ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

OBJECTIVE: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. BACKGROUND: ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. METHODS: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity [nuclear factor-κB ( NF-kB ), activator protein 1 ( AP-1 )], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein ( CREB )], and protective cellular responses [interferon-regulatory factor ( IRF ) and signal transducer and activator of transcription ( STAT )]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. RESULTS: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB , activator protein 1, down-regulated IRF , and signal transducer and activator of transcription) and SNS activation (up-regulated CREB ). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF . These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. CONCLUSIONS: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Does structural racism impact receipt of NCCN guideline-concordant breast cancer treatment?

PURPOSE: Disparities in breast cancer survival remain a challenge. We aimed to analyze the effect of structural racism, as measured by the Index of Concentration at the Extremes (ICE), on receipt of National Cancer Center Network (NCCN) guideline-concordant breast cancer treatment. METHODS: We identified patients treated at two institutions from 2005 to 2017 with stage I-IV breast cancer. Census tracts served as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed to create 5 models, controlling for economic segregation, non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models were used to determine the association between individual and neighborhood-level characteristics on receipt of NCCN guideline-concordant breast cancer treatment. RESULTS: 5173 patients were included: 55.2% were Hispanic, 27.5% were NHW, and 17.3% were NHB. Regardless of economic or residential segregation, a NHB patient was less likely to receive appropriate treatment [(OR)Model1 0.58 (0.45-0.74); ORModel2 0.59 (0.46-0.78); ORModel3 0.62 (0.47-0.81); ORModel4 0.53 (0.40-0.69); ORModel5 0.59(0.46-0.76); p < 0.05]. CONCLUSION: To our knowledge, this is the first analysis assessing receipt of NCCN guideline-concordant treatment by ICE, a validated measure for structural racism. While much literature emphasizes neighborhood-level barriers to treatment, our results demonstrate that compared to NHW patients, NHB patients are less likely to receive NCCN guideline-concordant breast cancer treatment, independent of economic or residential segregation. Our study suggests that there are potential unaccounted individual or neighborhood barriers to receipt of appropriate care that go beyond economic or residential segregation.

Associations Between Neighborhood-Level Income and Triple-Negative Breast Cancer in a Majority-Minority Population.

BACKGROUND: Previous studies on disparities in triple-negative breast cancer (TNBC) focus on race/ethnicity, with few exploring the impact of contextual factors such as neighborhood-level income. This study evaluates the effect of neighborhood-level income on disparities in TNBC among a racially and ethnically diverse cohort, after accounting for granular individual-level risk factors of TNBC. PATIENTS AND METHODS: Patients with stage I-IV breast cancer from 2005 to 2017 were identified from our local tumor registry. The primary outcome was diagnosis of TNBC. Using 5-years estimates from the American Community Survey, we obtained median household income for each census tract which was categorized into quartiles. Mixed effects logistic regression was conducted and stratified by race and ethnicity, controlling for individual-level sociodemographic, comorbidities, and tumor characteristics. RESULTS: Among 5377 breast cancer registry patients, 16.5% were diagnosed with TNBC. The majority were Hispanic (50.1%) followed by non-Hispanic Black (NHB) (28.0%). After controlling for individual-level covariables including race and ethnicity, comorbidities, and tumor characteristics, women from low-income neighborhoods had increased odds of TNBC compared with other breast cancer subtypes, compared with those in high-income neighborhoods [odds ratio (OR) 1.33; 95% confidence interval (CI) 1.04, 1.70, p < 0.001]. In stratified analyses, NHB patients from low-income neighborhoods had two times the odds of TNBC diagnosis compared with those from high-income neighborhoods (OR 2.11; 95% CI 1.02, 4.37). CONCLUSION: We found that living in a low-income neighborhood is associated with an increased odds of TNBC independent of granular individual-level TNBC risk factors, particularly NHB race. More striking, NHB living in low-income neighborhoods had increased odds of TNBC compared with NHB living in high-income neighborhoods. Our results suggest potential unaccounted gene-environment and/or social (api)genomic interactions between neighborhood-level income and TNBC subtype development.

A Multi-institutional Analysis of Factors Influencing the Rate of Positive MRI Biopsy Among Women with Early-Stage Breast Cancer.

