Triple Negative Breast Cancer: Molecular Subtype-Specific Immune Landscapes with Therapeutic Implications.

Triple Negative Breast Cancer (TNBC) is characterized by distinct molecular subtypes with unique biological and clinical features. This systematic review aimed to identify articles examining the differences in the tumor immune microenvironment (TIME) across different TNBC molecular subtypes. Six studies meeting inclusion criteria were analyzed, utilizing gene expression profiling and bioinformatic analyses to classify TNBC samples into molecular subtypes, as well as immunohistochemistry and cell deconvolution methods to characterize the TIME. Results revealed significant heterogeneity in immune cell composition among TNBC subtypes, with the immunomodulatory (IM) subtype demonstrating robust immune infiltration, composed mainly of adaptive immune cells along with an increased density of CTLA-4+ and PD-1+ TILs, high PD-L1 tumor cell expression, and upregulation of FOXP3+ Tregs. A more immunosuppressive TIME with a predominance of innate immune cells and lower levels of tumor-infiltrating lymphocytes (TILs) was observed in luminal androgen receptor (LAR) tumors. In mesenchymal stem-like (MSL) tumors, the TIME was mainly composed of innate immune cells, with a high number of M2 tumor-associated macrophages (TAMs), while the BL and M tumors displayed poor adaptive and innate immune responses, indicating an "immune-cold" phenotype. Differential activation of signaling pathways, genomic diversity, and metabolic reprogramming were identified as contributors to TIME heterogeneity. Understanding this interplay is crucial for tailoring therapeutic strategies, especially regarding immunotherapy.

Cancer Screening in Low- and Middle-Income Countries.

The worldwide cancer burden is growing, and populations residing in low- and middle-income countries (LMICs) are experiencing a disproportionate extent of this growth. Breast, colorectal, and cervical cancers are among the top 10 most frequently diagnosed malignancies, and they also account for a substantial degree of cancer mortality internationally. Effective screening strategies are available for all three of these cancers. Individuals from LMICs face substantial cost and access barriers to early detection programs, and late stage at diagnosis continues to be a major cause for cancer mortality in these communities. This chapter will review the epidemiology of breast, colorectal, and cervical cancers, and will explore prospects for improving global control through novel approaches to screening in cost-constrained environments.

Disaggregating the Asian-American Breast Cancer Population: Disparities in Reconstruction Rates.

INTRODUCTION: Breast cancer (BC) incidence has been increasing among Asian-Americans (AsAms); recent data suggest these patients are less likely to undergo postmastectomy breast reconstruction (PMBR) compared to non-Asian women. Historically, AsAm BC patients are reported in aggregate, masking heterogeneity within this population. We aim to identify patterns of postmastectomy reconstruction among disaggregated AsAm BC patients at our institution. METHODS: A retrospective chart review was performed for BC patients who underwent mastectomy between 2017 and 2021. Patient demographic and clinical information was collected including self-reported race/ethnicity and reconstruction at time of mastectomy. Self-identified Asian patients were disaggregated into East Asian, Southeast Asian, South Asian, and 'Asian Other.' We examined rates of reconstruction between the different races and the disaggregated Asian subgroups. Univariable and multivariable analysis was performed to examine patient factors associated with PMBR. RESULTS: Six hundred and five patients met inclusion criteria. Forty seven percent of patients identified as Asian, 36% of which as East Asian. Forty four percent of all patients underwent PMBR. Southeast Asian and South Asian women were least likely to undergo reconstruction, while Hispanic and non-Hispanic Black women were most likely to pursue PMBR (P = 0.020). On multivariable analysis, Hispanic, non-Hispanic White, and non-Hispanic Black women were more likely to undergo reconstruction compared to Asian women. Other factors associated with reconstruction were coverage with private insurance and diagnosis of noninvasive disease. CONCLUSIONS: Rates of PMBR are lower among AsAms than non-Asian patients and vary between Asian ethnic subgroups. Further investigation is needed to identify patterns of reconstruction among the disaggregated AsAm population to address disparities.

