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To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression.Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown.Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2-), ER+/HER2+, and ER-/HER2+ disease.Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001-1.126, P =0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151-0.781, P =0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: -0.987-1.116, P =0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ 2 =42004914 ( p =3.70×10 -5 ) in patients with TNBC.In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3 high CD11b − CD27 − immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell–mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti–programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56 bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC.

BACKGROUND: Skin-sparing (SSM) and nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) have significantly increased. There is limited information on complications of IBR in patients with prior cosmetic breast surgery (CBS). We compare IBR outcomes in patients undergoing SSM and/or NSM with and without prior CBS. MATERIALS AND METHODS: Patients undergoing mastectomy from January 1, 2017 to December 31, 2019 were selected. Patient characteristics, surgical approach, and complications were compared between mastectomy and IBR cases for breasts with and without prior CBS. Binary logistic regression analysis was performed to identify predictors of complications and reconstruction loss. RESULTS: 956 mastectomies were performed in 697 patients, with IBR performed for 545 mastectomies in 356 patients. Median age was 51 (range 19–83), 45.8% of patients were age < 50, 62.6% of mastectomies were performed for breast cancer. 95 mastectomies (17.4%) were performed in breasts with prior CBS and 450 (82.6%) without. NSM was more frequently utilized for breasts with prior CBS (P < .001). Complications occurred in 80 mastectomies (14.7%); reconstruction loss in 30 (5.5%). On multivariable analysis, age ≥ 50 (OR 1.76, 95%CI 1.01–3.09, P = .047) and NSM (OR 2.11, 95%CI 1.17–3.79, P = .013) were associated with an increased risk of any complication. Prior CBS was not associated with an increased risk of complications (OR 1.11, 95%CI 0.58–2.14, P = .743) or reconstruction loss (OR 1.32, 95%CI 0.51–3.38, P = .567). CONCLUSION: In this analysis of mastectomy and IBR, prior CBS was not associated with an increased risk of complications or reconstruction loss. In patients with prior CBS undergoing mastectomy, IBR may be safely performed.

OBJECTIVE: To analyze the effect of economic and racial/ethnic residential segregation on breast cancer-specific survival (BCSS) in South Florida, a diverse metropolitan area that mirrors the projected demographics of many United States (US) regions. SUMMARY BACKGROUND DATA: Despite advances in diagnosis and treatment, racial and economic disparities in BCSS. This study evaluates these disparities through the lens of racial and economic residential segregation, which approximate the impact of structural racism. METHODS: Retrospective cohort study of stage I-IV BC patients treated at our institution from 2005–2017. Our exposures include index of concentration at the extremes (ICE), a measurement of economic and racial neighborhood segregation, which was computed at the census-tract level using American Community Survey data. The primary outcome was BCSS. RESULTS: Random effects frailty models predicted that patients living in low-income neighborhoods had higher mortality compared to those living in high-income neighborhoods (HR:1.56, 95%CI:1.23–2.00). Patients living in low-income non-Hispanic Black (NHB) and Hispanic neighborhoods had higher mortality compared to those living in high-income non-Hispanic White (NHW) neighborhoods (HR: 2.43, 95%CI:1.72, 3.43) and (HR: 1.99, 95%CI: 1.39, 2.84), after controlling for patient characteristics, respectively. In adjusted race-stratified analysis, NHWs living in low-income NHB neighborhoods had higher mortality compared to NHWs living in high-income NHW neighborhoods (HR:4.09, 95%CI:2.34–7.06). CONCLUSIONS: Extreme racial/ethnic and economic segregation were associated with lower BCSS. We add novel insight regarding NHW and Hispanics to a growing body of literature that demonstrate how the ecological effects of structural racism—expressed through poverty and residential segregation—shape cancer survival.

Resistance to cancer treatment remains a major clinical hurdle. Here, we demonstrate that the CoREST complex is a key determinant for endocrine resistance and ER+ breast cancer plasticity. In endocrine sensitive cells, CoREST is recruited to ERα/FOXA1 co-bound regulatory regions to regulate the estrogen pathway. In contrast, during temporal reprogramming towards a resistant state, CoREST is recruited to AP-1 sites. In reprogrammed cells, CoREST favors chromatin opening, cJUN binding to chromatin, and gene activation by controlling SWI/SNF recruitment independently of the demethylase activity of the CoREST subunit, LSD1. Genetic and pharmacological CoREST inhibition reduce tumorigenesis and metastasis of endocrine sensitive and resistant xenografts models. Consistently, CoREST controls a gene signature in clinical breast tumors resistant to endocrine therapies involved in invasiveness. Our studies reveal CoREST functions that are co-opted to drive cellular plasticity and resistance to endocrine therapies and tumorigenesis, thus establishing CoREST as a potential therapeutic target for the treatment of advanced breast cancer.

Purpose Utilization of sentinel lymph node biopsy (SLNB) in breast cancer patients with positive nodes after neoadjuvant chemotherapy (NAC) has increased. We examine axillary response rates after NAC in patients with clinical N2-3 disease to determine whether SLNB should be considered. Methods Breast cancer patients with clinical N2-3 (AJCC 7th Edition) disease who received NAC followed by surgery were selected from our institutional tumor registry (2009-2018). Axillary response rates were assessed. Results Ninety-nine patients with 100 breast cancers were identified: 59 N2 (59.0%) and 41 (41.0%) N3 disease; 82 (82.0%) treated with axillary lymph node dissection (ALND) and 18 (18.0%) SLNB. The majority (99.0%) received multiagent NAC. In patients undergoing ALND, cCR was observed in 20/82 patients (24.4%), pathologic complete response (pCR) in 15 patients (18.3%), and axillary pCR in 17 patients (20.7%). In patients with a cCR, pCR was identified in 60.0% and was most common in HER2+ patients (34.6%). Conclusion In this analysis of patients with clinical N2-3 disease receiving NAC, 79.3% of patients had residual nodal disease at surgery. However, 60.0% of patients with a cCR also had a pCR. This provides the foundation to consider evaluating SLNB and less extensive axillary surgery in this select group.

Background: Breast cancer is the most common cancer diagnosed among Hispanic women in the US and is the leading cause of cancer-related death in this population. However, controversy remains as to whether this population has improved, or worse, overall survival (OS) outcomes compared to their non-Hispanic White (NHW) and non-Hispanic Black (NHB) counterparts. Given our location in South Florida, where Hispanics account for approximately 70% of the population we are perfectly poised to analyze breast cancer overall survival (OS) outcomes in a Hispanic population compared to a non-Hispanic population. Furthermore, given the diverse nature of our Hispanic population, this is the first study to also evaluate outcomes in Hispanic Whites (HW) compared to Hispanic Blacks (HB). Methods: Patients presenting to our medical campus with stage I-IV breast cancer from 2005-2017 were identified from the local tumor registry. Kaplan-Meier survival analysis was performed to identify patient, tumor, and NCCN-guideline based treatment characteristics associated with OS. Factors with a p Results: 5,951 breast cancer patients were evaluated from 2005-2017. Patient demographics, tumor characteristics, and treatments received are presented in Table 1. NHB tended to be more economically disadvantaged, presented with later stage disease, had rates higher triple negative disease, and were less likely to complete NCCN-guideline based treatment. The 5-year OS across all races/ethnicities was 82.5% with a median follow-up of 65 months. The 5-year OS stratified by race and ethnicity is as follows: NHW 85%, HW 84.8%, HB 79.4%, and NHB 72.7%. On Cox proportional hazards model, when adjusting for stage, race/ethnicity, insurance, marital status, income, smoking/alcohol, receptor status, tumor grade, and NCCN-guideline based treatment, NHB had a hazard ratio of 1.25 [(95% CI:1.01-1.52), p< 0.041)]. Conclusion: At our institution, located in South Florida, we treat a large number of patients with breast cancer from South Florida, Central and South America, and the Caribbean who self-report as Hispanic. Our study is the first to suggest survival differences amongst HW and HB. Moreover, HB had improved OS compared to NHB, suggesting unaccounted for protective factors associated with Hispanic ethnicity. Table 1: Patient demographics, tumor, and treatment characteristicsFactorNHWHispanic WhiteNHBHispanic BlackAllp-valueN=1647N=3127N=1070N=107N=5951PATIENT DEMOGRAPHICSAge at diagnosisp$64,600649 (40.1%)658 (21.5%)91 (8.9%)7 (6.7%)1405 (24.2%)Insurancep Citation Format: Sina Yadegarynia, Kristin Kelly, Seraphina Choi, Susan Kesmodel, Neha Goel. Breast cancer outcomes among a diverse racial/ethnic south Florida population [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 PS7-41.

