Expert Point of View: Ian Smith, MD

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Invited discussant Ian Smith, MD, of The Royal Marsden Hospital and Institute of Cancer Research in London, commented at the ESMO meeting that while all three arms of NeoALLTO, especially the arm with dual HER2 blockade, achieved good pathologic complete response rates, “the breast-conserving surgery rate is perhaps disappointingly low, so we are getting better [pathologic complete response rates] but no additional gains regarding the surgery.”

He said the finding that estrogen receptor (ER) negativity was used as a reason to avoid lumpectomy is “particularly disappointing, since ER-negative HER2-positive tumors have the best chance for a [pathologic complete response]—60% or greater.”

Dr. Smith noted that in the GeparQuattro study, which involved 445 HER2-positive women treated with trastuzumab and chemotherapy, the pathologic complete response rate was 32% and the breast-conservation rate was 63%.1 The reason for the higher rate of conservative surgery, he suggested, “could be that the trials’ surgeons were experienced in, and committed to, the neoadjuvant approach.” Nevertheless, he added, of 154 patients who had mastectomy, 21% had achieved a pathologic complete response; so even in this study the results were not optimal.

Part of the problem, he added, is that “the surgeon doesn’t know it’s a [pathologic complete response] until after the surgery.” An understanding of the short-term changes in molecular markers may help better predict who really needs mastectomy, he said.

Finally, Dr. Smith concluded, to achieve one of the goals in breast cancer care—to treat effectively while limiting morbidity—“we must train our surgeons that most patients with HER2-positsive breast cancer do not need mastectomy after neoadjuvant anti-HER2 therapy with chemotherapy.” ■

Disclosure: Dr. Smith receives occasional honoraria from Roche for lecturing and chairing meetings.


1. Untch M, Rezai M, Loibl S, et al: Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: Results from the GeparQuattro study. J Clin Oncol 28:2024-2031, 2010.

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