title: 25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.
abstract: Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.forename: Reena S
authors.initials: RS
authors.lastname: Cecchini
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Samantha
authors.initials: S
authors.lastname: Beddows
authors.forename: Nicola
authors.initials: N
authors.lastname: Hood
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Goodwin
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D016017:Odds Ratio; D012306:Risk; D013629:Tamoxifen / Q000627:therapeutic use*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007328:Insulin; D020738:Leptin; D013629:Tamoxifen; D014807:Vitamin D; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D