Public safety net hospitals (SNH) serve a disparate patient population; however, little is known about long-term oncologic outcomes of patients receiving care at these facilities. This study is the first to examine overall survival (OS) and the initiation of treatment in breast cancer patients treated at a SNH. Patients presenting to a SNH with stage I-IV breast cancer from 2005 to 2017 were identified from the local tumor registry. The hospital has a weekly breast tumor board and a multidisciplinary approach to breast cancer care. Kaplan-Meier survival analysis was performed to identify patient, tumor, and treatment characteristics associated with OS. Factors with a p 70 years, higher grade, and non-Hispanic ethnicity were associated with worse OS. Patients receiving surgery (HR = 0.33, p

The rate of mastectomy in lumpectomy-eligible patients with unilateral breast cancer is increasing. We sought to investigate the association between magnetic resonance imaging (MRI) and surgical management of patients with early-stage breast cancer by comparing the rate of mastectomy as first surgery in patients with and without preoperative MRI.A bi-institutional retrospective study included patients diagnosed between 2016 and 2020. Lumpectomy-eligible patients with in situ and invasive cancer were included. Those receiving preoperative therapy, MRI before diagnosis, or with known bilateral cancer were excluded. The risk factors for bilateral and multicentric disease were accounted for. Fisher's exact and chi-square tests compared categorical variables, Wilcoxon two-sample test analyzed continuous variables, and multivariate analyses were performed with Poisson regression.Four hundred twenty-eight participants met inclusion criteria. Patients who received MRI were younger (58 versus 67 y; P 0.001) and had denser breasts (group 3 or 4; 61% versus 25%; P 0.001). Mastectomy rate was twice as high in patients undergoing MRI (32% versus 15%, rate ratio 2.16; P 0.001), which remained significant in multivariate analysis (rate ratio 2.0; P 0.001). Contralateral mastectomy (12% versus 4%; P = 0.466) and reexcision (13% versus 12%; P = 0.519) rates were similar. Time to surgery was greater in those receiving MRI alone and MRI biopsy (34 [no MRI] versus 45 [MRI] versus 62 [MRI biopsy]; P 0.001 for both).MRI receipt is associated with a doubled rate of mastectomy in lumpectomy-eligible patients. Future work is needed to standardize patient selection for MRI to those with the highest likelihood of having additional undiagnosed disease.

Occult breast cancer (OBC) is a rare clinical entity. Current surgical management includes axillary lymphadenectomy (ALND) with or without mastectomy. We sought to investigate the role of sentinel lymph node biopsy (SLNB) in patients with OBC treated with neoadjuvant chemotherapy (NAC). Patients with clinical T0N+ breast cancer were selected from the National Cancer Data Base (NCDB, 2004–2014) and compared according to axillary surgical approach, SLNB (≤ 4 LNs) or ALND (> 4 LNs). Primary outcome was overall survival (OS), calculated using Kaplan–Meier methods. Secondary outcome was complete pathological response (pCR). A total of 684 patients with OBC were identified: 470 (68.7%) underwent surgery upfront and 214 (31.3%) received NAC. Of the NAC patients, 34 (15.9%) underwent SLNB and 180 (84.1%) ALND. One hundred and fifty-three (72%) patients received radiotherapy (RT). There was no difference in pCR rates between the ALND and SLNB (34.3% vs 24.5%, respectively p = 0.245). In patients undergoing surgery first, improved OS was observed with ALND compared to SLNB (106.9 vs 85.5 months, p = 0.013); however, no difference in OS was found in patients who received NAC (105.6 vs 111.3 months, p = 0.640). RT improved OS in patients who underwent NAC followed by SLNB (RT, 123 months vs no RT, 64 months, p = 0.034). Of NAC patients who did not undergo RT, ALND had superior survival compared to SLNB (113 vs 64 months, p = 0.013). This is the first comparative analysis assessing the surgical management of the axilla in patients with OBC who underwent NAC. In this population, there was a decrease in survival in patients who underwent SLNB alone; however, with the addition of RT, there was no difference in OS between SLNB and ALND. SLNB plus RT may be considered as an alternative to ALND in patients with OBC who have a good response to NAC.

Radiation-induced sarcoma of the breast is a rare complication that is primarily treated with surgical resection but in patients with advanced disease, a multimodality treatment approach is often required. This case report discusses a 37-year-old female with a history of a pT3N3M0, estrogen receptor (ER)+, progesterone receptor (PR)+, human epidermal growth factor receptor 2 (HER2)+, right breast cancer, and a germline tumor protein (TP) p53 mutation who underwent right modified radical mastectomy, adjuvant systemic therapy, and radiation therapy, and subsequently developed a radiation-induced sarcoma. The patient is a 37-year-old female who has a history of pT3N3M0, ER/PR+, HER2+, and right breast cancer diagnosed in 2014. At the time of diagnosis, she had locally advanced disease and underwent right modified radical mastectomy followed by adjuvant chemotherapy, radiation, delayed right breast implant-based reconstruction, and left breast augmentation with mastopexy. Upon completion of adjuvant chemotherapy, she was started on hormonal therapy. In February 2020, she underwent genetic testing given her early onset of breast cancer and was found to have a germline TP53 mutation. Routine MRI for breast implant evaluation showed two irregular enhancing masses with an additional satellite lesion in the right breast. Right breast ultrasound (US)-guided biopsy revealed two separate foci of high-grade pleomorphic fibroblastic/myofibroblastic sarcoma. Further staging workup with a whole-body MRI was negative for evidence of metastatic disease. Her case was discussed in multidisciplinary sarcoma tumor board and consensus was for surgical resection. She underwent radical resection of the right chest wall masses and subcutaneous tissue, removal of right breast implant and capsulectomy, and left breast mastectomy with left breast implant removal and capsulectomy. The final pathology revealed two separate foci of high-grade pleomorphic fibroblastic/myofibroblastic sarcoma, 1.2 cm and 1.1 cm in their greatest dimensions with negative margins. Her case was re-discussed in multidisciplinary sarcoma tumor board and due to T1 size of the tumors and the negative resection margins, close surveillance with annual whole-body MRI and quarterly chest MRI imaging was recommended. In patients with a germline TP53 mutation and breast cancer, the utilization of adjuvant radiotherapy should be considered cautiously given the increased risk of radiation-associated sarcoma.

