11158 Background: Sub-Saharan Africa (SSA) has very low breast cancer (BC) survival. South Africa, unlike most SSA countries, is an upper middle-income country where patients are less burdened with cancer diagnostic and treatment costs. We aimed to provide five-year overall survival (OS) estimates and determinants among South African women with BC diagnosed and treated within the public health system. Methods: The South African Breast Cancer and HIV Outcomes prospective cohort study enrolled adult women recently diagnosed with invasive BC from four South African academic hospitals. We collected detailed sociodemographic, clinical, treatment, and outcomes data. Women were followed for five years or until December 31, 2023, whichever was earlier, and our primary outcome was five-year OS. Impacts of potential determinants on OS were assessed using individual Cox proportional hazard models focused on nine variable domains ( i.e., treating hospital, social status, BC risk factors, smoking, cardiovascular disease (CVD), HIV status, BC type, BC treatments, and age) and a combined model that also included adjustments for background mortality. Results: Between July 2015 and Feb 2019, we enrolled 2,838 women newly diagnosed with histopathologically confirmed invasive BC, of whom 58% had III or IV disease. At the end of follow-up, 1555 (55%) of the women had died, 1191 (42%) survived for five years, 33 (1%) were censored at study’s end, and 59 (2%) were lost to follow up. The five-year OS was 44.3% (95% CI 42.5-46.2). In the full model, the variables with the largest impact on five-year survival were late-stage at diagnosis (HR 2.4 [95% CI 2.0-2.7] for stage III and HR 5.0 [95% CI 4.1-6.1] for stage IV disease, both compared with stage I/II) and differing degree of treatments received (no treatment received: HR 8.2 [95% CI 5.9-11.3]; chemotherapy and endocrine therapy: HR 1.9 [95% CI 1.4-2.6]; endocrine therapy only: HR 2.2 [95% CI 1.6-3.2]; chemotherapy only: HR 4.8 [95% CI 3.4-6.6]; surgery only: HR 3.0 [95% CI 1.9-4.8]; surgery and chemotherapy: HR 1.8 [95% CI 1.3-2.5], all compared with surgery and endocrine treatments). Other variables significantly associated with survival were treating hospital, relationship status, employment, education, family history of cancer, CVD, and HIV infection. Conclusions: Interventions to improve BC survival in South Africa’s public health system should prioritize earlier diagnosis of cancer and expansion of the infrastructure supporting diagnostic and treatment services. Concurrently, South African BC patients with low socioeconomic status, HIV infection, and/or comorbid CVD are uniquely vulnerable and their barriers to accessing care must be better understood.

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BACKGROUND:Breast cancer is the most common malignancy diagnosed among women in South Africa, with the aggressive triple-negative subtype comprising approximately 15% of breast cancers in this population. South Africa has the largest population of people with HIV in the world. This study aims to evaluate the association between HIV status and the proportion of patients with breast cancer with the triple-negative subtype. METHODS:We did a cross-sectional analysis of case-only data from the South African Breast Cancer and HIV Outcomes (SABCHO) study, a prospective cohort study recruiting patients with newly diagnosed breast cancer at six public hospitals in South Africa. We analysed data from patients who enrolled in SABCHO between Jan 1, 2015, and Jan 18, 2022. Women aged 18 years or older with newly diagnosed and histologically confirmed invasive breast cancer were eligible. Participants were classified as HIV-positive or HIV-negative by use of an ELISA-based HIV test done at the time of enrolment. We developed multivariable logistic regression models to test for an association between HIV status and the proportion of triple-negative relative to non-triple-negative breast cancers while adjusting for demographic and reproductive risk factors. FINDINGS:Of the 4122 patients enrolled in the SABCHO cohort within our study timeframe, 239 patients were excluded due to unknown breast cancer subtype (n=141), HIV status (n=97), or race (n=1). 3883 women with breast cancer were included in the study, of whom 637 (16·4%) had triple-negative breast cancer, 894 (23·0%) were HIV-positive, and 186 (4·8%) had triple-negative breast cancer and HIV. Triple-negative breast cancer accounted for 186 (20·8%) of 894 breast cancers among women who were HIV-positive and 451 (15·1%) of 2989 breast cancers among women who were HIV-negative (p<0·0001). In the fully adjusted logistic regression model, HIV-positive status was associated with an increased proportion of triple-negative breast cancer (adjusted odds ratio [OR] 1·39, 95% CI 1·12-1·74, compared with women who were HIV-negative). When compared with women who were HIV-negative, the association between HIV-positive status and the proportion of triple-negative breast cancer was strongest among the subgroup of women with a duration of HIV infection of 2 years or longer (1·57, 1·23-2·00) and those on antiretroviral therapy (ART; 1·47, 1·16-1·87). INTERPRETATION:Patients with breast cancer and chronic HIV who are on ART are more likely to have triple-negative breast cancer than patients with breast cancer without HIV. This association is independent of age, race, and reproductive factors. FUNDING:US National Institutes of Health, University of the Witwatersrand, South Africa Medical Research Council Common Epithelial Cancers Research Center, Conquer Cancer Foundation, and Varmus Global Scholars Fund.

