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e13090 Background: Young black women bear a disproportionate burden of breast cancer (BC), yet there is limited characterization of these cancers based on BRCA1 and BRCA2 ( BRCA) status and tumor genomics. In this pilot study, we characterized: tumor and clinical characteristics based on BRCA carrier status and overlap of basal-like (BL) and triple negative (TN) BC. Methods: A population-based sample of 481 black women diagnosed with invasive BC < age 50 were recruited through the Florida Cancer Registry (FCR). BRCA status was determined based on germline testing. TN status was determined based on pathology reports and FCR data. Among a subset of 90 participants, gene expression profiling (GEP) was conducted on tumor samples through PAM50 analyses to classify intrinsic subtypes and risk of recurrence (ROR) scores. Results: Mean age at BC diagnosis was 41.9 (range: 25-50) and mean ROR score was 49.6 (range: 8.7-80.7). Participants included 7 BRCA1 carriers, 5 BRCA2 carriers, 67 non-carriers (NC), and 11 with no confirmed testing. Of 46 BL tumors, 33 were TN (71.7%) constituting 94.3% of TN tumors (the remaining 5.7% were Luminal A). All BRCA1 carriers had BL tumors, of which 5 were TN. Sensitivity, positive predictive value, and negative predictive value in identifying BRCA1 carrier was higher based on BL compared to TN status (Table 1). BRCA2-associated tumors included 3 Luminal A, 1 Luminal B, and 1 BL. Mean ROR score was highest among BRCA1 carriers (57.7), followed by NC (50.5) and BRCA2 carriers (41.5). Conclusions: Study findings suggest BL status predicted BRCA1 positivity better than TN status. BRCA2- (compared to BRCA1-) associated tumors were more heterogeneous with over half being Luminal A, which may explain the lower ROR among BRCA2 carriers. Additional follow-up and expansion of this cohort with collection of clinical outcomes will be useful in assessing the predictive utility of ROR scores among young black women with BC. [Table: see text]

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.

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.

The purpose of this study was to assess potential differences in genetic counseling services delivered by board-certified genetic health-care providers versus non–genetic health-care providers. We evaluated (i) patient recall and content of pretest genetic counseling for hereditary breast and ovarian cancer and (ii) whether full BRCA1 and 2 gene sequencing was performed when less expensive single-site or Ashkenazi Jewish founder mutation testing may have been sufficient. Participants completed a questionnaire and provided BRCA test reports that included testing provider and type of test. Chi-square tests and logistic regression were used for analysis. Of 473 participants, >90% were white, female, and BRCA mutation carriers. Of the 276 (58%) with genetic health-care provider involvement, 97% recalled a pretest discussion as compared with 59% of those without genetic health-care provider involvement (P < 0.001). Among the subgroup who recalled a pretest discussion (n = 385), those with genetic health-care provider involvement indicated higher adherence to eight recognized genetic counseling elements, four of which were statistically significant. Furthermore, involvement of a genetic health-care provider halved the likelihood that comprehensive BRCA testing was ordered among the 266 for whom single-site or multisite-3 testing may have been sufficient (P = 0.02). Our results suggest that genetic health-care provider involvement is associated with adherence to nationally recommended genetic counseling practices and could potentially reduce costs of BRCA genetic testing. Genet Med advance online publication 12 June 2014

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.

Key Clinical Message A patient with syndromic Duane retraction syndrome harbors a chromosome 811.1q13.2 inversion and 8p11.1-q12.3 marker chromosome containing subregions with differing mosaicism and allele frequencies. This case highlights the potential requirement for multiple genetic methods to gain insight into genotype–phenotype correlation, and ultimately into molecular mechanisms that underlie human disease.

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.

