The impact of HIV on non-adherence for tamoxifen among women with breast cancer in South Africa.

PURPOSE: Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-negative women with BC, and poor adherence to prescribed tamoxifen is known to contribute to poor survival. We therefore investigated the association of HIV infection with adherence to adjuvant tamoxifen among women with localized hormone receptor (HR)-positive breast cancer in South Africa. METHODS: Among 4,097 women diagnosed with breast cancer at six hospitals in the prospective South African Breast Cancer and HIV Outcomes (SABCHO) cohort study between July 2015 and December 2020, we focused on black women with stages I-III HR-positive breast cancer who were prescribed 20 mg of adjuvant tamoxifen daily. We collected venous blood once from each participant during a routine clinic visit, and analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We defined non-adherence as a tamoxifen level < 60 ng/mL after 3 months of daily tamoxifen use. We compared tamoxifen-related side effects, and concurrent medication use among women with and without HIV and developed multivariable logistic regression models of tamoxifen non-adherence. RESULTS: Among 369 subjects, 78 (21.1%) were WLWH and 291 (78.9%) were HIV-negative. After a median (interquartile range) time of 13.0 (6.2-25.2) months since tamoxifen initiation, the tamoxifen serum concentration ranged between 1.54 and 943.0 ng/mL and 208 (56.4%) women were non-adherent to tamoxifen. Women < 40 years of age were more likely to be non-adherent than women > 60 years (73.4% vs 52.6%, odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.26-4.94); likewise, WLWH (70.5% vs 52.6%, OR = 2.16, 95% CI = 1.26-3.70) than HIV-negative women. In an adjusted model WLWH had twice the odds of non-adherence to tamoxifen, compared to HIV-negative women (OR = 2.40, 95% CI = 1.11-5.20). CONCLUSION: High rates of non-adherence to adjuvant tamoxifen may limit the overall survival of black South African women with HR-positive breast cancer, especially among WLWH.

Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer in a population with a high HIV prevalence in Johannesburg, South Africa.

BACKGROUND: Neoadjuvant (primary) chemotherapy (NACT) is the standard of care for locally advanced breast cancer. It also allows for the short-term assessment of chemotherapy response; a pathological complete responses correspond to improved long-term breast cancer outcomes. In sub-Saharan Africa, many patients are diagnosed with large nonresectable tumors. We examined NACT use in breast cancer patients who visited public hospitals in Johannesburg, South Africa. METHODS: We assessed demographic characteristics, tumor stage and grade, hormone receptor status, and human immunodeficiency virus (HIV) status of female patients diagnosed with nonmetastatic invasive carcinoma of the breast at Chris Hani Baragwanath Academic Hospital between January 1, 2009, and December 31, 2011. The patients received neoadjuvant, adjuvant, or no chemotherapy. Trastuzumab was unavailable. We developed logistic regression models to analyze the factors associated with NACT receipt in these patients. RESULTS: Of 554 women with nonmetastatic breast cancer, the median age at diagnosis was 52 years (range: 28-88 years). Only 5.8% of patients were diagnosed with stage I disease; 49.3% and 44.9% were diagnosed with stages II and III, respectively. Most patients had hormone-responsive tumors: luminal A, 38.1%; luminal B1 (human epidermal growth factor receptor 2 [HER2]-negative and high grade), 12.5%, and luminal B2 (HER2-positive any grade), 11.6%; 11.6% had a HER2-enriched tumor and 20.6% a triple-negative tumor. Eighty (14.4%) patients were HIV-positive. In total, 195 patients (35.2%) received NACT, 264 (47.7%) patients received adjuvant chemotherapy, and 95 patients (17.1%) received no chemotherapy, including 62 (11.2%) patients who received only hormonal therapy. Of patients receiving NACT, 125 (64.1%) were evaluable for clinical response. Eighty (64.0%) patients had a clinically significant response; 19 (15.2%) patients had a stable disease, and 26 (20.8%) patients had a progressive disease. Multivariate analysis showed age <40 years and disease stage to be independently associated with the receipt of NACT. CONCLUSION: Most women receiving NACT with available response data showed a clinical benefit. Stage III disease at diagnosis and age <40 years were predictors of neoadjuvant versus adjuvant chemotherapy treatment.

