METHODS: We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.
RESULTS: We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.
CONCLUSION: These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
MATERIALS AND METHODS: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle- related transcripts was analysed based on a previous microarray dataset.
RESULTS: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of ERα protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied.
CONCLUSIONS: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.
METHODS: This is a retrospective study over 8-year duration in which all the breast FNABs performed in our institution were recategorized in accordance to the IAC Yokohama reporting system. Kappa coefficient was used to evaluate the agreement between the proposed cytological category and corresponding histological diagnosis, with the level of significance set at 5%. Cyto-histopathological correlation and its diagnostic performance were also assessed.
RESULTS: A total of 1136 breast FNABs were analyzed, including 31 repeat FNABs. Of these, 521 (47.1%) cases had matched histopathological results. Respective ROM for each category was: "insufficient" 13.6%, "benign" 0.4%, "atypical" 25.0%, "suspicious" 85.7%, and "malignant" 100%. There was substantial agreement (κ=0.757) between cytology and histopathological results. Our data revealed a high-diagnostic specificity, sensitivity, positive and negative predictive value of 99.3% (95% CI: 97.6%-99.9%), 94.2% (95% CI: 87.9%-97.9%), 98.0% (95% CI: 92.5%-99.5%), 98.0% (95% CI: 96.1%-99.1%) respectively when both the "suspicious" and "malignant" cases were considered as positive tests, with area under the curve of 0.993.
CONCLUSIONS: The IAC Yokohama system is a reliable, evidence-based, and standardized reporting system that helps to facilitate communication among cytopathologists, radiologists, and surgeons toward individualized patient management.
METHODOLOGY: This is a multi-centre, cross-sectional study involving the University of Malaya Medical Centre (UMMC), Queen Elizabeth II Hospital (QEH), and Tengku Ampuan Rahimah Hospital (TARH). Patients diagnosed with invasive breast cancer from January 2014 to December 2015 were included, excluding stromal cancers and lymphomas. Univariate and multivariate analyses identified factors influencing BCS.
RESULTS: A total of 1005 patients were diagnosed with breast cancer in the allocated time frame. Excluding incomplete records and those who did not have surgery, 730 patients were analysed. Overall BCS rate was 32.9%. The BCS rate was highest at QEH (54.1%), followed by UMMC (29.5%), and TARH (17.4%). 16.9% had BCS after neoadjuvant therapy. Factors influencing BCS uptake included age, ethnic group, breast-surgeon led services, AJCC Stage, tumour size, HER-2 expression, and tumour grade.
CONCLUSIONS: The rate of BCS in Malaysia is low. A wide variation of rate exists among the studied hospitals. Younger age, earlier AJCC stage, and the presence of a Breast sub-specialist surgeon, would make it more likely that the patient has her breast conserved.