Multiple primary cancers are characteristic of hereditary cancer syndromes. A familial association between breast and thyroid cancer has been suggested, but a genetic basis for this association has not yet been established. To determine the extent to which double primary cancers of the breast and thyroid are due to common hereditary factors, we conducted a registry- and hospital-based study in Ontario and Quebec. We obtained family histories of 74 women diagnosed with both cancer of the breast and thyroid before 70 years of age. Cancer histories were obtained for the 533 first-degree relatives of these women. The observed cancer rate in the relatives was compared with the expected number, based on age-standardized Canadian cancer incidence rates, and relative risks were estimated. A total of 87 cancers were observed in the relatives, compared to 93.7 expected cancers, giving a relative risk of 0.9 (95% confidence interval (CI): 0.7–1.1). The risk for breast cancer was 1.1 (95% CI: 0.6–1.7) and the risk for thyroid cancer was 0.7 (95% CI: 0–3.8). Blood samples were collected on 53 patients for mutational analysis of the BRCA1, BRCA2, and PTEN genes. One woman was found to be a carrier of a BRCA1 mutation (exon 11 3227delT). Our findings do not support the hypothesis that a significant proportion of double primary cancers of the breast and thyroid are due to hereditary factors.

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.

Cleidocranial dysplasia (CCD) is typically an autosomal dominant condition. The possibility of alternative causes, such as an autosomal recessive form or germ line mosaicism, have been suggested in some families with CCD, but not proven. We present a family consisting of a mother having three sons affected with CCD. One of the affected boys is a half brother to the other two affected children. The diagnosis of CCD was confirmed by DNA analysis of the RUNX2 gene in all three of the boys in blood; however, initial DNA testing in the mother's blood did not detect the presence of a RUNX2 mutation in the mother. Further testing through heteroduplex analysis applying high-resolution melting analysis followed by subcloning detected low-level mosaicism in DNA isolated from maternal blood and buccal swab, confirming low-level mosaicism in somatic cells. We present the first case of confirmed germ line mosaicism in CCD.

With the expansion of genetic testing options due to tremendous advances in sequencing technologies, testing will increasingly be offered by a variety of healthcare providers in diverse settings, as has been observed with BRCA1 and BRCA2 (BRCA) gene testing over the last decade. In an effort to assess the educational needs and preferences of healthcare providers primarily in a community-based setting, we mailed a survey to healthcare providers across Florida who order BRCA testing. Within the packet, a supplemental card was included to give participants the opportunity to request free clinical educational resources from the investigative team. Of 81 eligible providers who completed the survey, most were physicians or nurse practitioners; and over 90 % worked in a community or private practice setting. Respondents provided BRCA testing services for a median of 5 years, but the majority (56 %) reported no formal training in clinical cancer genetics. Most respondents (95 %) expressed interest in formal training opportunities, with 3-day in-person weekend training representing the most highly preferred format. The most widely selected facilitators to participation were minimal requirement to take time off work and continuing education credits. Overall, 64 % of respondents requested free clinical educational resources. Preferences for informal education included written materials and in-person presentations; whereas accessing a DVD or website were less popular. Findings from our study highlight both the need for and interest in ongoing educational opportunities and resources among community providers who order BRCA testing. These results can be used to enhance participation of community-based providers in educational training programs by targeting educational resources to the most preferred format.

There is tremendous excitement about the promise of new genomic technologies to transform medical practice and improve patient care. Although the full power of genetic diagnosis has not yet been realized, paradigms of clinical decision-making are changing. In fact, recent policy level changes to promote genetic counseling by certified genetics professionals (GP) such as genetic counselors and clinical geneticists, are occurring at both the payer and state level. However, there remain opportunities to develop policies within the United States to: 1) enhance the access to the limited workforce of GPs; 2) revise reimbursement schemes such that costs to deliver these services may be recouped by institutions with GPs; and 3) protect against the potential for discrimination based on genetic information. Although many of these issues predate advances in genomic technologies, they are exacerbated by them, with increasing access and awareness as costs of testing decrease. Consequently, evolving shifts in national policies poise GPs to serve as a hub of information and may be instrumental in facilitating new models to deliver genetics-based care through promoting academic-community partnerships and interfacing with non-GPs. As we acknowledge the potential for genomics to revolutionize medical practice, the expertise of GPs may be leveraged to facilitate incorporation of this information into mainstream medicine.

