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Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice

BRCA deficiency predisposes to the development of invasive breast cancer. In BRCA mutation carriers this risk can increase up to 80%. Currently, bilateral prophylactic mastectomy and prophylactic bilateral salpingo-oophorectomy are the only preventive, albeit radical invasive strategies to prevent b...

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Autores principales: de Groot, Jolien S., van Diest, Paul J., van Amersfoort, Miranda, Vlug, Eva J., Pan, Xiaojuan, ter Hoeve, Natalie D., Rosing, Hilde, Beijnen, Jos H., Youssef, Sameh A., de Bruin, Alain, Jonkers, Jos, van der Wall, Elsken, Derksen, Patrick W.B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617383/
https://www.ncbi.nlm.nih.gov/pubmed/28977823
http://dx.doi.org/10.18632/oncotarget.18490
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author de Groot, Jolien S.
van Diest, Paul J.
van Amersfoort, Miranda
Vlug, Eva J.
Pan, Xiaojuan
ter Hoeve, Natalie D.
Rosing, Hilde
Beijnen, Jos H.
Youssef, Sameh A.
de Bruin, Alain
Jonkers, Jos
van der Wall, Elsken
Derksen, Patrick W.B.
author_facet de Groot, Jolien S.
van Diest, Paul J.
van Amersfoort, Miranda
Vlug, Eva J.
Pan, Xiaojuan
ter Hoeve, Natalie D.
Rosing, Hilde
Beijnen, Jos H.
Youssef, Sameh A.
de Bruin, Alain
Jonkers, Jos
van der Wall, Elsken
Derksen, Patrick W.B.
author_sort de Groot, Jolien S.
collection PubMed
description BRCA deficiency predisposes to the development of invasive breast cancer. In BRCA mutation carriers this risk can increase up to 80%. Currently, bilateral prophylactic mastectomy and prophylactic bilateral salpingo-oophorectomy are the only preventive, albeit radical invasive strategies to prevent breast cancer in BRCA mutation carriers. An alternative non-invasive way to prevent BRCA1-associated breast cancer may be local prophylactic treatment via the nipple. Using a non-invasive intraductal (ID) preclinical intervention strategy, we explored the use of combined cisplatin and poly (ADP)-ribose polymerase 1 (PARP1) inhibition to prevent the development of hereditary breast cancer. We show that ID cisplatin and PARP-inhibition can successfully ablate mammary epithelial cells, and this approach attenuated tumor onset in a mouse model of Brca1-associated breast cancer from 153 to 239 days. Long-term carcinogenicity studies in 150 syngeneic wild-type mice demonstrated that tumor incidence was increased in the ID treated mammary glands by 6.3% due to systemic exposure to cisplatin. Although this was only evident in aged mice (median age = 649 days), we conclude that ID cisplatin treatment only presents a safe and feasible local prevention option if systemic exposure to the chemotherapy used can be avoided.
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spelling pubmed-56173832017-10-03 Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice de Groot, Jolien S. van Diest, Paul J. van Amersfoort, Miranda Vlug, Eva J. Pan, Xiaojuan ter Hoeve, Natalie D. Rosing, Hilde Beijnen, Jos H. Youssef, Sameh A. de Bruin, Alain Jonkers, Jos van der Wall, Elsken Derksen, Patrick W.B. Oncotarget Priority Research Paper BRCA deficiency predisposes to the development of invasive breast cancer. In BRCA mutation carriers this risk can increase up to 80%. Currently, bilateral prophylactic mastectomy and prophylactic bilateral salpingo-oophorectomy are the only preventive, albeit radical invasive strategies to prevent breast cancer in BRCA mutation carriers. An alternative non-invasive way to prevent BRCA1-associated breast cancer may be local prophylactic treatment via the nipple. Using a non-invasive intraductal (ID) preclinical intervention strategy, we explored the use of combined cisplatin and poly (ADP)-ribose polymerase 1 (PARP1) inhibition to prevent the development of hereditary breast cancer. We show that ID cisplatin and PARP-inhibition can successfully ablate mammary epithelial cells, and this approach attenuated tumor onset in a mouse model of Brca1-associated breast cancer from 153 to 239 days. Long-term carcinogenicity studies in 150 syngeneic wild-type mice demonstrated that tumor incidence was increased in the ID treated mammary glands by 6.3% due to systemic exposure to cisplatin. Although this was only evident in aged mice (median age = 649 days), we conclude that ID cisplatin treatment only presents a safe and feasible local prevention option if systemic exposure to the chemotherapy used can be avoided. Impact Journals LLC 2017-06-15 /pmc/articles/PMC5617383/ /pubmed/28977823 http://dx.doi.org/10.18632/oncotarget.18490 Text en Copyright: © 2017 de Groot et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
de Groot, Jolien S.
van Diest, Paul J.
van Amersfoort, Miranda
Vlug, Eva J.
Pan, Xiaojuan
ter Hoeve, Natalie D.
Rosing, Hilde
Beijnen, Jos H.
Youssef, Sameh A.
de Bruin, Alain
Jonkers, Jos
van der Wall, Elsken
Derksen, Patrick W.B.
Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice
title Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice
title_full Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice
title_fullStr Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice
title_full_unstemmed Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice
title_short Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice
title_sort intraductal cisplatin treatment in a brca-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617383/
https://www.ncbi.nlm.nih.gov/pubmed/28977823
http://dx.doi.org/10.18632/oncotarget.18490
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