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Background: Despite numerous studies on racial/ethnic disparities among patients with breast cancer, there is a paucity of literature evaluating racial/ethnic differences in 21-gene recurrence score (RS) and survival differences stratified by RS risk categories. We thus performed an observational cohort study to examine racial/ethnic disparities in the context of RS., Methods: The National Cancer Database (NCDB) was queried for female patients diagnosed between 2006 and 2018 with estrogen receptor (ER)-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy and had RS data available. Logistic multivariable analysis (MVA) was built to evaluate variables associated with RS ≥ 26. Cox MVA was used to evaluate OS. Subgroup analyses were performed to compare the magnitude of racial/ethnic differences stratified by RS. P values less than 0.017 were considered statistically significant based on Bonferroni correction., Results: A total of 140,133 women were included for analysis. Of these, 115,651 (82.5%), 8,213 (5.9%), 10,814 (7.7%), and 5,455 (3.9%) were NHW, Hispanic, Black, and API women, respectively. Median (IQR) follow up was 66.2 months (48.0-89.8). Logistic MVA showed that, compared with NHW women, Black women were associated with higher RS (≥ 26 vs < 26: adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12-1.26, p < 0.001), while HW (aOR 0.93, 95% CI 0.86-1.00, p = 0.04) and API women (aOR 1.03, 95% CI 0.95-1.13, p = 0.45) were not. Cox MVA showed that, compared with NHW women, Black women had worse OS (adjusted hazards ratio [aHR] 1.10, 95% CI 1.02-1.19, p = 0.012), while HW (aHR 0.85, 95% CI 0.77-0.94, p = 0.001) and API (aHR 0.66, 95% CI 0.56-0.77, p < 0.001) women had better OS. In subgroup analysis, similar findings were noted among those with RS < 26, while only API women were associated with improved OS among others with RS ≥ 26., Conclusion: To our knowledge, this is the largest study using nationwide oncology database to suggest that Black women were associated with higher RS, while HW and API women were not. It also suggested that Black women were associated with worse OS among those with RS < 26, while API women were associated with improved OS regardless of RS when compared to NHW women., (© 2024. The Author(s).)

Purpose: The potential disparities in palliative care delivery for underrepresented minorities with breast cancer are not well known. We sought to determine whether race and ethnicity impact the receipt of palliative care for patients with metastatic breast cancer (MBC)., Methods: We retrospectively reviewed the National Cancer Database for female patients diagnosed with stage IV breast cancer between 2010 and 2017 who received palliative care following diagnosis of MBC to assess the proportion of patients who received palliative care, including non-curative-intent local-regional or systemic therapy. Multivariable logistic regression analysis was performed to identify variables associated with receiving palliative care., Results: 60,685 patients were diagnosed with de novo MBC. Of these, only 21.4% (n = 12,963) received a palliative care service. Overall, there was a positive trend in palliative care receipt from 18.2% in 2010 to 23.0% in 2017 (P < 0.001), which persisted when stratified by race and ethnicity. Relative to non-Hispanic White women, Asian/Pacific Islander women (aOR 0.80, 95% CI 0.71-0.90, P < 0.001), Hispanic women (adjusted odds ratio [aOR] 0.69, 95% CI 0.63-0.76, P < 0.001), and non-Hispanic Black women (aOR 0.94, 95% CI 0.88-0.99, P = 0.03) were less likely to receive palliative care., Conclusions: Fewer than 25% of women with MBC received palliative care between 2010 and 2017. While palliative care has significantly increased for all racial/ethnic groups, Hispanic White, Black, and Asian/Pacific Islander women with MBC still receive significantly less palliative care than non-Hispanic White women. Further research is needed to identify the socioeconomic and cultural barriers to palliative care utilization., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP., Methods: Based on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women's Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases., Results: We identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in β-adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women and did not differ by tumor estrogen receptor (ER) status., Conclusions: In a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the β-adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues, which might be relevant to cancer development and progression., (© 2023. The Author(s).)

Background: Progesterone receptor (PR)-negative tumors have been shown to have worse prognosis and were underrepresented in recent trials on patients with estrogen receptor (ER)-positive breast cancer. The role of PR-negative status in the context of 21-gene recurrence score (RS) and nodal staging remains unclear., Methods: The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer. Logistic and Cox multivariable analyses (MVA) were performed to identify association of PR status with high RS (> 25) and overall survival (OS), respectively., Results: Among 143,828 women, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23-17.13). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10-1.31). There was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the chemotherapy benefit was greater among those with pN1a, PR-negative tumors than pN1a, PR-positive tumors (PR-positive: aHR 0.57, 95% CI 0.47-0.67; PR-negative: aHR 0.31, 95% CI 0.20-0.47). It was comparable among those with pN0 tumors regardless of PR status (PR-positive: aHR 0.74, 95% CI 0.66-0.82; PR-negative: aHR 0.63, 95% CI 0.51-0.77)., Conclusion: PR-negative tumors were independently correlated with higher RS and were associated with greater OS benefits from chemotherapy for pN1a tumors, but not pN0 tumors., (© 2023. The Author(s).)