Background: The oncology consultation following surgery for colorectal cancer (CRC) is usually the first step in the receipt of chemotherapy. Non-compliance with this consultation results in non-receipt of recommended chemotherapy, when appropriate, and worse clinical outcomes. This study sought to explore South African patients’ attitudes and perceptions around attending scheduled oncology consultations following their CRC surgery.Methods: Semi-structured qualitative interviews were conducted with patients who had surgery for CRC at a quaternary South African hospital and who had to decide whether they would return for an oncology consultation. The “Model of health services use” informed the design of the interview guide, which included questions on factors that impact health seeking behavior. Demographics of participants, CRC disease stage, and compliance with scheduled oncology consultations were also collected. Descriptive statistics were used to analyse the quantitative data, while deductive thematic analysis was used to analyse the qualitative data.Results: Seven participants were interviewed. The median age was 60.0 years and four participants (57.1%) were female. Black African, White, and Asian participants accounted for 85.7% of the study sample. Most participants had stage III CRC (71.4%). The oncology consultation no-show rate was 14.3%. Participant’s knowledge and beliefs around CRC proved to be an important predisposing factor that influenced follow-up decisions. Family support and religion were cited as important enabling factors. Travel costs to the hospital and frustrations related to the clinic appointment booking/scheduling process were cited as important disabling factors. Lastly, the participant’s self-perceived need for additional oncology care also appeared to influence their decision to return for ongoing oncology consultation after the initial surgery.Conclusion: Several contextual factors can potentially influence a patient’s compliance with a scheduled oncology consultation following CRC surgery. A multipronged approach which addresses these factors is required to improve compliance with oncology consultations.

Background Breast cancer survival in South Africa is low, but when diagnosed with breast cancer, many women in South Africa also have other chronic conditions. We investigated the impact of multimorbidity (≥ 2 other chronic conditions) on overall survival among women with breast cancer in South Africa. Methods Between 1 July 2015 and 31 December 2019, we enrolled women newly diagnosed with breast cancer at six public hospitals participating in the South African Breast Cancer and HIV Outcomes (SABCHO) Study. We examined seven chronic conditions (obesity, hypertension, diabetes, HIV, cerebrovascular diseases (CVD), asthma/chronic obstructive pulmonary disease, and tuberculosis), and we compared socio-demographic, clinical, and treatment factors between patients with and without each condition, and with and without multimorbidity. We investigated the association of multimorbidity with overall survival using multivariable Cox proportional hazard models. Results Of 3,261 women included in the analysis, 45% had multimorbidity; obesity (53%), hypertension (41%), HIV (22%), and diabetes (13%) were the most common individual conditions. Women with multimorbidity had poorer overall survival at 3 years than women without multimorbidity in both the full cohort (60.8% vs. 64.3%, p = 0.036) and stage groups: stages I–II, 80.7% vs. 86.3% ( p = 0.005), and stage III, 53.0% vs. 59.4% ( p = 0.024). In an adjusted model, women with diabetes (hazard ratio (HR) = 1.20, 95% confidence interval (CI) = 1.03–1.41), CVD (HR = 1.43, 95% CI = 1.17–1.76), HIV (HR = 1.21, 95% CI = 1.06–1.38), obesity + HIV (HR = 1.24 95% CI = 1.04–1.48), and multimorbidity (HR = 1.26, 95% CI = 1.13–1.40) had poorer overall survival than women without these conditions. Conclusions Irrespective of the stage, multimorbidity at breast cancer diagnosis was an important prognostic factor for survival in our SABCHO cohort. The high prevalence of multimorbidity in our cohort calls for more comprehensive care to improve outcomes for South African women with breast cancer.

