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Abstract Background Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. Results Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12–100.00], and specificity of 91% [95% CI 62.26–99.53] to 96% [95% CI 79.01–99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00–1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77–70.84] to 89% [95% CI 67.20–98.03], specificity of 93% [95% CI 84.07–97.38] to 96% [95% CI 79.01–99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68–0.89] to 0.99 [95% CI 0.97–1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45–92.69], specificity 95% [95% CI 88.64–98.18], and ROC AUC = 0.925 [95% CI 0.878–0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11–80.44), specificity of 94% (95% CI 88.30–97.40), and ROC AUC = 0.884 (95% CI 0.822–0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. Conclusions This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Abstract Introduction In East and Southern Africa, people with HIV (PWH) experience worse cancer-related outcomes and are at higher risk of developing certain cancers. Siloed care delivery pathways pose a substantial barrier to co-management of HIV and cancer care delivery. Methods We conducted cross-sectional studies of adult cancer patients at public radiotherapy and oncology units in Malawi (Kamuzu Central Hospital), Zimbabwe (Parirenyatwa Group of Hospitals), and South Africa (Charlotte Maxeke Hospital) between 2018 and 2019. We abstracted cancer- and HIV-related data from new cancer patient records and used Poisson regression with robust variance to identify patient characteristics associated with HIV documentation. Results We included 1,648 records from Malawi (median age 46 years), 1,044 records from South Africa (median age 55 years), and 1,135 records from Zimbabwe (median age 52 years). Records from all three sites were predominately from female patients; the most common cancers were cervical (Malawi [29%] and Zimbabwe [43%]) and breast (South Africa [87%]). HIV status was documented in 22% of cancer records from Malawi, 92% from South Africa, and 86% from Zimbabwe. Patients with infection-related cancers were more likely to have HIV status documented in Malawi (adjusted prevalence ratio [aPR]: 1.92, 95% confidence interval [CI]: 1.56–2.38) and Zimbabwe (aPR: 1.16, 95%CI: 1.10–1.22). Patients aged ≥ 60 years were less likely to have HIV status documented (Malawi: aPR: 0.66, 95% CI: 0.50–0.87; Zimbabwe: aPR: 0.76, 95%CI: 0.72–0.81) than patients under age 40 years. Patient age and cancer type were not associated with HIV status documentation in South Africa. Conclusion Different cancer centers have different gaps in HIV status documentation and will require tailored strategies to improve processes for ascertaining and recording HIV-related information in cancer records. Further research by our consortium to identify opportunities for integrating HIV and cancer care delivery is underway.

Abstract Background Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first‐line treatment for stage IV PCa. Objective To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. Design, Setting, and Participants Men diagnosed with prostate cancer (3/22/2016–10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate‐specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. Outcomes Measures and Statistical Analysis We used Kaplan–Meier statistics to estimate OS and Cox regression models to identify predictors of OS. Results and Limitations Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64–73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%–noncalculable), while biochemical progression‐free survival was 2.36 years (95% CI: 2.03%–3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%–6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%–7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%–5.83%), and hemoglobin at diagnosis

There is a rising noncommunicable disease (NCD) burden in low- and middle-income countries. Sub-Saharan Africa (SSA) bears a higher burden than the global average with South Africa (SA) enduring the highest regional burden. SA among other southern African countries also bears a high prevalence of HIV and other chronic communicable diseases. Having a perspective on common chronic diseases in the ever-increasing numbers of adult cancer patients in SA will inform our understanding of approaches to better manage them. This commentary reviews regional and national studies and data of low- and middle-income countries and particularly SA on the chronic infectious and NCD multimorbidity burden among adult cancer patients. It also reflects on the considerable health system challenges of managing discordant multimorbidity among adult cancer patients within the SA Public Health System. Despite the critical need to better manage the growing MM burden in general and particularly the high prevalence of discordant multimorbidity among cancer patients, there is a dearth of research into MM management generally and in LMICs particularly.

Abstract 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.