One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) patients is axillary downstaging to avoid axillary dissection.The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response.A prospectively collected database was queried for node-positive, ER+, HER2- breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model.A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p = 0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p = 0.03). NET patients with ypN0 were younger and were treated for a longer period of time (6 months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR.For patients with node-positive, ER+, HER2- breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response.

PurposePost-mastectomy breast reconstruction (PMBR) is an important component of breast cancer treatment, but disparities relative to insurance status persist despite legislation targeting the issue. We aimed to study this relationship in a large health system combining a safety net hospital and a private academic center.MethodsData were collected on all patients who underwent mastectomy for breast cancer from 2011-2019 in a private academic center and an adjacent public safety-net hospital served by same surgical teams. Multivariable logistic regression was used to assess the effect of insurance status on PMBR, controlling for covariates that included socioeconomic, demographic, and clinical factors.ResultsOf 1,554 patients undergoing mastectomy for breast cancer, 753 (48.5%) underwent PMBR. Out of them, 741 had insurance type recorded, with 592 (79.9%) privately insured patients, 50 (6.7%) Medicare, 68 (9.2%) Medicaid, and 31 (4.2%) uninsured patients. Multivariable logistic regression showed a significantly lower likelihood of undergoing PMBR for uninsured (OR 6.9, 95% CI: 4.1-11.7; p

Racial disparities in accessing postmastectomy breast reconstruction persist despite expansion of insurance coverage. An updated examination with a broad assessment of mediating factors in a "majority minority" community is needed.Data were collected on all patients undergoing mastectomy for breast cancer from 2011 to 2019 in a private academic center and adjacent safety-net hospital. Multivariable logistic regression was used to assess the effect of race on postmastectomy breast reconstruction, controlling for predetermined potentially mediating and confounding variables.Of 1,554 patients, 63.8% (n = 203) of non-Hispanic White, 33.4% (n = 102) of Black, and 47.9% (n = 438) of Hispanic patients underwent postmastectomy breast reconstruction. Multivariable logistic regression showed that Black patients (odds ratio [OR] 3.6, 95% confidence internal [CI]: 2.2-5.9; P.0001) undergo significantly less postmastectomy breast reconstruction than White patients. Age, insurance status, stage, and hospital type mediated this relationship.Black patients have substantially reduced rates of postmastectomy breast reconstruction compared with White patients, which is mediated by socioeconomic factors.

OBJECTIVE To understand the impact of Black race on breast cancer (BC) presentation, treatment, and survival among Hispanics. SUMMARY OF BACKGROUND DATA It is well-documented that non-Hispanic Blacks (NHB) present with late-stage disease, are less likely to complete treatment, and have worse survival compared to their non-Hispanic White (NHW) counterparts. However, no data evaluates whether this disparity extends to Hispanic Blacks (HB) and Hispanic Whites (HW). Given our location in Miami, gateway to Latin America and the Caribbean, we have the diversity to evaluate BC outcomes in HB and HW. METHODS Retrospective cohort study of stage I-IV BC patients treated at our institution from 2005-2017. Kaplan-Meier survival curves were generated and compared using the log-rank test. Multivariable survival models were computed using Cox proportional hazards regression. RESULTS Race/ethnicity distribution of 5951 patients: 28% NHW, 51% HW, 3% HB, and 18% NHB. HB were more economically disadvantaged, had more aggressive disease, and less treatment compliant compared to HW. 5-year OS by race/ethnicity was: 85% NHW, 84.8% HW, 79.4% HB, and 72.7% NHB (P < 0.001). After adjusting for covariates, NHB was an independent predictor of worse OS [hazard ratio:1.25 (95% confidence interval: 1.01-1.52), P < 0.041)]. CONCLUSIONS In this first comprehensive analysis of HB and HW, HB have worse OS compared to HW, suggesting that race/ethnicity is a complex variable acting as a proxy for tumor and host biology, as well as individual and neighborhood-level factors impacted by structural racism. This study identifies markers of vulnerability associated with Black race and markers of resiliency associated with Hispanic ethnicity to narrow a persistent BC survival gap.

Background: There are disparities in breast cancer (BC) diagnosis. Black and Hispanic women have a lower rate of screening mammography while the uninsured are less likely to seek medical care even if a palpable mass is found in the breast. Jackson Memorial Hospital is the Safety-Net Hospital that serves the 2.5 million residents of Miami-Dade County which is the most populous county in the State of Florida. The Affordable Care Act (ACA) was signed into law on March 3, 2010 and the goal was to increase the number of insured individuals. In January 2011, it was mandated that health insurance providers cover the cost of screening mammograms. The decision to expand Medicaid was left to the individual states. Florida did not expand Medicaid coverage. Prior to the implementation of the ACA it was estimated that 25-35% of the residents of Miami-Dade County were uninsured or underinsured. By January 2017, more than 1.3 million Floridians had signed up for health insurance through the ACA. Currently almost one in five Americans receiving health coverage via Healthcare.gov or the Spanish language version, CuidadodeSalud.gov, resides in Florida. South Florida is home to the eight congressional districts with the highest concentrations of ACA enrollees in the US. The top 38 zip codes for ACA sign-ups in Florida are in South Florida. We postulated that evaluating the number of patients diagnosed, the stage at which they are diagnosed and the type of insurance used for the period of time 6 years before (2007-2012) and 4 years after the implementation of the ACA (2014-2017) should give a picture of the effect of the ACA on breast cancer diagnosis in an underserved population. Methods: A retrospective review of patients diagnosed with invasive and in situ breast cancer at the Breast Diagnostic Center at Jackson Memorial Hospital between 1/1/2007 – 12/31/2017 was approved by the University of Miami IRB. We collected data including: age, stage at diagnosis and type of insurance. In keeping with other similar studies, the year 2013 was excluded since it was a transition period. The trends were compared using ANOVA and chi-squared tests. Results: A total of 2155 patients were analyzed. The absolute number of patients with stage 0 seen every year remained stable (30 per year) throughout the time period. The percentage of patients with Stage 0 increased from 12.5% to 16.02% (p=0.049).Both the absolute number and percentage of patients with stage IV decreased, from 15 to 8 patients per year (6.42% to 4.12% (p=0.016)). The total number of patients diagnosed yearly with breast cancer decreased from 233 to 186 (p= 0.005). The absolute number and percentage of insured patients increased from 75 to 126 patients per year (23.5% to 38.3% (p= 0.02)). Conclusions: Fewer patients were diagnosed with breast cancer at the safety net hospital in Miami-Dade County after the initiation of the ACA. More patients had insurance and there was a stage shift towards lower stage at presentation. Availability of insurance to residents of Miami-Dade County decreased the burden on the safety net hospital and resulted in the diagnosis of lower stage breast cancer. Citation Format: Sandoval Leon AC, Ghanta S, Richardson A, Kesmodel S, Hurley J. The effect of the affordable care act on the initial stage of presentation of breast cancer in a safety-net hospital [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-03.