Objective In low- and middle-income countries (LMICs), advanced-stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. Understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. Methods Within the South African Breast Cancers and HIV Outcomes (SABCHO) cohort, we examined factors affecting the stage at diagnosis of histologically confirmed invasive breast cancer at five tertiary hospitals in South Africa (SA). The stage was assessed clinically. To examine the associations of the modifiable health system, socio-economic/household and non-modifiable individual factors, hierarchical multivariable logistic regression with odds of late-stage at diagnosis (stage III-IV), was used. Results The majority (59%) of the included 3497 women were diagnosed with late-stage BC disease. The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adjusted for both socio-economic- and individual-level factors. Women diagnosed in a tertiary hospital that predominantly serves a rural population were 3 times (OR = 2.89 (95% CI: 1.40–5.97) as likely to be associated with late-stage BC diagnosis when compared to those diagnosed at a hospital that predominantly serves an urban population. Taking more than 3 months from identifying the BC problem to the first health system entry (OR = 1.66 (95% CI: 1.38–2.00)), and having luminal B (OR = 1.49 (95% CI: 1.19–1.87)) or HER2-enriched (OR = 1.64 (95% CI: 1.16–2.32)) molecular subtype as compared to luminal A, were associated with a late-stage diagnosis. Whilst having a higher socio-economic level (a wealth index of 5) reduced the probability of late-stage BC at diagnosis, (OR = 0.64 (95% CI: 0.47–0.85)). Conclusion Advanced-stage diagnosis of BC among women in SA who access health services through the public health system was associated with both modifiable health system-level factors and non-modifiable individual-level factors. These may be considered as elements in interventions to reduce the time to diagnosis of breast cancer in women.

6583 Background: Breast cancer (BC) mortality in South Africa (SA) is double that of the United States. The aggressive triple-negative breast cancer (TNBC) subtype comprises 20.9% of BC cases among Black women in Southern Africa. SA has the second highest HIV prevalence worldwide, but if and how HIV affects the risk of developing TNBC is not well understood. Methods: Using the South African Breast Cancer and HIV Outcomes (SABCHO) prospective cohort of newly diagnosed BC patients from six public hospitals in SA, we evaluated the association of HIV with risk of TNBC relative to other BC subtypes. We developed multivariable logistic regression models to test for this association while adjusting for key demographic and reproductive risk factors. Results: Of 3,883 women with BC, 16.4% had TNBC and 23.0% were HIV-positive. The overall median age of BC diagnosis was 55 years. Among HIV positive patients, the median age of BC diagnosis was 45 years, without a difference between TNBC and non-TNBC cases (p = 0.244). Only 7.2% of women were nulliparous (4.6% in TNBC and 7.6% in non-TNBC subgroups). Of women who had at least 1 full-term pregnancy, 11.2% did not breastfeed, without a difference between TNBC and non-TNBC cases (p = 0.292). In our final multivariable logistic regression model, HIV-positive status was associated with increased risk of TNBC relative to non-TNBC (OR: 1.40; 95% CI: 1.12-1.74, compared to HIV-negative with BC). Parity without breastfeeding was also associated with increased risk of TNBC relative to non-TNBC (OR: 1.72; 95% CI: 1.07-2.84, compared to nulliparous with BC). HIV status and the combined parity/breastfeeding variable had no statistically significant interaction. In exploratory analyses, measures of HIV control at time of BC diagnosis were not associated with BC subtype. Conclusions: In this large prospective case-only study conducted in SA, we found that women living with HIV were more likely than HIV-negative women to have TNBC (relative to other BC subtypes), regardless of the extent of HIV control. Whether this relationship is mediated by immune mechanisms or other factors should be the focus of future research. Our findings highlight the importance of rigorous BC screening and early detection among HIV-positive women given their increased relative risk of developing TNBC. [Table: see text]

