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Background: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. Methods: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow‐up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow‐up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan–Meier method. Results: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk‐reducing mastectomy and bilateral salpingo‐oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. Conclusion: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately. Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer after age 50 and should be counseled appropriately. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the impact of various surgical, hormonal, and lifestyle factors on memory and attention in women with a BRCA1 or BRCA2 mutation. Methods: BRCA mutation carriers enrolled in a longitudinal study were invited to complete an online brain health assessment tool designed to screen for cognitive deficits. Four measures of memory and executive attention were assessed individually, and an overall score was compiled adjusting for age. Exposures, including preventive surgery, hormone use, and lifestyle factors, were captured by questionnaire. Performance on each of the 5 subtasks was analyzed according to various exposures. Analysis of covariance was used to compare overall scores. Results: In total, 880 women completed the online cognitive assessment. The average age of the participants was 54 years (range, 23‐86 years). The mean overall test score was 54.4 (range, 0‐93). The individual subtask scores declined with age at test completion (P <.0001) and increased with level of education (P ≤.01). Women who underwent a preventive oophorectomy had a significantly higher overall score compared with women who did not undergo this surgery (55.5 vs 50.5; P =.01). Reconstructive breast surgery was also associated with a higher overall score (56.5 vs 52.3; P =.005). Chemotherapy and hormone‐replacement therapy were not predictive of the overall score. Conclusions: These findings are reassuring to high‐risk women who undergo early surgical menopause for their cancer predisposition. Further studies are needed to evaluate cognitive function over time when memory deficits become more prevalent. In a study of 880 women with a BRCA mutation, there is no impact of preventive surgery, cancer treatment, or hormonal factors on attention or memory. These findings are reassuring to patients who undergo early surgical menopause for the management of hereditary cancer predisposition. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hyperinsulinemia and the metabolic syndrome are both risk factors for breast cancer. It is not clear if diabetes is associated with the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. METHODS: The authors reviewed the medical histories of 6052 women with a BRCA1 or BRCA2 mutation, half of whom had been diagnosed with breast cancer. They estimated the odds ratio for breast cancer, given a self-report of diabetes. They then estimated the hazard ratio for a new diagnosis of diabetes associated with a history of breast cancer. RESULTS: There was no excess of diabetes in the period before the diagnosis of breast cancer, compared with controls with no diagnosis of breast cancer. The risk of diabetes was doubled among BRCA carriers in the 15-year period after the diagnosis of breast cancer (relative risk, 2.0; 95% confidence interval [CI], 1.4-2.8; P = .0001), compared with carriers without cancer. The risk was particularly high for women with a body mass index (BMI) >25.0 kg/m² (odds ratio, 5.8; 95% CI, 4.0-8.6; P = .0001). CONCLUSIONS: After a diagnosis of breast cancer, women with a BRCA1 or BRCA2 mutation face a 2-fold increase in the risk of diabetes, which is exacerbated by a high BMI. [ABSTRACT FROM AUTHOR]

Summary. The receptor for granulocyte–macrophage colony-stimulating factor (GM-CSF) can exist as both transmembrane (tmGMRα) and soluble (solGMRα) isoforms, and the latter, is a normal constituent of human plasma. We investigated if aberrant solGMRα expression occurs in haematopoietic malignancies and whether or not solGMRα expression levels correlated with clinical presentation. Compared with the normal population, patients with acute lymphoblastic leukaemia (ALL) had low levels of solGMRα whereas clonal disorders of the myeloid lineage demonstrated higher levels of solGMRα. Patients with acute myelogenous leukaemia (AML) and high levels of solGMRα presented with a distinct clinical picture. These patients were older, predominantly belonged to the M4 and M5 French–American–British (FAB) subtypes, and they had higher white blood cell counts at presentation including myeloid precursors and myeloblasts. They often presented with either unexplained lung infiltrates or hypoxia and lower rates of microbiologically defined infections. Elevated solGMRα levels were not associated with decreased relapse-free and overall survival in the AML population. On multivariate analysis, the correlation between elevated solGMRα levels and age, M4 and M5 FAB subtypes and decreased numbers of infections persisted. Our study is the first to describe that distinct clinical presentations are associated with aberrant solGMRα levels in haematological malignancies. [ABSTRACT FROM AUTHOR]