Young Black women are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. In a sample of Black women with early onset breast cancer, we evaluated BRCA mutations and explored personal and system-level clinical characteristics. Black women diagnosed with invasive breast cancer (age ≤50) were recruited through the state cancer registry. Participants completed a questionnaire, genetic counseling and BRCA testing. Of the 48 women who consented to study participation, 46 provided a usable biologic specimen for BRCA testing. The overall prevalence of BRCA mutations and variants of uncertain significance (VUS) in participants was 6.5% and 34.8%, respectively. Of these, only 14 were referred for genetic counseling prior to study enrollment. Overall, those participants who chose to undergo bilateral mastectomy had a higher number of relatives with breast and ovarian cancer (p = 0.024) and a higher household income (p = 0.009). BRCA mutation prevalence and the high prevalence of VUS in participants are consistent with prior studies. Furthermore, clinical factors such as family history and financial means may influence type of surgery recommended and chosen, at both the provider and patient level, respectively. Finally, the limited number of patients referred for genetic counseling prior to surgical treatment for breast cancer may represent a missed clinical opportunity to inform surgical decisions.

Utility of immunohistochemistry (IHC) for mismatch repair (MMR) protein expression has been demonstrated in colorectal cancer but remains incompletely defined in ovarian cancer. We evaluated MMR protein expression in three population-based samples of epithelial ovarian cancers.IHC staining was performed on full-section (FS) or tissue microarray (TMA) slides for MLH1, MSH2, and MSH6 expression.Out of 487 cases, 147 and 340 were performed through FS and TMA, respectively. Overall, Loss of Expression (LoE) of at least one MMR protein was observed in 12.7% based on an expression score of ≤3 (on a scale of 9). Notably, LoE was significantly higher in TMAs (17.9%) compared to FS cases (0.7%) (p0.001).A substantial proportion of epithelial ovarian cancers have a loss of MMR protein expression. Protein expression results vary significantly by the tissue sampling methodology utilized, raising concerns about the clinical utility of this test for ovarian tumors.

LBA1504 Background: Rates of risk-reducing bilateral mastectomy (RRM) or risk-reducing prophylactic oophorectomy (RRSO) among BRCA carriers are based on studies of non-Hispanic whites (NHW), with little known among blacks or Hispanics. Methods: A population-based sample of NHW, black, and Hispanic women diagnosed with invasive BC < age 50 in 2009-12 were recruited through the Florida State Cancer Registry and completed a baseline survey. Among the subset of BRCA carriers, we compared risk management for: 1) ovarian cancer (OC) through RRSO; and 2) BC through RRM or MRI screening, by calculating percentages and conducting logistic regression to control for other variables. Results: Of 1570 participants, 884 reported BRCA testing. Of the 91 BRCA carriers, 1) RRSO was 71% (36/51) among NHW, 32% (9/28) among blacks, and 83% (10/12) among Hispanics; 2) either breast MRI or RRM was 98% (50/51) among NHW, 85.7% (24/28) among blacks, and 100% (12/12) among Hispanics. BC risk management modality differed across groups, with lower rates of RRM among blacks (67%) compared to Hispanics (83%) and NHW (94%). After controlling for age at enrollment, time since diagnosis, income, family history of BC, family history of OC and private insurance at diagnosis: 1) Hispanics and NHW were significantly more likely than blacks to have RRSO (p = 0.01 and 0.02 respectively); and 2) NHW were also significantly more likely than blacks to have RRM (p = 0.03), although Hispanic race approached statistical significance (p = 0.10). Conclusions: The racial disparities in uptake of RRSO observed among blacks is particularly concerning given that RRSO is strongly recommended as the main OC prevention option due to the absence of effective OC early detection methods. The benefit from genetic testing comes from uptake of cancer risk management options, rather from testing itself. Future studies are needed to better understand and develop methods to improve cancer risk management practices across all populations.