This systematic review was conducted to investigate predictors of treatment refusal in colorectal cancer (CRC) patients. An understanding of these predictors would inform statistical models for the identification of high-risk patients who might benefit from interventions that seek to improve treatment compliance. We performed a search of PubMed and Scopus to identify potentially relevant studies on predictors of treatment refusal in CRC patients that were published between January 1, 2000 and December 31, 2021. We screened manuscripts using predefined eligibility criteria. Information on study design, study location, patient characteristics, treatments, rates and predictors of treatment refusal, and the impact of treatment refusal on mortality or survival were collected from eligible studies. Study quality was assessed using the Newcastle-Ottawa score. The overall findings of the review process were summarized using descriptive statistics and a narrative synthesis. A total of 13 studies were included in this review. Ten studies reported on refusal of CRC surgery, refusal rate: 0.25%-3.26%; three studies reported on chemotherapy refusal (one of which reported on both surgery and chemotherapy refusal), refusal rate: 7.8%-41.5%; and one study reported on refusal of any cancer treatment, refusal rate: 8.7%. The bulk of the published literature confirmed the harmful association between treatment refusal and poor survival outcomes in CRC patients. Frequently cited predictors of treatment refusal included patient demographic characteristics (age, race, gender), clinical characteristics (disease stage, comorbidity), and factors that impact access to cancer care services (healthcare insurance, facility level). Potentially high rates of treatment refusal pose a challenge to CRC control. This review has identified several factors which must be considered when attempting to reduce treatment refusal in CRC patients. Furthermore, these factors should be tested as components of predictive risk models for this important outcome.

The South African Breast Cancer and HIV Outcomes prospective cohort (SABCHO) study was established to investigate survival determinants among HIV-positive and HIV-negative SA women with breast cancer. This paper describes common and unique characteristics of the cancer centres and their participants, examining disparities in pathways to diagnosis, treatment resources and approaches adopted to mitigate resource constraints. The Johannesburg (Jhb), Soweto (Sow), and Durban (Dbn) sites treat mainly urban, relatively better educated and more socioeconomically advantaged patients whereas the Pietermaritzburg (Pmb) and Empangeni (Emp) sites treat predominantly rural, less educated and more impoverished communities The Sow, Jhb, and Emp sites had relatively younger patients (mean ages 54 ±14.5, 55±13.7 and 54±14.3 respectively), whereas patients at the Dbn and Pmb sites, with greater representation of Asian Indian women, were relatively older (mean age 57 ±13.9 and 58 ±14.6 respectively). HIV prevalence among the cohort was high, ranging from 15%-42%, (Cohort obesity (BMI ≥ 30 kg/m2) at 60%, self-reported hypertension (41%) and diabetes (13%). Direct referral of patients from primary care clinics to cancer centre occurred only at the Sow site which uniquely ran an open clinic and where early stage (I and II) proportions were highest at 48.5%. The other sites relied on indirect patient referral from regional hospitals where significant delays in diagnostics occurred and early-stage proportions were a low (15%- 37.3%). The Emp site referred patients for all treatments to the Dbn site located 200km away; the Sow site provided surgery and endocrine treatment services but referred patients to the Jhb site 30 Km away for chemo- and radiation therapy. The Jhb, Dbn and Pmb sites all provided complete oncology treatment services. All treatment centres followed international guidelines for their treatment approaches. Findings may inform policy interventions to address national and regional disparities in breast cancer care.

