Multimorbidity and overall survival among women with breast cancer: results from the South African Breast Cancer and HIV Outcomes Study.

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.

The Impact of HIV Infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Patients with Breast Cancer.

INTRODUCTION: In the South African Breast Cancer and HIV Outcomes (SABCHO) study, we previously found that breast cancer patients living with HIV and treated with neoadjuvant chemotherapy achieve lower rates of complete pathologic response than patients without HIV. We now assess the impact of comorbid HIV on receipt of timely and complete neoadjuvant and adjuvant chemotherapy. MATERIALS AND METHODS: Since June 2015, the SABCHO study has collected data on women diagnosed with breast cancer at 6 South African hospitals. We selected a sample of participants with stages I-III cancer who received ≥2 doses of neoadjuvant or adjuvant chemotherapy. Data on chemotherapies prescribed and received, filgrastim receipt, and laboratory values measured during treatment were captured from patients' medical records. We calculated the mean relative dose intensity (RDI) for all prescribed chemotherapies. We tested for association between full regimen RDI and HIV status, using linear regression to control for demographic and clinical covariates, and for association of HIV with laboratory abnormalities. RESULTS: The 166 participants living with HIV and 159 without HIV did not differ in median chemotherapy RDI: 0.89 (interquartile range (IQR) 0.77-0.95) among those living with HIV and 0.87 (IQR 0.77-0.94) among women without HIV. Patients living with HIV experienced more grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs. 1.9%, P = .001; leukopenia: 8.4% vs. 1.9%, P = .008) and were more likely to receive filgrastim (24.7% vs. 10.7%, P = .001). CONCLUSIONS: HIV status did not impact neoadjuvant or adjuvant chemotherapy RDI, although patients with breast cancer living with HIV experienced more myelotoxicity during treatment.

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.

Impact of HIV infection on survival among women with stage I-III breast cancer: Results from the South African breast cancer and HIV outcomes study.

In some countries of sub-Saharan Africa, the prevalence of HIV exceeds 20%; in South Africa, 20.4% of people are living with HIV. We examined the impact of HIV infection on the overall survival (OS) of women with nonmetastatic breast cancer (BC) enrolled in the South African Breast Cancer and HIV Outcomes (SABCHO) study. We recruited women with newly diagnosed BC at six public hospitals from 1 July 2015 to 30 June 2019. Among women with stages I-III BC, we compared those with and without HIV infection on sociodemographic, clinical, and treatment factors. We analyzed the impact of HIV on OS using multivariable Cox proportional hazard models. Of 2367 women with stages I-III BC, 499 (21.1%) had HIV and 1868 (78.9%) did not. With a median follow-up of 29 months, 2-year OS was poorer among women living with HIV (WLWH) than among HIV-uninfected women (72.4% vs 80.1%, P < .001; adjusted hazard ratio (aHR) 1.49, 95% confidence interval (CI) = 1.22-1.83). This finding was consistent across age groups ≥45 years and <45 years, stage I-II BC and stage III BC, and ER/PR status (all P < .03). Both WLWH with <50 viral load copies/mL and WLWH with ≥50 viral load copies/mL had poorer survival than HIV-uninfected BC patients [aHR: 1.35 (1.09-1.66) and 1.54 (1.20-2.00), respectively], as did WLWH who had ≥200 CD4+ cells/mL at diagnosis [aHR: 1.39 (1.15-1.67)]. Because receipt of antiretroviral therapy has become widespread, WLWH is surviving long enough to develop BC; more research is needed on the causes of their poor survival.

The Impact of Breast Cancer Treatment Delays on Survival Among South African Women.

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.

Impact of HIV infection on overall survival among women with stage IV breast cancer in South Africa.

PURPOSE: Advanced breast cancer (BC) at diagnosis is common in sub-Saharan Africa (SSA), including among women living with HIV (WLWH). In public hospitals across South Africa (SA), 10-15% of women present with stage IV BC, compared to < 5% in the United States (US); 20% of new BC diagnoses in SA are in WLWH. We evaluated the impact of HIV on overall survival (OS) among women with stage IV BC. METHODS: We conducted a prospective cohort study of women diagnosed with stage IV BC between February 2, 2015 and September 18, 2019 at six public hospitals in SA. Multivariate Cox regression models were used to estimate the association between HIV status and OS. RESULTS: Among 550 eligible women, 147 (26.7%) were WLWH. Compared to HIV-negative BC patients, WLWH were younger (median age 45 vs. 60 years, p < 0.001), predominantly black (95.9% vs. 77.9%, p < 0.001), and more likely to have hormone receptor-negative (hormone-negative) BC (32.7% vs. 22.6%, p = 0.016). Most women received systemic cancer-directed therapy (80.1%). HIV status was not associated with treatment or OS (Hazard Ratio (HR) 1.13 [95%CI 0.89-1.44]). On exploratory subgroup analysis, WLWH and hormone-negative BC had shorter OS compared to HIV-uninfected women (1-year OS: 27.1% vs. 48.8%, p = 0.003; HR 1.94 [95%CI 1.27-2.94]; p = 0.002), which was not observed for hormone receptor-positive BC. CONCLUSION: HIV status was not associated with worse OS in women with stage IV BC in SA and cannot account for the poor survival in this cohort. Subgroup analysis revealed that WLWH with hormone-negative BC had worse OS, which warrants further investigation.

