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Background CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have a well-established role in the management of hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC). The benefit of continuing CDK4/6i beyond progression in combination with a different ET has not been confirmed. Preclinical data suggest synergy between CDK4/6i and PD-L1 inhibition. The PACE trial prospectively evaluates whether continuation of the CKD4/6i palbociclib beyond progression on prior CDK4/6i and aromatase inhibitor (AI), with a change in ET to fulvestrant, improves outcomes beyond change to fulvestrant alone, as well as explores the activity of the palbociclib, fulvestrant, and avelumab triplet. Methods PACE is a multicenter randomized open-label investigator-initiated phase II trial, open at 11 U.S. sites. Eligible patients (pts) had HR+/HER2- evaluable MBC with prior progression on AI and any CDK4/6i after > 6 months (mo) of therapy in the MBC setting, or during/within 12 mo in the adjuvant setting, with no more than 1 prior line of chemotherapy for MBC. Pts were randomized 1:2:1 to fulvestrant alone (F); fulvestrant and palbociclib (F+P); or fulvestrant, palbociclib, avelumab (F+P+A), with tumor assessments every 8 weeks. Blood for circulating tumor DNA (ctDNA) analysis was collected at baseline, at times of tumor assessments, and at progression. The primary objective was to evaluate progression-free survival (PFS) with F+P vs F; secondary objectives included PFS with F+P+A vs F, objective response rate (ORR) in all arms, and safety. A sample size of 220 patients was planned to provide 80% power to detect an improvement in PFS with HR 0.6154 with F+P vs F (6.5 vs 4 mo; α(1)=0.05). Results A total of 220 pts were randomized from 9/2017-2/2022 (F: n=55, F+P: n=111, F+P+A: n=54); median age 57 years (range 25-83), 85% non-Hispanic (7.7% non-Hispanic black), 8.6% Hispanic, 6.4% unknown. 40% had de novo MBC, 60% had visceral disease, and 14% bone-only disease. 16% had 1 prior line of chemotherapy for MBC, 90% had received prior palbociclib, 4.5% ribociclib, 4.1% abemaciclib, 1.4% palbociclib and ribociclib. Pts entered the trial after a median 19 mo of prior CDK4/6i plus AI (interquartile range 12-31 mo). A total of 10 (5%) pts received protocol therapy as first line ET for MBC, 169 (77%) as second line, and 41 (17%) as beyond second line. 88% entered the trial directly after progression on CDK4/6i. After a median follow-up of 24 mo, 18 pts remained on protocol treatment. PFS was not improved with F+P vs F (median 4.6 vs 4.8 mo; HR=1.11, 90% CI 0.79-1.55; 2-sided p=0.62). Median PFS was 8.1 mo with F+P+A (HR=0.75 vs F, 90% CI 0.50-1.12; 2-sided p=0.23). ORR was 7.3% (90%CI 1.5-13.0) with F, 9.0% F+P (4.5-13.5%) and 13.0% F+P+A (5.4-20.5%). No new safety signals have been observed. Analysis of ctDNA panel sequencing encompassing 70 genes from 184 baseline samples, including correlation with known and hypothesized resistance genes, will be presented. Conclusions For ER+/HER2- breast cancer, combining palbociclib with fulvestrant beyond progression on prior CDK4/6i and AI did not significantly improve PFS compared with using fulvestrant alone. The observed longer PFS when a PD-L1 inhibitor was added to fulvestrant plus palbociclib is an intriguing signal in this ER+ population. Translational studies of blood and tumor tissue are ongoing and will be presented. Citation Format: Erica L. Mayer, Yue Ren, Nikhil Wagle, Reshma Mahtani, Cynthia Ma, Angela DeMichele, Massimo Cristofanilli, Jane Meisel, Kathy D. Miller, Trevor Jolly, Elizabeth Riley, Rubina Qamar, Priyanka Sharma, Sonya Reid, Natalie Sinclair, Meredith Faggen, Caroline Block, Naomi Ko, Ann Partridge, Wendy Y. Chen, Michelle K. DeMeo, Victoria Attaya, Amanda Okpoebo, Yuan Liu, Eric Gauthier, Harold Burstein, Meredith Regan, Sara Tolaney. GS3-06 Palbociclib After CDK4/6i and Endocrine Therapy (PACE): A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab for Endocrine Pre-treated ER+/HER2- Metastatic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS3-06.

