As antiretroviral therapy (ART) improves survival among HIV-infected individuals, they become susceptible to the diseases of middle and older ages, including epithelial malignancies. In sub-Saharan Africa, where HIV prevalence approaches 20%, breast cancer has become the most common malignancy and cause of cancer-related death among women. Few studies have addressed the effects of HIV infection and ART on the clinical presentation, treatment, and prognosis of breast cancer. We propose to investigate those effects amongst women in South Africa. We plan to compare HIV-infected and -uninfected breast cancer patients with respect to the presentation (including stage) of the cancer, tolerance and toxicity of treatment, and ultimately survival, taking ART and other prognostic factors into account. In our prior work, we studied demographic and clinical characteristics of 1200 breast cancer patients, of whom 18% were HIV+, diagnosed between 2007 and 2012 at the Chris Hani Baragwanath Academic Hospital Breast Clinic (CHBBC) located in Soweto, Johannesburg. This collaborative research program involving University of the Witwatersrand (Wits), Columbia University Medical Center (CUMC) and International Agency for Research on Cancer (IARC) partners has yielded 3 publications to date (the Wits contact PI and PD are former CUMC D43 trainees). We are now adding to our collaboration breast surgeons and oncologists at 5 other South African urban, peri-urban, and rural academic hospital centers where 3000 subjects will be recruited and followed for treatment and survival. Biomarkers relevant to HIV and aggressive tumor biology will be studied in a subset of patients using the PAM50 genomic assay on the NanoString Counter Platform. The Consortium constitutes a pan-South African network and base for further research on HIV and breast (and other) cancers. The CUMC collaborators will continue to provide guidance, especially for new investigators in the Consortium. Senior biostatisticians from Wits and CUMC will develop and guide the data analysis plan. Experienced CHBBC database developers in collaboration with our IARC consultant and m-Health Mobenzi platform developer in South Africa will integrate the standardized data collected from real-time m-Health technologies with existing databases at the 6 hospital sites to enable access-controlled data sharing. Two Wits PIs and the CUMC PI will lead the Consortium and meet on a regular schedule as will other senior investigators, as detailed in the proposal. Letters confirming enthusiastic participation and of support from Wits, the U KwaZulu- Natal, U Cape Town IARC and CANSA South Africa are attached.
No prior large-scale multicenter, multiethnic prospective study has evaluated the impact of HIV and ART on breast cancer survival in sub-Saharan Africa. Given the rising incidence rates of breast cancer in regions with high HIV prevalence, such research is essential for optimum management of this most female cancer. These analyses will contribute to the development of evidence-based guidelines for management of breast cancer in HIV-positive women and will yield new insights into both HIV and breast cancer