Cancer stem cells (CSCs) initiate tumors, resist treatment, and seed lethal metastases; yet CSC-specific treatments are lacking. Aggressive, treatment-resistant triple-negative breast cancers (TNBC) exhibit WNT pathway activation and are CSC enriched. Here, we show that Limb-Bud- and-Heart (LBH), a WNT/β-catenin target required for normal mammary stem cell self-renewal, marks poor prognosis, stem-like TNBC, and is a key controller of breast cancer stemness. LBH is specifically expressed in tumor-initiating CD44+CD24-/low breast CSCs. LBH overexpression confers stem-like, metastatic traits on both TNBC and luminal origin, non-TNBC breast cancer cells by activating stem cell transcriptional programs. Importantly, silencing LBH potently suppresses tumor initiation and metastasis in vivo, and sensitizes TNBC cells to chemotherapy. LBH knockout in the MMTV-Wnt1 breast cancer mouse model, furthermore, revealed LBH is required for WNT-driven breast CSC expansion. Our findings identify LBH as an essential CSC driver downstream of WNT, and a new molecular target for anti-cancer stem cell therapy.

Many inflammation-associated diseases, including cancers, increase in women after menopause and with obesity. In contrast to anti-inflammatory actions of 17β-estradiol, we find estrone, which dominates after menopause, is pro-inflammatory. In human mammary adipocytes, cytokine expression increases with obesity, menopause, and cancer. Adipocyte:cancer cell interaction stimulates estrone- and NFκB-dependent pro-inflammatory cytokine upregulation. Estrone- and 17β-estradiol-driven transcriptomes differ. Estrone:ERα stimulates NFκB-mediated cytokine gene induction; 17β-estradiol opposes this. In obese mice, estrone increases and 17β-estradiol relieves inflammation. Estrone drives more rapid ER+ breast cancer growth in vivo. HSD17B14, which converts 17β-estradiol to estrone, associates with poor ER+ breast cancer outcome. Estrone and HSD17B14 upregulate inflammation, ALDH1 activity, and tumorspheres, while 17β-estradiol and HSD17B14 knockdown oppose these. Finally, a high intratumor estrone:17β-estradiol ratio increases tumor-initiating stem cells and ER+ cancer growth in vivo. These findings help explain why postmenopausal ER+ breast cancer increases with obesity, and offer new strategies for prevention and therapy., This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 845104

Sentinel lymph node biopsy provides prognostic information in patients with thick melanoma but is often underutilized. We examine regional lymph node evaluation (RLNE) in patients with thick melanoma and the effect on treatment and overall survival (OS).Patients with clinical T4N0M0 melanoma were selected from the National Cancer Database (2004-2015). Binary logistic regression analysis was used to identify factors associated with RLNE and treatment. Overall survival analysis was performed.A total of 14 286 patients with clinical T4N0M0 melanoma were identified; RLNE was performed in 70.2% of patients, and positive LNs were identified in 27.1%. RLNE was more likely in males (OR:1.44, 95%CI: 1.32-1.56, p .001), and patients treated at academic centers (OR:1.58, 95%CI:1.46-1.71, p .001). Immunotherapy was more commonly used in patients with RLNE (13.9% vs 3.4%, p .001) and was associated with positive LNs (OR:2.50, 95%CI:2.19-2.86, p .001). The 5-year OS for RLNE was 56.9% and for no RLNE was 32.7%. Independent factors associated with better OS were treatment at an academic center (HR:0.88, 95%CI:0.84-0.93, p .001), and immunotherapy use (HR:0.86, 95%CI:0.76-0.96, p .001).The use of RLNE in patients with thick melanoma is important for prognosis and to risk stratify patients for selection of adjuvant therapies and clinical trials.

Management of the axilla in patients with early-stage breast cancer (ESBC) has evolved. Recent trials support less extensive axillary surgery in patients undergoing mastectomy. We examine factors affecting regional lymph node (RLN) surgery and outcomes in patients with ESBC undergoing mastectomy. Women with clinical T1/2 N0 M0 invasive BC who underwent mastectomy with 1–2 positive nodes were selected from the National Cancer Database (2004–2015). Axillary surgery was defined by number of RLNs examined: 1–5 sentinel LN dissection (SLND), and ≥ 10 axillary LND (ALND). Binary logistic regression and survival analyses were performed to assess the association between axillary surgery and clinical characteristics, and overall survival (OS), respectively. 34,243 patients were included: 13,821 SLND (40%) and 20,422 ALND (60%). SLND significantly increased from 21% (2004) to 45% (2015) (p

Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy.Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence.Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8).Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

514 Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. SLYMPHA is a safe and relatively simple method, which decreases incidence of LE dramatically. Our initial study showed an 88% decrease in clinical LE rate after a median follow up of 15 months. The aim of this study was to confirm these results after a longer follow up period. Methods: All patients, undergoing ALND between January 2014 and November 2020 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. The incidence of clinical LE was compared between patients with and without SLYMPHA. Univariate and multivariate analysis were used to assess the role of other factors in the appearance of clinical LE. Results: 580 patients were included in the study. 35% of cohort underwent SLYMPHA. Mean follow-up time was 44 ±31.9 months. Patients, who underwent SLYMPHA, had a significantly lower LE rate (10% vs 26%; p=0.002; OR 0.4 [0.31-0.77]). Diabetes and removing ³22 lymph nodes also correlated with increased LE however this effect disappeared on multivariate analysis. Conclusions: SLYMPHA is a safe and relatively simple method, which continued its efficacy after 4-years follow up. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.[Table: see text]

Simple Summary Primary angiosarcoma of the breast (PAS) and radiation-associated angiosarcoma of the breast (RAAS) are rare sarcomas that affect the inner lining of blood vessels in the breast with incidences of 0.05% and 0.02%, respectively. This study demonstrates that multimodal treatment with neoadjuvant chemotherapy, radiation therapy (in some patients), surgery, and adjuvant chemotherapy may result in optimal clinical outcomes, including prolonged survival. While this study reflects a small sample size, it demonstrates that neoadjuvant chemotherapy, especially when associated with a pathologic complete response, may contribute to these substantial results. Breast angiosarcoma, however, remains a rare disease and prospective, multi-institutional studies need to be performed to overcome the inherent limitations associated with low incidence. Abstract Background: The optimal management of primary angiosarcoma (PAS) and radiation-associated angiosarcoma (RAAS) of the breast remains undefined. Available data show persistently poor survival outcomes following treatment with surgery or chemotherapy alone. The objective of this study was to evaluate long-term outcomes in patients treated with multimodality therapy. Methods: Patients diagnosed with stage I–III PAS or RAAS of the breast were identified from our local tumor registry (2010–2020). Patient demographics, tumor characteristics, and treatment were collected. Primary outcomes were local recurrence (LR), distant recurrence (DR), and median overall survival (OS). A secondary outcome was pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC). Mann–Whitney U, chi-squared, or Fisher exact tests were used to analyze data. Kaplan–Meier curves compared OS for PAS and RAAS. Results: Twenty-two patients met inclusion criteria, including 11 (50%) with RAAS and 11 (50%) with PAS. Compared to PAS patients, RAAS patients were older and had more comorbidities. For RAAS patients, median time from radiation to diagnosis was 6 years (IQR: 5–11). RAAS patients were more likely to have a pCR to NAC (40% vs. 20%, p = 0.72). RAAS patients had a higher LR rate (43% vs. 38%, p = 0.83), and PAS patients were more likely to develop a DR (38% vs. 0%, p = 0.07). Median OS was 81 months in PAS patients and 90 months in RAAS patients (p = 1.00). Discussion: Long-term survival can be achieved in patients with PAS and RAAS who undergo multimodality treatment. NAC can result in pCR. The long-term clinical implications of pCR warrant further investigation.