Abstract Background In South Africa, androgen deprivation therapy (ADT) is commonly given as primary therapy for prostate cancer (PCa) due to many patients presenting with advanced disease. The metabolic adverse effects of ADT on lipid profile and weight gain have been reported mainly in Caucasian populations, but few studies have been performed in African populations. Men of African descent generally have favorable lipid profiles compared to other populations, and our study looked to analyze the effect of medical castration on lipid levels in black South African men with PCa. Methods The aim of this study is to describe the changes in blood total cholesterol, triglycerides, LDL and HDL at 6 months and at 1 year in men with prostate cancer newly initiated on ADT. Changes to BMI, waist circumference and HbA1c were also measured after 1 year of ADT. Our study was conducted at Chris Hani Baragwanath Academic Hospital which is a teaching hospital affiliated with the University of the Witwatersrand. It is located in Soweto, South of Johannesburg, and serves the 1.3 million local residents who are predominantly black and of the lower-income bracket. This study enrolled 38 black South African men who were starting to receive ADT for PCa. Subjects were evaluated at baseline and at 6 and 12 months. Lipid profiles and HbA1C levels were measured using blood samples, and body composition was measured using BMI and waist circumference. Results In this prospective single-center study, we found that ADT resulted in a significant rise in triglyceride levels and weight gain in black South African men reaching mean levels of obesity using ethnic-specific definitions. High-density lipoproteins levels decreased significantly particularly in the first 6 months of treatment and thereafter began to rise. ADT also resulted in an increased HbA1C level which is a marker for insulin resistance. Conclusions Androgen deprivation therapy unfavorably changed the body habitus and lipid profile of men with PCa. It was demonstrated that even black South Africans who generally have favorable lipid profiles compared to their counterparts are at risk of developing metabolic syndrome while being treated with ADT.

Abstract Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

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.

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.

PURPOSEHigh-quality histopathology reporting forms the basis for treatment decisions. The quality indicator for pathology reports from the European Society of Breast Cancer Specialists was applied to a cohort from four South African breast units.METHODSThe study included 1,850 patients with invasive breast cancer and evaluated 1,850 core biopsies and 1,158 surgical specimen reports with cross-center comparisons. A core biopsy report required histologic type; tumor grade; and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status, with a confirmatory test for equivocal HER2 results. Ki-67 was regarded as optional. Pathologic stage, tumor size, lymphovascular invasion, and distance to nearest invasive margin were mandatory for surgical specimens. Specimen turnaround time (TAT) was added as a locally relevant indicator.RESULTSSeventy-five percent of core biopsy and 74.3% of surgical specimen reports were complete but showed large variability across study sites. The most common reason for an incomplete core biopsy report was missing tumor grade (17.9%). Half of the equivocal HER2 results lacked confirmatory testing (50.6%). Ki-67 was reported in 89.3%. For surgical specimens, the closest surgical margin was reported in 78.1% and lymphovascular invasion in 84.8% of patients. Mean TAT was 11.9 days (standard deviation [SD], 10.8 days) for core biopsies and 16.1 days (SD, 11.3) for surgical specimens.CONCLUSIONHistopathology reporting is at a high level but can be improved, especially for tumor grade, HER2, and Ki-67, as is reporting of margins and lymphovascular invasion. A South African pathology consensus will reduce variability among laboratories. Routine use of standardized data sheets with synoptic reports and ongoing audits will improve completeness of reports over time.

Purpose: Breast cancer outcomes in sub-Saharan Africa is reported to be poor, with an estimated five-year survival of 50% when compared to almost 90% in high-income countries. Although several studies have looked at the effect of HIV in breast cancer survival, the effect of ARTs has not been well elucidated. Methods: All females newly diagnosed with invasive breast cancer from May 2015–September 2017 at Charlotte Maxeke Johannesburg Academic and Chris Hani Baragwanath Academic Hospital were enrolled. We analysed overall survival and disease-free survival, comparing HIV positive and negative patients. Kaplan-Meier survival curves were generated with p-values calculated using a log-rank test of equality while hazard ratios and their 95% confidence intervals (CIs) were estimated using Cox regression models. Results: Of 1019 patients enrolled, 22% were HIV positive. The overall survival (95% CI) was 53.5% (50.1–56.7%) with a disease-free survival of 55.8% (52.1–59.3) after 4 years of follow up. HIV infection was associated with worse overall survival (HR (95% CI): 1.50 (1.22–1.85), p