BACKGROUND:In high-income settings, delays from breast cancer (BC) diagnosis to initial treatment worsen overall survival (OS). We examined how time to BC treatment initiation (TTI) impacts OS in South Africa (SA). METHODS:We evaluated women enrolled in the South African BC and HIV Outcomes study between July 1, 2015 and June 30, 2019, selecting women with stages I-III BC who received surgery and chemotherapy. We constructed a linear regression model estimating the impact of sociodemographic and clinical factors on TTI and separate multivariable Cox proportional hazard models by first treatment (surgery and neoadjuvant chemotherapy (NAC)) assessing the effect of TTI (in 30-day increments) on OS. RESULTS:Of 1260 women, 45.6% had upfront surgery, 54.4% had NAC, and 19.5% initiated treatment >90 days after BC diagnosis. Compared to the surgery group, more women in the NAC group had stage III BC (34.8% vs 81.5%). Living further away from a hospital and having hormone receptor positive (vs negative) BC was associated with longer TTI (8 additional days per 100 km, P = .003 and 8 additional days, P = .01, respectively), while Ki67 proliferation index >20 and upfront surgery (vs NAC) was associated with shorter TTI (12 and 9 days earlier; P = .0001 and.007, respectively). Treatment initiation also differed among treating hospitals (P < .0001). Additional 30-day treatment delays were associated with worse survival in the surgery group (HR 1.11 [95%CI 1.003-1.22]), but not in the NAC group. CONCLUSIONS:Delays in BC treatment initiation are common in SA public hospitals and are associated with worse survival among women treated with upfront surgery.

Background: Brain metastases are relatively common and carry a poor prognosis. In a resource-constrained environment, the judicious use of radiotherapy must be considered in the context of its benefit. The Recursive Partitioning Analysis (RPA) scoring system is internationally validated to predict median survival in patients with brain metastases. It may be used to guide appropriate management of patients with brain metastases. Aim: To establish the relevance of applying the RPA prognostic scoring system to the local setting. Setting: The Department of Oncology, Greys Hospital, Pietermaritzburg, South Africa. Methods: A retrospective chart review of patients treated for brain metastases for the period 01 January 2014 to 31 December 2019 was performed. Data was collected to determine the RPA class for each patient. Multivariate analysis of potential factors which could impact survival was done, and the actual survival of each patient was calculated. Results: The commonest primary cancer in the study cohort was breast (67%), followed by lung (17%). Survival differences between RPA classes were statistically significant ( p < 0.001). Actual survival relative to that predicted by the RPA model was 4.5 versus 7–12 months, 3.6 versus 4–7 months, and 0.8 versus 2–4 months, for classes I, II and III, respectively. Conclusion: Results support the use of the RPA classification to risk stratify patients in this setting – and therefore may be used in treatment decision-making. However, it over-predicts the median survival for the local population. Larger studies are warranted in diagnostically homogenous patient groups with brain metastases, to determine survival more accurately.

INTRODUCTION:the burden of colorectal carcinoma (CRC), once considered rare in Africa, may be changing with the disease being increasingly diagnosed and there is a suggestion that age and race influence tumour behaviour. We sought to describe the clinicopathological spectrum of CRC among the different race and age groups in a South African setting. METHODS:analysis of prospectively collected data from an on-going colorectal cancer database, including demographics, clinical presentation, site, staging and grading on all patients enrolled over an 18-year period. RESULTS:a total of 2232 patients with CRC were accrued over the study period (Africans, 798; Indians, 890; Coloureds, 104; and Whites, 440). Mean age was 57.7 (SD 14.4) but varied considerably by race (p < 0.001) with Africans being significantly younger. Young adults (aged < 40 years) totalled 305 and older patients (aged > 40 years) totalled 1927. The proportion of young patients (< 40 years old) was 28%, 7%, 9% and 3% among Africans, Indian, Coloured and White patients respectively. There were minimal variations in anatomical sub-site distribution. There was no difference in tumour stage between the various races and between older and young adults. Mucinous differentiation was more common in Africans and in young patients and poor differentiation was more common in African patients. Africans had a significantly lower resection rate compared to the other race groups (p < 0.001). Younger patients had a significantly lower resection rate compared to the older age group (p < 0.001). CONCLUSION:African patients were the youngest compared to the other race groups. Mucinous differentiation predominated in Africans and young adults. Poor differentiation predominated in Africans. Resection rate was lower for African patients and in young patients.