Results from four major hypofractionated whole-breast radiotherapy (HF-WBRT) trials have demonstrated equivalence in select patients with early-stage breast cancer when compared with conventionally fractionated WBRT (CF-WBRT). Because relatively little data were available on patients receiving neoadjuvant or adjuvant chemotherapy, consensus guidelines published in 2011 did not endorse the use of HF-WBRT in this population. Our goal is to evaluate trends in utilization of HF-WBRT in patients receiving chemotherapy.We retrospectively analyzed data from 2004 to 2013 in the National Cancer DataBase on breast cancer patients treated with HF-WBRT who met the clinical criteria proposed by consensus guidelines (i.e., age 0 years, T1-2N0, and breast-conserving surgery), regardless of receipt of chemotherapy. We employed logistic regression to delineate and compare clinical and demographic factors associated with utilization of HF-WBRT and CF-WBRT.A total of 56,836 women were treated with chemotherapy and WBRT (without regional nodal irradiation) from 2004 to 2013; 9.0% (n = 5093) were treated with HF-WBRT. Utilization of HF-WBRT increased from 4.6% in 2004 to 18.2% in 2013 (odds ratio [OR] 1.21/year; P 0.001). Among patients receiving chemotherapy, factors most dramatically associated with increased odds of receiving HF-WBRT on multivariate analysis were academic facilities (OR 2.07; P 0.001), age 80 (OR 2.58; P 0.001), west region (OR 1.91; P 0.001), and distance 50 miles from cancer reporting facility (OR 1.43; P 0.001). Factors associated with decreased odds of receiving HF-WBRT included white race, income $48,000, lack of private insurance, T2 versus T1, and higher grade (all P 0.02).Despite the absence of consensus guideline recommendations, the use of HF-WBRT in patients receiving chemotherapy has increased fourfold (absolute = 13.6%) over the last decade. Increased utilization of HF-WBRT should result in institutional reports verifying its safety and efficacy.

Occult breast cancer (OBC) is a rare clinical entity. Current surgical management includes axillary lymphadenectomy (ALND) with or without mastectomy. We sought to investigate the role of sentinel lymph node biopsy (SLNB) in patients with OBC treated with neoadjuvant chemotherapy (NAC).Patients with clinical T0N+ breast cancer were selected from the National Cancer Data Base (NCDB, 2004-2014) and compared according to axillary surgical approach, SLNB (≤ 4 LNs) or ALND ( 4 LNs). Primary outcome was overall survival (OS), calculated using Kaplan-Meier methods. Secondary outcome was complete pathological response (pCR).A total of 684 patients with OBC were identified: 470 (68.7%) underwent surgery upfront and 214 (31.3%) received NAC. Of the NAC patients, 34 (15.9%) underwent SLNB and 180 (84.1%) ALND. One hundred and fifty-three (72%) patients received radiotherapy (RT). There was no difference in pCR rates between the ALND and SLNB (34.3% vs 24.5%, respectively p = 0.245). In patients undergoing surgery first, improved OS was observed with ALND compared to SLNB (106.9 vs 85.5 months, p = 0.013); however, no difference in OS was found in patients who received NAC (105.6 vs 111.3 months, p = 0.640). RT improved OS in patients who underwent NAC followed by SLNB (RT, 123 months vs no RT, 64 months, p = 0.034). Of NAC patients who did not undergo RT, ALND had superior survival compared to SLNB (113 vs 64 months, p = 0.013).This is the first comparative analysis assessing the surgical management of the axilla in patients with OBC who underwent NAC. In this population, there was a decrease in survival in patients who underwent SLNB alone; however, with the addition of RT, there was no difference in OS between SLNB and ALND. SLNB plus RT may be considered as an alternative to ALND in patients with OBC who have a good response to NAC.

e12581 Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of LE dramatically. Our initial study showed an 88% decrease in clinical LE rate. In the initial study, we used arm circumference measurement for the diagnosis of LE and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting LE. Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (± 10 L-Dex unit) or >10 L-Dex unit increase above patient’s baseline was considered as LE. The incidence of LE was compared between patients with and without SLYMPHA. Results: 194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ±37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of LE (16% vs 32%; p=0.01; OR 0.4 [0.2-0.8]). Conclusions: SLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery. [Table: see text]

Background: Breast conserving therapy is an established option for early stage breast cancer. Shorter postoperative radiotherapy (RT) regimens have similar efficacy in lower risk breast cancer, including hypofractionated whole breast RT and Accelerated Partial Breast Irradiation (APBI). Despite similar efficacy results for APBI, RAPID trial showed worse cosmetic outcomes for patients receiving APBI compared to whole breast RT. Larger postoperative lumpectomy cavity volumes and the used dose regimen could have had an impact on cosmesis. There are only few published preoperative APBI pilot studies with different dosimetric schemes treating smaller RT target volumes that would potentially translate into less toxicity. Our study is designed to evaluate the safety and feasibility of preoperative ablative RT in patients with early stage breast cancer. An array of ancillary imaging, blood and tissue biomarker collection is also planned in order to study the radiation response in breast cancer. Trial Design: This phase I study uses a modification of the standard 3+3 Phase I design to identify the recommended phase 2 dose of preoperative SABER for treatment of selected breast cancer patients. Participants will be treated with assigned dose level of preoperative SABER, once a day, for 5 fractions given on non-consecutive days, over a period of 2 weeks. The tested dose levels are: Level I=35 Gy (7 Gy x 5), Level II (starting dose)= 40 Gy (8 Gy x 5), Level III=45 Gy (9 Gy x 5), Level IV=50 Gy (10 Gy x 5). Standard partial mastectomy and axillary surgery will be performed 4-6 weeks after preoperative SABER. Adjuvant systemic therapy will be per standard of care. Exploratory studies will be performed pre/post RT and postoperative, including multiparametric breast MRI, biomarkers in blood (CTC’s, SNPs, cytokines, CRP) and tissue (assessment of radiation response, expression of PD-L1, PD1, TILs). Cosmesis and QoL assessment will be performed at scheduled 1, 6, 12, 24 months follow-up. Eligibility criteria: Women, 50 or older, clinical stage T1 unifocal, N0, ER/PR+/HER2 negative, ECOG 0-1, able to undergo MRI with contrast are eligible. Specific Aims: Aim 1. To identify the recommended phase II dose of preoperative SABER; Aims 2.a) to determine the safety, tolerability, Dose Limiting Toxicity (DLT) and toxicity profile of delivering SABER; b) to determine the rate of complete pathological response after preoperative SABER; c) To assess cosmetic results (by MD and patient’s assessment) and QoL after SABER and standard partial mastectomy/axillary surgery. Exploratory aims: a) to determine biomarkers in blood and tissue, and multiparametric MRI radiographic changes and associate them with toxicity and radiation tumor response; b) to assess locoregional recurrence, disease-free survival, and overall survival; c) to assess sentinel lymph node biopsy identification rates after SABER. Statistical Methods: In this novel phase I study, escalation to the next higher dose level will occur only if 0 or only 1 out of 6 patients has DLT. Present accrual and target accrual: A total of 12 to 18 evaluable patients will be enrolled. Expected enrollment period is 3 years and time to complete the study is about 5 years. Open for accrual in 06/2020. Clinical trial information: NCT04360330 Citation Format: Cristiane Takita, Isildinha M. Reis, Radka Stoyanova, John C. Ford, Brian Marples, Jose Net, Monica Yepes, Carmen Gomez, Susan Kesmodel. Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer [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 OT-19-01.

