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.

A prospective study of receptor profiles in breast cancer and the ipsilateral axillary lymph node metastases measured simultaneously in treatment naïve cases.

BACKGROUND: The heterogeneity of receptor profiles in breast cancer is well known. The differing receptor profiles of primary breast cancer and nodal metastases have been investigated and found to range between 10-50% depending on the hormone receptor tested. A study comparing the hormone status of primary breast cancers and the synchronous ipsilateral involved sentinel lymph node has not been performed in a South African population. METHOD: This is a prospective study where two specialist radiologists performed the simultaneous core needle biopsies of the primary breast cancer and the clinically positive axillary nodes. All receptor status analysis was conducted by one specialist histopathologist. RESULTS: Of 141 patients who gave written informed consent for this study, 29 were excluded; 112 patients met the inclusion criteria. Anonymised demographics of age, clinical stage, HIV status and metastatic screening were recorded. The simultaneous biopsies and receptor measurements identified 10 patients with discordant receptor status in the positive axillary lymph nodes. In each case, the receptor profile of the axillary lymphatic metastases was more aggressive than that of the primary tumour. The luminal A subtype had a significantly greater risk of discordance than other subtypes (p = 0.02). CONCLUSION: Core needle biopsy and receptor analysis should be considered on the positive axillary nodes in breast cancer patients. Adjuvant treatment should be targeted to the receptor profile of the lymph node metastases.

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.

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.

Disarrangement of fiber tracts and decline of neuronal density correlate in glioma patients--a combined diffusion tensor imaging and 1H-MR spectroscopy study.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) and MR spectroscopy are noninvasive, quantitative tools for the preoperative assessment of gliomas with which the quantitative parameter fractional anisotropy (FA) and the concentration of neurometabolites N-acetylaspartate (NAA), choline (Cho), creatine (Cr) of the brain can be determined. Measurements of FA and NAA reflect the integrity of fiber tracts and the presence of neurons, respectively. This investigation examines changes of FA and NAA and compares these different aspects in architecture of gliomas after spatial coregistration. METHODS: DTI and chemical shift (1)H-MR spectroscopy was performed in 34 healthy volunteers and 69 patients with histologically confirmed (n = 48) or morphologically suspected (n = 21) non-necrotic brain glioma. Volumes of interest (VOIs) were placed in the tumor center (TC), the tumor border (TB), the normal-appearing white matter adjacent to the tumors (TNWM), and in the white matter of the contralateral hemisphere (NWMC). Median FA values and NAA/Cr and NAA/Cho ratios were calculated in the patients' VOIs and the gray and white matter of the volunteers. Correlations of FA values and NAA ratios were calculated. RESULTS: Continuous changes of FA and NAA from the tumor center to the periphery (the adjacent white matter and the contra-lateral hemisphere, respectively) were observed, where median values were: TC: 0.73 +/- 0.45, 0.47 +/- 0.58, 0.17 +/- 0.15 (NAA/Cr, NAA/Cho, FA); TB: 1.06 +/- 0.53, 1.00 +/- 0.15, 0.23 +/- 0.08; TNWM: 1.42 +/- 2.48, 1.21 +/- 0.95, 0.34 +/- 0.09; and NWMC: 1.63 +/- 0.72, 1.56 +/- 1.34, 0.38 +/- 0.08. Correlation of median FA values and NAA ratios in the cumulative group of patients was high (r = 0.99 [NAA/Cr], 0.95 [NAA/ Cho] at P < .01). Correlation between the individual NAA ratios and the FA values was moderate (r = 0.53 [NAA/Cr], 0.51 [NAA/Cho] at P < .01). CONCLUSION: In gliomas, the degree of tissue organization decreases continuously from the surrounding tissue toward the center of the tumor accompanied by a concordant decrease of NAA. This uniform behavior of FA and NAA reflects a decreasing integrity of both neuronal structures and fibers.