Women who carry germline mutations in the BRCA1 gene (BRCA1 carriers) have the highest individual lifetime risk for breast cancer (BCa) known [1-3], with 50% of carriers developing breast cancer by age 50. BRCA2 carriers also have a higher risk but relatively lower than BRCA1 carriers. Currently available options for both BRCA1 and BRCA2 carriers include high-risk surveillance, risk reducing mastectomy or chemoprevention with the ant-estrogens Tamoxifen (TAM) and Raloxifene. Chemoprevention has been controversial in that BRCA1 carriers tend to make estrogen receptor negative tumors. Selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene reduce the risk of estrogen receptor positive breast cancers. For example, results from the National Surgical Adjuvant Breast and Bowel Project (NSABP1) Tamoxifen chemoprevention study suggested that TAM is not effective in carriers of a BRCA1 mutation [4]. Regardless, there is conflicting evidence on this point and both TAM and Raloxifene are offered to BRCA1 carriers as well as BRCA2 carriers [5]. As a chemoprotective agent in the general population, Raloxifene shows a similar reduction in risk for invasive breast cancer to TAM, but not for in situ cancers, which comprise >20% of newly diagnosed cases; the incidence of noninvasive breast cancer is approximately 40% lower for women on TAM compared with Raloxifene [6,7]. Both TAM and Raloxifene are effective only against estrogen receptor-positive tumors [8], and Raloxifene is typically only prescribed in women who are postmenopausal and have decreased bone density [9]. Both drugs increase risk for serious side effects, including venous thrombosis and pulmonary embolism [10,11]. TAM is also associated with an increased risk for endometrial cancer and stroke [12-14]. Other side effects of both drugs include dyspareunia, cataracts, musculoskeletal complaints including leg cramps, weight gain, hot flashes, vaginal discharge, bone loss in premenopausal women and bladder control problems [15]. More recently, long-term administration of TAM was observed to cause hepatic tumors in rats, induced via a genotoxic mechanism [16]. Compounding the unfavorable side affect profile studies have determined that approximately 5 – 10% of the population carries a homozygous variant of the CYP2D6 gene that imparts low activity to convert TAM from its less active form to its active metabolite [17]. This research led the FDA to require a change in the labeling of Tamoxifen to include this information [18]. Concerns about the risk: benefit ratio have thus limited the use of TAM for prevention. Recent evidence suggests that only approximately 8.4% of BRCA carriers who have not undergone prophylactic mastectomy and are eligible to take Tamoxifen or Raloxifene [19], for risk reduction do so [20]. Certainly, there is an urgent need to identify other agents for breast cancer prevention in this high-risk group. In fact, data from our own Inherited Cancer Registry (ICARE) at Moffitt indicated that of 253 female BRCA1 and BRCA2 mutation carriers, 127 had remaining at risk breast tissue (including 40 with a prior breast cancer diagnosis). Of these women, 18.1% indicated that they had taken either TAM or Raloxifene (including 7/60 (11.7%) of BRCA1 carriers and 16/67 (23.9%) of BRCA2 carriers. Consequently, the poor uptake of existing breast cancer prevention options, which appears to be more marked in those with BRCA1 compared to BRCA2, serves to illustrate the urgent need to identify other agents for breast cancer prevention in this high-risk group.

immunohistochemistry (IHC) for MMR protein expression. Although the utility of IHC has been demonstrated in colorectal cancer, its utility in ovarian cancer remains incompletely defined. We sought to evaluate the loss of protein expression of the MMR proteins (MLH1, MSH2 and MSH6) in three population-based samples of epithelial ovarian cancers. Methods: IHC staining was performed on full section slides or tissue microarray (TMA) slides for MLH1, MSH2, and MSH6 protein expression in paraffin-embedded tumor samples. Samples were considered to have loss of expression (LoE) if one or more proteins had an expression score of < 3 (on a scale of 9). Collection of demographic, clinical and family history information was attempted in all women. Results: Of 487 participants in whom IHC was completed, 147 were performed through full section slides and 340 were performed through TMA slides. In the overall sample, LoE of one or more of the MMR proteins was observed in 12.7%. Notably, the proportion of tumors with LoE was significantly higher in TMAs (17.9%) compared to full section slides (0.7%) (p

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.

We sought to understand the factors associated with recruitment activities while conducting a registry-based study of black women found to have breast cancerage 50 to investigate mutations in the BRCA1 and BRCA2 genes.State mandated recruitment methods included TWO mailings, followed by a telephone response card for patients who did not wish to be contacted by phone. If no response was received within 3 weeks of the second mailing, the study team contacted the patient by phone.Of the 209 eligible patients identified by the cancer registry, contact was established in 87, of whom 82 were eligible for study participation. The overall rate of interest in study participation was 80% (including 93% for those with passive follow-up and 68% for those with active follow-up), with the primary factor cited being the desire to understand more about the risk of cancer for family members.This is the first study conducted through a State Cancer Registry, in which the primary goal was to recruit participants for genetic counseling and testing for inherited breast cancer. In contrast to many prior studies, our results suggest that young black women with breast cancer are interested in participating in genetics studies.