BACKGROUND: The use of preoperative magnetic resonance imaging (MRI) for early-stage breast cancer (ESBC) is increasing, but its utility in detecting additional malignancy is unclear and delays surgical management (Jatoi and Benson in Future Oncol 9:347-353, 2013. https://doi.org/10.2217/fon.12.186 , Bleicher et al. J Am Coll Surg 209:180-187, 2009. https://doi.org/10.1016/j.jamcollsurg.2009.04.010 , Borowsky et al. J Surg Res 280:114-122, 2022. https://doi.org/10.1016/j.jss.2022.06.066 ). The present study sought to identify ESBC patients most likely to benefit from preoperative MRI by assessing the positive predictive values (PPVs) of ipsilateral and contralateral biopsies. METHODS: A retrospective cohort study included patients with cTis-T2N0-N1 breast cancer from two institutions during 2016-2021. A "positive" biopsy result was defined as additional cancer (PositiveCancer) or cancer with histology often excised (PositiveSurg). The PPV of MRI biopsies was calculated with respect to age, family history, breast density, and histology. Uni- and multivariate logistic regression determined whether combinations of age younger than 50 years, dense breasts, family history, and pure ductal carcinoma in situ (DCIS) histology led to higher biopsy yield. RESULTS: Of the included patients, 447 received preoperative MRI and 131 underwent 149 MRI-guided biopsies (96 ipsilateral, 53 contralateral [18 bilateral]). PositiveCancer for ipsilateral biopsy was 54.2%, and PositiveCancer for contralateral biopsy was 17.0%. PositiveSurg for ipsilateral biopsy was 62.5%, and PositiveSurg for contralateral biopsy was 24.5%. Among the contralateral MRI biopsies, patients younger than 50 years were less likely to have PositiveSurg (odds ratio, 0.02; 95% confidence interval, 0.00-0.84; p = 0.041). The combinations of age, density, family history, and histology did not lead to a higher biopsy yield. CONCLUSION: Historically accepted factors for recommending preoperative MRI did not appear to confer a higher MRI biopsy yield. To prevent delays to surgical management, MRI should be carefully selected for individual patients most likely to benefit from additional imaging.

Omission of Completion Lymph Node Dissection in Sentinel Node Biopsy Positive Head and Neck Cutaneous Melanoma Patients.

BACKGROUND: Recent studies evaluating patients with a positive sentinel lymph node biopsy (SLNB+) show no melanoma-specific survival difference between patients undergoing lymph node basin surveillance and completion lymph node dissection (CLND). This has been broadly applied, despite underrepresentation of head and neck (HN) cutaneous melanoma patients. We evaluated whether this was upheld in the HN melanoma cohort. METHODS: Patients with HN melanoma with a SLNB+ were selected from the National Cancer Database (NCDB) from 2012 to 2019. Overall survival (OS) of patients who underwent SLNB only versus SLNB + CLND were compared. Subgroup analyses were performed based on pathologic N (pN) and receipt of immunotherapy. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were calculated. RESULTS: Analysis of 634 patients with multivariable Cox regression showed no difference in OS in SLNB only versus SLNB + CLND cohorts (hazard ratio [HR] 1.13; 95% confidence interval [CI] 0.71-1.81; p = 0.610). Charlson-Deyo score (CDS) 1 versus 0 (HR 1.70; 95% CI 1.10-2.63; p = 0.016), pN2+ versus pN1 (HR 1.74; 95% CI 1.23-2.45; p = 0.002), and lymphovascular invasion (LVI) versus no (HR 2.07; 95% CI 1.34-3.19; p = 0.001) were associated with worse prognosis. Subgroup analysis by pN showed no OS benefit for CLND in either pN1 (HR 1.04; 95% CI 0.51-2.10; p = 0.922) or pN2+ (HR 1.31; 95% CI 0.67-2.57; p = 0.427) patients or in patients who received immunotherapy (HR 1.32; 95% CI 0.54-3.22; p = 0.549). CONCLUSIONS: This study of SLNB + HN melanoma patients showed no OS difference in SLNB only versus SLNB + CLND. Further studies need to be performed to better define the role of CLND.

