CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women's Circle of Health Study and the Women's Circle of Health Follow-Up Study.

BACKGROUND: Tumor-associated macrophages (TAMs) are a prominent immune subpopulation in the tumor microenvironment that could potentially serve as therapeutic targets for breast cancer. Thus, it is important to characterize this cell population across different tumor subtypes including patterns of association with demographic and prognostic factors, and breast cancer outcomes. METHODS: We investigated CD163+ macrophages in relation to clinicopathologic variables and breast cancer outcomes in the Women's Circle of Health Study and Women's Circle of Health Follow-up Study populations of predominantly Black women with breast cancer. We evaluated 611 invasive breast tumor samples (507 from Black women, 104 from White women) with immunohistochemical staining of tissue microarray slides followed by digital image analysis. Multivariable Cox proportional hazards models were used to estimate hazard ratios for overall survival (OS) and breast cancer-specific survival (BCSS) for 546 cases with available survival data (median follow-up time 9.68 years (IQR: 7.43-12.33). RESULTS: Women with triple-negative breast cancer showed significantly improved OS in relation to increased levels of tumor-infiltrating CD163+ macrophages in age-adjusted (Q3 vs. Q1: HR = 0.36; 95% CI 0.16-0.83) and fully adjusted models (Q3 vs. Q1: HR = 0.30; 95% CI 0.12-0.73). A similar, but non-statistically significant, association was observed for BCSS. Macrophage infiltration in luminal and HER2+ tumors was not associated with OS or BCSS. In a multivariate regression model that adjusted for age, subtype, grade, and tumor size, there was no significant difference in CD163+ macrophage density between Black and White women (RR = 0.88; 95% CI 0.71-1.10). CONCLUSIONS: In contrast to previous studies, we observed that higher densities of CD163+ macrophages are independently associated with improved OS and BCSS in women with invasive triple-negative breast cancer. Trial registration Not applicable.

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer.

Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. Design, Setting, and Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. Main Outcome and Measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). Conclusions and Relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.

Adherence to Cancer Prevention Lifestyle Recommendations Before, During, and 2 Years After Treatment for High-risk Breast Cancer.

Importance: The American Institute for Cancer Research and American Cancer Society regularly publish modifiable lifestyle recommendations for cancer prevention. Whether these recommendations have an impact on high-risk breast cancer survival remains unknown. Objective: To investigate whether adherence to cancer prevention recommendations before, during, and 1 and 2 years after breast cancer treatment was associated with disease recurrence or mortality. Design, Setting, and Participants: The Diet, Exercise, Lifestyles, and Cancer Prognosis Study (DELCaP) was a prospective, observational cohort study designed to assess lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment completion, implemented ancillary to the Southwest Oncology Group (SWOG) S0221 trial, a multicenter trial that compared chemotherapy regimens in breast cancer. Participants were chemotherapy-naive patients with pathologic stage I to III high-risk breast cancer, defined as node-positive disease with hormone receptor-negative tumors larger than 1 cm or any tumor larger than 2 cm. Patients with poor performance status and comorbidities were excluded from S0221. The study was conducted from January 1, 2005, to December 31, 2010; mean (SD) follow-up time for those not experiencing an event was 7.7 (2.1) years through December 31, 2018. The analyses reported herein were performed from March 2022 to January 2023. Exposure: An aggregated lifestyle index score comprising data from 4 time points and 7 lifestyles, including (1) physical activity, (2) body mass index, (3) fruit and vegetable consumption, (4) red and processed meat intake, (5) sugar-sweetened beverage consumption, (6) alcohol consumption, and (7) smoking. Higher scores indicated healthier lifestyle. Main Outcomes and Measures: Disease recurrence and all-cause mortality. Results: A total of 1340 women (mean [SD] age, 51.3 [9.9] years) completed the baseline questionnaire. Most patients were diagnosed with hormone-receptor positive breast cancer (873 [65.3%]) and completed some education beyond high school (954 [71.2%]). In time-dependent multivariable analyses, patients with highest vs lowest lifestyle index scores experienced a 37.0% reduction in disease recurrence (hazard ratio, 0.63; 95% CI, 0.48-0.82) and a 58.0% reduction in mortality (hazard ratio, 0.42; 95% CI, 0.30-0.59). Conclusions and Relevance: In this observational study of patients with high-risk breast cancer, strongest collective adherence to cancer prevention lifestyle recommendations was associated with significant reductions in disease recurrence and mortality. Education and implementation strategies to help patients adhere to cancer prevention recommendations throughout the cancer care continuum may be warranted in breast cancer.

Mechanisms involved in the production of differently colored feathers in the structurally colored swallow tanager (Tersina viridis; Aves: Thraupidae).

Non-iridescent, structural coloration in birds originates from the feather's internal nanostructure (the spongy matrix) but melanin pigments and the barb's cortex can affect the resulting color. Here, we explore how this nanostructure is combined with other elements in differently colored plumage patches within a bird. We investigated the association between light reflectance and the morphology of feathers from the back and belly plumage patches of male swallow tanagers (Tersina viridis), which look greenish-blue and white, respectively. Both plumage patches have a reflectance peak around 550 nm but the reflectance spectrum is much less saturated in the belly. The barbs of both types of feathers have similar spongy matrices at their tips, rendering their reflectance spectra alike. However, the color of the belly feather barbs changes from light green at their tips to white closer to the rachis. These barbs lack pigments and their morphology changes considerably throughout. Toward the rachis, the barb is almost hollow, with a reduced area occupied by spongy matrix, and has a flattened shape. By contrast, the blue back feathers' barbs have melanin underneath the spongy matrix resulting in a much more saturated coloration. The color of these barbs is also even along the barbs' length. Our results suggest that the color differences between the white and greenish-blue plumage are mostly due to the differential deposition of melanin and a reduction of the spongy matrix near the rachis of the belly feather barbs and not a result of changes in the characteristics of the spongy matrix.