Breast cancer survival in Soweto, Johannesburg, South Africa: A receptor-defined cohort of women diagnosed from 2009 to 11.

BACKGROUND: South Africa's public healthcare system is better equipped to manage breast cancer than most other SSA countries, but survival rates are unknown. METHODS: A historical cohort of 602 women newly diagnosed with invasive breast carcinoma during 2009-2011 at Chris Hani Baragwanath Academic Hospital, Soweto, Johannesburg, was followed using health systems data to December 2014. 'Overall survival' time was defined from diagnosis to death or terminal illness. Cox regression was used to estimate hazard ratios (HR) associated with woman and tumour characteristics. RESULTS: During a median 2.1 years follow-up (IQR 0.5-3.8), 149 women died or were classified terminally ill; 287 were lost-to-follow-up. 3-year survival was 84% for early stage (I/II) and 56% for late stage (III/IV) tumours (late v early: HR 2.8 (95% confidence interval (CI): 1.9-4.1), however the 42% cumulative losses to follow-up over this period were greater for late stage, half of which occurred within 6 months of diagnosis. After mutual adjustment for stage, grade, age, receptor subtype and HIV status, lower survival was also associated with triple negative (HR 3.1 (95% CI: 1.9-5.0)) and HER2-enriched (2.5 (95% CI: 1.4-4.5)) compared to ER/PR+ HER2- tumours, but not with age or HIV-infection (1.4 (95% CI: 0.8, 2.3)). CONCLUSION: In this South African cohort, breast cancer survival is suboptimal, but was better for early stage and hormone receptor-positive tumours. Efforts to reduce clinic losses in the immediate post-diagnosis period, in addition to early presentation and accelerated diagnosis and treatment, are needed to prevent breast cancer deaths, and survival improvements need to be monitored using prospective studies with active follow-up.

Breast conservation surgery versus total mastectomy among women with localized breast cancer in Soweto, South Africa.

PURPOSE: Breast conserving surgery (BCS) has become the preferred surgical option for the management of patients with nonmetastatic breast cancer in high-income countries. However, little is known about the distribution and determinants of BCS in low-and middle-income countries, especially those with high HIV prevalence. METHODS: We compared demographic and clinical characteristics of female patients who received BCS and those who received total mastectomy (TM) for nonmetastatic invasive carcinoma of the breast in Soweto, South Africa, 2009-2011. We also developed a multivariable logistic regression model of predictors of type of surgery. RESULTS: Of 445 patients, 354 (80%) underwent TM and 91 (20%) BCS. Of 373 patients screened for HIV, 59 (15.8%) tested positive. Eighty-two of 294 patients with stage I/II disease (28%), but just 9 of 151 (6%) with stage III disease had BCS (p<0.001). All women who received BCS (except for seven who received completion mastectomy within 6 weeks of BCS) and 235 (66.4%) women who received TM were referred for radiation therapy (RT). In our multivariable analysis, age group 50-59 years (OR = 2.28, 95% CI = 1.1-4.8) and ≥70 years (OR = 9.55, 95% CI = 2.9-31.2) vs. age group <40 years, stage at diagnosis (stage II (OR = 3.79, 95% CI = 1.6-8.2) and stage III (OR = 27.8, 95% CI = 9.0-78.8) vs. stage 1, HIV (HIV positive (OR = 3.19, 95% CI = 1.3-7.9) vs. HIV negative) and HER2-enriched subtype (OR = 3.50, 95% CI = 1.2-10.1) vs. triple negative were independently associated with TM. CONCLUSION: TM was more common than BCS among patients with nonmetastatic breast cancer in Soweto, not only among patients with locally advanced disease at diagnosis, but also among women with stage I and II disease.