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

AI Article Synopsis

  • Deficiency in BRCA genes significantly increases the risk of developing invasive breast cancer, with mutation carriers facing up to an 80% risk.
  • Current prevention methods involve radical surgeries like bilateral mastectomy, but researchers are exploring a non-invasive approach using intraductal treatment with cisplatin and PARP1 inhibition.
  • Preclinical studies show promise in delaying tumor onset in mice, but caution is advised due to a slight increase in tumor incidence linked to systemic exposure to cisplatin, especially in older mice.

Article Abstract

deficiency predisposes to the development of invasive breast cancer. In 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 -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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617383PMC
http://dx.doi.org/10.18632/oncotarget.18490DOI Listing

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