Alterations in immunohistochemical biologic markers following neoadjuvant chemotherapy in breast carcinoma

Bromfield, Michael Jared
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BACKGROUND: Neoadjuvant chemotherapy is an alternate treatment modality in which patients receive treatment before surgery. The use thereof in patients with breast carcinoma is not without practical and therapeutic implications. Neoadjuvant chemotherapy may allow for the in vivo selection of resistant tumour cells. In addition, neoadjuvant chemotherapy may cause an alteration in the status of hormone receptors and human epidermal growth factor receptor 2 (HER2). Although the impact of primary chemotherapy has generated considerable literature, studies continue to report conflicting results. This report is the first from South Africa and provides valuable insight into the need for repeat testing in a resource constrained setting. OBJECTIVES: The aim of this study was to determine the effect of neoadjuvant chemotherapy on biologic marker status in patients with primary invasive breast carcinoma. METHOD: A non-interventional, cross-sectional, retrospective and comparative analysis was performed. Data was collected over an 18-month period between 1 January 2014 and 30 June 2015 from the databases of the department of Anatomical Pathology and the Breast Unit in the department of Surgery at Chris Hani Baragwanath Academic Hospital. Biopsies and the corresponding post-primary chemotherapy surgical excision specimens from seventy-four patients were investigated for any change in hormone receptor status, HER2 receptor status and Ki67. RESULTS: Three hundred and seventy-three patients were newly diagnosed with an invasive mammary carcinoma. Invasive carcinoma of no special type was the most frequent diagnosis (86%) with 320 cases identified. Seventy-four patients (20%) underwent neoadjuvant chemotherapy followed by excision biopsy. Pathological complete response was identified in 7 patients (9%). In patients with residual post-primary chemotherapy tumours, significant reductions in progesterone receptor expression (p=0.003) and Ki67 proliferation index (p=<0.001) were found when compared with the needle core biopsies. No significant alterations were identified for oestrogen receptor (p=0.08) and HER2 receptor (p=0.655) expression. CONCLUSION: Hormone receptor status should be re-evaluated in the surgical excision specimen following neoadjuvant chemotherapy, as there can be an alteration in biomarker status that may impact treatment strategy. In current practice, with available resources limited, the repeat testing of HER2 may be of little value in the absence of neoadjuvant trastuzumab
A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the degree of Masters of Medicine in Anatomical Pathology, 2020
Bromfield, Michael Jared (2020) Alterations in immunohistochemical biologic markers following neoadjuvant chemotherapy in breast carcinoma, University of the Witwatersrand, Johannesburg, <>