Background:Racial and economic residential segregation remains a problem within the United States (US). Although advances in screening, detection, diagnosis, and treatment have reduced overall breast cancer mortality, well-documented socioeconomic and racial/ethnic survival disparities persist. The objective of this study was to analyze the effect of economic and racial/ethnic residential segregation as measured by the Index of Concentration at the Extremes (ICE) on breast cancer survival in South Florida. Methods:Patients treated at our medical campus with stage I-IV breast cancer from 2005-2017 were identified from our local tumor registry. Census tracts were used as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed: economic (high vs. low), race/ethnicity (non-Hispanic White (NHW) vs. non-Hispanic Black (NHB) and NHW vs. Hispanic) and racialized economic (low-income NHB vs high-income NHW and low-income Hispanics vs. high-income NHW) segregation. ICE captures spatial socioeconmic and racial/ethnic segregation by literally mapping a critical dimension of social inequality not otherwise captured by metrics that characterize areas solely in terms of the proportion of the population at a specified socioeconomic level or identified as belonging to a particular racial/ethnic group. Random effects frailty models were conducted for all patients and then stratified by race/ethnicity controlling for sociodemographics, tumor characteristics, and NCCN-guideline appropriate treatment. Results:The study population included 6,145 breast cancer patients. 52.6% were Hispanic, 26.3% were NHW, and 17.2% were NHB. After controlling for multiple covariates, those living in extreme economically disadvantaged neighborhoods had a statistically significant increased mortality compared to those living in more economically advantaged neighborhoods (HR: 1.58 95%CI: 1.29, 1.92, p Conclusion:This is the first study to evaluate breast cancer survival by ICE, which identifies inequitable associations by conveying extreme concentrations of both economic deprivation/privilege and racial/ethnic segregation. Our study suggests that breast cancer survival disparities is partly influenced by extreme racial/ethnic and economic segregation. Even when accounting for sociodemographics, tumor characteristics, and NCCN-guideline appropriate treatment, survival disparities remained, suggesting potential social and environmental factors impacting survival. To address these disparities, effective interventions are needed that account for the social and environmental contexts in which cancer patients live and are treated. Table 1: Breast Cancer Hazard Ratio by Economic, Racial/Ethnic, and Racialized Economic Residential Segregation Residential SegregationType of Segregation (ICE)QuartileModel 1Model 2Model3HR (95% CI)HR (95% CI)HR (95% CI)Economic SegregationQ11.83 (1.1, 3.03)*1.64 (0.89, 3.02)1.58 (1.29, 1.92)*Economic SegregationQ22.36 (1.48, 3.76)*2.45 (1.38, 4.34)*1.44 (1.16, 1.79)*Economic SegregationQ31.16 (0.72, 1.8)1.08 (0.61, 1.9)1.16 (0.94, 1.44)Economic SegregationQ4111NHB SegregationQ11.6 (0.9, 2.84)1.42 (0.72, 2.82)1.41 (0.96, 2.07)NHB SegregationQ20.92 (0.52, 1.6)0.91 (0.47, 1.77)1 (0.68, 1.48)NHB SegregationQ30.61 (0.29, 1.26)0.85 (0.37, 1.94)0.82 (0.52, 1.31)NHB SegregationQ4111Hispanic SegregationQ11.38 (0.83, 2.28)1.13 (0.61, 2.08)1.36 (1.12, 1.66)*Hispanic SegregationQ279 (0.47, 1.32)0.74 (0.4, 1.38)0.86 (0.67, 1.08)Hispanic SegregationQ30.94 (0.59, 1.49)0.98 (0.57, 1.67)1.05 (0.86, 1.29)Hispanic SegregationQ4111NHB Economic SegregationQ12.68 (1.6, 4.47)*2.02 (1.09, 3.74)2 (1.54, 2.6)*NHB Economic SegregationQ21.85 (1.15, 2.97)*1.39 (0.79, 2.44)1.56 (1.22, 2.02)*NHB Economic SegregationQ31.2 (0.69, 2.07)1.09 (0.58, 2.06)1.19 (0.88, 1.6)NHB Economic SegregationQ4111Hispanic Economic SegregationQ11.91 (1.19, 3.07)*1.45 (0.83, 2.54)1.64 (1.24, 2.15)*Hispanic Economic SegregationQ21.45 (0.8, 2.62)1.06 (0.52, 2.17)1.44 (1.06, 1.96)*Hispanic Economic SegregationQ31.26 (1.73, 2.18)0.95 (0.49, 1.84)1.11 (0.8, 1.54)Hispanic Economic SegregationQ4111Model 1: Adjusted for ICE, race/ethnicity, age, insuranceModel 2: Adjusted for Model 1 covariates plus receptor status, clinical stageModel 3: Adjusted for Model 1 and 2 covariates plus stage appropriate treatmentQ1: Most disadvantaged neighborhoods; Q4: Reference: most advantaged neighborhoods.*p < 0.05 Citation Format: Neha Goel, Kristin N Kelly, Sina Yadegarynia, Seraphina Choi, Susan B Kesmodel, Ashly Westrick. Where you live matters: Impact of economic, racial/ethnic, and racialized economic residential segregation on breast cancer survival [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 SS1-01.

Highlights • Desmoid tumors are rare neoplasms with unpredictable clinical behavior. • Intra-abdominal desmoid tumors are uncommon in pregnancy. • Spontaneous regression of pregnancy-associated desmoid tumors may occur post-partum. • Desmoid tumors may be initially managed with observation alone. • Surgical resection may be required for large, symptomatic tumors., Introduction The clinical behavior of desmoid tumors can be unpredictable, particularly when they arise in the ante-partum or post-partum period. We present a case of an intra-abdominal desmoid tumor that was identified in the ante-partum period, progressed rapidly in the post-partum period, and was subsequently resected. Presentation of case The patient is a 19 year-old female who was found to have a 12 cm intra-abdominal mass on a fetal assessment ultrasound. The decision was made to observe the patient and monitor the mass for growth. However, the mass rapidly grew in the post-partum period. The patient was transferred to our institution after an exploratory laparotomy revealed a large intra-abdominal mass emanating from the small bowel mesentery. The 30 cm × 24 cm × 16 cm mass was successfully resected with negative margins, and the pathologic diagnosis of desmoid tumor was confirmed. The patient had an uncomplicated post-operative course and was discharged on post-operative day 6. Discussion The majority of pregnancy-associated desmoid tumors are in the abdominal wall, arising from the rectus abdominus muscle or from previous Cesarean section scars. These tumors may spontaneously regress in the post-partum period and therefore, patients with these tumors are often observed. Close follow-up is important so that rapid tumor progression, which may lead to unresectability, can be identified and managed appropriately. Conclusion A patient with a rare case of a giant pregnancy-associated, intra-abdominal desmoid tumor that rapidly progressed in the post-partum period and was successfully treated with surgical resection with negative margins.