Predictors of initial engagement with an asynchronous cognitive behavioral stress management website among older women with nonmetastatic breast cancer.

PURPOSE: Digital interventions, like websites, offer greater access to psychosocial treatments; however, engagement is often suboptimal. Initial use may be a target to "hook" participants. Few studies examine engagement with cognitive behavioral stress management (CBSM). We tested predictors of engagement in the first week of using a CBSM website among women with breast cancer (BC). METHODS: Older women (≥ 50 years) with nonmetastatic BC enrolled in an on-going trial (8/2016-4/2022, #NCT03955991) and were randomized to receive 10 synchronous, virtual CBSM group sessions immediately (n = 41) or after a 6-month waitlist (n = 34). All received simultaneous access to an asynchronous website, where supplemental videos and resources were released weekly. Engagement was tracked via breadth (features used) and depth (clicks within content). Multilevel modeling tested predictors of engagement (i.e., time, condition, age, daily stress, depression, race, ethnicity, disease stage). RESULTS: Breadth decreased over the first week of CBSM (b = -0.93, p < .01), and women with more advanced stage disease engaged with more breadth (b = 0.52, p < .01) and depth (b = 14.06, p < .01) than women with earlier stage disease. Non-Hispanic (b = -0.59, p = .03) and White (b = -0.97, p < .01) women engaged with more features. Cancer stage and intervention timing interacted. Women with more advanced cancer stage who received CBSM later engaged with the most depth (b = -11.73, p = .04). All other characteristics did not predict engagement. CONCLUSIONS: Disease stage, race, ethnicity, and intervention timing predicted engagement with a CBSM website in older BC patients. IMPLICATIONS FOR CANCER SURVIVORS: Delivering CBSM later in cancer treatment may mitigate competing demands. Fostering greater engagement in racial/ethnic minorities is needed.

Translational Epidemiology: An Integrative Approach to Determine the Interplay Between Genetic Ancestry and Neighborhood Socioeconomic Status on Triple Negative Breast Cancer.

OBJECTIVE: To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Structural Racism and Breast Cancer-specific Survival: Impact of Economic and Racial Residential Segregation.

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 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 to IV breast cancer patients treated at our institution from 2005 to 2017. Our exposures include index of concentration at the extremes, 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 [hazard ratios (HR): 1.56, 95% confidence interval (CI): 1.23-2.00]. Patients living in low-income non-Hispanic Black 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 non-Hispanic Black 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.

Impact of genomic assays on treatment and outcomes in locally advanced breast cancer.

PURPOSE: Genomic profiling in early-stage breast cancer provides prognostic and predictive information. Genomic profiling assays have not been validated in locally advanced breast cancer (LABC). We examined a large cancer registry to evaluate genomic profiling in LABC and its effect on treatment decisions and survival. METHODS: Females with ER+/HER2- LABC who did not receive neoadjuvant therapy were selected from the National Cancer Database 2004-2017. We compared characteristics between patients with and without genomic profiling and with low genomic risk, 21-gene recurrence score ≤ 25 or low-risk 70-gene signature, treated with endocrine therapy ± chemotherapy. Propensity score methods were utilized to account for covariates that may have predicted treatment. Univariable and multivariable survival analyses were performed. RESULTS: Of 18,437 patients with LABC, 1258 (7%) had genomic profiling and 1022 (81%) had low genomic risk results. 562 patients (55%) with low genomic risk received chemotherapy and endocrine therapy (chemoendocrine). Patients who received chemoendocrine therapy were younger, had fewer comorbidities, presented with higher stage disease, had higher grade tumors, more frequently had partial mastectomy, and more often received radiation than those who received endocrine therapy alone. On multivariable analysis, endocrine therapy alone was associated with worse OS compared to chemoendocrine therapy (HR 1.77, 95% CI 1.13-2.78, p = 0.013). CONCLUSION: In women with LABC and low genomic risk, endocrine therapy alone was associated with worse OS compared to chemoendocrine therapy. This suggests that genomic profiling is not predictive in LABC. Accordingly, genomic profiling should not be routinely utilized to make adjuvant treatment decisions in LABC in the absence of further data which shows a benefit.

Stalled at the intersection: insurance status and disparities in post-mastectomy breast reconstruction.

