Simona Coco1, Simona Boccardo2, Marco Mora3, Vincenzo Fontana4, Irene Vanni5, Carlo Genova5, Angela Alama2, Sandra Salvi3, Maria Giovanna Dal Bello2, Silvia Bonfiglio6, Erika Rijavec7, Claudio Sini8, Giulia Barletta2, Federica Biello9, Franca Carli3, Zita Cavalieri2, Giovanni Burrafato2, Luca Longo2, Alberto Ballestrero10, Francesco Grossi7. 1. Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: simona.coco@hsanmartino.it. 2. Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 3. Department of Pathology. 4. Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 5. Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa. 6. Centre for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy. 7. UOC Oncologia Medica, IRCCS Cà Granda Foundation, Ospedale Maggiore Policlinico, Milan, Italy. 8. Oncologia Medica e CPDO, ASSL di Olbia-ATS Sardegna, Olbia, Italy. 9. SCDU Oncologia, AOU Maggiore della Carità, Novara, Italy. 10. Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa.
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.
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.