Background Racial and economic residential segregation remains a problem within the United States (US). Although advances in screening, detection, diagnosis, and treatment have reduced overall breast cancer mortality, well-documented socioeconomic and racial/ethnic survival disparities persist. The objective of this study was to analyze the effect of economic and racial/ethnic residential segregation, as measured by the Index of Concentration at the Extremes (ICE), on breast cancer survival. Methods Patients treated at our medical campus, comprised of a safety-net hospital and an academic cancer center, with stage I-IV breast cancer from 2005-2017 were identified from our tumor registry. Census tracts were used as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed: economic (high vs. low), race/ethnicity (non- Hispanic White (NHW) vs. non-Hispanic Black (NHB) and NHW vs. Hispanic) and racialized economic (low-income NHB vs high-income NHW and low-income Hispanics vs. high-income NHW) segregation. ICE uniquely captures spatial economic and racial/ethnic segregation by mapping social inequality not otherwise captured by evaluating a population of a specific socioeconomic level or belonging to a particular racial/ethnic group. Random effects frailty models were conducted for all patients and then stratified by race/ethnicity controlling for demographics, tumor characteristics, and NCCN-guideline appropriate treatment subtype. Results The study population included 6,145 breast cancer patients. 52.6% were Hispanic, 26.3% were NHW, and 17.2% were NHB. After controlling for multiple covariates, those living in extreme economically disadvantaged neighborhoods had an increased hazard ratio (HR) of death compared to those living in more economically advantaged neighborhoods (HR: 1.58 95% CI: 1.29-1.92, p Citation Format: Neha Goel, Sina Yadegarynia, Kristin N. Kelly, Susan B. Kesmodel, Erin N. Kobetz, Ashly Westrick. Where you live matters: Impact of economic, racial/ethnic, and racialized economic residential segregation on breast cancer survival [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-005.

To evaluate the practice patterns for the use of regional nodal irradiation (RNI) in treatment of elderly women with low volume node-positive breast cancer in the setting of breast conservation surgery (BCS). Women aged 70–89 diagnosed with unilateral, pathologic T1-2N1M0 breast cancer from 2004 to 2013, who underwent BCS and received radiotherapy were identified from the National Cancer Database. In 2011, two major trials were presented that helped define indications for RNI. Patients were dichotomized into “early”, i.e. diagnosed up to 2010, and “late” cohorts. Patient and treatment characteristics were compared between the cohorts and logistic regression used to determine independent factors associated with the receipt of RNI. 7228 women met inclusion criteria; 4330 (59.9%) in early and 2898 (40.1%) in late cohorts. Utilization of RNI increased from 33.9% in early to 42.5% in late cohorts (P ≤ 0.001) and was independent of a general increase in RNI utilization. RNI in the early and late cohorts was not different between the study population and younger women (P > 0.05). RNI utilization increased in both cohorts with increasing number of positive lymph nodes. In the early cohort, RNI was also associated with higher grade, white race and lower income. In the late cohort, RNI increased with the presence of multiple, predefined risk factors. There was an increase in utilization of RNI for elderly patients from 2004 to 2013. In more recent years, the primary factors associated with receipt of RNI were tumor related with declining importance of demographic factors.

Angiosarcoma (AS) of the breast is a rare malignancy most commonly encountered as a secondary malignancy after the treatment of breast cancer with or without adjuvant radiation. The prognosis for secondary AS is poor, with reported five-year overall survival rates ranging from 10%-43%. The establishment of local control is vital to prognosis, yet patients often die with locally progressive disease. Multiple local therapies have been employed including surgery alone, surgery followed by radiation, and concurrent radiation and hyperthermia. Here, we report a case of secondary AS that occurred after breast conserving therapy and adjuvant radiation for ductal carcinoma in situ (DCIS). After initial surgical excision and subsequent local recurrence, our patient was treated with a novel treatment intensification strategy including neoadjuvant, accelerated hyperfractionated radiation with concurrent hyperthermia, followed by total mastectomy and flap reconstruction. The final pathologic evaluation demonstrated a near-complete response to induction thermoradiotherapy.

In the era of combination antiretroviral therapy (ART), there has been a shift in the type of malignancies affecting patients with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS).1 Incidence of the three AIDS-defining malignancies (ADCs) (Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) has significantly declined. Non-AIDS defining malignancies (NADCs) now account for a larger fraction of malignancies compared with the pre-ART era.2,3 In a recent review of the cancer burden in the HIV-infected population in the United States between 1991 and 2005,4 certain NADCs, including breast cancer, had significantly increased in incidence over time. This increase likely reflects the aging of the HIV-infected population as well as an expansion of HIV/AIDS prevalence among women in the U.S. From a global perspective, breast cancer is the most frequently diagnosed malignancy in women, representing 23% of all cancer cases and 14% of cancer deaths.5 It is the leading cause of cancer death in females in the developing world.5 In the past, the incidence of breast cancer has been lower in the AIDS population compared to the general population,6,7 with little variation in incidence by CD4 count or duration of HIV infection.8 However, the incidence of breast cancer in HIV-infected patients is increasing over time and now approaches the general population risk.9 African-Americans account for nearly half of new HIV infections in the U.S. despite comprising a minority of the general U.S. population.10 Eighty-five percent of HIV/AIDS patients are African-American in Baltimore city.11 For some cancers, including breast cancer, inferior treatment outcomes have been reported both for African-Americans12–15 and for HIV-infected patients.16 The impact of cancer on urban, predominantly African-American, HIV-infected patients in the late ART era is understudied. Given these shifts in cancer incidence and the changing face of the HIV epidemic in this country, we sought to better understand the characteristics and outcomes of breast cancer in HIV-infected patients at our large, urban, academic medical center in Baltimore, Maryland.

Background: In the US, the majority of BC is diagnosed by screening XRAY mammography (MM) but up to ∼20% of BC are undetected by MM. The development of reliable, blood-based BC screening test to increase the sensitivity and specificity of currently existing BC screening methods such as MM. Rationale: GP88 is expressed & secreted by BC cells & is not expressed by normal mammary epithelial cells. Two retrospective randomized multi-site trials (one training study & one validating study with about 300 cases each) have demonstrated that elevated GP88 expression in ER+ IDC was statistically correlated with a 4-fold increase in the risk of 5-yr disease recurrence. Multivariate analysis showed that GP88 as a risk predictor was independent from PR expression, tumor size, grade, lymph node status & disease stage. The quantitative GP88 EIA developed to determine the amount of GP88 in biological fluids was developed at A&G. The assay is highly specific for GP88 & both sensitive & linear over a wide dynamic range, i.e. detection of GP88 concentrations from 0.1 to 20ng/ml. A baseline (28.4 ± 5 ng/ml) was established for healthy volunteers (HV). In BC pts a statistically significant increase of serum GP88 was seen for early stage pts (40.7 ± 16 ng/ml; p=0.007). Additionally, a stratification of pts according to their clinical outcomes shows that pts having no evidence of disease (NED) have serum GP88 levels within the range of HV. These data suggest that pts with breast tumors express & secrete high levels of GP88. Objectives: 1. To determine prospectively GP-88 blood levels in HV at average risk of developing BC who are undergoing screening MM & in women with biopsy-confirmed BC. 2. To establish the statistical distribution of GP88 serum levels in these women by baseline BIRAD classification (1-6). 3. To determine if baseline GP88 level is predictive of change in BIRADS classification from baseline to 12-mos follow-up. 4. To determine if baseline GP88 level is predictive of the appearance of BC at 12 mos follow-up in HV who were cancer-free at baseline. Inclusion Criteria: Female, aged >=40 yrs old, presenting to UM Breast Center for screening MM or for diagnostic MM or diagnostic workup and/or biopsy due to BIRADS 0 MM at an outside facility Study procedures: Serum levels of GP88 in subjects with average BC risk factors will be measured prospectively at baseline; 3-6 mos & 6-12 mos. & correlated with BIRADS reading of the screening MM, BIRADS 1 or 2 (benign), BIRADS 3 (short term MM follow-up) & BIRADS 4 or 5 (suspicious and tissue diagnosis needed immediately). GP88 blood level will be correlated with pathologic results of breast biopsies performed on subjects with suspicious BIRADS (4 & 5) MM & final pathologically confirmed diagnosis of BC as BIRADS 6. Statistical Considerations The total number of pts will be 725 & screened up to 1400 subjects. Study is UM IRB approved & just started accruing. Funding is provided by Maryland Industry Partnership Grant (MIPS)& Avon Grant No. 02-2013-018. Contact: Ntait@umm.edu. Citation Format: Katherine HR Tkaczuk, Cristina Campassi, Susan Kesmodel, Emily Bellavance, John Olson, Elizabeth Nichols, Steven J Feigenberg, Binbin Yue, David Hicks, Ginette Serrero. A prospective study of glycoprotein 88 GP-88 blood test in healthy women with Gail model risk

