPA)). The sole provider of clinical BRCA genetic testing in the United States is Myriad Genetics Laboratories, the company which owns the patent on these genes. When BRCA testing is ordered through this company, the standard test is called ‘Comprehensive BRCAnalysis’, which includes BRCA sequencing and testing for five rearrangements in BRCA1. In addition, testing for large rearrangements has been available since 2006, but is ordered and billed as a separate test from Comprehensive BRCAnalysis (at a cost of $700, often as an out-of-pocket expense). Objectives: In a cancer registry-based sample of Black women with early onset breast cancer, we evaluated prevalence of: 1) BRCA mutations; and 2) individuals who had BRCA testing (+counseling) predating study enrollment. Methods: Black women diagnosed with invasive breast cancer < age 50 in 2009-2010 were recruited through the Florida Cancer Registry utilizing state-mandated recruitment methods. Participants completed genetic counseling and a comprehensive risk factor questionnaire which included uptake of clinical BRCA testing pre-dating study enrollment. All participants consented to medical record release, including release of prior genetic test results. Saliva specimens were collected and BRCA testing was performed on all individuals through full gene sequencing and comprehensive rearrangement testing. Results: Of the first 48 participants in whom results of genetic testing are currently available through the study, two mutations in the BRCA genes were detected. Both mutations were identified in women who had undergone comprehensive BRCAnalysis pre-dating study enrollment. This included one participant identified to have a deleterious BRCA2 mutation through prior clinical testing (BRCA2 exon11 5844del5), in whom the same mutation was detected through the study. The second mutation was identified through comprehensive rearrangement testing (BRCA1 delExon8) in a woman who had previously had clinical BRCA testing during her breast cancer treatment in whom no mutation was detected through ‘Comprehensive BRCAnalaysis’. Of note, 15 women overall (31.3%) had clinical BRCA testing pre-dating study enrollment, which included both women identified as mutation carriers. Conclusions: Our findings suggest that it is critical to offer comprehensive rearrangement testing as part of BRCA testing in African American women, as one of the two mutations identified in our study was only identified through MLPA. Furthermore, in contrast to prior publications which suggest low uptake of BRCA testing in African American women, our results suggest reasonable uptake of BRCA testing in a registry-based sample of African American women with rates comparable to that previously reported in White women. Citation Format: Tuya PalDevon Bonner, Mohammad Akbari, Steven Narod, Susan Vadaparampil. How important is comprehensive rearrangement testing for BRCA mutations in African American women with early-onset breast cancer? [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A34.

Background: On average, Black women develop breast cancer ten years earlier than White women and are more likely to die from the disease. Early onset breast cancer is a hallmark feature of the BRCA1 and BRCA2 (BRCA) gene mutations and may contribute to a portion of breast cancers in Black women. Widespread availability of genetic testing for hereditary breast cancer has resulted in an increasing number of women considering their BRCA test results prior to surgical treatment decisions for their breast cancer surgery (e.g., consideration of a risk-reducing bilateral mastectomy, contralateral prophylactic mastectomy). However, little is known about use of BRCA testing prior to definitive surgery specifically among Black women. The purpose of this abstract is to describe baseline utilization of BRCA testing in Black breast cancer patients prior to surgery and to document the prevalence of BRCA mutations in a cohort of Black women with early onset breast cancer. Methods: Black women diagnosed with invasive breast cancer ≤ age 50 between the years of 2005 and 2006 were recruited through the Florida Cancer Registry utilizing state-mandated recruitment methods. Participants completed genetic counseling and a comprehensive risk factor questionnaire including 7 items specific to referral and uptake of genetics clinical services. Biological specimens (either blood or saliva) were collected, and BRCA testing was performed. Results: Of the 209 eligible cases, 48 women consented to study participation. Of the 46 women with usable biological specimens: the average age of diagnosis was 42.8 ±6.14 and 50% (n=23) reported a positive family history of breast cancer (i.e., ≥ 1 first and/or second-degree relative with breast cancer). A previous BRCA test was reported by 30.4% (n=14) of those completing the study with only 2 participants (4.3%) receiving a genetic test result prior to making a breast surgery decision. Seven women (15.2 %) chose a bilateral mastectomy, 4 of which were risk reducing. No association was observed between family history and the type of breast surgery elected. Mutations in the BRCA genes were identified in three participants (including 1 in BRCA1 and 2 in BRCA2). In 16 additional participants, there were a total of 28 variants of uncertain significance (VUS) identified. Conclusions: Our results suggest that few Black women utilized genetic test results and/or family history to make surgical decisions for their breast cancer treatment despite data documenting similar BRCA prevalence rates in Black women with early onset breast cancers as those previously reported in White women. These findings highlight an important health disparity in access to and utilization of genetics services among Black women with breast cancer. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A71.