Objective With increases in chronic disease, men with prostate cancer are likely to have at least one other chronic health condition. The burden and complexity of each additional chronic disease may complicate prostate cancer treatment and reduce survival. In this paper, we describe the frequency of multimorbid chronic diseases, HIV and depression among men in Soweto, South Africa (SA) with and without prostate cancer and determine whether the presence of multimorbid diseases is associated with metastatic and high-risk, non-metastatic prostate cancer. Methods A population-based case-control study on prostate cancer was conducted among black men in Soweto. All participants completed a baseline survey on sociodemographics, lifestyle, and comorbid medical conditions. All participants completed a depression screening survey and HIV testing at enrolment. Blood pressure measurements and blood testing for fasting glucose, total cholesterol, and high-density lipoprotein were performed on a subset of randomly selected cases and controls. For men with prostate cancer, clinical T staging was assessed with the digital rectal examination, the diagnosis was confirmed with a biopsy and PSA levels were assessed at presentation. The metastatic staging was assessed by bone scans, and this was confirmed with PSMA PET scans, CT scans and X-rays, standard for our resource-constrained setting. Normal PSA scores were used as an inclusion criterion for controls. Results Of the 2136 men (1095 with prostate cancer and 1041 controls) included in the analysis, 43.0% reported at least one chronic metabolic disease; 24.1% reported two metabolic diseases; 5.3% reported three metabolic diseases; and 0.3% reported four metabolic diseases. Men with prostate cancer were more likely to report a multimorbid chronic metabolic disease compared to controls (p20ng/ml; 233 (21.7%) had confirmed metastatic prostate cancer at diagnosis. Older age was associated with metastatic prostate cancer (OR = 1.043 95% CI:1.02–1.07) and NCCN defined high-risk non-metastatic prostate cancer (OR = 1.03 95% CI:1.01–1.05), whilst being hypertensive was protective (OR = 0.63 95% CI:0.47–0.84 and OR = 0.55 95% CI:0.37–0.83) respectively for metastatic and high-risk, non-metastatic prostate cancer. Conclusion The high prevalence of multimorbid metabolic diseases and HIV among men with prostate cancer represents a public health concern in South Africa. There is a need to effectively address multiple chronic diseases among men with prostate cancer by incorporating coordinated care models.

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.

BackgroundLung cancer is the highest incident cancer globally and is associated with significant morbidity and mortality particularly if identified at a late stage. Poor patient outcomes in low- and middle-income countries (LMIC's) might reflect contextual patient and health system constraints at multiple levels, that act as barriers to prevention, disease recognition, diagnosis, and treatment. Lung cancer screening, even for high-risk patients, is not available in the public health sector in South Africa (SA), where the current HIV and tuberculosis (TB) epidemics often take precedence. Yet, there has been no formal assessment of the individual and health-system related barriers that may delay patients with lung cancer from seeking and accessing help within the public health care system and receiving the appropriate and effective diagnosis and treatment. This study aimed to derive consensus from health-system stakeholders in the urban Gauteng Province of SA on the most important challenges faced by the health services and patients in achieving optimum lung cancer management and to identify potential solutions.MethodsThe study was undertaken among 27 participant stakeholders representing clinical managers, clinicians, opinion leaders from the public health sector and non-governmental organisation (NGO) representatives. The study compromised two components: consensus and engagement. For the consensus component, the Delphi Technique was employed with open-ended questions and item ranking from five rounds of consensus-seeking, to achieve collective agreement on the most important challenges faced by patients and the health services in achieving optimal lung cancer management. For the engagement component, the Nominal Group Technique was used to articulate ideas and reach an agreement on the group's recommendations for solution strategies and approaches.ResultsPublic health sector stakeholders suggested that a lack of knowledge and awareness of lung cancer, and the apparent stigma associated with the disease and its risk factors, as well as symptoms and signs, are critical to treatment delay. Furthermore, delays in up-referral of patients with suspected lung cancer from district health care level were attributed to inadequate knowledge arising from a lack of in-service training of nurses and doctors regarding oncologic symptoms, risk factors, need for further investigation, interpretation of x-rays and available treatments. At a tertiary level, participants suggested that insufficient availability of specialised diagnostic resources (imaging, cytological and pathological services including biomolecular assessment of lung cancer), theatres, cardiothoracic surgeons, and appropriate therapeutic modalities (chemotherapeutic agents and radiation oncology) are the main barriers to the provision of optimal care. It was suggested that a primary prevention programme initiated by the government that involves private-public partnerships may improve lung cancer management nationally.ConclusionsConsiderable barriers to the early identification and treatment of lung cancer exist. Finding solutions to overcome both individual and health-system level obstacles to lung cancer screening and management are vital to facilitate early identification and treatment, and to improve survival. Furthermore, research on inexpensive biomarkers for asymptomatic disease detection, the introduction of diagnostic imaging tools that utilise artificial intelligence to compensate for inadequate human resources and improving clinical integration across all levels of the healthcare system are essential.