Printed educational materials (PEM) can serve as important tools to enhance and reinforce information presented during genetic counseling (GC) for BRCA1/2 testing, yet few such materials have been specifically developed for the Black community. The goal of the current study was to develop a BRCA1/2 genetic education booklet for Black women at increased risk for hereditary breast and ovarian cancer (HBOC). Investigators identified available PEM about BRCA1/2 targeted toward Blacks. To obtain possible perspectives of the target population regarding modified and newly developed materials, a Community Advisory Panel (CAP) comprising breast cancer survivors, advocates, and community leaders was convened. While the CAP felt PEM were an important adjunct to GC, the panel recommended developing materials that were more personalized and relevant to Black women. A 12-page booklet that follows the flow of a standard GC session was developed; it includes a limited amount of technical information, incorporates familiar terms and images to describe key concepts, and contains vignettes and photographs of Black women. Upon review of the newly developed booklet, CAP members agreed their input had been well implemented, and only had minor suggestions. The booklet is currently being used in a population-based study of BRCA1/2 mutations among Black women diagnosed with early-onset breast cancer. Involving members of the target community is critical to the development of culturally tailored PEM. Further evaluation of the utility of our booklet in increasing awareness and understanding of HBOC and promoting informed decision-making regarding genetic testing and medical management among Black women is needed.

This chapter reviews the molecular and histopathologic characteristics of ovarian cancers due to genetic defects in the MMR pathway, highlighting the clinical significance of these findings, including implications for diagnosis, prognosis and treatment as well as interactions between DNA mismatch repair (MMR) pathway and environmental risk factors for ovarian cancer. At least ten per cent of cases of ovarian cancer are due to mutations in BRCA1 and BRCA2 and an additional percentage are due to mutations in other genes, including the mismatch repair genes, MSH2, MLH1 and MSH6. Since the mismatch repair pathway may be impaired in up to one-fifth of ovarian tumors, categorization of ovarian cancers into subtypes based on mismatch repair deficiency is likely to permit more accurate assessment of potential etiologic associations. Furthermore, specific chemotherapeutic regimens may exist specifically for ovarian cancers with microsatellite instability, to improve treatment efficacy and reduce toxicity of drugs which may provide no added benefit. Hence clarification of epigenetic—environment interactions in a large-scale study of ovarian cancers may stimulate the development of novel chemotherapy agents.

Purpose: A meta-analytic approach was used to estimate the frequency of: (a) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and (b) various histologic subtypes of mismatch repair (MMR)-deficient epithelial ovarian cancers. Methods: A systematic search of the Medline electronic database was conducted to identify articles published between January 1, 1966, and December 31, 2007, that examined MMR deficiency in ovarian cancers. Data were extracted on the study population, sample size, MSI-H frequency, and histology of MMR-deficient ovarian tumors. Results: The pooled proportion of MSI-H ovarian cancers was 0.12 [95% confidence interval (CI), 0.08-0.17] from 18 studies with 977 cases. The proportion of histologic subtypes in the pooled analysis from 15 studies with 159 cases was serous at 0.32 (95% CI, 0.20-0.44), mucinous at 0.19 (95% CI, 0.12-0.27), endometrioid at 0.29 (95% CI, 0.22-0.36), clear cell at 0.18 (95% CI, 0.09-0.28), and mixed at 0.24 (95% CI, 0.07-0.47). There was significant heterogeneity between studies. Conclusions: The frequency of the MSI-H phenotype in unselected ovarian cancers approximates 12%. MMR-deficient ovarian cancers also seem to be characterized by an overrepresentation of nonserous histologic subtypes. Knowledge of histologic subtype may aid clinicians in identifying the relatively large proportion of ovarian cancers due to MMR defects; such knowledge has potential implications for medical management.

6549 Background: Concerns about genomic advances to increase health disparities have been raised. We sought to explore factors associated with receipt of BRCA1 and BRCA2 (BRCA) testing and assess f...

e12552 Background: Recently the ability to tailor therapies to particular somatic mutations present in a patient’s tumor has grown significantly. However mutations found in a tumor may have implica...

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

It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population-based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area.Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing.Of 209 women with invasive ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20 BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside the "ovarian cancer cluster region" (OCCR). Variants of uncertain significance were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were identified in women with borderline or invasive mucinous tumors. Among the BRCA mutation-positive women, 63% had serous tumors. A family history of breast and/or ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1 carriers, BRCA2 carriers, and non-BRCA1/BRCA2 carriers, respectively.The data from this study suggested that 1) previous studies may have underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas, especially outside the OCCR; 2) it may be reasonable to offer genetic counseling to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among patients with invasive ovarian carcinoma, family history is not sufficiently accurate to predict mutation status.

