Raised cardiovascular disease mortality after central nervous system tumour diagnosis:Analysis of 171 926 patients from UK and USA

BACKGROUND: Patients with central nervous system (CNS) tumors may be at risk of dying from cardiovascular disease (CVD). We examined CVD mortality risk in patients with different histological subtypes of CNS tumors. METHODS: We analyzed UK(Wales)-based Secure Anonymized Information Linkage (SAIL) for 8743 CNS tumors patients diagnosed in 2000-2015, and US-based National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) for 163,183 patients in 2005-2015. We calculated age-, sex-, and calendar-year-adjusted standardized mortality ratios (SMRs) for CVD comparing CNS tumor patients to Wales and US residents. We used Cox regression models to examine factors associated with CVD mortality among CNS tumor patients. RESULTS: CVD was the second leading cause of death for CNS tumor patients in SAIL (UK) and SEER (US). Patients with CNS tumors had higher CVD mortality than the general population (SAIL SMR = 2.64, 95% CI = 2.39-2.90, SEER SMR = 1.38, 95% CI = 1.35-1.42). Malignant CNS tumor patients had over 2-fold higher mortality risk in US and UK cohorts. SMRs for nonmalignant tumors were almost 2-fold higher in SAIL than in SEER. CVD mortality risk particularly cerebrovascular disease was substantially greater in patients diagnosed at age younger than 50 years, and within the first year after their cancer diagnosis (SAIL SMR = 2.98, 95% CI = 2.39-3.66, SEER SMR = 2.14, 95% CI = 2.03-2.25). Age, sex, race/ethnicity in USA, deprivation in UK and no surgery were associated with CVD mortality. CONCLUSIONS: Patients with CNS tumors had higher risk for CVD mortality, particularly from cerebrovascular disease compared to the general population, supporting further research to improve mortality outcomes

Reproductive history differs by molecular subtypes of breast cancer among women aged ≤50 years in Scotland in 2009-16:A cross-sectional study

BACKGROUND: The aetiology of breast cancers diagnosed ≤ 50 years of age remains unclear. We aimed to compare reproductive risk factors between molecular subtypes of breast cancer, thereby suggesting possible aetiologic clues, using routinely collected cancer registry and maternity data in Scotland. METHODS: We conducted a cross-sectional study of 4108 women aged ≤ 50 years with primary breast cancer diagnosed between 2009 and 2016 linked to maternity data. Molecular subtypes of breast cancer were defined using immunohistochemistry (IHC) tumour markers, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and tumour grade. Age-adjusted polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of number of births, age at first birth and time since last birth with IHC-defined breast cancer subtypes. Luminal A-like was the reference compared to luminal B-like (HER2−), luminal B-like (HER2+), HER2-overexpressed and triple-negative breast cancer (TNBC). RESULTS: Mean (SD) for number of births, age at first birth and time since last birth was 1.4 (1.2) births, 27.2 (6.1) years and 11.0 (6.8) years, respectively. Luminal A-like was the most common subtype (40%), while HER2-overexpressed and TNBC represented 5% and 15% of cases, respectively. Larger numbers of births were recorded among women with HER2-overexpressed and TNBC compared with luminal A-like tumours (> 3 vs 0 births, OR 1.87, 95%CI 1.18–2.96; OR 1.44, 95%CI 1.07–1.94, respectively). Women with their most recent birth > 10 years compared to < 2 years were less likely to have TNBC tumours compared to luminal A-like (OR 0.63, 95%CI 0.41–0.97). We found limited evidence for differences by subtype with age at first birth. CONCLUSION: Number of births and time since last birth differed by molecular subtypes of breast cancer among women aged ≤ 50 years. Analyses using linked routine electronic medical records by molecularly defined tumour pathology data can be used to investigate the aetiology and prognosis of cancer

Associations of Genetic Ancestry with Terminal Duct Lobular Unit Involution among Healthy Women

Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer. Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined the association between genetic ancestry and TDLU involution in normal breast tissue donated by 2014 healthy women in the United States. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR](trend) = 1.36, 95% confidence interval [CI] = 1.07 to 1.74), acini counts per TDLU (OR = 1.47, 95% CI = 1.06 to 2.03), and median TDLU span (OR(trend) = 1.44, 95% CI = 1.08 to 1.91), indicating lower involution, whereas East Asian descendants were associated with decreased TDLU counts (OR(trend) = 0.52, 95% CI = 0.35 to 0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of triple-negative breast cancer in the United States and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk

Benign Breast Tissue Composition in Breast Cancer Patients: Association with Risk Factors, Clinical Variables, and Gene Expression

Breast tissue composition (epithelium, non-fatty stroma, and adipose) changes qualitatively and quantitatively throughout the lifespan, and may mediate relationships between risk factors and breast cancer initiation. We sought to identify relationships between tissue composition, risk factors, tumor characteristics, and gene expression