Introduction: Although African American (AA) women are more likely to be diagnosed with early onset breast cancer (i.e., ≤ age 50) during their reproductive years, little is known about patient awareness of or provider discussion related to fertility concerns in this specific demographic group. In an effort to better understand how fertility concerns are addressed in the context of clinical care, this study seeks to document the prevalence of patient awareness and patientprovider discussion of infertility risk associated with cancer treatment in AA breast cancer patients. Method: As part of a larger study examining the role of genetic factors in AA women with early onset breast cancer, data were collected using a cross-sectional survey. Demographic and clinical variables were compared using chisquare tests for equal proportions or exact tests between participants who: (a) did and did not indicate awareness about potential fertility loss, and (b) did and did not report discussion of potential fertility loss with their health care providers. Results: Approximately 46% of the women in our sample (N = 48) reported awareness and 56.3% reported provider discussion of the potential impact of cancer treatment on fertility. Bivariate analyses demonstrated that awareness was significantly higher in women who were diagnosed at age ≤ 45 (p < .05), were nulliparous (p < .01), and/or did not have tubal ligation (p < .001). Provider discussion was more often reported by patients who were diagnosed in stages 2–3 (p < .05) and/or had no children (p < .01). Nearly half of early onset AA breast cancer patients are unaware and/or report no provider discussion of the potential impact of cancer treatment on fertility. Study results underscore missed clinical opportunities to provide fertility information that may impact long-term quality of life in early onset AA breast cancer patients. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A52.

Purpose: Community-based participatory research methods were utilized to culturally tailor an educational cancer clinical trials DVD for Black women. The DVD, “Clinical Trials: Are they right for you?” provides answers to common questions and discusses concerns about cancer clinical trials. Focus groups with Black women were conducted to obtain knowledge, attitudes, and perceptions about the cultural relevance of the words, people and stories of DVD. Learner verification techniques were employed to identify participant's viewpoints on the appearance, self-efficacy enhancement, acceptability, and persuasiveness of the educational DVD. A community advisory panel (CAP) was used to review results and develop recommendations for future media products. Methods: The study took place in two phases. In the first phase, four focus groups (n=32) were held with Black women without a personal cancer diagnosis in the area of Hillsborough, Pasco and Pinellas counties. The focus groups questions were based on learner verification techniques which assessed the user-friendliness, perceived intention, and visual attractiveness of the educational DVD. The duration of the focus groups was 90 minutes. All focus groups were audio taped and transcribed verbatim. Thematic coding, using a crystallized-immersion framework was conducted by the research team. A combination of hand-coding and Atlas TI software were employed using the learner verification content as a priori codes. The frequency and nature of the emergent themes were compared across the groups with concentration on potential differences between participants who had prior experience as a caregiver and those who had not. In the second phase, de-indentified focus group findings were presented to the CAP to obtain recommendations for improvement of the cancer clinical trials DVD and future educational efforts aimed at the Black community. Results: Preliminary findings from the focus groups included differences between caregiver and non-caregiver with prior caregiver participants providing more detailed recommendations due to exposure to some cancer clinical trials educational materials and personal experience with events and/or instructions received while caring for a loved one. Both groups felt the representation of Black women should be increased on the DVD. Findings from both the focus groups and the recommendations from the study's CAP will be utilized to develop more culturally relevant educational materials in regard to cancer clinical trials in the future. Additionally, future research will continue collaborations with the CAP to ensure that educational materials are centered on the concerns of the community as to readily engage the Black community. In light of low rates of participation among Black women in cancer clinical trials, working collaboratively with the Black community to ascertain their perspectives on cancer clinical trials is integral to developing culturally relevant educational materials that may improve understanding of clinical trials and lead to informed decision making. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A29.

Introduction: Genetic counseling (GC) services for inherited breast and ovarian cancer (HBOC) are underutilized by African American (AA) women. One barrier may be availability of in-person GC services. Telephone-based counseling may be one way to increase access to GC services. However, little is known about AA women's reactions to and satisfaction with phone-based GC services. We sought to evaluate experiences associated with phone-based GC for HBOC among AA women diagnosed with early-onset breast cancer. Methods: Through a cancer registry-based study, phone-based GC for HBOC was provided to AA women diagnosed with breast cancer at or before age 50. A brief baseline survey to evaluate the experience with the GC and testing process was administered when women were being scheduled to receive results of BRCA testing. After phone-based results disclosure with a genetic counselor, a follow-up phone survey was administered to assess results disclosure experiences. Results: To date, baseline and follow-up surveys have been completed by 33 (72%) of 46 women who completed pre-test GC. Findings from the baseline questionnaire (n=36) showed that the majority of women were glad to have pursued testing (95%), felt that they had taken charge of their healthcare (90%), and were pleased with the telephone GC provided through the study (71 %). Almost 40% of participants indicated that the GC and testing process increased their feelings of control and empowerment. Among the follow-up survey participants (n=33), the majority indicated very positive experiences with various aspects of phone-based results disclosure. Conclusion: Our results suggest that telephone-based GC and testing for HBOC in a registry-based sample of AA women was perceived favorably by participants. Thus, telephone-based GC may be one approach to reduce barriers in access to GC and testing services in the AA community. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A34.

