Background: Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear. Methods: In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%. Results: Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history. Conclusions: Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.

Background: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilization in a multi-ethnic Asian population.Methods: This study included 3739 BC patients from the Singapore Breast Cancer Cohort (2010–2018). Self-reported sociodemographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤ 2 years before diagnosis), non-screeners (aware but did not attend or last screen > 2years), and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression.Results: Patients unaware of screening were more likely diagnosed with late stage (OR_{stage III vs stage I (Ref)}[95% CI]: 4.94 [3.45–7.07],p< 0.001), high grade (OR_{poorly vs well-differentiated (reference)}: 1.53 [1.06–2.20],p= 0.022), nodal-positive, large size (OR_{>5cm vs ≤2cm (reference)}: 5.06 [3.10–8.25],p< 0.001), and HER2-positive tumours (OR_{HER2-negative vs HER2-positive (reference)}: 0.72 [0.53–0.97],p= 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups (HR_{non-screeners}: 1.89 [1.22–2.94],p= 0.005; HR_unaware: 2.90 [1.69–4.98],p< 0.001).Non-screeners and those unaware were less health conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers, and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer.Conclusions: Mammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.

Physical activity (PA) is known to reduce breast cancer (BC) risk and improve patient prognosis. However, the association between pre-diagnostic PA and the aggressiveness of BC is unclear. We investigated the associations between PA, BC tumour characteristics, and survival. This retrospective observational study included 7688 BC patients from the Singapore Breast Cancer Cohort (2010–2016). PA information from the questionnaire included intensity (light/moderate/vigorous) and duration (2 h per week). A PA score (1–5) incorporating intensity and duration was calculated. Associations between PA score and tumour characteristics such as stage, histological grade, nodal and hormone receptor status were examined using multinomial regression. Moreover, 10-year overall survival was estimated using Cox regression analysis in 6572 patients after excluding patients with invalid survival data and stage IV disease. Breast tumours associated with higher PA score were more likely to be non-invasive (OR_{invasive vs. non-invasive(reference)} [95% CI]: 0.71 [0.58–0.87], p-trend = 0.001), of lower grade (OR_{poorly vs. well differentiated(reference)}: 0.69 [0.52–0.93], p = 0.014), ER-positive (OR_{ER-negative vs. ER-positive(reference)}: 0.94 [0.89–1.00], p-trend = 0.049), PR-positive (OR_{PR-negative vs. PR-positive(reference)}: 0.82 [0.67–0.99], p = 0.041), HER2-negative (OR_{HER2-negative vs. HER2-positive(reference)}: 1.29 [1.02–1.62], p-trend = 0.002), and less likely to be of HER2-overexpressed subtype (OR_{HER2-overexpressed vs. Luminal A(reference)}: 0.89 [0.81–0.98], p-trend = 0.018). These associations (odds ratios) were more pronounced among post-menopausal patients. A higher PA score did not improve survival. Higher levels of pre-diagnostic PA were associated with less aggressive tumours in BC patients. This illustrated another benefit of PA in addition to its known role in BC risk reduction.