Tumor-Associated Lymphocytes and Breast Cancer Survival in Black and White Women.

This case series evaluates whether differences in immune filtration are associated with breast cancer risk in Black vs White women.

Breast Cancer Incidence Among Asian American Women in New York City: Disparities in Screening and Presentation.

BACKGROUND: Asian American (AsAm) women have some of the lowest rates of up-to-date breast cancer screening, and lack of disaggregated racial/ethnic data can mask disparities. We evaluated presentation patterns among AsAms at two hospitals with distinct communities: New York Presbyterian-Queens (NYPQ), in Flushing, Queens and Weill Cornell Medical Center (WCM), on the Upper East Side (UES) neighborhood of Manhattan. PATIENTS AND METHODS: Patients with newly diagnosed breast cancer between January 2019 and December 2022 were identified using a prospective database and clinical data collected. Patients were categorized as self-reported Asian versus Non-Asian. The Asian group was disaggregated as Chinese-Asian versus Other-Asian. Physician workforce data were obtained from public records. RESULTS: A total of 3546 patients (1162 NYPQ, 2384 WCM) were included. More NYPQ patients identified as Asian compared with WCM (49 vs. 14%, p < 0.001). Asian patients were mostly East Asian Chinese (NYPQ 61%, WCM 53%). More Chinese patients at NYPQ reported Chinese as their preferred language (81 vs. 33%, p < 0.001). Greatest differences of screen-detected disease frequency were seen between NYPQ and WCM Chinese patients (75 vs. 59%, p < 0.001). Eighty percent of NYPQ Chinese patients presented with stage 0/I disease versus 69% at WCM (p = 0.007), a difference not observed between Other-Asian patients (75% NYPQ, 68% WCM, p = 0.095). 3% of UES physicians versus 16% in Flushing reported speaking Chinese. CONCLUSIONS: Chinese patients residing in a neighborhood with more Chinese-speaking physicians more frequently presented with screen-detected, early-stage breast cancer. Stage distribution differences were not apparent among the aggregated pool of Other-Asian patients, suggesting cancer disparities may be masked when ethnic groups are studied in aggregate.

Top Breast Oncology Articles from 2021 to Inform Your Cancer Practice.

Breast oncology generates extensive literature and widespread media attention every year because of the high worldwide burden of this disease and also because of the rapid pace at which treatment advances have progressed. The year 2021 was no different, and this review will summarize some of the practice-changing, practice-validating, and practice-challenging publications of that year. These studies cover a broad range of topics including multidisciplinary care with gene expression profiling; breast cancer disparities; breast cancer screening; and prophylactic mastectomy surgery.

Social Determinants of Cancer Disparities.

Cancer is a major public health issue that is associated with significant morbidity and mortality across the globe. At its root, cancer represents a genetic aberration, but socioeconomic, environmental, and geographic factors contribute to different cancer outcomes for selected population subsets. The disparities in the delivery of healthcare affect all aspects of cancer management from early prevention to end-of-life care. In an effort to address the inequality in the delivery of healthcare among socioeconomically disadvantaged populations, the World Health Organization defined social determinants of health (SDOH) as conditions in which people are born, live, work, and age. These factors play a significant role in the disproportionate cancer burden among different population groups. SDOH are associated with disparities in risk factor burden, screening modalities, diagnostic testing, treatment options, and quality of life of patients with cancer. The purpose of this article is to describe a more holistic and integrated approach to patients with cancer and address the disparities that are derived from their socioeconomic background.

Racial and Ethnic Disparities in Outcomes After Breast-Conserving Therapy and Endocrine Therapy for DCIS: A Post-Hoc Analysis of the NSABP B-35 Randomized Clinical Trial.

