Purpose Intensive screening in BRCA1/2 mutation carriers aims to improve breast cancer (BC) prognosis. Our aim is to clarify the prognostic impact of tumor size in BRCA mutation carriers with a pT1... Show morePurpose Intensive screening in BRCA1/2 mutation carriers aims to improve breast cancer (BC) prognosis. Our aim is to clarify the prognostic impact of tumor size in BRCA mutation carriers with a pT1 BC, which is currently unclear. We are especially interested in differences between pT1a, pT1b, and pT1c regarding the prognosis of node-negative breast cancer, the effect of chemotherapy, and the prevalence of lymph node involvement. Methods For this study, BRCA1/2-associated BC patients were selected from a nationwide cohort. Primary outcomes were 10-year overall survival (OS) per pT1a-b-c group and the effect of chemotherapy on prognosis of node-negative BC, using Kaplan-Meier and Cox models. Finally, we evaluated lymph node involvement per pT1a-b-c group. Results 963 women with pT1 BRCA1/2-associated BC diagnosed between 1990 and 2017 were included, of which 679 had pN0 BC. After a median follow-up of 10.5 years, 10-year OS in patients without chemotherapy was 77.1% in pT1cN0 and lower than for pT1aN0 (91.4%, p = 0.119) and pT1bN0 (90.8%, p = 0.024). OS was better with than without chemotherapy for pT1cN0 (91.6% vs. 77.1%, p = 0.001; hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.21-1.48). Lymph node involvement was 24.9% in pT1c, 18.8% in pT1b, and 8.6% in pT1a. Conclusion Smaller tumor size is associated with better OS and less lymph node involvement in pT1 BRCA1/2-associated BC patients. The results suggest that early detection in BRCA1/2 mutation carriers of pT1a/b BC may reduce mortality and the need for systemic therapy. Show less
Background The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific... Show moreBackground The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific breast cancer treatment recommendations from week 12 of 2020. We aimed to investigate the impact of COVID-19 on the diagnosis, stage and initial treatment of breast cancer. Methods Women included in the Netherlands Cancer Registry and diagnosed during four periods in weeks 2-17 of 2020 were compared with reference data from 2018/2019 (averaged). Weekly incidence was calculated by age group and tumor stage. The number of women receiving initial treatment within 3 months of diagnosis was calculated by period, initial treatment, age, and stage. Initial treatment, stratified by tumor behavior (ductal carcinoma in situ [DCIS] or invasive), was analyzed by logistic regression and adjusted for age, socioeconomic status, stage, subtype, and region. Factors influencing time to treatment were analyzed by Cox regression. Results Incidence declined across all age groups and tumor stages (except stage IV) from 2018/2019 to 2020, particularly for DCIS and stage I disease (p < 0.05). DCIS was less likely to be treated within 3 months (odds ratio [OR](wks2-8): 2.04, ORwks9-11: 2.18). Invasive tumors were less likely to be treated initially by mastectomy with immediate reconstruction (ORwks12-13: 0.52) or by breast conserving surgery (ORwks14-17: 0.75). Chemotherapy was less likely for tumors diagnosed in the beginning of the study period (ORwks9-11: 0.59, ORwks12-13: 0.66), but more likely for those diagnosed at the end (ORwks14-17: 1.31). Primary hormonal treatment was more common (ORwks2-8: 1.23, ORwks9-11: 1.92, ORwks12-13: 3.01). Only women diagnosed in weeks 2-8 of 2020 experienced treatment delays. Conclusion The incidence of breast cancer fell in early 2020, and treatment approaches adapted rapidly. Clarification is needed on how this has affected stage migration and outcomes. Show less
Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the... Show moreBackground: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear.Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium.Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer.Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer. Show less
Lakeman, I.M.M.; Schmidt, M.K.; Asperen, C.J. van; Devilee, P. 2019
Purpose of ReviewBreast cancer is the most common cancer among females in developed countries. Strategies such as early detection by breast cancer screening can reduce the burden of disease but... Show morePurpose of ReviewBreast cancer is the most common cancer among females in developed countries. Strategies such as early detection by breast cancer screening can reduce the burden of disease but have disadvantages including overdiagnosis and increased cost. Stratification of women according to the risk of developing breast cancer, based on genetic and lifestyle risk factors, could improve risk-reduction and screening strategies by targeting those most likely to benefit.Recent FindingsBreast cancer risk is partly determined by genetic factors including rare pathogenic variants in susceptibility genes and common low-risk variants. Other risk factors include alcohol use, smoking, reproductive factors, hormonal factors, family history, mammographic density, BMI, and body height. Ideally, all risk factors are combined into an individual breast cancer lifetime risk score, but this requires knowledge about their interactions as well as accurate effect sizes. A few risk models seem to be sufficiently developed to inform clinical risk management to minimise cancer risk of those at increased risk and avoid overtreatment of those at decreased risk.SummaryIn this review, we briefly summarise the breast cancer susceptibility factors and discuss avenues towards combining all these factors to create individual risk scores. Show less