Purpose Among patients diagnosed with breast cancer (BC), women also living with HIV (WLWH) have worse survival than women without HIV. Chronic HIV infection may interfere with the effectiveness of BC treatment, contributing to this disparity. We attempted to determine the impact of HIV infection on response to neoadjuvant chemotherapy (NACT) among South African women with BC. Methods We evaluated women from the South African Breast Cancer and HIV Outcomes cohort study who had stage I-III disease, initiated NACT, underwent definitive breast surgery, and had available surgical pathology reports. We compared pathologic complete response (pCR) rates among women with and without HIV infection, using multivariable logistic regression to control for differences in tumor characteristics. We also evaluated the impact of HIV infection on pCR within subgroups based on patient and tumor factors. Results Of 715 women, the 173 (24.2%) WLWH were less likely to achieve pCR than women without HIV (8.7% vs 16.4%, [odds ratio (OR) 0.48, 95% confidence interval (95% CI) 0.27-0.86]). WLWH continued to have lower likelihood of achieving pCR on multivariable analysis (OR 0.52, 95% CI 0.28-0.98). A similar pattern was seen within subgroups, although HIV infection appeared to affect pCR more in ER/PR-positive BC (OR 0.24, 95% CI 0.08-0.71) than in ER/PR-negative BC (OR 0.94, 95% CI 0.39-2.29). Conclusion WLWH were less like to achieve pCR following NACT for BC than women without HIV. This reduced response to systemic therapy may contribute to the poorer BC outcomes seen in WLWH.

PURPOSE: The quality of breast cancer care in sub-Saharan Africa contributes to the region’s dismal breast cancer mortality. ASCO has issued quality measures focusing on delivery of adjuvant chemotherapy, radiotherapy, and endocrine therapy. We applied these measures in five South African public hospitals and analyzed factors associated with care concordance. MATERIALS AND METHODS: Among 1,736 women with breast cancer who were enrolled in the South African Breast Cancer and HIV Outcomes study over 24 months, we evaluated care using ASCO’s three measures. We also evaluated adjuvant chemotherapy receipt in 957 women with an indication. We used logistic regression to estimate associations between measure-concordant care and patient factors. RESULTS: Of 235 women with hormone receptor–negative cancer, 173 (74%) began adjuvant chemotherapy within 120 days from diagnosis. Of 194 patients who received breast-conserving surgery, 73 (37%) began radiotherapy within 365 days from diagnosis. Of 999 women with hormone receptor–positive cancer, 719 (72%) initiated endocrine therapy within 365 days from diagnosis. Chemotherapy and radiotherapy measure-concordant care were more common among women residing < 20 km from the hospital (odds ratio [OR], 1.79; 95% CI, 1.32 to 2.44 and OR, 3.17; 95% CI, 1.57 to 6.42). Endocrine therapy measure-concordant care was more common among English-speaking women (OR, 2.12; 95% CI, 1.12 to 4.02). Participating hospitals varied in care concordance. HIV infection did not affect care quality. CONCLUSION: More timely delivery of chemotherapy, radiotherapy, and endocrine therapy is needed in South Africa, particularly for women living > 20 km from the hospital or not speaking English. Focused quality improvement efforts could support that goal.

Multimorbidity in women with breast cancer may delay presentation, affect treatment decisions and outcomes. We described the multimorbidity profile of women with breast cancer, its determinants, associations with stage at diagnosis and treatments received. We collected self‐reported data on five chronic conditions (hypertension, diabetes, cerebrovascular diseases, asthma/chronic obstructive pulmonary disease, tuberculosis), determined obesity using body mass index (BMI) and tested HIV status, in women newly diagnosed with breast cancer between January 2016 and April 2018 in five public hospitals in South Africa. We identified determinants of ≥2 of the seven above‐mentioned conditions (defined as multimorbidity), multimorbidity itself with stage at diagnosis (advanced [III–IV] vs. early [0–II]) and multimorbidity with treatment modalities received. Among 2,281 women, 1,001 (44%) presented with multimorbidity. Obesity (52.8%), hypertension (41.3%), HIV (22.0%) and diabetes (13.7%) were the chronic conditions that occurred most frequently. Multimorbidity was more common with older age (OR = 1.02; 95% CI 1.01–1.03) and higher household socioeconomic status (HSES) (OR = 1.06; 95% CI 1.00–1.13). Multimorbidity was not associated with advanced‐stage breast cancer at diagnosis, but for self‐reported hypertension there was less likelihood of being diagnosed with advanced‐stage disease in the adjusted model (OR 0.80; 95% CI 0.64–0.98). Multimorbidity was associated with first treatment received in those with early‐stage disease, p = 0.003. The prevalence of multimorbidity is high among patients with breast cancer. Our findings suggest that multimorbidity had a significant impact on treatment received in those with early‐stage disease. There is need to understand the impact of multimorbidity on breast cancer outcomes.

