NEOADJUVANT CHEMOTHERAPY WITHOUT HERCEPTIN INCREASES HER2 LOSS

NEW YORK (Reuters Health) Sep 24 - Loss of HER2 positivity is higher in breast cancer patients receiving neoadjuvant chemotherapy without anti-HER2 agents, according to new research.

Loss of HER2 amplification following neoadjuvant trastuzumab-based (anti-HER2) therapy is associated with reduced relapse-free survival, but the biological basis for this remains unclear.

Dr. Valentina Guarneri from University of Padova in Italy and colleagues used a prospective database to evaluate the rate of HER2 loss and its prognostic significance in 107 HER2-positive breast cancer patients; 40 of the patients were treated with neoadjuvant chemotherapy and 67 received neoadjuvant chemotherapy plus anti-HER2 agents.

Loss of HER2 expression was significantly more common among women with residual disease after chemotherapy alone (14/35, 40%) than among women with residual disease after chemotherapy plus anti-HER2 agents (5/34, 14.7%), according to the report, online September 7 in Annals of Oncology.

"We would have expected a higher rate of HER2 conversion after anti-HER2 agents, as a consequence of the selective pressure on resistant HER2-negative clones and the induction of HER2 loss as a mechanism of resistance," the researchers write. "However, in our study, the addition of anti-HER2 to chemotherapy seems to even lower the rate of HER2 loss."

Women who did not achieve pathologic complete response (pCR) were 9.55 times more likely to relapse than were women who did achieve pCR (p=0.028), and there was a trend towards a higher risk of relapse among women who had a loss of HER2 expression (p=0.063).

"These observations suggest the importance of retesting HER2 status after primary therapy, to better refine the patient's prognosis," the researchers conclude.

"This population with particularly poor outcome may benefit from the inclusion in the clinical trial investigating further adjuvant treatment approaches," they add. "Although in our series HER2 loss after primary systemic treatment seems to occur more frequently when patients are treated with chemotherapy alone rather than combined with anti-HER2 agents, there are no available data that could help to explain these observations."

Dr. Guarneri did not respond to a request for comments.

SOURCE: http://bit.ly/1bsGpQB

Ann Oncol 2013.