Background: Vitamin D has been shown, in vitro, to promote differentiation and apoptosis while suppressing proliferation of breast cancer cells. Breast cancer cell lines show improved responsiveness to chemotherapy after pretreatment with vitamin D. This relationship has not been explored in breast cancer patients. The objective of this study was to determine whether pretreatment vitamin D levels were associated with response to neoadjuvant chemotherapy. Secondary aims examined relationships between serum vitamin D levels, tumor biomarkers and survival.

Methods: Study patients were enrolled on the I-SPY TRIAL of neoadjuvant chemotherapy for locally-advanced breast cancer, had tumors that were Her2-negative and had pretreatment serum available. Vitamin D levels were measured using the Diasorin radioimmunoassay. Outcomes included pathologic complete response (pCR)/residual cancer burden (RCB) and 3-year recurrence-free survival (RFS). The study had 80% power to detect an increase in the odds of response of 9.8% or more for every one ng/mL increase in serum vitamin D with a two sided α=0.05. Statistical analyses were performed using STATA software (Version 12). Logistic regression was used for multivariate modeling.

Results: 157 subjects with Her2-negative tumors were enrolled on I-SPY1; 82 of these patients had serum available for analysis. The mean vitamin D value was 22.7ng/mL (SD 11.9), the median was 23.1ng/mL (IQR 13.08 to 30.52ng/mL); only 28% had “sufficient” levels (>30ng/mL). Vitamin D level was significantly lower in those of non-Caucasian race (p = 0.0001), with blood collected in winter/spring (p = 0.009) and with increasing body mass index (BMI; p-trend=0.01). Higher vitamin D levels were also associated with lower tumor Ki67 (OR 0.95, 95%CI 0.91, 0.99, p = 0.017). Vitamin D level was not associated with achievement of pCR in univariable analysis (OR 1.01, 95% CI 0.96, 1.05) and after adjustment for hormone receptor status (HRS; OR 1.02, 95%CI 0.97, 1.07), tumor grade (OR 1.01, 95%CI 0.96, 1.06), Ki67 (OR 1.02, 95%CI 0.97, 1.07) or BMI (OR 1.00, 95%CI 0.96, 1.05). Vitamin D was independently associated with Ki67 (OR 0.95, 95%CI 0.91, 0.99). Vitamin D level was also not associated with 3 year RFS in univariable analysis (HR 0.98, 95% CI 0.95, 1.02), and after adjustment for HRS (HR 0.99, 95%CI 0.95, 1.03), tumor grade (HR 0.99, 95%CI 0.95, 1.02), Ki-67 (HR 0.99, 95%CI 0.95, 1.03), BMI (HR 0.96, 95% CI 0.92, 1.01) or pCR (HR 0.99, 0.95, 1.02); no interaction was seen when stratifying on HRS (p-interaction= 0.71).

Conclusions: The majority of patients in this study had insufficient vitamin D levels (<30ng/mL) at the time of diagnosis of breast cancer. Pre-chemotherapy vitamin D level did not predict response to neoadjuvant chemotherapy in these Her2-negative patients, despite being significantly associated with tumor proliferation, as measured by Ki-67; nor was it independently associated with RFS.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-10.