Isolated ductal carcinoma in situ in patients presenting to two breast units in Johannesburg.

BACKGROUND: Ductal carcinoma in situ (DCIS) represents approximately 20% of all new breast cancers in countries with population-based mammography screening. South Africa is an upper middle-income country with no such screening programmes in place, and the proportion of isolated DCIS appears much lower than this. Most patients present with symptomatic disease and high-risk features. There are numerous controversies regarding the diagnosis and optimal management strategy for this premalignant condition, and the issue of overtreatment is much debated. Our study aimed to determine the proportion of patients presenting with isolated DCIS, to describe the clinical presentation and to describe the treatment provided. METHODS: This is a retrospective cohort study of patients with histologically confirmed isolated DCIS at Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital from July 2015 to March 2018. Records were collected from the existing clinical databases in both breast units and from the South African National Health Laboratory System. RESULTS: Out of 1 813 patients diagnosed and managed with breast malignancies in this period, 58 (3.1%) patients were identified with isolated DCIS. Forty-three (74.1%) of these patients were symptomatic. Thirty-four (58.6%) patients had a primary mastectomy, and 12 (20.6%) had breast-conserving surgery. CONCLUSION: The diagnosis of isolated DCIS is rare in our setting, and the majority of patients present with more advanced, symptomatic disease that is not deemed suitable for breast-conserving surgery. The short-term follow-up of our patients has shown a low rate of recurrence and mortality thus far. However, further long-term follow-up is needed.

Axillary lymph node dissection for patients with invasive breast cancer at Charlotte Maxeke and Chris Hani Baragwanath Academic Hospitals.

BACKGROUND: The extent of axillary surgery correlates with its morbidity and sentinel lymph node biopsy (SLNB) has become the standard of care in clinically node-negative (cN0) patients.This study aims to evaluate the application of SLNB and axillary lymph node dissection (ALND) and the associated risk factors for node-negative ALND in our units. METHODS: We included female patients with primary breast cancer who underwent axillary surgery in the breast units at Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital from March 2013 to March 2015. Univariate and multivariable logistic regression models were used to determine factors associated with pathological node-negative (pN0) ALND. RESULTS: 505 patients were included and 344 patients were staged clinically node-positive (68.1%), 161 (31.9%) were assessed as clinically node-negative and deemed eligible for SLNB. Sensitivity of clinical nodal staging was 85.9% with a positive predictive value of 76.5%. The majority of patients (313, 61.9%) underwent primary surgery while 192 (38.1%) underwent surgery after NACT. We performed 118 SLNBs and 387 ALNDs of which 97 were pathologically node-negative. Risk was not increased after NACT (OR 1.06, p = 0.790). We identified a significant risk in patients with triple-negative and HER-2 enriched subtypes compared to hormone receptor-positive patients (OR 3.05, 95% CI: 1.6-5.7, p = 0.001 and OR 2.25, 95% CI: 1.1-4.8, p = 0.035). CONCLUSION: The prevalence of pN0 ALND was 25.06%. In our cohort a significantly higher risk was found in hormone receptor-negative tumours. Preoperative nodal assessment needs to be optimised and include pathological confirmation. SLNB needs to be extended to patients after NACT despite resource-constraints.

Prevalence of comorbidities in women with and without breast cancer in Soweto, South Africa: Results from the SABC study.

BACKGROUND: Comorbidities occurring concurrently in breast cancer patients can be burdensome, as they may negatively influence time and stage of presentation. OBJECTIVES: To describe the comorbid health conditions among South African (SA) black women with and without breast cancer and to determine factors associated with advanced-stage presentation of breast cancer. METHODS: A population-based case-control study on breast cancer was conducted in black women in Soweto, SA, the SABC (South Africa Breast Cancer) study. Lifestyle information and blood samples were collected from 399 women with histologically confirmed new cases of invasive primary breast cancer, recruited prior to any therapy, and 399 age- and neighbourhood-matched controls without breast cancer. We compared self-reported metabolic diseases, depression, anthropometric measurements, blood pressure, HIV status and point-of-care lipid and glucose levels between patients with breast cancer and the control group. RESULTS: In the whole population, the mean (standard deviation) age was 54.6 (12.9) years, the majority (81.2%) of the participants were overweight or obese, 85.3% had abdominal adiposity, 61.3% were hypertensive, 47.1% had impaired fasting plasma glucose, 8.4% had elevated total cholesterol, 74.8% had low high-density lipoprotein and 10.9% were assessed to be depressed. Ninety-one percent of the whole cohort had at least one metabolic disease. In the breast cancer group, 72.2% had one or more metabolic diseases only (HIV-negative and no evidence of depression), compared with 64.7% of the control group. From a multivariate logistic regression adjusted model, higher household socioeconomic status conferred a 19% reduction in the odds of having advanced-stage breast cancer at diagnosis, while hypertension, dyslipidaemia and HIV were not significantly associated with stage at breast cancer diagnosis in the adjusted model. CONCLUSIONS: A large proportion of women experience several comorbidities, highlighting the need to address the chronic non-communicable disease epidemic in SA and to co-ordinate multidisciplinary primary-, secondary- and tertiary-level care in the country's complex healthcare system for better outcome.

