Research ArticleCancer

Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism

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Science Translational Medicine  05 Jul 2017:
Vol. 9, Issue 397, eaan0026
DOI: 10.1126/scitranslmed.aan0026

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  • Comment on “The Neoadjuvant chemotherapy (NAC) setting provides an opportunity to study mechanisms of resistance to therapy but should not be portrayed as inducing clinical breast cancer metastasis”
    • Laura Esserman, University of California, San Francisco
    • Other Contributors:
      • Andres Forero, University of Alabama, Birmingham
      • Hope Rugo, University of California, San Francisco
      • Anna Barker, Arizona State University
      • Angie DeMichele, University of Pennsylvania
      • Jane Perlmutter, janep@gemini-grp.com, University of California, San Francisco
      • Christina Yau, cyau@buckinstitute.org, Buck Institute for Research and Aging
      • Denise Wolf, University of California, San Francisco
      • Kathy Albain, Loyola University Medical Center
      • Michael Alvarado, University of California, San Francisco
      • Doug Yee, University of Minnesota, Masonic Cancer Center

    The findings reported by Karaglannis et al. (1) demonstrate a potentially important advance in our understanding of how metastases occur in some tumor types. However, the data presented are far from sufficient to justify the conclusion that neoadjuvant chemotherapy causes metastases in breast cancer patients (2).
    The mouse data demonstrate a mechanism whereby taxane-resistant cancer can escape and metastasize. Transgenic aggressive murine models were used and the responses obtained to paclitaxel were partial at best - a control group of mouse tumors highly responsive to taxanes that illuminated TMEM function in responsive tumors would be required to conclude that taxanes induce metastases in all tumors. Furthermore, the duration of treatment regimens used were not comparable to typical clinical neoadjuvant taxanes protocols.
    Evidence that this mechanism is clinically active comes from only a limited number of cases (7 from one series and 5 from another), all of which had residual tumor following neoadjuvant chemotherapy. Residual disease at time of surgery is a well established predictor of poor outcome (metastasis), which over multiple trials and meta-analyses has clearly been shown to be associated with an increased risk of metastatic disease. Cases where pathologic complete response (pCR) was achieved were not evaluated in this manuscript, however, 13-50% of high-risk breast cancers achieve a pCR following taxane-based chemotherapy. Patients who achieve comp...

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    Competing Interests: None declared.