Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer

S. Coco, S. Boccardo, M. Mora, V. Fontana, I. Vanni, C. Genova, A. Alama, S. Salvi, M.G. Dal Bello, S. Bonfiglio, E. Rijavec, C. Sini, G. Barletta, F. Biello, F. Carli, Z. Cavalieri, G. Burrafato, L. Longo, A. Ballestrero, F. Grossi

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Abstract

Introduction: Breast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk. Patients and Methods: Thirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups. Results: Estrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer. Conclusion: The decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation. © 2020 The Author(s) In order to identify biomarkers able to predict lung cancer risk in women surviving breast cancer, the hormone status and the expression of markers involved in DNA repair, DNA synthesis, and cell division were investigated. Breast cancer patients reporting alteration of DNA-repair machinery (BRCA1/2) and reduction of microtubule dynamicity (TUBB3) seem more susceptible to developing lung cancer after therapy-related DNA-damaging effects. © 2020 The Author(s)
Original languageEnglish
JournalClin. Breast Cancer
DOIs
Publication statusPublished - 2021

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