1. BREAST CANCER IN SETTING OF HIGH HIV PREVALENCE
Agnes Moses MD, MMED
U54 MCC Mentee/UNC PROJECT

2. Comparison of Clinical and Pathological Features of Breast Cancers between HIV positive Women and HIV negative Women in Malawi

3. Background/ Significance
Breast cancer is the second most common cancer among women in sub-Saharan Africa (SSA) and 4th commonest in Malawi. Recent prospective studies from Mali and Ethiopia describe high prevalence of triple-negative disease as a challenge but these studies were conducted in countries with low HIV prevalence and without specific consideration of HIV status among breast cancer cases.

4. Breast Cancer in the Context of HIV
An unpublished single center retrospective( Zimbabwe), suggested HIV infection worsened the course of breast cancer and conferred poor treatment tolerability.
The impact of HIV on clinical presentations, and outcomes in HIV-infected patients is still unclear.
Therefore, the intersection of these two diseases needs to be better understood to guide optimal management.

5. Available Data
Our previous work at KCH revealed that 55% of women diagnosed with breast cancer at KCH were <50 years ( median age of 34),with most women having histological grade 3 tumors.
KCH Cancer Registry in Malawi records approximately 50 new breast cancer cases per year. Of the available data from registry, of the 369 breast cancer cases, 23.4% are HIV-positive.

6. Objectives
Describe and compare clinical and pathological characteristics including Hormonal Receptor(HR) status of HIV-positive and HIV-negative breast cancer cases at KCH.
Describe and compare chemotherapy tolerability and outcomes including toxicities, completion rates, and achievable cumulative dose between HIV-positive and HIV-negative breast cancer patients.

7. Methodology
Prospective cohort, initially 60 women now will increase to likely 100 after NHSRC response.
All consenting women 18 years or above, with, pathologically confirmed breast cancer at KCH will be eligible to participate.
Standardised clinical forms for collection of demographic, clinical information will be administered
duration: 2 yrs

8. Procedures
At entry,an initial standardized assessment will include collection of sociodemographic data, Clinical examination plus staging, HIV testing, as well as results of laboratory and radiologic studies.
Confirmed breast cancer cases will have hormone receptor (HR) and Ki-67 assessed by IHC, as well as histologic grade, using the full Nottingham grading scale, all of which can be done on-site in Lilongwe.
Data will be entered into a dedicated breast cancer database by trained study staff.

9. Schedule of Events

10. Statistical Consideration
Sample size: initial sample size of 60
with p value of 0.05 and Power of 0.8, we will need 15 HIV positive cases and 45 HIV negative cases to be able to reject the Null Hypothesis that HIV Positive women with breast cancer have same chemotherapy tolerability as their HIV negative counterparts
Correlations between HIV status and clinical features and pathological features will be assessed using Pearson’s Chi-square and t-tests

11. Outcome measures Pathology, Histology grade including HR status
Chemotherapy tolerability will be measured NCI Common Terminology Criteria
Overall and progression-free survival rates
Quality of Life

12. Impact
These data will allow for preliminary baseline estimates of progression-free and overall survival for Malawian women with breast cancer including those with breast cancer and HIV infection.
Additionally, these data will allow assess impact of HIV on breast cancer; define hormonal status of breast tumors in Malawi, and guide use of tamoxifen in local setting.

13. Progress Submitted to NHRS Under Breast Cancer Cohort in Malawi
Initial responses received and protocol being reviewed for resubmission
Breast cancer data base draft form initiated and currently and review
Slated to start October .