B10 Background Due to low levels of awareness about hereditary breast cancer and underutilization of genetic counseling and testing services in the Black community, there is an urgent need to provide information about these topics to Black women. Existing genetic education materials have generally been developed by and for White women and thus may have reduced relevance for Black women. Objective: To create a culturally tailored, educationally relevant brochure to increase awareness about hereditary breast cancer within the Black community. Methods: Three focus groups were conducted with female members of Black community based organizations representing a diverse set of sociodemographic (e.g., age, education) and clinical (e.g., breast cancer status) characteristics. Discussions were led using a standardized guide with probes to assess the creative and educational aspects of a mock brochure (n=46). Trained, race-concordant moderators with previous experience discussing preventive health behaviors were used for each focus group. Each focus group was audio-taped and handwritten notes were taken by at least 3 members of the research team. Summaries of each focus group were created using these data sources. Content analysis based on Grounded Theory was conducted using an iterative process, and each summary was independently coded by three members of the research team. Results The majority of participants were over age 41 (67%) and married (43%). Thirty-seven percent were college graduates or beyond and 72% had children. The key content areas related to improvement of the brochure were to: (1) Include additional information about aspects of breast cancer specific to Black women; (2) Use the term Black rather than African American or Women of Color; (3) Provide more details about the process of genetic counseling and testing; and (4) Include a color scheme representative of the Black community. Positive aspects of the brochure that were well received included: (1) Using patient photos and personal vignettes; (2) Targeting Black women with the race specific information about risk; and 3) Acknowledgment of common misperceptions about hereditary breast cancer. Conclusion Black women in this study expressed a strong desire for culturally relevant information related to genetic counseling and testing for hereditary breast cancer. When provided an opportunity to offer feedback prior to finalizing a brochure, women identified important areas for improvement that are likely to lead to more culturally tailored and acceptable educational materials. By implementing these suggestions, the study team expects the brochure will provide meaningful information about inherited breast cancer that is appropriate for widespread dissemination to Black women. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B10.

PR-2 Background Defects in the mismatch repair (MMR) pathway are believed to be etiologically important in a reasonable proportion of epithelial ovarian cancers. Various laboratory methods can be used to identify MMR-deficient ovarian cancers, including microsatellite instability (MSI) analysis and immunohistochemistry (IHC). Specifically, in colorectal cancers (CRC), tumor characteristics previously shown to be useful in identifying MMR-deficient tumors include MSI-high (MSI-H) phenotype and loss of MMR protein expression on IHC analyses. Similar findings have been demonstrated in ovarian cancer, however the sample sizes of those studies have been limited. Objectives/Methods We sought to investigate tumor characteristics including: (1) MSI-high status, (2) Expression of 3 MMR proteins (MLH1, MSH2, and MSH6) through IHC studies, and (3) The concordance between MSI and IHC results. The tumors analyzed came from women between the ages of 18 and 80 years with newly-diagnosed epithelial ovarian cancer ascertained between December 13, 2000 and September 30, 2003in a population-based study covering a 2-county region of west central Florida. MSI-H was defined by instability in 2 or more of the 5 NCI-standardized microsatellite markers (ie: BAT25, BAT26, D2S123, D17D250, D5S346). Tissue microarrays were created to evaluate the loss of MMR protein expression on IHC based on a scoring system of 0-9 to evaluate both stain and intensity, and take the product of these 2 numbers; loss of expression of protein expression was defined as Results Of the 232 who agreed to participation, tumor samples were collected on 219 (94%). The distribution of by race and ethnicity of study participants was similar to the distribution of cancer cases in the catchment area, with ~90% of participants being non-Hispanic Whites. The distribution of histologic subtypes, stage and median age at diagnosis was also similar to that seen in the general population. Of the 219 cases, all had IHC analysis and 201 had MSI analysis. The frequency of MSI-H was 29%. The frequency of loss of expression on IHC was 17%. The numbers of tumors which were concordant for MSI and IHC results was 141 (including 16 cases with MSI-H and loss of MMR protein expression and 125 cases with no MSI-H and presence of MMR protein expression). Conversely, there were 60 discordant cases (including 42 cases which were MSI-H, but MMR protein expression was present; and 18 cases which were not MSI-H, with loss of MMR protein expression). Conclusions In contrast to previous studies of CRC, our results indicate limited concordance between MSI-H status and loss of MMR protein expression. Thus, MSI analysis and IHC studies for MMR protein expression may be of limited utility in the identification of ovarian tumors with MMR deficiency. Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-2.