PURPOSE: Post-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. METHODS: Data were collected on all patients who underwent mastectomy for breast cancer from 2011 to 2019 in a private academic center and an adjacent public safety-net hospital served by the 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. RESULTS: Of 1554 patients undergoing mastectomy for breast cancer, 753 (48.5%) underwent PMBR, of which 592 (79.9%) were privately insured, 50 (6.7%) Medicare, 68 (9.2%) Medicaid, and 31 (4.2%) uninsured. Multivariable logistic regression showed a significantly higher likelihood of not undergoing PMBR for uninsured (OR 6.0, 95% CI 3.7-9.8; p < 0.0001), Medicare (OR 1.9, (95% CI 1.2-3.0; p = 0.006), and Medicaid (OR 1.5, 95% CI 1.0-2.3; p = 0.04) patients compared with privately insured patients. Age, stage, race and ethnicity, and hospital type confounded this relationship. CONCLUSION: Patients without health insurance have dramatically reduced access to PMBR compared to those with private insurance. Expanding access to this important procedure is essential to achieve greater health equity for breast cancer patients.

Axillary Response to Neoadjuvant Therapy in Node-Positive, Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: Predictors and Oncologic Outcomes.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Association of Preoperative Magnetic Resonance Imaging (MRI) With Surgical Management in Patients With Early-Stage Breast Cancer.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Racial and Ethnic Disparities in Breast Cancer Survival: Emergence of a Clinically Distinct Hispanic Black Population.

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.

Overcoming disparities: Multidisciplinary breast cancer care at a public safety net hospital.

PURPOSE: 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. METHODS: 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 < 0.1 were included in the Cox proportional hazards model. RESULTS: 2709 breast cancer patients were evaluated from 2005 to 2017. The patient demographics, tumor characteristics, and treatments received were analyzed. Five-year OS was 78.4% (93.9%, 87.4%, 70.9%, and 23.5% for stages I, II, III, and IV, respectively). On multivariable analysis, higher stage, age > 70 years, higher grade, and non-Hispanic ethnicity were associated with worse OS. Patients receiving surgery (HR = 0.33, p < 0.0001), chemotherapy (HR = 0.71, p = 0.006), and endocrine therapy (HR = 0.61, p < 0.0001) had better OS compared to those who did not receive these treatments. CONCLUSION: Despite serving a vulnerable minority population that is largely poor, uninsured, and presenting with more advanced disease, OS at our SNH approaches national averages. This novel finding indicates that in the setting of multidisciplinary cancer care and with appropriate initiation of treatment, SNHs can overcome socioeconomic barriers to achieve equitable outcomes in breast cancer care.

Axillary response rates to neoadjuvant chemotherapy in breast cancer patients with advanced nodal disease.

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.

Surgical Management of the Axilla in Patients with Occult Breast Cancer (cT0 N+) After Neoadjuvant Chemotherapy.

BACKGROUND: 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). METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Extent of regional lymph node surgery and impact on outcomes in patients with early-stage breast cancer and limited axillary disease undergoing mastectomy.

PURPOSE: 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. METHODS: 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. RESULTS: 34,243 patients were included: 13,821 SLND (40%) and 20,422 ALND (60%). SLND significantly increased from 21% (2004) to 45% (2015) (p < .001). Independent factors associated with SLND were treatment year, non-Academic centers, geographic region, tumor histology, and postmastectomy radiotherapy (PMRT). Multivariable survival analysis showed that ALND was associated with better OS (HR 0.78, 95% CI 0.72-0.83, p < .001) relative to SLND; however, there was no difference in patients with LN micrometastases treated without RT (HR 0.87, 95% CI 0.73-1.05, p = .153) or patients receiving PMRT (HR 0.92, 95% CI 0.76-1.13, p = .433). CONCLUSIONS: SLND has significantly increased in patients undergoing mastectomy with limited axillary disease and is influenced by patient, tumor, and treatment factors. Survival outcomes did not differ by axillary treatment for patients with LN micrometastases treated without RT or patients who received PMRT. SLND may be considered in select patients with ESBC and limited axillary disease undergoing mastectomy.

Utilization of hypofractionated whole-breast radiation therapy in patients receiving chemotherapy: a National Cancer Database analysis.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.