Blacks tend to have a stronger inflammatory immune response than Whites. We hypothesized that racial differences in host immunity also manifest in the tumor microenvironment, constituting part of a distinct aggressive tumor biology underlying higher mortality in Black women. Pathological and gene expression profiling approaches were used for characterizing infiltrating immune cells in breast tumor microenvironment from 1315 patients from the Women’s Circle of Health Study. Racial differences in tumor immune phenotypes were compared, with results validated in a publicly accessible dataset. Prognostic associations of immune phenotypes were assessed in 3 independent cohorts. We found marked and consistent differences in tumor immune responses between Black and White patients. Not only did tumors from Blacks display a stronger overall immune presence but also the composition and quality of immune infiltrates differed, regardless of tumor subtypes. Black patients had a stronger CD4⁺ and B-cell response, and further, a more exhausted CD8⁺ T-cell profile. A signature indicating a higher ratio of exhausted CD8⁺ T cells to total CD8⁺ T cells (ExCD8-r) was consistently associated with poorer survival, particularly among hormone receptor–positive patients. Among hormone receptor–negative patients, combinations of the absolute fraction of CD8⁺ T cells and ExCD8-r signature identified the CD8^lowExCD8-r^high subgroup, the most prevalent among Blacks, with the worst survival. Our findings of a distinct exhausted CD8⁺ T-cell signature in Black breast cancer patients indicate an immunobiological basis for their more aggressive disease and a rationale for the use of immune checkpoint inhibitors targeting the exhaustion phenotype.

Loss of muscle mass and waning in muscle strength are common in older adults, and inflammation may play a key role in pathogenesis. This study aimed to examine associations of C-reactive protein (CRP) and systemic immune-inflammation index (SII) with sarcopenia and sarcopenic obesity in older adults with chronic comorbidities. Cross-sectional data from the National Health and Nutrition Examination Survey (1999–2006) were obtained for participants aged ≥60 years. Sarcopenia was defined by a lean mass and body height (males < 7.26 kg/m², females < 5.45 kg/m²). Sarcopenic obesity was defined by the concurrent presence of sarcopenia and obesity (defined by relative fat mass). Logistic regression was used to assess the associations of CRP and SII with sarcopenia and sarcopenic obesity. The dose–response relationship was examined via restricted cubic splines. Of the participants (n = 2483), 23.1% (n = 574) and 7.7% (n = 190) had sarcopenia and sarcopenic obesity, respectively. The multivariable logistic regression models suggested a positive association of SII with sarcopenia and sarcopenic obesity, but a positive statistically significant association was not consistently observed for CRP. Dose–response curves suggested similar association patterns for these biomarkers. In clinical practice, measures to prevent sarcopenia and sarcopenic obesity are needed for older vulnerable people with high systemic inflammation.

Vitamin A, including retinol and provitamin A carotenoids, regulates cell growth and differentiation. Low vitamin A intake is associated with increased risk of chronic diseases and mortality.¹ Research suggests a lower vitamin A status among Black and Hispanic individuals than White individuals.² We investigated whether a difference exists in dietary vitamin A intake as a marker of consumption of vitamin A–rich foods (ie, fruits, leafy green vegetables, fish, and dairy) among Black, Hispanic, and White adults in the US.

To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Patients with primary non–small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)–α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = –15.8, P = .003) and nuclear ER-β (β = –12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = –42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.

Purpose: The importance of body composition on cancer outcomes is of great clinical interest. Measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. We investigated whether the risk of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Our secondary aim was a subgroup analysis assessing the role of race within these associations. Methods: Participants included 1682 adult cancer survivors who had undergone a dual-energy X-ray absorptiometry (DXA) examination to measure body composition, from the 1999–2006 and 2011–2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was considered as having an appendicular skeletal muscle mass index less than 7.26 kg/m² for males and less than 5.45 kg/m² for females. Multivariable Cox proportional hazard models estimated the adjusted hazard ratio (aHR) and 95% confidence interval (CI). Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. The prevalence of sarcopenia was 25.0% (N = 304), and 33.4% (N = 561) had a high total fat mass. Participants with a higher fat mass (aHR = 1.30, 95% CI = 1.06–1.61) and with sarcopenia (aHR = 1.51, 95% CI = 1.22–1.88) had a 30% and 51% increased risk of all-cause mortality compared to participants with a low fat mass and with no sarcopenia, respectively. Further, sarcopenia (aHR = 1.74, 95% CI = 1.23–2.29) was associated with a higher risk of cancer-specific mortality in cancer survivors. The association between sarcopenia and all-cause mortality was twice as strong in Black people (aHR = 2.99, 95% CI = 1.39–6.06) compared to White people (aHR = 1.53, 95% CI = 1.19–1.95). Conclusions: Our findings show the opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and that the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.