1506 Background: Young Black women are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. Prior studies suggest BRCA mutatio...

The genetic basis for nonmedullary forms of thyroid cancer (NMTC) is less well established than that of medullary thyroid cancer. However, epidemiological and family studies suggest that a proportion of NMTC may be due to inherited predisposition. To estimate the familial risk of thyroid cancer, we conducted a hospital-based case-control study at the Princess Margaret Hospital in Toronto, Ontario, Canada, and at 2 university hospitals in Montréal, Québec, Canada. We obtained pedigrees from 339 unselected patients diagnosed with NMTC and from 319 unaffected ethnically matched controls. Family histories of cancer were obtained from the cases and controls for 3292 first degree relatives of cases and controls. Seventeen cases (5.0%) and 2 controls (0.6%) reported at least one first degree relative with thyroid cancer. In relatives of patients with thyroid cancer, the incidence of any type of cancer (including NMTC) was 38% higher than in relatives of controls (incidence rate ratio, 1.4; 95% confidence interval, 1.1–1.7). The relative risk for thyroid cancer was 10-fold higher in relatives of cancer patients than in controls (incidence rate ratio, 10.3; 95% confidence interval, 2.2–47.6). Our findings suggest that hereditary or other familial factors are important in a small proportion of NMTC. Molecular studies are needed to determine the genetic basis of cancer susceptibility in these families.

Editor—Familial tendencies have previously been observed for congenital pyloric stenosis, endometriosis, and breast cancer. These conditions have never been considered to have shared aetiological origins and consequently no previous attempts have been made to investigate an association. For example, when obtaining family history information for a child with pyloric stenosis, one would not routinely request a description of adult onset conditions such as endometriosis or breast cancer. Two families sharing an unusual clustering of these three conditions (pyloric stenosis, endometriosis, and breast cancer) were ascertained at the familial cancer clinics of the Women's College and Princess Margaret Hospitals in Toronto. Family 1 (fig 1) contains four confirmed cases of breast cancer (below age 60), seven cases of endometriosis, five cases of congenital pyloric stenosis, nine cases of polycystic ovaries, and four cases of non-insulin dependent diabetes. In a second unrelated family, a woman previously diagnosed …

Mismatch repair (MMR) gene mutations cause hereditary nonpolyposis colorectal cancer (HNPCC), a common form of familial colorectal cancer. Among MMR genes, germline MSH6 mutations are often observed in HNPCC-like families with an increased frequency of endometrial cancer. We have previously shown that a proportion of women affected with double primary cancers of the colorectum and endometrium carry germline MSH2 or MLH1 mutations and, thus, belong to HNPCC families. In this study, we have investigated the specific contribution of MSH6 defects to such double primary patients. By sequence analysis of the entire coding region of MSH6, three putative missense mutations were identified in patients with atypical family histories that do not meet HNPCC criteria. Moreover, one of these mutations, a novel substitution Arg901 His, was found in a patient previously shown to carry a truncating germline MLH1 mutation. Thus, MSH6 mutations are likely to contribute to the etiology of double primary cancers of the colorectum and endometrium.