High-grade appendiceal adenocarcinoma is a rare malignancy with propensity for peritoneal metastases (PM). The impact of neoadjuvant chemotherapy on operative cytoreduction (CRS) and intraperitoneal chemotherapy (HIPEC) and patient survival was reviewed. A total of 45 patients with PM from high-grade appendiceal adenocarcinoma were identified from a prospective database. All patients had laparotomy with intent to undergo CRS and HIPEC. Operative parameters, complications, and survival outcomes were analyzed. Of the 45 patients (male: 27, female: 18; median age: 55 years), 26 received neoadjuvant chemotherapy ± bevacizumab. Of the 26, 15 (58 %) had a response based on improvement in imaging, biomarkers, or both and 9 (34 %) had stable disease. The median peritoneal cancer index (PCI) was 27. Also, 30 (67 %) had a completeness of cytoreduction score (CCR) of ≤1 and 37 (82 %) received HIPEC. There were no differences in PCI, CCR score, operative blood loss, or major organ resection between those who received or did not receive neoadjuvant chemotherapy. Operative time was significantly shorter in those who did not receive neoadjuvant chemotherapy. Major complications and length of hospital stay were similar between the groups. The median actuarial overall survival calculated from the date of initial therapeutic intervention was not different in those treated with or without neoadjuvant therapy. Neoadjuvant chemotherapy has marked clinical activity in patients with PM from high-grade appendiceal adenocarcinoma and does not adversely affect operative outcomes. These data support conducting a prospective clinical trial to define the role of neoadjuvant chemotherapy in this clinical setting.

Introduction: The most practical approach to assessment of medication adherence in clinical practice is via patient self-reporting, which can be measured using the 8-item Morisky Medication Adherence Scale (MMAS). The 8-item MMAS was developed from a previously validated 4-item scale by supplementing additional items measuring specific medication-taking behaviors to better capture barriers surrounding adherence behavior and has been determined to have better reliability than 4-item scale. Validated medication adherence surveys such as an 8-item MMAS, are untested in oncology, but have been validated in HTN, HIV, DM and other disorders in the setting of multiple chronic medications. Thus this study will serve as a pilot study of the MMAS in the oncology population. Methods: This is a prospective study conducted at the University of Maryland Greenebaum Cancer Center (UMGCC). The primary objective was to identify the adherence level (high, medium, low) to adjuvant (AI) in early stage (1–3) breast cancer (BC) patients in order to identify predictors of adherence. Subjects were stratified according to duration of therapy with AI (≤ 2 yrs or >2 yrs) at the time of the survey. The secondary objective was to identify baseline predictors for adherence. Patients received a maximum 8 points for maximum adherence to medication treatment or high adherence, 6–7 points for medium adherence and < 6 points for low adherence. Eligibility: Adult females, postmenopausal, signed consent, hormone receptor-positive BC (ER and/or PR >=1%), pathologically confirmed Stage 1–3 BC, completed surgery, adjuvant chemotherapy, and/or radiation therapy, and were recommended by their medical oncologist to take adjuvant AI for 5 years. Pts received a prescription for adjuvant AIs (anastrozole, letrozole or exemestane) after completion of adjuvant chemotherapy. Results: Patient characteristics: 73 BC pts were sequentially accrued so far at the UMGCC and filled out the self-reported questionnaire; Causcasian-62%, African American (AAF)-37%, Asian-1%, median age at diagnosis-54 (range33-84); stage 1–36%, stage 2–47%, stage 3–17%; mastectomy-61%; lumpectomy-39%; local radiation therapy 62%; ER+ 95%; PR+ 78%, HER2+ 17 %; tumor type ductal-75%; lobular-20%; mixed ductal/lobular-5%; tumor grade-1–46%, 2–41%,3–12%; adjuvant chemotherapy- 63%. Educational level- N/A- 3%, Conclusions: Overall adherence to AI treatment measured by MMAS was High in 50.7%, Medium in 35.6% and Low in 13.7% pts; there was no difference in adherence by duration of treatment with AI ≤ 2 vs. > 2 years. Univariable regression models for continuous predictors and rxc contingency tables for categorical ones revealed that the adherence to AI therapy is not affected by age, marital status, education, prior cancer therapy, tumor stage, and concurrent medication. However, there was a trend for better adherence to AI therapy in Caucasian women vs. AAF (p = 0.013). The study is ongoing. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-05.

Purpose Reduction mammoplasty (RM) during breast-conserving surgery is popular among women with large-volume breasts because it reduces redundant breast folds and may decrease skin-related morbidity from radiation therapy. However, RM may obscure the lumpectomy cavity (LC) and pose challenges to administering an LC boost, potentially affecting local control. We investigated the impact of RM on acute side effects and use of LC boosts. Methods and materials The records of 645 consecutive women treated with whole-breast irradiation at an urban university and 2 community practices between January 2012 and December 2014 were reviewed on an institutional review board–approved study. The primary endpoint was grade ≥3 radiation dermatitis; the secondary endpoint was use of LC boost. Student 2-sample t tests, Pearson χ2 tests, Fisher exact tests, and univariate and multivariable logistic regression analyses were performed. Results Forty-three (7%) RMs were performed in 650 treated breasts. No significant differences in grade 3 toxicities were identified among RM and non-RM patients. LC boost was delivered to 474 breasts. Fewer (16/43) RM patients received LC boosts compared with non-RM patients (458/607), P = .0001. RM patients were more likely to have neoadjuvant chemotherapy, stage III or multifocal disease, higher body mass index, larger planning treatment volumes, and conventional fractionation (P Conclusions RM was associated with decreased use of LC boost without significant differences in acute toxicities. Further investigation to delineate LCs in patients undergoing RM or identify alternative strategies for delivering LC dose is needed.

To assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy.This was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 (3 cm), N0 tumors. Patients received 38.5 Gy in 3.85-Gy fractions delivered twice daily. Surgery was performed21 days after radiation therapy. Adjuvant therapy was given as per standard of care.Twenty-seven patients completed treatment. With a median follow-up of 3.6 years (range, 0.5-5 years), there have been no local or regional failures. A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment.Preoperative 3-dimensional conformal radiation therapy-APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm.