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ADJUVANT TRASTUZUMAB One year of adjuvant trastuzumab has been the standard treatment for human epidermal growth factor receptor 2positive (HER2-positive) early breast cancer since the mid2000s. From the outset, the expense and cardiac toxicity associated with trastuzumab use led to questioning of treatment duration (1 year), which was chosen based on a slim scientific base. The results of the FinHER trial, which showed tangible benefits with 9 weeks of trastuzumab treatment, suggest that a shorter and cheaper regimen could still be effective. Later, the lack of added benefit of extended trastuzumab treatment seen in the HERA 2-year arm reinforced the notion of a “ceiling effect”—a point beyond which extending trastuzumab treatment duration does not lead to further improvement in outcomes. The PHARE, HORG, SOLD, SHORT-HER and PERSEPHONE trials were launched to determine whether a shorter regimen would be non-inferior to the standard regimen. Though the first four trial failed to prove non-inferiority, the recently presented non-inferior results of PERSEPHONE have led to considerable debate. Figure 1 depicts the design of these trials and Table 1 summarizes their results.

PERSEPHONE: are we ready to de-escalate adjuvant trastuzumab for HER2-positive breast cancer?