The addition of pertuzumab plus trastuzumab to neoadjuvant chemotherapy has improved the outcomes of women with high-risk HER2+ breast cancer, although the risk of adverse events remains problematic. Now, data from a phase II trial suggest that a reduction in tumour metabolic activity on PET imaging at 15 days after treatment initiation is a biomarker of pathological complete response (pCR).

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In this single-arm trial, a total of 88 women with stage II/III, oestrogen receptor (ER)–, HER2+ breast cancer received four cycles of neoadjuvant pertuzumab plus trastuzumab and underwent 18FDG-PET–CT imaging before and 15 days after the start of treatment. Determining the relationship between early changes in maximum standard uptake value corrected for lean body mass (SULmax) and pCR after four cycles of therapy was the primary objective. Highlighting the motivations for this trial, lead author Roisin Connolly explains: “several clinical trials have revealed a subset of patients who have a pCR to neoadjuvant pertuzumab plus trastuzumab alone, and could thus be spared chemotherapy; however, robust biomarkers are required in order to consistently identify such patients”.

A total of 28 patients (34%) had a pCR after four cycles of therapy. Patients with a pCR had a significantly greater median reduction in SULmax at 15 days than those without a pCR (63.8% versus 33.5%; P < 0.001). Applying an exploratory cut-off value of a 40% reduction in SULmax yielded an 86% level of sensitivity and a specificity of 55%. Most notably, this threshold also provides a high negative predictive value (88%). “These data suggest that patients who do not have a substantial reduction in SULmax by day 15 are unlikely to have a pCR to targeted therapies alone,” Connolly summarizes.

This finding suggests that the majority of patients with an initial response to targeted therapy could be safely spared chemotherapy and the associated risk of adverse events. Furthermore, because these changes occur early in the course of treatment, patients who do not have a substantial reduction in SULmax could potentially be assigned to other therapies. Further clinical validation of this biomarker is necessary and eagerly awaited.