Abstract 5728: HIV tropism and decreased risk of breast cancer among women in the United States
Authors: Goedert James J. , Napolitano Laura A. , Lie Yolana , Smith Dawn , Levine Alexandra , Young Mary , Cohen Mardge , Minkoff Howard , Anastos Kathryn , D'Souza Gypsyamber , Greenblatt Ruth M. , Hessol Nancy 
Published: February 2011

Abstract
Objective: Envelope (env) of X4 strains of HIV binds exclusively to the CXCR4 chemokine receptor, which is commonly and highly expressed on neoplastic breast duct cells. Binding of X4-env protein, but not R5-env protein, can induce apoptosis of neoplastic breast cells. We postulated that HIV viral tropism, specifically strains that use CXCR4, may account for the &gt;30% reduction in breast cancer incidence observed in HIV-infected women in the USA before effective antiretroviral therapy was available.
Methods: A retrospective case-control study of women who developed breast cancer during 1993-2008 in the WIHS and HERS longitudinal studies. Cases were HIV-infected women who had stored plasma samples within 24 months (before or after) of a confirmed breast adenocarcinoma diagnosis and who had HIV viral load ≥500 copies/mL. Three HIV-infected women controls, without breast cancer, were matched to each case based on age (±2 yrs) and date of plasma specimen collection. The Monogram Biosciences Trofile assay was used to classify women who had X4-tropic (including X4/R5-tropic) versus exclusively R5-tropic HIV. Unadjusted and adjusted conditional logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for breast cancer associated with tropism, contemporaneous HIV viral load and CD4 count, antiretroviral therapy, and classical breast cancer risk factors from questionnaires.
Results: 22 breast cancer cases and 66 matched controls met the inclusion criteria and had valid HIV tropism results. Only 2 (9.1%) breast cancer cases had CXCR4-using HIV, compared to 19 (28.8%) of the matched controls (OR=0.20, 95% CI 0.04-1.0). In univariate analysis of 19 variables, breast cancer was inversely associated with CXCR4-using HIV (P=0.05), and marginally associated with menstrual status (P=0.10). In multivariate conditional regression analysis adjusted for CXCR4-using HIV and menstruation in the past 12 months, both variables were significantly associated with reduced odds of breast cancer (CXCR4-using HIV ORadj=0.10, 95% CI 0.01-0.93; menstruation in the past 12 months ORadj=0.07, 95% CI 0.005-0.92). Other classical breast cancer risk factors, HIV viral load, CD4 cell count, antiretroviral therapy, and race/ethnicity had no detectable impact on these associations. Our results imply that CXCR4-using HIV may account for a 24-27% reduction in breast cancer incidence, assuming our population is representative of HIV-infected women in the USA.
Conclusion: These results support the hypothesis that the low breast cancer incidence observed in women with HIV/AIDS is specifically tied to circulating variants of HIV that bind to and signal through CXCR4, a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. If confirmed, these findings of a large risk reduction, suggest that pharmacologic therapy directed at CXCR4 might reduce breast cancer risk for women in general.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5728.