The South African Breast Cancer and HIV Outcomes prospective cohort (SABCHO) study was establishe... more 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). ...
Phyllodes tumours (PT) of the vulva are uncommon tumours. The gold standard treatment for these l... more Phyllodes tumours (PT) of the vulva are uncommon tumours. The gold standard treatment for these lesions is unknown but is intuitively presumed to be wide local excision. Incomplete resection is associated with recurrence although the time to recurrence is not known. Pregnancy is hypothesised to increase recurrence due to the production of steroid hormones oestrogen and progesterone. We report on a patient who had recurrence of a PT at a rare site (labia minora) and on the contralateral side from the original lesion, during pregnancy. These findings support that oestrogen and progesterone hormones could have played a role in the recurrence of the PT although margins were not free at the initial surgery.
Purpose Treatment decision making for patients with breast cancer increasingly depends on analysi... more Purpose Treatment 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. Method RNA 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-value...
Purpose Breast cancer is a heterogeneous disease with different gene expression profiles, treatme... more Purpose Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment. Methods In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay. Results IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the ...
Purpose Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-... more 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. 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 20mg of adjuvant tamoxifen daily. We analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We defined non-adherence as a tamoxifen level < 60ng/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-negativ...
Background Breast cancer survival in sub-Saharan Africa (SSA) is low, but when diagnosed with bre... more Background Breast cancer survival in sub-Saharan Africa (SSA) is low, but when diagnosed with breast cancer, many women in SSA 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 July 1, 2015 and December 31, 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 inclu...
Background In high-income settings, delays from breast cancer (BC) diagnosis to initial treatment... more 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 positiv...
Objective In low- and middle-income countries (LMICs), advanced stage diagnosis of breast cancer ... more Objective In low- and middle-income countries (LMICs), advanced stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. By understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. MethodsWithin 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. The stage was assessed clinically. To examine the associations of the health system, socio-economic/household and individual factors, hierarchical multivariate 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 (59%). The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adju...
In some countries of sub-Saharan Africa, the prevalence of HIV exceeds 20%; in South Africa, 20.4... more 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 non-metastatic 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 July 1, 2015, to June 30, 2019. Among women with stages I-III BC, we compared those with and without HIV infection on socio-demographic, 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<0.001; 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<0.03). 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 are surviving long enough to develop BC; more research is needed on the causes of their poor survival. This article is protected by copyright. All rights reserved.
Advanced breast cancer (BC) at diagnosis is common in sub-Saharan Africa (SSA), including among w... more 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. 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. 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 the...
The South African Breast Cancer and HIV Outcomes prospective cohort (SABCHO) study was establishe... more 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). ...
Phyllodes tumours (PT) of the vulva are uncommon tumours. The gold standard treatment for these l... more Phyllodes tumours (PT) of the vulva are uncommon tumours. The gold standard treatment for these lesions is unknown but is intuitively presumed to be wide local excision. Incomplete resection is associated with recurrence although the time to recurrence is not known. Pregnancy is hypothesised to increase recurrence due to the production of steroid hormones oestrogen and progesterone. We report on a patient who had recurrence of a PT at a rare site (labia minora) and on the contralateral side from the original lesion, during pregnancy. These findings support that oestrogen and progesterone hormones could have played a role in the recurrence of the PT although margins were not free at the initial surgery.
Purpose Treatment decision making for patients with breast cancer increasingly depends on analysi... more Purpose Treatment 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. Method RNA 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-value...
Purpose Breast cancer is a heterogeneous disease with different gene expression profiles, treatme... more Purpose Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment. Methods In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay. Results IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the ...
Purpose Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-... more 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. 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 20mg of adjuvant tamoxifen daily. We analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We defined non-adherence as a tamoxifen level < 60ng/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-negativ...
Background Breast cancer survival in sub-Saharan Africa (SSA) is low, but when diagnosed with bre... more Background Breast cancer survival in sub-Saharan Africa (SSA) is low, but when diagnosed with breast cancer, many women in SSA 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 July 1, 2015 and December 31, 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 inclu...
Background In high-income settings, delays from breast cancer (BC) diagnosis to initial treatment... more 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 positiv...
Objective In low- and middle-income countries (LMICs), advanced stage diagnosis of breast cancer ... more Objective In low- and middle-income countries (LMICs), advanced stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. By understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. MethodsWithin 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. The stage was assessed clinically. To examine the associations of the health system, socio-economic/household and individual factors, hierarchical multivariate 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 (59%). The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adju...
In some countries of sub-Saharan Africa, the prevalence of HIV exceeds 20%; in South Africa, 20.4... more 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 non-metastatic 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 July 1, 2015, to June 30, 2019. Among women with stages I-III BC, we compared those with and without HIV infection on socio-demographic, 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<0.001; 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<0.03). 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 are surviving long enough to develop BC; more research is needed on the causes of their poor survival. This article is protected by copyright. All rights reserved.
Advanced breast cancer (BC) at diagnosis is common in sub-Saharan Africa (SSA), including among w... more 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. 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. 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 the...
Uploads
Papers by Boitumelo Phakathi