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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.

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. 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. 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)). 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.

PurposeTreatment decision making for patients with breast cancer increasingly depends on analysis of markers or systems for estimating risk of breast cancer recurrence. Breast cancer intrinsic subtypes and risk of recurrence (ROR) scores have been found to be valuable in predicting survival and determining optimal treatment for individual patients. We studied the association of breast cancer survival with the PAM50 gene expression assay in HIV-positive and HIV-negative patients.MethodRNA was extracted from formalin-fixed paraffin-embedded specimens of histologically confirmed invasive carcinoma and was purified using the AllPrep® DNA/RNA FFPE kit, Qiagen (Hilden, Germany). The NanoString RUO PAM50 algorithm was used to determine the molecular subtype and the risk of recurrence score of each sample. The overall and disease-free survival were determined with comparison made among HIV-positive and -negative patients. We then generated Kaplan–Meier survival curves, calculated p-values and estimated hazard ratios and their 95% confidence intervals using Cox regression models.ResultsOf the 384 RNA samples analysed, 98.4% met the required RNA quality standard and the specified QC threshold for the test. Luminal B was the most common PAM50 intrinsic subtype and 82.1% of patients were at high risk for disease recurrence based on ROR score. HIV infection, PAM50-based HER2-enriched and basal-like intrinsic subtypes, and high ROR were associated with poor overall and disease-free survival. HIV-positive patients with luminal A & B subtypes had significantly worse survival outcomes than HIV-negative luminal patents.ConclusionAggressive tumour biology was common in our cohort. HIV infection, PAM50 HER2-enriched,basal-like intrinsic subtypes and high ROR score were associated with poor overall and disease-free survival. HIV infection impacted survival in patients with luminal subtypes only.

Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. Methods: We performed a systematic review on localization techniques for non-palpable breast cancer. Results: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons’ and radiologists’ attitudes towards these techniques. Conclusions: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

Abstract Background Breast cancer survival rates in sub-Saharan Africa are low. In a prospective, multi-center cohort study, we estimated 5-year overall survival rates, overall survival determinants, and mediating effects between socioeconomic status on overall survival among South African women diagnosed with invasive BC. Patients and methods Patients from 4 public hospitals were enrolled between July 1, 2015 and January 31, 2019. Survival determinants were assessed using Cox proportional hazard models adjusted for age, background mortality, and treatments. Socioeconomic pathway effects on overall survival were determined through generalized structural equation models. Results Of 2838 participants, 58% had advanced-stage (III/IV) disease. Five-year crude overall survival was 44.3% (95% CI 42.5-46.2). Significant mortality risks were late stage at diagnosis (hazard ratio [HR] = 2.31 [95% CI 1.99-2.69] [stage III]; 4.79 [95% CI 3.96-5.80] [stage IV]), HIV-positive status (HR = 1.45 [95% CI 1.25-1.67]), unemployment HR = 1.25 [95% CI 1.09-1.44], and low education HR 1.19 [95% CI 1.04-1.37]). Age and treatment-adjusted socioeconomic status effects on overall survival were mediated through HIV status (81.7% of the effect) and stage at diagnosis (81.7%), both P < .001. Poor breast cancer knowledge had an indirect effect on overall survival, accounting for 77.6% of the total effect (P = .001), fully mediated by late-stage presentation. Socioeconomic status had no significant direct path to mortality after accounting for these mediators. Conclusion Interventions should prioritize early breast cancer detection. For patients with low socioeconomic status, particularly those with comorbid HIV, we must mitigate multifaceted barriers to healthcare access, including limited awareness and knowledge of breast cancer.

PurposeWomen 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.MethodsAmong 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.ResultsAmong 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).ConclusionHigh 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.

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.

Abstract 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. This article examines how time to breast cancer treatment initiation affects overall survival in South African public hospitals.

PurposeAdvanced 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.MethodsWe 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.ResultsAmong 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.ConclusionHIV 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.