The multimorbidity profile of South African women newly diagnosed with breast cancer.

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.

A comparison of complete pathologic response rates following neoadjuvant chemotherapy among South African breast cancer patients with and without concurrent HIV infection.

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.

Neoadjuvant Chemotherapy Use for Nonmetastatic Breast Cancer at Five Public South African Hospitals and Impact on Time to Initial Cancer Therapy.

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.

Elevation of Serum CEA in Patients with Squamous Cell Carcinoma of the Anus.

The proportion of anal cancer cases that produce elevated carcinoembryonic antigen (CEA) levels is not well described in the medical literature. In this study, we used electronic health record data from a single urban cancer center to identify patients from 2004-2018 with anal cancer who have also had a pre-initial treatment CEA measurement. We identified 40 patients who met our eligibility criteria. Of those, 11 (27.5%) had an elevated pretreatment CEA. Elevated CEA was not associated with any of the clinical or demographic covariates; however, three out of five patients with a recurrence had an elevated CEA.

Associations between HIV infection status, psychosocial factors, and adjuvant endocrine therapy adherence among South African women with early-stage breast cancer.

Purpose: We aimed to evaluate for associations between HIV status, psychosocial factors, and adjuvant endocrine therapy (AET) adherence in South African (SA) women with estrogen receptor positive (ER+) breast cancer (BC). Methods: We enrolled South African women with early-stage ER + BC in remission and prescribed tamoxifen or an aromatase inhibitor to the prospective observational study. We performed AET pill counts at enrollment, 12 weeks, and 24 weeks, and calculated adherence ratios of pills consumed between visits to days between visits. Women completed questionnaires on social support, attitude towards medication, health literacy, self-efficacy, mental health, and AET toxicity. We collected household wealth data. We used hierarchical linear (HLM) and structural equation modelling (SEM) to compare adherence ratios between women with and without HIV while adjusting for psychosocial factors. Results: We collected adherence data from 239 women, 63 (26.4%) with co-morbid HIV. Comparing women with and without HIV, median AET adherence ratio was 0.88 vs 0.89, respectively (HLM p = 0.31). In our SEM model for the full cohort, mental health, healthcare savvy, and side effect burden latent variables were not significantly associated with adherence. In the subgroup of women living with HIV, lower SES quintile (ß 0.04, SE 0.02, p = 0.08) and poorer mental health (ß -0.02, SE 0.01, p = 0.10) showed trends toward association with adherence. Conclusions: HIV status is not predictive of AET adherence among SA women with ER + BC, though decreasing SES status and increasing mental health symptoms are marginally associated with adherence in women with BC and HIV.

A qualitative study to explore healthcare providers' perspectives on barriers and enablers to early detection of breast and cervical cancers among women attending primary healthcare clinics in Johannesburg, South Africa.

Low-and-middle income countries (LMICs) contribute approximately 70% of global cancer deaths, and the cancer incidence in these countries is rapidly increasing. Sub-Saharan African (SSA) countries, including South Africa (SA), bear some of the world's highest cancer case fatality rates, largely attributed to late diagnosis. We explored contextual enablers and barriers for early detection of breast and cervical cancers according to facility managers and clinical staff at primary healthcare clinics in the Soweto neighbourhood of Johannesburg, South Africa. We conducted qualitative in-depth interviews (IDIs) between August and November 2021 amongst 13 healthcare provider nurses and doctors as well as 9 facility managers at eight public healthcare clinics in Johannesburg. IDIs were audio-recorded, transcribed verbatim, and entered into NVIVO for framework data analysis. Analysis was stratified by healthcare provider role and identified apriori around the themes of barriers and facilitators for early detection and management of breast and cervical cancers. Findings were conceptualised within the socioecological model and then explored within the capability, opportunity and motivation model of behaviour (COM-B) for pathways that potentially influence the low screening provision and uptake. The findings revealed provider perceptions of insufficient South African Department of Health (SA DOH) training support and staff rotations resulting in providers lacking knowledge and skills on cancer, screening policies and techniques. This coupled with provider perceptions of poor patient cancer and screening knowledge revealed low capacity for cancer screening. Providers also perceived opportunity for cancer screening to be undermined by the limited screening services mandated by the SA DOH, insufficient providers, inadequate facilities, supplies and barriers to accessing laboratory results. Providers perceived women to prefer to self-medicate and consult with traditional healers and access primary care for curative services only. These findings compound the low opportunity to provide and demand cancer screening services. And because the National SA Health Department is perceived by providers not to prioritize cancer nor involve primary care stakeholders in policy and performance indicator development, overworked, unwelcoming providers have little motivation to learn screening skills and provide screening services. Providers reported that patients preferred to go elsewhere and that women perceived cervical cancer screening as painful. These perceptions must be confirmed for veracity among policy and patient stakeholders. Nevertheless, cost-effective interventions can be implemented to address these perceived barriers including multistakeholder education, mobile and tent screening facilities and using existing community fieldworkers and NGO partners in providing screening services. Our results revealed provider perspectives of complex barriers to the early detection and management of breast and cervical cancers in primary health clinic settings in Greater Soweto. These barriers together appear potentially to produce compounding effects, and therefore there is a need to research the cumulative impact but also engage with stakeholder groups to verify findings and create awareness. Additionally, opportunities do exist to intervene across the cancer care continuum in South Africa to address these barriers by improving the quality and volume of provider cancer screening services, and in turn, increasing the community demand and uptake for these services.