Summary: Background: Breast cancer is the second leading cause of death from cancer in women in sub-Saharan Africa, yet there are few well characterised large-scale survival studies with complete follow-up data. We aimed to provide robust survival estimates in women in this setting and apportion the survival gaps. Methods: The African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort study was done at eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, South Africa, Uganda, and Zambia). We prospectively recruited women (aged ≥18 years) who attended these hospitals with suspected breast cancer. Women were actively followed up by use of a telephone call once every 3 months, and a mobile health application was used to keep a dynamic record of follow-up calls due. We collected detailed sociodemographic, clinical, and treatment data. The primary outcome was 3-year overall survival, analysed by use of flexible proportional mortality models, and we predicted survival under scenarios of modified distributions of risk factors. Findings: Between Sept 8, 2014, and Dec 31, 2017, 2313 women were recruited from these eight hospitals, of whom 85 did not have breast cancer. Of the remaining 2228 women with breast cancer, 58 women with previous treatment or recurrence, and 14 women from small racial groups (white and Asian women in South Africa), were excluded. Of the 2156 women analysed, 1840 (85%) were histologically confirmed, 129 (6%) were cytologically confirmed, and 187 (9%) were clinically confirmed to have breast cancer. 2156 (97%) women were followed up for up to 3 years or up to Jan 1, 2019, whichever was earlier. Up to this date, 879 (41%) of these women had died, 1118 (52%) were alive, and 159 (7%) were censored early. 3-year overall survival was 50% (95% CI 48–53), but we observed variations in 3-year survival between different races in Namibia (from 90% in white women to 56% in Black women) and in South Africa (from 76% in mixed-race women to 59% in Black women), and between different countries (44–47% in Uganda and Zambia vs 36% in Nigeria). 215 (10%) of all women had died within 6 months of diagnosis, but 3-year overall survival remained low in women who survived to this timepoint (58%). Among survival determinants, improvements in early diagnosis and treatment were predicted to contribute to the largest increases in survival, with a combined absolute increase in survival of up to 22% in Nigeria, Zambia, and Uganda, when compared with the contributions of other factors (such as HIV or aggressive subtypes). Interpretation: Large variations in breast cancer survival in sub-Saharan African countries indicate that improvements are possible. At least a third of the projected 416 000 breast cancer deaths that will occur in this region in the next decade could be prevented through achievable downstaging and improvements in treatment. Improving survival in socially disadvantaged women warrants special attention. Funding: Susan G Komen and the International Agency for Research on Cancer.