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)

PURPOSE. To evaluate the association between obesity and the relative prevalence of tumor subtypes among Black women with breast cancer (BC). METHODS: We conducted a pooled case-only analysis of 1,793 Black women with invasive BC recruited through three existing studies in the southeastern US. Multivariable case-only polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between obesity, measured by pre-diagnostic body mass index (BMI), and human epidermal growth factor receptor 2+ (HER2+) and triple negative BC (TNBC) subtype relative to hormone receptor (HR)+/HER2− status (referent). RESULTS. Among 359 premenopausal women, 55.4% of cases were HR+/HER2−, 20.1% were HER2+, and 24.5% were TNBC; corresponding percentages among 1,434 postmenopausal women were 59.3%, 17.0%, and 23.6%. Approximately 50–60% of both pre- and postmenopausal women were obese (BMI>30 kg/m(2)), regardless of BC subtype. We did not observe a significant association between obesity and BC subtype. Among postmenopausal women, class I obesity (BMI 35+ kg/m(2)) was not associated with the development of HER2+ BC (OR 0.69; 95% CI 0.42–1.14) or TNBC (OR 0.93; 95% CI 0.60–1.45) relative to HR+/HER2− tumors. Corresponding estimates among premenopausal women were 1.03 (95% CI 0.43–2.48) and 1.13 (95% CI 0.48–2.64). CONCLUSION. In this large study of Black women with BC, there was no evidence of heterogeneity of BMI by BC subtype.

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

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

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

PURPOSE: There is an urgent need to understand the biological factors contributing to the racial survival disparity among women with hormone receptor-positive (HR+), HER2− breast cancer. In this study, we examined the impact of PAM50 subtype on 10-year mortality rate in women with HR+, HER2− breast cancer by race. METHODS: Women with localized, HR+, HER2− breast cancer diagnosed between 2002 to 2012 from two population-based cohorts were evaluated. Archival tumors were obtained and classified by PAM50 into four molecular subtypes (i.e., luminal A, luminal B, HER2-enriched, and basal-like). The molecular subtypes within HR+, HER2− breast cancers and corresponding 10-year mortality rate were compared between Black and Non-Hispanic White (NHW) women using Cox proportional hazard ratios and survival analysis, adjusting for covariates. RESULTS: In this study, 318 women with localized, HR+, HER2− breast cancer were included—227 Black (71%) and 91 NHW (29%). Young Black women (age≤50) had the highest proportion of HR+,non-luminal A tumors (47%), compared to young NHW (10%), older Black women (31%), and older NHW (30%). Overall, women with HR+,non-luminal A subtypes had a higher 10-year mortality rate compared to HR+, luminal A subtypes after adjustment for age, stage and income (HR 4.21 for Blacks, 95% CI=1.74–10.18 and HR 3.44 for NHW, 95% CI=1.31–9.03). Among HR+, non-luminal A subtypes there was however no significant racial difference in 10-yr mortality observed (Black vs. NHW: HR 1.23, 95% CI=0.58–2.58). CONCLUSION: Molecular subtype classification highlights racial disparities in PAM50 subtype distribution among women with HR+, HER2− breast cancer. Among women with HR+, HER2− breast cancer, racial survival disparities are ameliorated after adjusting for molecular subtype.