Background In the U.S., neoadjuvant chemotherapy (NAC) for nonmetastatic breast cancer (BC) is used with extensive disease and aggressive molecular subtypes. Little is known about the influence of demographic characteristics, clinical factors, and resource constraints on NAC use in Africa. Materials and Methods We studied NAC use in a cohort of women with stage I-III BC enrolled in the South African Breast Cancer and HIV Outcomes study at five hospitals. We analyzed associations between NAC receipt and sociodemographic and clinical factors, and we developed Cox regression models for predictors of time to first treatment with NAC versus surgery. Results Of 810 patients, 505 (62.3%) received NAC. Multivariate analysis found associations between NAC use and black race (odds ratio [OR] 0.49; 95% confidence limit [CI], 0.25-0.96), younger age (OR 0.95; 95% CI, 0.92-0.97 for each year), T-stage (T4 versus T1: OR 136.29; 95% CI, 41.80-444.44), N-stage (N2 versus N0: OR 35.64; 95% CI, 16.56-76.73), and subtype (triple-negative versus luminal A: OR 5.16; 95% CI, 1.88-14.12). Sites differed in NAC use (Site D versus Site A: OR 5.73; 95% CI, 2.72-12.08; Site B versus Site A: OR 0.37; 95% CI, 0.16-0.86) and time to first treatment: Site A, 50 days to NAC versus 30 days to primary surgery (hazard ratio [HR] 1.84; 95% CI, 1.25-2.71); Site D, 101 days to NAC versus 126 days to primary surgery (HR 0.49; 95% CI, 0.27-0.89). Conclusion NAC use for BC at these South African hospitals was associated with both tumor characteristics and heterogenous resource constraints. Implications for Practice Using data from a large breast cancer cohort treated in South Africa's public healthcare system, the authors looked at determinants of neoadjuvant chemotherapy use and time to initiate treatment. It was found that neoadjuvant chemotherapy was associated with increasing tumor burden and aggressive molecular subtypes, demonstrating clinically appropriate care in a lower resource setting. Results of this study also showed that time to treatment differences between chemotherapy and surgery varied by hospital, suggesting that differences in resource limitations were influencing clinical decision making. Practice guidelines and care quality metrics designed for low- and middle-income countries should accommodate heterogeneity of available resources.

Purpose: In low- and middle-income, HIV-endemic regions of sub-Saharan Africa, morbidity and mortality from the common epithelial cancers of the developed world are rising. Even among HIV-infected individuals, access to antiretroviral therapy has enhanced life expectancy, shifting the distribution of cancer diagnoses toward non–AIDS-defining malignancies, including breast cancer. Building on our prior research, we recently initiated the South African Breast Cancer and HIV Outcomes study. Methods: We will recruit a cohort of 3,000 women newly diagnosed with breast cancer at hospitals in high (average, 20%) HIV prevalence areas, in Johannesburg, Durban, Pietermaritzburg, and Empangeni. At baseline, we will collect information on demographic, behavioral, clinical, and other factors related to access to health care. Every 3 months in year 1 and every 6 months thereafter, we will collect interview and chart data on treatment, symptoms, cancer progression, comorbidities, and other factors. We will compare survival rates of HIV-infected and uninfected women with newly diagnosed breast cancer and their likelihood of receiving suboptimal anticancer therapy. We will identify determinants of suboptimal therapy and context-specific modifiable factors that future interventions can target to improve outcomes. We will explore molecular mechanisms underlying potentially aggressive breast cancer in both HIV-infected and uninfected patients, as well as the roles of pathogens, states of immune activation, and inflammation in disease progression. Conclusion: Our goals are to contribute to development of evidence-based guidelines for the management of breast cancer in HIV-positive women and to improve outcomes for all patients with breast cancer in resource-constrained settings.