Breast cancer trends differ by ethnicity: a report from the South African National Cancer Registry (1994-2009).

Background: To describe breast cancer (BC) incidence and mortality by ethnicity in South Africa (SA). Methods: Sources of data included the South African National Cancer Registry (NCR) pathology-based reports (1994­2009) and Statistics South Africa (SSA) mortality data (1997­2009). Numbers of cases, age-standardised incidence rates (ASIR) and lifetime risk (LR) were extracted from the NCR database for 1994­2009. Age-specific incidence rates were calculated for five-year age categories. The direct method of standardisation was employed to calculate age-standardised mortality rates (ASMR) using mortality data. Results: Between 1994 and 2009, there were 85 561 female BC. For the Black, Coloured and Asian groups, increases in ASIR and LR were observed between 1994 and 2009. In 2009, the ASIR for the total population, Blacks, Whites, Coloureds and Asians were 26.9, 18.7, 50.2, 40.9 and 51.2 per 100 000, respectively. For Asians, an increase in proportion of BC as a percentage of all female cancers was observed between 1994 and 2002 (11.1%) and continued to increase to 2009 (a further 4.5%). Whites and Asians presented higher incidences of BC at earlier ages compared with Blacks and Coloureds in 2009. In 1998, there were 1618 BC deaths in SA compared with 2784 deaths in 2009. ASMR between 1997 and 2004 increased but stabilised thereafter. Conclusion: This paper demonstrated that SA BC incidence rates are similar to other countries in the region, but lower than other countries with similar health systems. Ethnic differences in BC trends were observed. However, the reasons for observed ethnic differences are unclear.

BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer.

BACKGROUND: Current knowledge of the aetiology of hereditary breast cancer in the four main South African population groups (black, coloured, Indian and white) is limited. Risk assessments in the black, coloured and Indian population groups are challenging because of restricted information regarding the underlying genetic contributions to inherited breast cancer in these populations. We focused this study on premenopausal patients (diagnosed with breast cancer before the age of 50; n = 78) and triple negative breast cancer (TNBC) patients (n = 30) from the four South African ethnic groups. The aim of this study was to determine the frequency and spectrum of germline mutations in BRCA1, BRCA2 and PALB2 and to evaluate the presence of the CHEK2 c.1100delC allele in these patients. METHODS: In total, 108 South African breast cancer patients underwent mutation screening using a Next-Generation Sequencing (NGS) approach in combination with Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large rearrangements in BRCA1 and BRCA2. RESULTS: In 13 (12 %) patients a deleterious mutation in BRCA1/2 was detected, three of which were novel mutations in black patients. None of the study participants was found to have an unequivocal pathogenic mutation in PALB2. Two (white) patients tested positive for the CHEK2 c.1100delC mutation, however, one of these also carried a deleterious BRCA2 mutation. Additionally, six variants of unknown clinical significance were identified (4 in BRCA2, 2 in PALB2), all in black patients. Within the group of TNBC patients, a higher mutation frequency was obtained (23.3 %; 7/30) than in the group of patients diagnosed before the age of 50 (7.7 %; 6/78). CONCLUSION: This study highlights the importance of evaluating germline mutations in major breast cancer genes in all of the South African population groups. This NGS study shows that mutation analysis is warranted in South African patients with triple negative and/or in premenopausal breast cancer.

The challenges of managing breast cancer in the developing world - a perspective from sub-Saharan Africa.

Communicable diseases are the major cause of mortality in lower-income countries. Consequently, local and international resources are channelled mainly into addressing the impact of these conditions. HIV, however, is being successfully treated, people are living longer,and disease patterns are changing. As populations age, the incidence of cancer inevitably increases. The World Health Organization has predicted a dramatic increase in global cancer cases during the next 15 years, the majority of which will occur in low- and middle-income countries. Cancer treatment is expensive and complex and in the developing world 5% of global cancer funds are spent on 70% of cancer cases. This paper reviews the challenges of managing breast cancer in the developing world, using sub-Saharan Africa as a model.