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dlaxague · 10-26-2008, 04:10 PM

Hi, that's the first I've heard of that. It makes sense but I thought that studies had showed no correlation. Is my memory failing me on this also (sigh)? Although it is a very small study - actually only 77 were FISH +. I went looking for full text without success but I did find an abstract that had some more numbers (copied below). I wonder many things but first - what was the cut-off used for low vs. high expression? Anyone have access?

Other questions would be whether neoadjuvant studies and short-term information like PCR are useful for predicting longterm stats (answer unknown at this point, as far as I know).

I think that most of the previous information about this came from researchers trying to decide what to use as the cut-off for HER2+ with FISH?
Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification.

Arnould L, Arveux P, Couturier J, Gelly-Marty M, Loustalot C, Ettore F, Sagan C, Antoine M, Penault-Llorca F, Vasseur B, Fumoleau P, Coudert BP.
CLCC G-F Leclerc and 1FR100, Dijon, France. larnould@dijon.fnclcc.fr
PURPOSE: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer. EXPERIMENTAL DESIGN: Breast biopsies from 93 HER-2-positive patients treated with trastuzumab-based neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+. RESULTS: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low- and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low- plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen, T or N stage, tumor grade, or hormonal receptors. CONCLUSIONS: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.

10-26-2008, 04:10 PM	#6
dlaxague Senior Member Join Date: May 2006 Posts: 221	very interesting, jacqueline Hi, that's the first I've heard of that. It makes sense but I thought that studies had showed no correlation. Is my memory failing me on this also (sigh)? Although it is a very small study - actually only 77 were FISH +. I went looking for full text without success but I did find an abstract that had some more numbers (copied below). I wonder many things but first - what was the cut-off used for low vs. high expression? Anyone have access? Other questions would be whether neoadjuvant studies and short-term information like PCR are useful for predicting longterm stats (answer unknown at this point, as far as I know). I think that most of the previous information about this came from researchers trying to decide what to use as the cut-off for HER2+ with FISH? Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification. Arnould L, Arveux P, Couturier J, Gelly-Marty M, Loustalot C, Ettore F, Sagan C, Antoine M, Penault-Llorca F, Vasseur B, Fumoleau P, Coudert BP. CLCC G-F Leclerc and 1FR100, Dijon, France. larnould@dijon.fnclcc.fr PURPOSE: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer. EXPERIMENTAL DESIGN: Breast biopsies from 93 HER-2-positive patients treated with trastuzumab-based neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+. RESULTS: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low- and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low- plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen, T or N stage, tumor grade, or hormonal receptors. CONCLUSIONS: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.