Background. Uterine papillary serous carcinoma (UPSC) shares common pathologic, genetic, and clinical features with other serous cancers of mullerian origin. The most common histologic type of ovarian tumor associated with BRCA mutations is papillary serous. Because of these histologic similarities, we postulated that, in some cases, UPSC may be a manifestation of a field defect in BRCA1 carriers, which also includes ovarian carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods. Fifty-six living patients with UPSC were contacted through their treating physicians and agreed to a family history interview and to provide a blood specimen for BRCA testing. The protein truncation test was used to detect mutations in exons 10 and 11 of BRCA1 and in exon 11 of BRCA2. The presence of four common mutations was assessed by PCR-based specific assays. Results. A high proportion of patients had a past history of breast cancer (11%) or a first-degree relative with breast cancer (29%). Four patients were from families with site-specific hereditary breast cancer. However, there was no clear example of the hereditary breast–ovarian cancer syndrome, and none of the 56 patients was found to carry a BRCA1 or BRCA2 mutation. Conclusions. BRCA mutations do not appear to predispose to UPSC and this type of cancer does not appear to be a manifestation of the classical hereditary breast–ovarian cancer syndrome. The observed association between UPSC and breast cancer may be due to the presence of mutations in other cancer predisposing genes.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition predisposing to cancers of the colorectum and endometrium. Endometrial cancer is the most commonly occurring extracolonic cancer in HNPCC. Estimates of the cumulative incidence of endometrial cancer in women with mutations in the HNPCC genes range from 22-43%. In order to determine how frequently double primary cancers of the colorectum and endometrium are the result of a hereditary factor, we conducted a registry based study in Ontario and Quebec, Canada. We obtained pedigrees on 80 women diagnosed with double primary cancers of the colorectum and endometrium at less than 70 years of age. Family histories of cancer were obtained for all first degree relatives of these women and cancer rates were compared with age standardised provincial incidence rates in order to estimate the relative risks. There was a total of 82 cancers observed in relatives below the age of 55, compared with 31.2 expected, giving a relative risk of 2.6 (95% confidence interval (CI) 2.1-3.3). The relative risk for colorectal cancer below 55 was 16.1 (95% CI 11.6-21.8). This risk decreased with increasing age of onset of cancers in probands. For probands with both colorectal and endometrial cancer diagnosed under the age of 55, the relative risk of colorectal cancer in relatives below the age of 55 was 30.5 (95% CI 18.8-46.6). Similar patterns were observed for endometrial and pancreatic cancer. There were non-significant increases in rates of cancer of the oesophagus, stomach, small intestine, and bladder. There was no increased risk of breast cancer. The risk of lung cancer was decreased, especially in older relatives. Our findings indicate the presence of a significant genetic component of cancer in women with double primary cancers of the colorectum and endometrium.

e12556 Background: Biobanks are a promising way to identify links between genetic and environmental factors in relation to disease, particularly cancer. However, there has been skepticism among the general public about the purpose of biospecimen donation. Healthy people are beginning to be approached for participation in biobanking based on NIH initiative to establish national repositories. There is a great need to address public concerns about biospecimen donation. There may be additional and unique concerns among families with a history of hereditary cancer. Methods: Participants were recruited through research networks of families across the US who had received genetic counseling/testing. At-risk individuals (18 and over, no personal cancer diagnosis, first degree family member with cancer, had a test for hereditary cancer) completed a 15-item biobanking statement rating worksheet, selecting from 1 (strongly disagree), 2 (agree), 3 (not sure), 4 (disagree) and 5 (strongly agree). Results: 39 participants (100% white, 92.5% female) completed the worksheet. Most participants (87%) agreed confidentiality with medical information was important. 89% thought genetic research and biobanks were useful even if they only produced scientific knowledge instead of cancer cures. 87% felt the public should be consulted on ethical issues in biospecimen research, and permission should be acquired before conducting research on their samples (74%). 56% were unsure if they were exposing themselves to risk if they donated a specimen, while 46% were concerned that their specimen would be connected to their identity. Participants were uncertain if researchers should explain the use of each biospecimen (36% agreed, 33% unsure, 31% disagreed). 92% felt public education about biobanking would increase biospecimen donation. Conclusions: While participants were supportive of genetic research and biobanks, concerns regarding confidentiality and loss of privacy remain among unaffected carriers. There is a need to enhance existing training for researchers to improve understanding of high genetic risk community members’ perceptions about biobanking.

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.