Background Poly (ADP-ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in treating solid tumors with Homologous Recombination Deficiency (HRD), the inability to repair DNA double-stranded breaks through the Homologous Recombination Repair (HRR) pathway. Specific genetic and epigenetic alterations result in defective HRR function. Bi-allelic loss of BRCA1 or BRCA2 principally drives HRR deficiency. While BRCA1/2 are instrumental to HRR, multiple genes, including PALB2, impact the HRR pathway. PALB2 mutations occur in an estimated 0.97% to 3.66% of solid tumors [AACR GENIE PALB2] and are associated with susceptibility to various cancers. No clinically approved therapies specifically targeting PALB2 currently exist. Emerging evidence suggests that patients with germline or somatic PALB2 mutations may benefit from PARPi treatment, which has potential to be a new tumor agnostic therapy option across a wide range of solid tumors. Methods PAVO is a pan-tumor, single-arm, multicenter Phase-II study assessing the safety and efficacy of niraparib (a PARPi) in patients who harbor a confirmed PALB2 mutation. The study plans to enroll up to 110 adult subjects. Eligible participants must have: locally advanced or metastatic solid tumor(s); confirmed pathogenic or likely pathogenic somatic or germline PALB2 mutation; received all standard of care (SOC) therapy for their tumor type, or are unlikely to derive benefit from SOC therapy in the opinion of the treating physician; ECOG performance status of 0 or 1; life expectancy of ≥ 12 weeks with adequate organ/bone marrow function. Exclusion criteria include a confirmed somatic or germline BRCA1/2 mutation, prior treatment with any PARPi, ovarian or prostate cancer, or rapid progression while on platinum-based therapy in the metastatic setting. Niraparib will be administered in 28 day cycles with daily dosing, as outlined in the protocol. Participants will continue study treatment until documented radiographic progression, unacceptable toxicity, death, or consent withdrawal. The primary study endpoint is objective response rate (ORR), defined as the proportion of participants who have partial or complete response to therapy as assessed by Independent Central Review. Secondary endpoints include DOR, PFS, and CBR. PAVO is sponsored by Tempus with support from GSK (GlaxoSmithKline). The trial opened in March 2022. Tempus molecular data tracking (integrated NGS and EMR data) and the TIME Trial program (rapid match of patients to Just in TIME sites for clinical trials), enable patient identification and prescreening. Enrollment occurs through a combination of TIME and prospective clinical sites, where individualized prescreening models are in development. New site identification and referral of molecularly eligible patients to enrolling centers are ongoing. Clinical Trial Registry: NCT05169437 Citation Format: Tian Zhang, Thomas Weart, Matthias Weiss, Drew Murray, Minaxi Jhawer, Edward Huynh, Shumei Kato, Amy Cummings, Lydia Usha, Arvinder Bhinder, Rajiv Desai, Brad Johnson, Anjali Avadhani, Cecile Rose T. Vibat, Lauren Lopez, Brynna Driscoll, Annajane Ward, Christie K. Rice, Blathnaid Donovan, Scott Sherrin, Mykel Robble, Stephanie O'Leary, Kimberly Blackwell, Amine Aziez, Stephanie Petrone, Kathleen Harnden, Kimberly Strickland, Sonya Reid, Mark Robson, Andrew S. Paulson, Afshin Dowlati. PAVO: A phase-II, open label, single arm study of niraparib in patients with locally advanced/metastatic PALB2 mutated tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT055.

High-salt (sodium chloride) diets have been associated with several chronic inflammatory diseases. While the role of chronic inflammation in cancer is well established, the specific role of high salt diet in carcinogenesis is unknown. Previous studies with syngeneic murine breast cancer models, both in our laboratory and others, have shown that high salt (HS) diet induced tumor regression through inflammatory activation of anti-tumor adaptive immune responses. We tested this counter-intuitive and suspiciously beneficial role of HS diet by performing sequential passage studies in preclinical murine models. Six week old mice were placed on high salt diet for 2 weeks prior to injection with syngeneic 4T1 and Py230 triple negative breast cancer cells (into BALB/c and C57Bl/6J mice, respectively, referred to as passage-1). Tumors were harvested after four weeks of injection. The cancer cells depleted of immune cells were collected from these harvested tumors and reinjected into new non-tumor bearing mice. This cycle was repeated three times. In passage-1 cohort, by day 28, HS diet induced reduced tumor progression in both 4T1-BALB/c (267 ± 59 mm3) and Py230-C57Bl/6J (238 ± 54 mm3) as compared to regular salt (RS) diet cohort (611 ± 94 mm3 and 473 ± 69 mm3, respectively; p Citation Format: Lisa Tucker, Sonya Reid, Jeffrey C. Rathmell, Venkataswarup Tiriveedhi. High salt diet induced tumor initiating stem cells mediate breast cancer progression. [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 4850.

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.

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: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case–control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: Pathogenic variants in 12 established breast cancer–predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor–negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor–positive breast cancer. Pathogenic variants in 16 candidate breast cancer–predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer–predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.)