Background: Breast cancer is the most common cancer globally and among South African women. Women from socioeconomically disadvantaged South African communities more often present later and receive total mastectomy compared to those from more affluent communities who have more breast conserving surgery (which is less invasive but requires mandatory radiation treatment post-operatively). Standard chemotherapy and total mastectomy treatments are known to cause traumatizing side effects and emotional suffering among South African women; moreover, many women face limited communication with physicians and psychological support. Objective: This article investigates the experiences of women seeking breast cancer treatment at the largest public hospital in South Africa. Methods We interviewed 50 Black women enrolled in the South African Breast Cancer Study to learn more about their health system experiences with detection, diagnosis, treatment, and follow-up care for breast cancer. Each interview was between 2–3 hours, addressing perceptions, experiences, and concerns associated with breast cancer and comorbidities such as HIV and hypertension. Results: We found most women feared diagnosis, in part, because of the experience of chemotherapy and physical mutilation related to mastectomy. The importance of social support from family, religion, and clinical staff was fundamental for women coping with their condition and adhering to treatment and medication. Conclusions: These findings exemplify how interventions might promote early detection of breast cancer and better adherence to treatment. Addressing community perceptions of breast cancer, patient needs and desires for treatment, structural barriers to intensive therapies, and the burden of invasive treatments are imperative next steps for delivering better breast cancer care in Soweto and other resource-constrained settings.

Purpose: Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. Methods: We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. Results: We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. Conclusion: We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Purpose: Health research in low- and middle-income countries can generate novel scientific knowledge and improve clinical care, fostering population health improvements to prevent premature death. Project management is a critical part of the success of this research, applying knowledge, skills, tools, and techniques to accomplish required goals. Here, we describe the development and implementation of tools to support a multifaceted study of prostate cancer in Africa, focusing on building strategic and operational capacity. Methods: Applying a learning organizational framework, we developed and implemented a project management toolkit (PMT) that includes a management process flowchart, a cyclical center-specific schedule of activities, periodic reporting and communication, and center-specific monitoring and evaluation metrics. Results: The PMT was successfully deployed during year one of the project with effective component implementation occurring through periodic cycles of dissemination and feedback to local center project managers. A specific evaluation was conducted 1 year after study initiation to obtain enrollment data, evaluate individual quality control management plans, and undertake risk log assessments and follow-up. Pilot data obtained identified areas in which centers required mentoring, strengthening, and capacity development. Strategies were implemented to improve project goals and operational capacity through local problem solving, conducting quality control checks and following compliancy with study aims. Moving forward, centers will perform quarterly evaluations and initiate strengthening measures as required. Conclusion: The PMT has fostered the development of both strategic and operational capacity across project centers. Investment in project management resources is essential to ensuring high-quality, impactful health research in low- and middle-income countries.

Purpose: The understanding of patients with cancer of their condition and their wishes regarding care as they approach end of life (EoL) have been studied more in high-income countries than in low- and middle-income countries (LMICs). Patients and Methods: Data were analyzed from a cohort study (N = 221) of patients with advanced cancer who were recruited from a palliative care center in Soweto, South Africa (LMIC), between May 2016 and June 2017. Patients were asked about their understanding of their illness, estimated life expectancy, EoL care communication, and EoL care preferences. Results: Only 13 patients (5.9%) acknowledged that they were terminally ill; nine patients (4.1%) estimated accurately that they had months, not years, left to live. A total of 216 patients (97.7%) reported that they had not had an EoL care discussion with their physician, and 170 patients (76.9%) did not want to know their prognosis even if the doctor knew it. Most patients preferred comfort care (72.9%; n = 161) to life-extending care (14.0%; n = 31), and did not want to be kept alive using extreme measures (80.5%; n = 178) or have their doctors do everything possible to extend their lives (78.3%; n = 173). Finally, 127 patients (57.5%) preferred to die at home, and 51 (23.1%) preferred to die in the hospital. Most patients (81.0%; n = 179) had funeral plans. Conclusion: South African patients demonstrated less awareness of the fact that they were terminally ill, were less likely to have discussed their prognosis with their doctor, and more strongly preferred comfort care to life-extending EoL care than US and other LMIC patients in prior research. These differences highlight the need for culturally appropriate, patient-centered EoL care for South African patients with advanced cancer as well as to determine individual preferences and needs in all EoL settings.