Objectives: The population of individuals who identify as transgender (TG) is increasing in the United States, yet disparities in cancer screening services are widening. It is imperative that interpersonal and systemic barriers to cancer care are identified and removed for this vulnerable population. Our study sought to examine the difference in self-reported breast and cervical cancer screening rates between TG and cisgender (CG) people., Materials and Methods: Cross-sectional data from the 2014 to 2016 and 2018 Behavioral Risk Factor Surveillance System (BRFSS) was obtained on individuals who identified as CG or TG (male-to-female [MTF] and female-to-male [FTM]), including their responses to questions regarding breast and cervical screening history and their primary care access and associated barriers., Results: Compared with the CG population, TG participants were less likely to adhere to or have undergone breast (FTM: odds ratio [OR] 0.47 and 0.32; MTF: OR 0.04 and 0.02, respectively; all P<0.001) and cervical cancer (FTM: OR 0.42 and 0.26, respectively; all P<0.001) screening. They were also less likely to have a primary care physician (FTM: OR 0.79; MTF: OR 0.58; all P<0.001) and less likely to seek primary care within a year owing to medical costs (FTM: OR 1.44; MTF: OR 1.36; all P<0.001)., Conclusions: Disparities exist in the uptake of routine cancer screening in the TG population despite their increased risk for breast and cervical cancer. Interventions are urgently needed to mitigate delays to cancer screening, close gaps in provider and patient knowledge about cancer screening, and improve health care experiences of gender minorities in the United States., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the association of various gene expression assays with pathologic complete response (pCR) in the setting of neoadjuvant chemotherapy among patients with breast cancer METHODS: The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with stage I-III breast cancer who underwent neoadjuvant chemotherapy and either 21-gene recurrence score (RS) or 70-gene signature (GS). Logistic multivariable analysis (MVA) was performed to identify variables associated with pCR., Results: A total of 3009 patients met our inclusion criteria. The median follow up was 48.0 months (interquartile range 32.2-66.7 months). On logistic MVA for all patients, those with a high risk from GS (adjusted odds ratio [aOR] 3.23, 95% confidence interval [CI] 1.49-8.13, p = 0.006) or with RS ≥ 31 (aOR 1.99, 95% CI 1.41-2.82, p < 0.001) were more likely to have pCR. When compared to RS ≥ 31, a high risk from GS was not associated with pCR (aOR 1.01, 95% CI 0.75-1.37, p = 0.94). However, among those with favorable hormone receptor status, similar findings were noted, except that those with a high risk group from GS were less likely to have pCR compared to those with RS ≥ 31 (aOR 0.65, 95% CI 0.43-0.96, p = 0.03). When analyses were repeated using a high risk group from RS defined as RS ≥ 26 among those with favorable hormone receptor status, RS ≥ 26 was not associated with pCR when compared to the high risk from GS (aOR 0.74, 0.50-1.07, p = 0.12)., Conclusions: To our knowledge, this is the largest study using a nationwide oncology database suggesting that high recurrence risk groups in both assays were associated with pCR. Among those with favorable hormone receptor status, RS ≥ 31 may be a more selective prognostic marker for pCR., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Among patients with early-stage breast cancer and a high 21-gene recurrence score (RS) ≥ 26, it remains unclear on whether those with RS 26-30 would benefit from chemotherapy with a comparable magnitude as those with RS > 30. In addition, RS > 30 as an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) compared to RS 26-30 also remains unclear. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed between 2010 and 2013 with hormone receptor-positive, HER2-negative, and T1-2N0 breast cancer with a RS ≥ 26. Primary end points were OS and BCSS, evaluated by using Kaplan-Meier method, log-rank test, and Cox multivariable analysis. Subgroups of RS 26-30 and RS > 30 were examined using propensity score matching to address selection bias. Among 5054 patients who met the inclusion criteria, adjuvant chemotherapy was associated with improved OS (HR 0.66, 95% CI 0.53-0.83, P < .001) and BCSS (HR 0.61, 95% CI 0.45-0.83, P = .001). In the subgroup of 943 matched pairs of patients with RS 26-30, the addition of chemotherapy remained statistically significant (OS: HR 0.52, 95% CI 0.34-0.79, P = .003; BCSS: HR 0.42, 95% CI 0.22-0.81, P = .009). Among 1194 matched pairs who underwent adjuvant chemotherapy, those with RS > 30 had worse outcomes than others with RS 26-30 (OS: HR 1.68, 95% CI 1.17-2.42, P = .005; BCSS: HR 1.92, 95% CI 1.17-3.15, P = .01). Our study builds on prior literature using a population-based database to suggest the association of adjuvant chemotherapy with improved survival among those with RS 26-30 and worse mortality associated with RS > 30 compared to RS 26-30., (© 2020 Wiley Periodicals LLC.)

