The γ-H2AX foci as an indicator for double-stranded DNA breaks and response to ongoing chemotherapy in breast cancer women: a pilot study

M. Aitmagambetova, G. Smagulova, S. Sakhanova, N. Kereyeva, A. Koishybaev, A. Amanzholkyzy, A. Tulyaeva, D. Zholmukhamedova, G. Kandygulova, N. Imanbaev, A. Donayeva, I.A. Abdelazim, S. Saparbayev, Z. Khamidullina, G. Gubasheva

Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan. dr.ibrahimanwar@gmail.com

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• Oncology

OBJECTIVE: The double-stranded breaks (DSBs) of the DNA can predispose to cancer development. The γH2AX foci have been proposed for prediction of tumor growth and response to radiotherapy. We aimed to evaluate the γ-H2AX foci as an indicator for DSBs and response to ongoing chemotherapy in breast cancer women.

PATIENTS AND METHODS: Twenty-nine (29) breast cancer women, scheduled for adjuvant chemotherapy were included in this pilot study after obtaining written informed consent and approval of the study by the WKMU ethics committee. Participants received adjuvant chemotherapy, according to the treatment protocol of the Republic of Kazakhstan. A peripheral blood sample was collected from each studied participant for analysis of the γ-H2AX foci in the participants’ lymphocytes using the immunofluorescent staining kit. Data of the Fluorescein isothiocyanate (FITC) rupture, and Adenomatous Polyposis Coli (APC) repair channels were analyzed to evaluate the γ-H2AX foci as an indicator for DSBs, and response to ongoing chemotherapy.

RESULTS: About 10.3% (3/29) of the studied breast cancers were luminal A, 72.4% (21/29) were luminal type B, 13.8% (4/29) were basal-like, and 3.5 (1/29) were HER2 positive. The FITC rupture channel during the ongoing chemotherapy showed significantly decreased foci intensity means (p=0.0075), and significantly increased colocalization (p=0.02). The APC repair channels during the ongoing chemotherapy showed significantly increased nuclei intensity (p=0.046), foci overall (p=0.0007), clusters (p=0.002), foci mean (p<0.0001), and foci mean + clusters (p=0.0003). It also showed significantly increased clusters positive cells (p<0.0001), foci low intensity (p<0.0001), foci low intensity + clusters (p=0.0003), and clusters of low-intensity positive cells (p=0.002).

CONCLUSIONS: The γ-H2AX foci, the changes in the FITC rupture, and APC repair channels can serve as real-time indicators for the response to ongoing chemotherapy in breast cancer women. The γ-H2AX foci as an indicator for DSBs/repair pathway, and for the response to ongoing chemotherapy in breast cancer should be evaluated in further studies.

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