1585 Background: Anthracycline related cardiac toxicity (CT) is a concern in treating women with breast cancer. The prevalence of heart failure (HF) affects 2% of the population, less so in women. Patients receiving anthracycline based therapy (ABT) have a dose-dependent risk of reduction in ejection fraction. Recent work by Dr. Verma suggests that BRCA-deficient mice manifest increased levels of cardiac failure. We sought to explore the risk for CT and evaluate the association between ABT and HF in female BRCA mutation carriers. Methods: An online survey was developed to collect information about breast cancer treatment (including HF) in BRCA mutation carriers through the national BRCA patient advocacy organization FORCE via their 2011 conference and their website as well as the Moffitt-based Inherited Cancer Registry (ICARE). The prevalence of CT and HF was calculated in both BRCA 1 and 2 breast cancer patients and compared to general population risks. Data from those that received ABT was compared to published HF rates from ABT. Results: Our sample included 227 BRCA1 carriers and 164 BRCA2 carriers in whom 6.4% reported cardiac toxicity (i.e., either HF and/or CT). This included similar proportions in BRCA1 vs BRCA2 carriers (i.e., 6.6% and 6.1%, respectively). These proportions are significantly higher than the published rate of 2% (all p-values < 0.001). Specifically regarding ABT, 112 mutation carriers had doxorubicin (Adriamycin) for treatment of whom 8% reported HF, similar to the 11 who had Epirubicin (11 patients), of whom 9% reported HF. Conclusions: Our data suggests that BRCA mutation carriers may have an increased risk of CT compared to the general population. In particular, women with BRCA mutations treated with ABT also appear to have a higher risk of developing CT and/or HF. This exploratory study provides the basis upon which larger retrospective and prospective studies are currently being planned. The high percentage of CT observed in this study requires confirmation as they could inform recommendation for cardiac screening and review of the current standard for ABT use in this population.

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.

1536 Background: Current educational materials about inherited breast and ovarian cancer (HBOC) have not been culturally tailored for the Black community, which may contribute to lower levels of awareness about this topic. Through an academic and community partnership, realized through a Community Advisory Panel (CAP) comprised of breast cancer survivors, advocates, community leaders, and health care providers, this need was identified. Methods: Utilizing a phased approach implemented through this academic and community partnership, a culturally tailored brochure and booklet about HBOC for the Black community were developed and reviewed. To evaluate the brochure, three focus groups were conducted by race-concordant moderators. HBOC was discussed with Black women from diverse backgrounds, including those with and without breast cancer (n = 46). Summaries were created from audiotapes and handwritten notes and content was analyzed based on Grounded Theory, after which the brochure was revised. Similarly, revisions to the booklet were made based on feedback obtained about the brochure. Materials were then presented to the CAP for re-review. Results: From this iterative process, the key content identified as areas for improvement were: (1) Inclusion of breast cancer information specific to Black women; (2) Use of the term “Black”; (3) Inclusion of African American flag colors; (4) Clarification of the concept of genetic counseling; and (5) Enhancing relevance of information for young women. Conclusions: The CAP and study participants recognized the need for culturally relevant educational materials addressing HBOC in the Black community. Their feedback identified important areas for improvement which have been implemented in the design of a culturally tailored brochure that is available for widespread dissemination. Further evaluation of the booklet is currently in progress. No significant financial relationships to disclose.

e17505 Background: Immunohistochemistry (IHC) for mismatch repair (MMR) protein (MLH1, MSH2, MSH6) expression has been a useful strategy for identifying tumors with MMR deficiency. However, despite its wide use, interpretation of results suffers from poor reproducibility. Methods: To assess inter-observer (IO) and inter-laboratory (IL) variability of MMR protein expression, 41 epithelial ovarian cancer (EOC) samples were arrayed in triplicate for construction of a tissue microarray (TMA). Six slides were made from this donor TMA block, of which 3 were stained at the Moffitt Cancer Center (MCC) and 3 were stained at the University of South Florida (USF), using different lab procedures. IHC for MMR protein expression was performed using the avidin-biotin-complex (ABC) method with appropriate controls. Subsequently, all slides were independently scored for protein expression by two pathologists. The Concordance Correlation Coefficient (CCC) value was computed to evaluate IO and IL concordance, with a value >0.75 indicating excellent concordance. Results: The CCC value for the IO analysis was 0.95 (for MCC-stained slides; 95% C.I.: 0.89–0.98) and 0.85 (for USF-stained slides; 95% C.I.: 0.66, 0.93), indicating excellent concordance. The CCC value for IL analysis was 0.53 (95% C.I.: 0.37–0.66). Conclusions: Our findings demonstrate that variability in IHC protocols may contribute to the interpretation of IHC results. Our data suggest that when pathologists are given the same slide, there is excellent agreement between two observers; however, when the same slides are stained in a separate laboratory using the same method (ABC) but different protocol, there may be considerable disagreement. These findings are of great clinical significance due to the widespread use of IHC as diagnostic, prognostic and therapeutic tools in cancer care. No significant financial relationships to disclose.

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.