PURPOSE This study sought to provide a detailed analysis of breast cancer–specific mortality in Jamaica on the basis of reported deaths between 2010 and 2014. METHODS A cross-sectional study was done to analyze breast cancer–specific mortality data from the Registrar General’s Department, the statutory body responsible for registering all deaths across Jamaica. RESULTS A total of 1,634 breast cancer–related deaths were documented among Jamaican women between 2010 and 2014, which accounted for 24% of all female cancer deaths. The age-standardized breast cancer mortality rate increased from 21.8 per 100,000 in 2010 to 28 per 100,000 in 2014 for the total female population. The overall difference in breast cancer mortality rates between the 2014 and 2010 rates was not statistically significant ( P = .114). Analysis of the year-by-year trend reflected by the annual percentage of change did show, however, a statistically significant increasing trend in breast cancer mortality ( P = .028). Mortality rates varied by age, with statistically significant annual increases observed in the 35-44–, 65-74–, and ≥ 75-year age groups ( P = .04, .03, and .01, respectively). CONCLUSION Breast cancer remains the leading cause of cancer-related death among Jamaican women. Despite global advances in breast cancer screening and management, breast cancer remains a major public health challenge and represents a public health priority in Jamaica. The increasing breast cancer–specific mortality in Jamaica over the 5-year period contrasts with decreasing mortality rates among US women with breast cancer. This study highlights the critical need to address the implementation of a national organized breast cancer screening program in Jamaica and to focus future research efforts on the biology of breast cancer, especially among young Jamaican women.

Breast cancer is the most common cancer among women worldwide [1], with 268,600 new cases diagnosed in the United States in 2019 [2]. An estimated 5–10% of all breast cancer cases are due to heredi...

With technological advances, multi-gene panel testing has become increasingly used to identify patients at risk for hereditary breast cancer (HBC). There are currently evidence-based interventions and breast cancer screening strategies that exist for cancer prevention and early detection among patients with HBC. Moreover, in addition to the personal impact of identifying HBC, this information may be shared with at-risk family members to amplify the benefits of testing and subsequent care among those at high risk. Opportunities and challenges with the utilization of updated multi-gene panel testing for HBC, including: (a) tumor sequencing with germline consequences; (b) genetic counseling implications; and (c) strategies to improve the communication of genetic test results to family members will be reviewed. With the advances and expansion of genetic testing, all health care providers need to be updated on both the importance and complexities of HBC counseling and testing, in order to optimize patient care.

PURPOSE OF REVIEW: Despite a steady improvement in breast cancer survival rates over the past several decades, mortality disparities remain among Black women, who have a 42% higher death rate compared to non-Hispanic white (NHW) women. Hereditary breast cancer (HBC) accounts for 5–10% of all breast cancer cases, the majority of which are due to the BRCA1 and BRCA2 (BRCA) genes. Despite the availability of BRCA testing for over 25 years, there remain disproportionately lower rates of genetic testing among Blacks compared to NHW due to a multitude of factors. The intent of this review is to discuss racial disparities focused on HBC across diverse populations and review the existing gaps to be addressed when delivering gene-based care. RECENT FINDINGS: The factors contributing to the racial survival disparity are undoubtedly complex and likely an interplay between tumor biology, genomics, patterns of care and socioeconomic factors. Advances in genomic technologies that now allow for full characterization of germline DNA sequencing are integral in defining the complex and multifactorial cause of breast cancer and may help to explain the existing racial survival disparities. SUMMARY: Identification of inherited cancer risk may lead to cancer prevention, early cancer detection, treatment guidance, and ultimately has great potential to improve outcomes. Consequently, advances in HBC diagnosis and treatment without widespread implementation have the potential to further widen the existing breast cancer mortality gap between Black and NHW women.

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

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.