BACKGROUND: Racial and ethnic disparities in outcomes after treatment for ductal carcinoma in situ (DCIS) are largely unknown. The objective of this study was to examine breast cancer outcomes by race and ethnicity in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 clinical trial. PATIENTS AND METHODS: The NSABP B-35 trial randomized postmenopausal women with hormone receptor-positive DCIS treated with breast-conserving therapy to 5 years of tamoxifen or anastrozole. In total, 3104 women were enrolled between 2003 and 2006. For this analysis, patients without complete self-reported race and ethnicity or with immediate trial dropout were excluded. Kaplan-Meier curves and adjusted Cox-proportional hazards models were used for analyses. RESULTS: Of the 3061 women included, 2614 (85.4%) were non-Hispanic white (NHW), 255 (8.3%) were non-Hispanic Black (NHB), 95 (3.1%) were Hispanic, and 96 (3.1%) were Asian or Pacific Islander (API). Endocrine therapy assignment and duration were well balanced between racial and ethnic groups. Median follow-up was 9 years; unadjusted Kaplan-Meier curves did not show any racial differences in disease events. Adjusted Cox-proportional hazards models found API (versus NHW) race to be associated with higher local recurrence [hazard ratio (HzR) 2.45, p = 0.035] and NHB race to be associated with higher distant recurrence (HzR 5.03, p = 0.020) and breast cancer mortality (HzR 3.83, p = 0.046). CONCLUSIONS: Despite similar locoregional treatments and standard endocrine therapy in a clinical trial population, racial and ethnic disparities exist in long-term outcomes for hormone-receptor-positive DCIS. These findings suggest that factors outside of access and treatment may impact DCIS outcomes by race and ethnicity.

Landmark Series: The Cancer Genome Atlas and the Study of Breast Cancer Disparities.

Race-related variation in breast cancer incidence and mortality are well-documented in the United States. The effect of genetic ancestry on disparities in tumor genomics, risk factors, treatment, and outcomes of breast cancer is less understood. The Cancer Genome Atlas (TCGA) is a publicly available resource that has allowed for the recent emergence of genome analysis research seeking to characterize tumor DNA and protein expression by ancestry as well as the social construction of race and ethnicity. Results from TCGA based studies support previous clinical evidence that demonstrates that American women with African ancestry are more likely to be afflicted with breast cancers featuring aggressive biology and poorer outcomes compared with women with other backgrounds. Data from TCGA based studies suggest that Asian women have tumors with favorable immune microenvironments and may experience better disease-free survival compared with white Americans. TCGA contains limited data on Hispanic/Latinx patients due to small sample size. Overall, TCGA provides important opportunities to define the molecular, biologic, and germline genetic factors that contribute to breast cancer disparities.

A Prospective Evaluation of the Quality of Life and Mental Health Implications of Mastectomy Alone on Women in sub-Saharan Africa.

OBJECTIVE: Assess quality of life and mental health implications of mastectomy for breast cancer on sub-Saharan African women. BACKGROUND: Mortality rates amongst women diagnosed with breast cancer in sub-Saharan Africa (SSA) are high, with disparities in survival relative to women in high income countries partly attributed to advanced disease at presentation. Fears of the sequelae of mastectomy are a prominent reason for presentation delays. There is a critical need to better understand the effects of mastectomy on women in SSA to inform preoperative counseling and education for women with breast cancer. METHODS: Women with breast cancer in Ghana and Ethiopia undergoing mastectomy were followed prospectively. Breast related quality-of-life and mental health measures were evaluated preoperatively, 3 and 6 months postoperatively, using BREAST-Q, PHQ-9, and GAD-7. Bivariate and logistic regression analyses evaluated changes in these measures for the total cohort and between sites. RESULTS: A total of 133 women from Ghana and Ethiopia were recruited. The majority of women presented with unilateral disease (99%) and underwent unilateral mastectomy (98%) with axillary lymph node dissection. Radiation was more common in Ghana ( P <0.001). Across most BREAST-Q subscales, women from both countries reported significantly decreased scores at 3 months postoperative. At 6 months, the combined cohort reported decreased scores for breast satisfaction (mean difference, -3.4). Women in both countries reported similar improvements in anxiety and depression scores postoperatively. CONCLUSIONS: Women from Ghana and Ethiopia who underwent mastectomy experienced a decline in breast-related body image while also experiencing decreased levels of depression and anxiety.

