FGFR2 genetic variants in women with breast cancer.

Black African populations are more genetically diverse than others, but genetic variants have been studied primarily in European populations. The present study examined the association of four single nucleotide polymorphisms (SNPs) of the fibroblast growth factor receptor 2, associated with breast cancer in non­African populations, with breast cancer in Black, southern African women. Genomic DNA was extracted from whole blood samples of 1,001 patients with breast cancer and 1,006 controls (without breast cancer), and the rs2981582, rs35054928, rs2981578, and rs11200014 polymorphisms were analyzed using allele­specific Kompetitive allele­specific PCR™, and the χ2 or Fisher's exact tests were used to compare the genotype frequencies. There was no association between those SNPs and breast cancer in the studied cohort, although an association was identified between the C/C homozygote genotype for rs2981578 and invasive lobular carcinoma. These results show that genetic biomarkers of breast cancer risk in European populations are not necessarily associated with risk in sub­Saharan African populations. African populations are more heterogenous than other populations, and the information from this population can help focus genetic risks of cancer in this understudied population.

Discordance between PAM50 intrinsic subtyping and immunohistochemistry in South African women with breast cancer.

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 lowest concordance. By altering the cutoff for Ki67, and realigning the HER2/ER/PR-positive patients to IHC-HER2, we improved concordance with the intrinsic subtypes. CONCLUSION: We suggest that the Ki67 be changed to a cutoff of 20-25% in our population to better reflect the luminal subtype classifications. This change would inform treatment options for breast cancer patients in settings where genomic assays are unaffordable.

The effect of HIV infection on the surgical, chemo- and radiotherapy management of breast cancer. A prospective cohort study.

INTRODUCTION: Breast cancer is the most common cancer of women in the world. Twenty-five percent of people living with the human immunodeficiency virus (HIV) reside in South Africa. The coincidence of breast cancer and HIV infection is therefore common in South Africa. There is a perception that systemic and local surgical complications are more common in HIV-infected patients, and that these patients tolerate chemo- and radiotherapy poorly. AIM: The aim of the study was to determine the effect of HIV infection on the management of breast cancer by comparing HIV-infected to -noninfected patients. The outcomes of surgery and adjuvant/neoadjuvant therapy were examined in these groups. METHOD: The study was performed at the Steve Biko Academic Hospital, Pretoria, South Africa, during 2009-2014. Patients scheduled for surgery for breast cancer were recruited prospectively and their HIV status was determined. All patients were managed according to standard guidelines for breast cancer. Patients were followed up for 30 days and local and systemic surgical complications documented. Completion or non-completion of courses of chemo- and radiotherapy, and reasons for non-completion were documented. HIV-infected and -noninfected patients respectively were grouped, and compared statistically. RESULTS: One hundred and sixty patients (31 HIV-infected) were included. The frequency of surgical complications did not differ significantly between HIV-noninfected and infected patients (p = 0.08), more occurring in the HIV-noninfected patients. The risk ratio of HIV infection for surgical complications was 0.20 and the odds ratio 0.23. The completion of courses of chemo- and radiotherapy did not differ between the HIV-infected and -noninfected patients. Twenty-five of 27 HIV-infected patients (93%) and 100 of 113 HIV-noninfected patients (94%) completed their courses of chemotherapy (p = 0.68). Twelve of 14 HIV-infected patients (86%) and 40 of 41 HIV-noninfected patients (98%) completed their courses of radiotherapy (p = 0.16). CONCLUSION: These results suggest that HIV-infected patients with breast cancer do not experience more treatment-related complications and can be treated according to standard guidelines.