Background Implementing genetic testing for inherited cancer predisposition into routine clinical care offers a tremendous opportunity for cancer prevention and early detection. However, genetic testing itself does not improve outcomes; rather, outcomes depend on implemented follow-up care. The IMPACT study is a hybrid type I randomized effectiveness-implementation trial to simultaneously evaluate the effectiveness of two interventions for individuals with inherited cancer predisposition focused on: 1) increasing family communication (FC) of genetic test results; and 2) improving engagement with guideline-based cancer risk management (CRM). Methods This prospective study will recruit a racially, geographically, and socioeconomically diverse population of individuals with a documented pathogenic/likely pathogenic (P/LP) variant in an inherited cancer gene. Eligible participants will be asked to complete an initial trial survey and randomly assigned to one of three arms: A) GeneSHARE, a website designed to increase FC of genetic test results; B) My Gene Counsel’s Living Lab Report, a digital tool designed to improve understanding of genetic test results and next steps, including CRM guidelines; or C) a control arm in which participants continue receiving standard care. Follow-up surveys will be conducted at 1, 3, and 12 months following randomization. These surveys include single-item measures, scales, and indices related to: 1) FC and CRM behaviors and behavioral factors following the COM-B theoretical framework (i.e., capability, opportunity, and motivation); 2) implementation outcomes (i.e., acceptability, appropriateness, exposure, and reach); and 3) other contextual factors (i.e., sociodemographic and clinical factors, and uncertainty, distress, and positive aspects of genetic test results). The primary outcomes are an increase in FC of genetic test results (Arm A) and improved engagement with guideline-based CRM without overtreatment or undertreatment (Arm B) by the 12-month follow-up survey. Discussion Our interventions are designed to shift the paradigm by which individuals with P/LP variants in inherited cancer genes are provided with information to enhance FC of genetic test results and engagement with guideline-based CRM. The information gathered through evaluating the effectiveness and implementation of these real-world approaches is needed to modify and scale up adaptive, stepped interventions that have the potential to maximize FC and CRM. Trial registration This study is registered at Clinicaltrials.gov (NCT04763915, date registered: February 21, 2021). Protocol version September 17th, 2021 Amendment Number 04.

Background: We investigated the association between reproductive risk factors and breast cancer subtype in Black women. On the basis of the previous literature, we hypothesized that the relative prevalence of specific breast cancer subtypes might differ according to reproductive factors. Methods: We conducted a pooled analysis of 2,188 (591 premenopausal, 1,597 postmenopausal) Black women with a primary diagnosis of breast cancer from four studies in the southeastern United States. Breast cancers were classified by clinical subtype. Case-only polytomous logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for HER2+ and triple-negative breast cancer (TNBC) status in relation to estrogen receptor–positive (ER+)/HER2− status (referent) for reproductive risk factors. Results: Relative to women who had ER+/HER2− tumors, women who were age 19–24 years at first birth (OR, 1.78; 95% CI, 1.22–2.59) were more likely to have TNBC. Parous women were less likely to be diagnosed with HER2+ breast cancer and more likely to be diagnosed with TNBC relative to ER+/HER2− breast cancer. Postmenopausal parous women who breastfed were less likely to have TNBC [OR, 0.65 (95% CI, 0.43–0.99)]. Conclusions: This large pooled study of Black women with breast cancer revealed etiologic heterogeneity among breast cancer subtypes. Impact: Black parous women who do not breastfeed are more likely to be diagnosed with TNBC, which has a worse prognosis, than with ER+/HER2− breast cancer.

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.

e12591 Background: Hormone receptor-positive, HER2-negative breast cancer (HR+/HER2- BC) has the highest incidence and mortality rate across all racial/ethnic groups. HR+/HER2- BC is clinically and biologically heterogenous. Gene expression profiling assays can provide prognostic information and predict risk of late recurrence among women with HR+/HER2- BC. Prior studies have shown worse clinical outcomes among black women with HR+/HER2- BC. We sought to compare the distribution of intrinsic subtypes among young black women with HR+/HER2- BC, compared to published data from a young white cohort in the Carolina Breast Cancer Study (CBCS). Methods: Two population-based cohorts of black women diagnosed with BC between 2002 to 2012 at or below age 50 years were analyzed. Participants were recruited from twelve Southeastern states. All participants were asked to complete release of medical records and tissue/tumor forms to verify clinical information and to obtain primary tumor samples for future analyses. We compared the distribution of intrinsic subtypes and associations to clinical characteristics as compared to white female counterparts using Pearson chi-squared test. Results: Of 569 black participants, 124 women had HR+/HER2- BC and tumor samples available for analysis. There were 66 Luminal A (53%), 35 Luminal B (28%), 19 Basal (15%), and 4 HER2-enriched (3%) tumors. Black women with non-Luminal A tumors were younger ( < 40) with larger tumors ( > 2cm) and had higher risk of recurrence (ROR-T) scores as compared to black women with Luminal A tumors (p = 0.065, 0.006, and < 0.001, respectively). Compared to young white women in the CBCS, black women in our study had a significantly higher percentage of non-Luminal HR+/HER2- BC (p = 0.037). Conclusions: Our results suggest that among young women with HR+/HER2- BC, black women have a higher proportion of non-Luminal tumors compared to their white counterparts. Non-Luminal HR+/HER2- tumors (i.e., basal and HER2-enriched) are more aggressive and may be less sensitive to endocrine therapy. These results suggest that overrepresentation of aggressive HR+/HER2- BC subtypes may contribute to the racial survival disparity observed among black women.