Patient-reported outcome measures (PROM) for monitoring treatment toxicity improve quality of life (QoL) and clinical outcomes. However, no such PROMs exist for sub-Saharan African cancer patients. We aimed to validate the Patient Reported Symptoms-South Africa (PRS-SA) survey, a novel PROM for measuring distress and chemotherapy-related symptoms in South African cancer patients. We enrolled patients at the oncology clinic at Charlotte Maxeke Hospital, Johannesburg. At three separate visits, participants simultaneously completed the PRS-SA survey and several previously validated questionnaires. We constructed a receiver operator characteristics curve for distress levels predicting a Hospital Anxiety and Depression Scale (HADS) score ≥15. We evaluated construct validity for symptom items by comparing severity to the EORTC Core Quality of Life Questionnaire (QLQ-C30) summary score (Pearson correlation tests) and ECOG performance status (Mann–Whitney U tests). We assessed symptom item responsiveness by comparing change in severity to change in QLQ-C30 summary score and comparing standardized mean scores with negative, no, or positive change on the Global Impression of Change (GIC) questionnaire (Jockheere–Terpstra trend test). Overall, 196 participants with solid tumors completed instruments. A distress score of 4 had 82% sensitivity and 55% specificity for clinical depression/anxiety. All symptom items showed construct validity by association with either QLQ-C30 score or performance status (highest p = 0.03). All but cough showed responsiveness to change in QLQ-C30 score (highest p = 0.045). In South African cancer patients, the PRS-SA’s stress scale behaves similarly to the distress thermometer in other populations, and the symptom items demonstrated construct validity and responsiveness. Of note, 46% and 74% of participants who completed the PRS-SA in English or isiZulu, respectively, required assistance reading half or more of the instrument.

A total of 396 breast cancer cases and 396 population-based controls from the South African Breast Cancer study (SABC) matched on age and demographic settings was included. Validated questionnaires were used to collect dietary and epidemiological data. Dietary patterns were derived using principal component analysis with a covariance matrix from 33 food groups. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression. A traditional, a cereal-dairy breakfast and a processed food dietary pattern were identified, which together explained 40.3% of the total variance in the diet. After adjusting for potential confounders, the traditional dietary pattern and cereal-dairy breakfast dietary pattern were inversely associated with breast cancer risk (highest tertile versus lowest tertile) (OR = 0.72, 95%CI: 0.57–0.89, p-trend = 0.004 and OR = 0.73, 95%CI: 0.59–0.90, p-trend = 0.004, respectively). The processed food dietary pattern was not significantly associated with breast cancer risk. The results of this study show that a traditional dietary pattern and a cereal-dairy breakfast dietary pattern may reduce the risk of developing breast cancer in this population.

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.

Reported breast cancer incidence is rising in South Africa, where some women are diagnosed late and have poor outcomes. We studied patient and provider factors associated with clinical stage at diagnosis among women diagnosed at the Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg in 2015-2016.From face-to-face interviewer-administered questionnaires we compared self-reported socioeconomics, demographics, comorbidities, risk factors, personal and health system barriers, and from patient clinical records, clinical staging, receptor subtype, and tumor grade among 499 consecutive women newly diagnosed with advanced stage (III/IV) breast cancer versus those diagnosed early (stage 0/I/II). Logistic regression models were used to identify factors associated with advanced stage at diagnosis.Among the women, 243 (49%) were diagnosed at early and 256 (51%) at advanced stages. In the multiple logistic regression adjusted model, completion of high school or beyond (odds ratio (OR) 0.59, and greater breast cancer knowledge and awareness (OR 0.86) were associated with lower stage of breast cancer at presentation. Advanced stage was associated with Luminal B (OR 2.25) and triple-negative subtypes (OR 3.17) compared to luminal A, with delays >3 months from first breast symptoms to accessing the health system (OR 2.79) and with having more than 1 visit within the referral health system (OR 3.19) for 2 visits; OR 2.73 for ≥3 visits).Limited patient education, breast cancer knowledge and awareness, and health system inefficiencies were associated with advanced stage at diagnosis. Sustained community and healthcare worker education may down-stage disease and improve cancer outcomes.

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.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.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