The proportion of breast cancer cases among elderly (over 70 years old) patients is expected to rise from 24% to 35% by the next decade. However, elderly patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative, node-negative breast cancer were underrepresented in prior landmark prospective trials. Using a nationwide hospital cancer registry, our study of 12 004 elderly patients demonstrates that adjuvant chemotherapy was not associated with overall survival (hazards ratio [HR] 0.96, 95% confidence interval [CI] 0.77-1.20, P = .71). Given the toxicities associated with systemic treatment, cautious recommendation or the omission of chemotherapy may be considered in select elderly patients., (© 2020 Wiley Periodicals LLC.)

Breast carcinomas are histologically diverse and have distinct prognostic significance. Early-stage breast cancers with favorable histopathologic features are managed comprehensively including adjuvant endocrine therapy at the discretion of clinicians. Using a de-identified large national cancer registry, we evaluated the overall survival benefit of endocrine therapy in patients diagnosed with HR-positive, HER2-negative, pT1-2N0 (tumor size < 3 cm), non-high-grade breast cancer with favorable histologies including tubular, mucinous, and cribriform types. On propensity score matching of 2482 matched pairs, the addition of adjuvant endocrine therapy was associated with improved OS (hazard ratio: 0.81; 95% CI: 0.67-0.98, P = .03). Our findings suggest a role for endocrine therapy in future risk mitigation for favorable histologies but should be balanced with the implications of prolonged utilization., (© 2020 Wiley Periodicals LLC.)

Patterns of care, utilization, and predictors of adjuvant radiation therapy (RT) for phyllodes tumors of the breast were retrospectively analyzed using the National Cancer Database. We identified 3080 patients; 53.4% received lumpectomy and 35.9% mastectomy. 25.9% of patients had lymph node sampling or dissection. 23.2% received adjuvant RT, which doubled in utilization over a decade. Predictors of RT were younger age, fewer comorbidities, less favorable pathologic features, and treatment at academic centers. There was no association between RT and overall survival (AHR 1.21, 95% CI 0.97-1.53, P = .097). Despite national guidelines recommending against nodal sampling or RT, it remains prevalent. Further research on indications for adjuvant radiation for phyllodes is needed., (© 2020 Wiley Periodicals, Inc.)

The aim of the present study was to investigate the correlation of enhancer of Zeste homolog 2 ( EZH2 ) and SET and MYND domain containing 3 ( SMYD3 ) gene polymorphisms with breast cancer susceptibility and prognosis. A total of 712 patients with breast cancer and 783 healthy individuals were selected. Normal breast epithelial cells MCF-10A and breast cancer cells MCF-7, MDA-MB-231, T47D, and Bcap-37 were cultured. Polymerase chain reaction (PCR)-restriction fragment length polymorphism method was applied for genotyping. Reverse-transcription quantitative PCR (RT-qPCR) and Western blotting were used to examine EZH2 and SMYD3 expression in breast cancer tissues and cells. The risk factors and prognostic factors for breast cancer were estimated. The C allele of EZH2 rs12670401 (odds ratio (OR) =1.255, 95% confidence interval (95% CI): 1.085-1.452), T allele of EZH2 rs6464926 (OR =1.240, 95% CI: 1.071-1.435), and three alleles of SMYD3 variable number of tandem repeats (VNTRs) (OR =1.305, 95% CI: 1.097-1.552) could increase susceptibility to breast cancer. Combined genotypes of EZH2 rs12670401 (TC + CC) and EZH2 rs6464926 (CT + TT) were associated with breast cancer susceptibility. Breast cancer tissues had higher EZH2 and SMYD3 expression. EZH2 rs12670401, EZH2 rs6464926, age of menarche, and menopausal status were associated with breast cancer susceptibility. Patients with TT genotype of EZH2 rs12670401 or with CC genotype of EZH2 rs6464926 had higher overall survival (OS). EZH2 rs12670401, EZH2 rs6464926, and clinical staging were independent prognostic factors for breast cancer. SMYD3 VNTR polymorphism exhibited no association with susceptibility and prognosis. EZH2 rs12670401 and rs6464926 polymorphisms, EZH2 and SMYD3 expression, clinical staging, lymph node metastasis, human epidermal growth factor receptor-2 (HER2) status, and metastasis may be correlated with breast cancer susceptibility and prognosis., (© 2018 The Author(s).)