PURPOSE OF REVIEW: Most women with hormone receptor (HR)-positive, HER2-negative (HR+/HER2−) breast cancer will ultimately develop endocrine-resistant disease, either primary or acquired. This review will discuss the proposed mechanisms underlying endocrine resistance and key advances in the treatment of endocrine-resistant breast cancer. RECENT FINDINGS: Estrogen receptor 1 mutations (ESR1) occur in the majority of patients with HR+/HER2− metastatic breast cancer after prolonged exposure to aromatase inhibitors. Data from the SoFEA trial showed that patients had improved progression-free survival (PFS) after taking fulvestrant compared with exemestane. Fulvestrant is currently the only selective estrogen receptor degrader (SERD) available and development of oral novel SERDs with higher bioavailability and potency are currently being investigated. SUMMARY: Despite significant advances in the treatment of HR+/HER2− breast cancer over the past four decades, a significant proportion of patients do still develop endocrine resistance following optimal endocrine therapy. In this review, we aim to provide an overview of the different classes of novel agents currently being investigated to overcome endocrine resistance.

The mainstay of treatment for early-stage and locally advanced triple-negative breast cancer (TNBC) is chemotherapy. Anthracycline−/alkylator- and taxane-based regimens are considered the standard of care for the systemic treatment of high-risk triple-negative disease. Common approaches include sequential anthracycline/alkylator followed by taxane or concurrent delivery of an anthracycline, an alkylator, and a taxane. Shorter courses of treatment are considered appropriate for lower-risk triple-negative, node-negative tumors less than 1 cm. Despite treatment with anthracycline- and taxane-based chemotherapy regimens, about 30% of early-stage TNBC develop recurrent and metastatic disease, and many efforts are focused on how to optimize our current neoadjuvant and adjuvant approaches. Incorporation of platinum agents in the neoadjuvant setting appears promising, but long-term outcome data are needed. Treatment of high residual disease burden with additional chemotherapy after completion of neoadjuvant therapy is becoming an important area of investigation. The hope is that newer biologically driven strategies and development of biomarkers will lead to more effective and individualized therapy for TNBC.

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.

1579 Background: Per national practice guidelines, pre-test genetic counseling (GC) through a board-certified or credentialed genetics health professional (GHP) is recommended when testing for hereditary cancer. We sought to compare differences in rates of pre-test GC among young breast cancer (BC) patients tested with or without GHP involvement across three racial groups (Black, Hispanic and non-Hispanic white (NHW)). Methods: A population-based sample of Black, Hispanic and NHW women diagnosed with invasive BC ≤ age 50 from 2009 to 2012 were recruited through the Florida State Cancer Registry. Participants were asked to complete a baseline questionnaire and release medical records for verification of clinical information and genetic testing. We compared the rates of pre-test GC across racial groups in women tested with or without GHP involvement using Analysis of Variance. Multivariate logistic regression analysis was also conducted to adjust for potential confounders. Results: Of 1618 participants, 828 had genetic testing based on medical records and/or self-reported on their questionnaire. There were 170 (20.5%) with GHP involvement (either through consultation and/or test ordering) and the remaining 658 women (79.5%) had no documentation of GHP involvement. Among patients tested without GHP involvement, rates of pre-test GC were significantly lower among Black women (34.8%) compared to Hispanics (80%) and NHW (78.7%) (p < 0.001). In contrast, among those with GHP involvement, rates of pre-test GC were similar among Black (89.7%), Hispanic (81.1%) and NHW (84.6%) (p = 0.89). Conclusions: Our results suggest that among young breast cancer patients tested for hereditary cancer without GHP involvement, Blacks were significantly less likely to receive pre-test GC, compared to the other two groups. In contrast, rates of pre-test GC among those with GHP involvement were similar across all groups. These results suggest a disparity in receipt of pre-test GC (which is standard of care per national guidelines) among Blacks tested without GHP involvement. These findings are concerning given the need to offer guideline-adherent care to all patients receiving hereditary cancer testing.