BackgroundVitamin D is postulated to decrease the risk of breast cancer by inhibiting cell proliferation via the vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNPs) in the VDR gene, rs1544410 (BsmI) and rs2228570 (FokI), are inconsistently associated with breast cancer risk in Caucasian populations, while data for Asians are scarce. Here, we investigated the possible contribution of these SNPs to breast cancer risk in Pakistani breast cancer patients and in controls participating in a hospital-based breast cancer case-control study (PAK-BCCC).MethodsGenotyping of the BsmI and FokI SNPs was performed by PCR-based restriction fragment length polymorphism (RFLP) analysis of 463 genetically enriched female breast cancer cases with known BRCA1/2 status and in 1,012 controls from Pakistan. The association between SNP genotypes and breast cancer risk was investigated by logistic regression adjusted for potential breast cancer risk factors and stratified by BRCA1/2 status and family history. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported.ResultsThe b allele of the BsmI was associated with an increased breast cancer risk (per b allele OR 1.28, 95% CI 1.09–1.49, P = 0.003). Subgroup analysis revealed that this effect was restricted to BRCA1/2 non-carriers (per b allele OR 1.33, 95% CI 1.11–1.59, P = 0.002) and was stronger in those who reported a positive family history of breast and/or ovarian cancer (per b allele OR 1.64, 95% CI 1.20–2.22, P = 0.002). No association with breast cancer risk was detected for the FokI SNP.ConclusionsThe BsmI polymorphism in the VDR gene may be associated with an increased breast cancer risk in Pakistani women negative for BRCA1/2 germline mutations.

Background and Aim: The five-year survival for women with stage I-II breast cancer is 93-100%. Despite standard of care treatment, a small subset of these women suffer early breast cancer-specific mortality and die within 12 months of diagnosis. This subset of women has not been previously described. The aim of this study is to characterize the incidence, demographics, and clinical characteristics of women with early stage breast cancer who suffer early breast cancer-specific mortality. Methods: Retrospective population study of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry of women diagnosed with stage I, IIA, or IIB breast cancer between 2004 and 2010. Data were filtered to histology codes 8500-8543 and 8575. Patient demographics (age, race, ethnicity) and clinical characteristics (stage, T stage, N stage, grade, ER status, PR status) of women in the early mortality subset were compared with those of women who survived > 12 months via the Chi-square test and the student t-test. Results: 259,380 women formed the basis of our analysis. 4,572 women (0.018%) died within 12 months of diagnosis. Compared with those who survived > 12 months, women who suffered early breast cancer-specific mortality were on average older (mean age 65.7 years versus 60.3 years, p<0.00001) and more likely to be Hispanic (14.3% versus 8.9%, p<0.00001) or black (11.0% versus 9.1%, p<0.00001). Clinical characteristics associated with early mortality included higher stage (stage IIA 34.2% versus 29.4%, stage IIB 21.8% versus 12.9%, p<0.00001), higher T stage (T2 40.5% versus 28.1%, T3 3.1% versus 1.6%, p<0.00001), higher N stage (N1 29.7% versus 23.2%, N2 0.8% versus 0.4%, N3 0.4% versus 0.1%, p<0.00001), higher grade (moderate 39.3% versus 42.5%, high 40.0% versus 31.5%, p<0.00001), higher rates of ER negativity (27.2% versus 19.0%, p<0.00001), and higher rates of PR negativity (38.5% versus 30.2%, p<0.00001). Conclusions: Breast cancer-specific mortality within 12 months of diagnosis of stage I-II breast cancer is a rare phenomenon which has not been previously characterized. There are several demographic and clinical features associated with early mortality, however further research is needed to identify specific prognostic factors that will allow identification of women at risk for early mortality at the time of diagnosis. Citation Format: Johnson HM, Wong JH, Vohra NA, Muzaffar M. Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-21.