Clinical relevance of double heterozygosity revealed by next-generation sequencing of homologous recombination repair pathway genes in South African breast cancer patients.

PURPOSE: Genetically predisposed breast cancer (BC) patients represent a minor but clinically meaningful subgroup of the disease, with 25% of all cases associated with actionable variants in BRCA1/2. Diagnostic implementation of next-generation sequencing (NGS) resulted in the rare identification of BC patients with double heterozygosity for deleterious variants in genes partaking in homologous recombination repair of DNA. As clinical heterogeneity poses challenges for genetic counseling, this study focused on the occurrence and clinical relevance of double heterozygous BC in South Africa. METHODS: DNA samples were diagnostically screened using the NGS-based Oncomine™ BRCA Expanded Research Assay. Data was generated on the Ion GeneStudio S5 system and analyzed using the Torrent Suite™ and reporter software. The clinical significance of the variants detected was determined using international variant classification guidelines and treatment implications. RESULTS: Six of 1600 BC patients (0.375%) tested were identified as being bi-allelic for two germline likely pathogenic or pathogenic variants. Most of the variants were present in BRCA1/2, including two founder-related small deletions in three cases, with family-specific variants detected in ATM, BARD1, FANCD2, NBN, and TP53. The scientific interpretation and clinical relevance were based on the clinical and tumor characteristics of each case. CONCLUSION: This study increased current knowledge of the risk implications associated with the co-occurrence of more than one pathogenic variant in the BC susceptibility genes, confirmed to be a rare condition in South Africa. Further molecular pathology-based studies are warranted to determine whether clinical decision-making is affected by the detection of a second pathogenic variant in BRCA1/2 and TP53 carriers.

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.

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.

Outcomes of breast conserving therapy: Recurrence, imaging findings and histological correlation.

Background: Breast conserving therapy (BCT) is the mainstay therapy in patients with early breast cancer and selected patients with locally advanced breast cancer. No formal audit has been performed on BCT at our institution. Objectives: To determine the incidence and risk factors for ipsilateral breast tumour recurrence (IBTR). Study the imaging features of IBTR. Determine adherence to the proposed annual mammographic surveillance schedule. Method: Clinical, radiological and histopathological records of patients who underwent BCT from 01 January 2011 to 31 December 2015 were reviewed. Patients were followed up for at least 5 years. Results: Ninety-two patients were included in the study with a mean age of 54.3 years. Eighty of the 92 (87.0%) patients were imaged within 1-year post-BCT. Ipsilateral breast tumour recurrence was 6/92 (6.5%) with mean time to IBTR of 34.4 months. One of the 92 (1.0%) patients had a contralateral metachronous recurrence with no IBTR and 11/92 (12.0%) had distant metastases only. Pathological tumour size and extent (pT2) (68.5%) and pathological lymph node (pN0) (65.2%) were the most common locoregional staging. Infiltrating ductal carcinoma was the most common histological type (88%). Age < 35 years was associated with breast cancer recurrence (p < 0.01). Imaging findings of recurrence were microcalcification (odds ratio [OR]: 4), asymmetric density (OR: 4) and skin thickening (OR: 2.5). Conclusion: The occurrence of IBTR following BCT in our unit is acceptable and comparable to local and international units. The accuracy of assessing the post-BCT breast for IBTR is in keeping with international standards. Contribution: Improved radiological imaging interpretation of the post-BCT breast.

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.

Mutations in BRCA-related breast and ovarian cancer in the South African Indian population: A descriptive study.