Assessing the Complex General Surgical Oncology Pipeline: Trends in Race and Ethnicity Among US Medical Students, General Surgery Residents, and Complex General Surgical Oncology Trainees.

BACKGROUND: Cancer incidence is expected to increase in coming decades, disproportionately so among minoritized communities. Racially and ethnically concordant care is essential to addressing disparities in cancer outcomes within at-risk groups. Here, we assess trends in racial and ethnic representation of medical students (MS), general surgery (GS) residents, and complex general surgical oncology (CGSO) fellows. METHODS: This is a retrospective review of data from the American Association of Medical Colleges and the Accreditation Council of Medical Education (ACGME) from 2015 to 2020. Self-reported race and ethnicity was obtained for MS, GS, and CGSO trainees. Race and ethnicity proportions were compared with respective representation in the 2020 US Census. Mann-Kendall, Wilcoxon rank sum, and linear regression were used to assess trends, as appropriate. RESULTS: A total of 316,448 MS applicants, 128,729 MS matriculants, 27,574 GS applicants, 46,927 active GS residents, 710 CGSO applicants, and 659 active CGSO fellows were included. With every progressive stage in training, there was a smaller proportion of URM active trainees than applicants. Further, URM, Hispanic/Latino, and Black/African American trainees were significantly underrepresented compared with 2020 Census data. While the proportion of White CGSO fellows increased over time (54.5-69.2%, p = 0.009), the proportion of Black/African American and Hispanic/Latino (URM) CGSO fellows did not significantly change over the study period, though URM representation was lower in 2020 as compared with 2015. DISCUSSION: From 2015 to 2020, minority representation decreased at every advancing stage in surgical oncology training. Efforts to address barriers for URM applicants to CGSO fellowships are needed.

Does the Type of Reconstruction Matter? A Propensity Score Analysis of Immediate Postmastectomy Implant and Flap Reconstruction.

BACKGROUND: No randomized controlled trials have compared implant and flap reconstruction. Recently, worse longitudinal outcomes have been suggested for flap reconstruction. The authors compared long-term oncologic outcomes of postmastectomy breast reconstruction using propensity score matching. METHODS: A retrospective study of postmastectomy reconstruction was achieved using the Weill Cornell Breast Cancer Registry between 1998 and 2019. Patients were matched using propensity scores based on demographic, clinical, and surgical characteristics. Kaplan-Meier estimates, Cox-regression models, and restricted mean survival times (RMST) were used to evaluate patient outcomes. RESULTS: Before matching, 1395 implant and 586 flap patients were analyzed. No difference in overall survival and recurrence were observed. Multivariable models showed decreased survival for Medicare/Medicaid [hazard ratio (HR), 3.09; 95% CI, 1.63 to 5.87; P < 0.001], pathologic stage II (HR, 2.98; 95% CI, 1.12 to 7.90; P = 0.028), stage III (HR, 4.88; 95% CI, 1.54 to 15.5; P = 0.007), 11 to 20 lymph nodes positive (HR, 3.66; 95% CI, 1.31 to 10.2; P = 0.013), more than 20 lymph nodes positive (HR, 6.41; 95% CI, 1.49 to 27.6; P = 0.013). RMST at 10 years after flap reconstruction showed 2 months of decreased survival time compared with implants (9.56 versus 9.74 years; 95% CI, -0.339 to -0.024; P = 0.024). After matching, 563 implant and 563 flap patients were compared. Reconstruction was not associated with overall survival and recurrence. RMST between implant and flap reconstruction showed no difference in each 5-year interval over 20 years. CONCLUSION: Postmastectomy breast reconstruction was not associated with a difference in long-term oncologic outcomes over a 20-year period. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.