• Retrospective study of patients (pts) receiving first-line trastuzumab-based treatment for metastatic disease.
• 275 T-naïve pts had a higher clinical benefit rate (68% versus 42%) and survival (36 versus 24 months) than 72 pts who received prior adjuvant T.

It has been more than 7 years since Dr George Sledge chaired the epic ASCO 2005 “educational session” during which we saw for the first time evidence of the impact of adjuvant trastuzumab. This therapeutic approach is now a well-ingrained standard of practice, altering the natural history of the disease, but some patients unfortunately still experience disease progression. This MD Anderson study compares the outcomes of individuals with metastatic HER2-positive disease who were and were not exposed to trastuzumab in the adjuvant setting and, not surprisingly, survival was shorter for patients receiving prior treatment (2 versus 3 years without prior trastuzumab). From a research perspective this paper is a reminder that the mechanisms of resistance to anti-HER2 therapies, including trastuzumab, remain a mystery, and from a practical standpoint these data suggest that even more and better strategies, such as pertuzumab and T-DM1, are needed to truly achieve the chronic disease model we hear so much about.