Knowledge of the genetic landscape of a specific population group is vital for population-specific diagnosis and treatment of familial breast cancer. Although BRCA-related diagnostic testing has long been implemented in South Africa, the genotyping approach previously failed for the SA Indian population as it was based on other SA population groups. Because this population is uniquely admixed, the lack of population-specific data resulted in the implementation of comprehensive mutation screens for BRCA1/2. A total of 223 female patients were screened for clinically actionable variants. High-resolution melting analysis (HRMA) was used to screen 88 patients for DNA alterations in the coding and splice site boundaries of BRCA1 exons 2-9, BRCA1 exons 11-23, BRCA2 exons 2-9 and BRCA2 exons 12-27. The protein truncation test (PTT) was used to screen the three larger exons (BRCA1 exon 10 and BRCA2 exons 10 and 11) for protein termination changes. Multiplex ligation-dependent probe amplification (MLPA) was used to determine the presence of larger indels and possible copy number differences. Next Generation Sequencing (NGS) was performed on the remaining 135 samples. All potential variants were confirmed by performing Sanger DNA sequencing. The search revealed 28 different pathogenic heterozygotic variants, together with nine variants of unknown significance (VUS). The results suggested that the SA Indian population represents a different genetic admixture compared to that of mainland India, as only five pathogenic variants corresponded to those reported for mainland India. Familial breast cancer testing for SA Indian patients should therefore be performed as comprehensively as possible as the pathogenic variants seem to be family- rather than population-specific. Furthermore, predictive testing of family members will contribute to relieve the financial burden on the country's healthcare system, as increased surveillance and appropriate management could prevent disease.

Quality of Histopathological Reporting in Breast Cancer: Results From Four South African Breast Units.

PURPOSE: High-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. METHODS: The 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. RESULTS: Seventy-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. CONCLUSION: Histopathology 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.

Improving breast cancer surgery: a classification and quadrant per quadrant atlas for oncoplastic surgery.

BACKGROUND: Oncoplastic surgery (OPS) has emerged as a new approach for extending breast conserving surgery (BCS) possibilities, reducing both mastectomy and re-excision rates, while avoiding breast deformities. OPS is based upon the integration of plastic surgery techniques for immediate reshaping after wide excision for breast cancer. A simple guide for choosing the appropriate OPS procedure is not available. OBJECTIVE: To develop an Atlas and guideline for oncoplastic surgery (OPS) to help in patient selection and choice of optimal surgical procedure for breast cancer patients undergoing BCS. METHODS: We stratify OPS into two levels based on excision volume and the complexity of the reshaping technique. For resections less than 20% of the breast volume (level I OPS), a step-by-step approach allows easy reshaping of the breast. For larger resections (level II OPS), a mammoplasty technique is required. RESULTS: We identified three elements that can be used for patient selection and for determination of the appropriate OPS technique: excision volume, tumor location, and glandular density. For level II techniques, we defined a quadrant per quadrant Atlas that offers a different mammoplasty for each quadrant of the breast. CONCLUSIONS: OPS is the "third pathway" between standard BCS and mastectomy. The OPS classification and Atlas improves patient selection and allows a uniform approach for surgeons. It proposes a specific solution for different scenarios and helps improve breast conservation outcomes.

Breast Cancer Care Quality in South Africa's Public Health System: An Evaluation Using American Society of Clinical Oncology/National Quality Forum Measures.

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.

Palliation of malignant hilar obstruction at a single centre--review of operative and non-operative techniques.

INTRODUCTION: Jaundice secondary to a malignant hilar obstruction can be relieved by operative bypass or percutaneous stenting. Comparative trials involving these techniques are scarce. We reviewed our experience with these competing techniques in the palliation of malignant hilar obstruction. PATIENTS AND METHODS: All patients with malignant hilar obstruction managed at our institution during the period 1992-2002 were identified for review. RESULTS: A total of 36 deeply jaundiced patients with hilar obstruction were identified. Twenty-two patients underwent exploration with the intention of performing an operative bypass and 14 patients underwent percutaneous transhepatic cholangiography (PTC) with intention to stent. Procedure-related mortality was similar in both groups. Morbidity was much higher in the operative group. Effective symptom relief was achieved with both techniques. In the PTC group recurrent biliary obstruction in 2 patients necessitated salvage non-operative procedures. Although survival rates were slightly longer in the operative group, this was not significant. There were no long-term survivors. CONCLUSION: Operative bypass provides better sustained relief of jaundice than PTC. However long-term survival in both groups is poor and operative bypass is best reserved for younger patients with no technical contraindications. Despite early and late procedural failures PTC is the method of choice for patients with advanced-stage disease and those with significant co-morbidities.

South African Breast Cancer and HIV Outcomes Study: Methods and Baseline Assessment.

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.