Effects of Genetic Polymorphisms of Drug Metabolizing Enzymes and co-Medications on Tamoxifen Metabolism in Black South African Women with Breast Cancer.

Clinical outcomes of tamoxifen (TAM) treatment show wide interindividual variability. Comedications and genetic polymorphisms of enzymes involved in TAM metabolism contributes to this variability. Drug-drug and drug-gene interactions have seldom been studied in African Black populations. We evaluated the effects of commonly co-administered medicines on TAM pharmacokinetics in a cohort of 229 South African Black female patients with hormone-receptor positive breast cancer. We also investigated the pharmacokinetic effects of genetic polymorphism in enzymes involved in TAM metabolism, including the variants CYP2D6*17 and *29, which have been mainly reported in people of African descent. TAM and its major metabolites, N-desmethyltamoxifen (NDM), 4-OH-tamoxifen, and endoxifen (ENDO), were quantified in plasma using the liquid chromatography-mass spectrometry. The GenoPharm open array was used to genotype CYP2D6, CYP3A5, CYP3A4, CYP2B6, CYP2C9, and CYP2C19. Results showed that CYP2D6 diplotype and CYP2D6 phenotype significantly affected endoxifen concentration (P < 0.001 and P < 0.001). CYP2D6*17 and CYP2D6*29 significantly reduced the metabolism of NDM to ENDO. Antiretroviral therapy had a significant effect on NDM levels and the TAM/NDM and NDM/ENDO metabolic ratios but did not result in significant effects on ENDO levels. In conclusion, CYP2D6 polymorphisms affected endoxifen concentration and the variants CYP2D6*17 and CYP2D6*29 significantly contributed to low exposure levels of ENDO. This study also suggests a low risk of drug-drug interaction in patients with breast cancer on TAM.

Time to Cancer Treatment and Chemotherapy Relative Dose Intensity for Patients With Breast Cancer Living With HIV.

Importance: Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer. Objective: To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV. Design, Setting, and Participants: A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023. Exposure: HIV infection detected before or within 90 days of participants' breast cancer diagnosis. Main Outcomes and Measures: The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests. Results: The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%]). Conclusions and Relevance: This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.

Drivers of disparities in stage at diagnosis among women with breast cancer: South African breast cancers and HIV outcomes cohort.

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.

The South African breast cancer and HIV outcomes study: Profiling the cancer centres and cohort characteristics, diagnostic pathways, and treatment approaches.

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.

Validating an Instrument for Direct Patient Reporting of Distress and Chemotherapy-Related Toxicity among South African Cancer Patients.

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.

Breast Cancer Early Detection in Eswatini: Evaluation of a Training Curriculum and Patient Receipt of Recommended Follow-Up Care.

[Figure: see text].

Quality indicators for the diagnosis and surgical management of breast cancer in South Africa.

INTRODUCTION: Quality indicators (QIs) for breast cancer care have been developed and applied in high-income countries and contributed to improved quality of care and patient outcomes over time. MATERIALS AND METHODS: A modified Delphi process was used to derive expert consensus. Potential QIs were rated by a panel of 17 breast cancer experts from various subspecialties and across South African provinces. Each QI was rated according to importance to measure, scientific acceptability and feasibility. Scoring ranged from 1 (no agreement) to 5 (strong agreement). Inclusion thresholds were set a priori at mean ratings ≥4 with a coefficient variation of ≥25%. Levels of evidence were determined for each indicator. RESULTS: The literature review identified 790 potential QIs. After categorisation and removal of duplicates, 52 remained for panel review. There was strong consensus for 47 which were merged to 30 QIs by exclusion of similar indicators and indicator grouping. The final set included eight QIs with level I or II evidence and two QIs with level III evidence which were deemed "mandatory" due to clinical priority and impact on care. The remaining QIs with lower-level evidence were grouped as eight "recommended" QIs (regarded as standard of care) and twelve "optional" QIs (not regarded as standard of care). CONCLUSION: A regional set of QIs was developed to facilitate standardised treatment and auditing of surgical care for breast cancer patients in South Africa. Routine monitoring of the ten mandatory QIs, which were selected to have the most substantial impact on patient outcome, is proposed.