Black Women Are Less Likely to Be Classified as High-Risk for Breast Cancer Using the Tyrer-Cuzick 8 Model.

BACKGROUND: Breast cancer risk assessment is a powerful tool that guides recommendations for supplemental breast cancer screening and genetic counseling. The Tyrer-Cuzick 8 (TC8) model is widely used for calculating breast cancer risk and thus helps determine if women qualify for supplemental screening or genetic counseling. However, the TC8 model may underestimate breast cancer risk in Black women. This study sought to assess this disparity. METHODS: Data on race, breast density, body mass index (BMI), and TC8 scores were retrospectively extracted from the electronic medical record (EMR). Logistic regressions were run to evaluate racial differences in TC8 scores. Summary and correlation statistics determined relationships between BMI, breast density, and race. Rank biserial correlations were employed to explore the impact of breast density and BMI on TC8 scores. RESULTS: Of 15,356 patients, 5796 were White and 5813 were Black. Black patients had higher rates of BMI ≥ 27 compared with White women (79.2% vs. 45.7%), lower rates of breast density (35.1% vs. 56.2%), and lower rates of high-risk TC8 scores (10.7% vs. 17.5%, OR = 1.6646). There was an inverse relationship between TC8 score and BMI (rrb = - 0.04) and a direct relationship between TC8 score and breast density (rrb = 0.37). DISCUSSION: Black women are less likely to have high-risk TC8 scores despite having only marginally lower breast cancer incidence rates and higher breast cancer mortality rates than White women. This suggests that the TC8 model underestimates breast cancer risk in Black women, possibly due to lower rates of breast density and higher BMIs among Black women.

Impact of the 2018 ACR Supplemental Screening Recommendations on MRI Eligibility in Breast Cancer Survivors.

PURPOSE: The 2018 ACR recommendations for breast cancer screening in women at higher than average risk include new recommendations for supplemental breast MRI for patients with personal histories of breast cancer (PHBCs) who carry hereditary cancer gene mutations, have dense breast tissue, or were diagnosed before 50 years of age. In comparison, prior guidelines recommended supplemental MRI only for women with PHBCs who carried hereditary cancer gene mutations. The aim of this study was to quantify the increase in the number of patients with breast cancer for whom supplemental breast MRI would now be recommended. METHODS: Data were extracted from the electronic health records of patients presenting for screening or diagnostic mammography at an urban academic medical center between July 20, 2020, and July 19, 2021. Data extracted included patient-reported PHBC, age at time of breast cancer diagnosis, and hereditary cancer gene mutation carrier status. Descriptive statistics are reported, evaluating the rate of eligibility for supplemental breast MRI in a retrospective population given the new ACR guidelines. RESULTS: Of the 2,950 patients with self-reported PHBCs who presented for breast cancer screening in the year between July 2020 and July 2021, 1,805 (61%) met the criteria for supplemental breast MRI according to the 2018 guidelines compared with only 3.6% using pre-2018 guidelines. CONCLUSIONS: Measuring the impact of the 2018 ACR supplemental MRI recommendations using real-world data at a single urban academic medical center demonstrated a 15-fold increase in potential eligibility for supplemental breast MRI in patients with PHBCs.

Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort.

BACKGROUND: Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored. METHODS: RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria. Pooled and individual responder and non-responder microbiota were transplanted into a gnotobiotic mouse model of lung cancer and treated with ICIs. 16S rDNA and RNA sequencing was performed on patient fecal samples, 16S rDNA sequencing on mouse fecal samples, and flow cytometric analysis on mouse tumor tissue. RESULTS: Responder patients have both a different microbial community structure than non-responders (P = 0.004) and a different bacterial transcriptome (PC2 = 0.03) at baseline. Taxa significantly enriched in responders include amplicon sequence variants (ASVs) belonging to the genera Ruminococcus, Akkermansia, and Faecalibacterium. Pooled and individual responder microbiota transplantation into gnotobiotic mice decreased tumor growth compared to non-responder colonized mice following ICI (P = 0.023, P = 0.019, P = 0.008, respectively). Responder tumors showed an increased anti-tumor cellular phenotype following ICI treatment. Responder mice are enriched with ASVs belonging to the genera Bacteroides, Blautia, Akkermansia, and Faecalibacterium. Overlapping taxa mapping between human and mouse cohorts correlated with tumor size and weight revealed a network highlighting responder-associated ASVs belonging to the genera Colidextribacter, Frisingicoccus, Marvinbryantia, and Blautia which have not yet been reported. CONCLUSIONS: The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.