HIV tropism and decreased risk of breast cancer

Nancy A. Hessol, Laura A. Napolitano, Dawn Smith, Yolanda Lie, Alexandra Levine, Mary Young, Mardge Cohen, Howard Minkoff, Kathryn Anastos, Gypsyamber D'Souza, Ruth M. Greenblatt, James J. Goedert

Research output: Contribution to journalArticle

Abstract

Background: During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection. Methods and Findings: We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load ≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer. Conclusions: Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.

Original languageEnglish (US)
Article numbere14349
JournalPLoS One
Volume5
Issue number12
DOIs
StatePublished - 2010

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tropisms
Tropism
risk reduction
Human immunodeficiency virus
Viruses
breast neoplasms
HIV
Breast Neoplasms
Tropics
odds ratio
breasts
confidence interval
tropics
Breast
Odds Ratio
HIV infections
Virus Diseases
Confidence Intervals
viral load
Viral Load

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hessol, N. A., Napolitano, L. A., Smith, D., Lie, Y., Levine, A., Young, M., ... Goedert, J. J. (2010). HIV tropism and decreased risk of breast cancer. PLoS One, 5(12), [e14349]. https://doi.org/10.1371/journal.pone.0014349

HIV tropism and decreased risk of breast cancer. / Hessol, Nancy A.; Napolitano, Laura A.; Smith, Dawn; Lie, Yolanda; Levine, Alexandra; Young, Mary; Cohen, Mardge; Minkoff, Howard; Anastos, Kathryn; D'Souza, Gypsyamber; Greenblatt, Ruth M.; Goedert, James J.

In: PLoS One, Vol. 5, No. 12, e14349, 2010.

Research output: Contribution to journalArticle

Hessol, NA, Napolitano, LA, Smith, D, Lie, Y, Levine, A, Young, M, Cohen, M, Minkoff, H, Anastos, K, D'Souza, G, Greenblatt, RM & Goedert, JJ 2010, 'HIV tropism and decreased risk of breast cancer', PLoS One, vol. 5, no. 12, e14349. https://doi.org/10.1371/journal.pone.0014349
Hessol NA, Napolitano LA, Smith D, Lie Y, Levine A, Young M et al. HIV tropism and decreased risk of breast cancer. PLoS One. 2010;5(12). e14349. https://doi.org/10.1371/journal.pone.0014349
Hessol, Nancy A. ; Napolitano, Laura A. ; Smith, Dawn ; Lie, Yolanda ; Levine, Alexandra ; Young, Mary ; Cohen, Mardge ; Minkoff, Howard ; Anastos, Kathryn ; D'Souza, Gypsyamber ; Greenblatt, Ruth M. ; Goedert, James J. / HIV tropism and decreased risk of breast cancer. In: PLoS One. 2010 ; Vol. 5, No. 12.
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abstract = "Background: During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection. Methods and Findings: We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load ≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95{\%} confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9{\%}) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28{\%}) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95{\%} CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95{\%} CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer. Conclusions: Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.",
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AU - Smith, Dawn

AU - Lie, Yolanda

AU - Levine, Alexandra

AU - Young, Mary

AU - Cohen, Mardge

AU - Minkoff, Howard

AU - Anastos, Kathryn

AU - D'Souza, Gypsyamber

AU - Greenblatt, Ruth M.

AU - Goedert, James J.

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N2 - Background: During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection. Methods and Findings: We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load ≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer. Conclusions: Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.

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