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Apoptosis Induction by the Core Biopsy Procedure

Baylor College of Medicine, Houston, TX

To the Editor:

Dr Menard et al support our observation of tumor reduction in their pilot study, and cytocidal rather than cytostatic mechanism of action of trastuzumab. We acknowledge that there could be other mechanisms by which trastuzumab may assert its effect, including antibody dependent cytotoxicity through an intact immune system. Nonetheless, in our study, apoptosis was observed in 20 of 25 patients with matched baseline and week 1 specimens after trastuzumab exposure. If core biopsies were in fact responsible for the induction of apoptosis, then all the samples would demonstrate induction of apoptosis. Moreover, subsequent biopsies did not confer further increase in cleaved caspase 3, thereby reducing the likelihood that the biopsy procedure contributed to the increase in apoptosis. Finally, in neoadjuvant chemotherapy trials, similar biopsy procedures were performed. Most importantly, we and others have performed multiple biopsies of the primary tumor at the same time without intervening therapy, and demonstrated no increase in apoptosis with biopsies taken from different sites within the tumor.^1-3 We therefore stand by our findings that the main mechanism of action of trastuzumab is by induction of apoptosis, and not by cell cycle inhibition.

Authors' Disclosures of Potential Conflicts of Interest

Although all authors completed the disclosure declaration, the following author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other Jenny C. Chang Genentech, Inc (C)

Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C) $100,000 (N/R) Not Required

REFERENCES

1. Symmans WF, Volm MD, Shapiro RL, et al: Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: Implications for early prediction of breast cancer response to neoadjuvant treatment. Clin Cancer Res 6:4610-4617, 2000[Abstract/Free Full Text]

2. Stearns V, Singh B, Tsangaris T, et al: A prospective randomized pilot study to evaluate predictors of response in serial core biopsies to single agent neoadjuvant doxorubicin or paclitaxel for patients with locally advanced breast cancer. Clin Cancer Res 9:124-133, 2003[Abstract/Free Full Text]

3. Chang J, Ormerod M, Powles TJ, et al: Apoptosis and proliferation as predictors of chemotherapy response in patients with breast carcinoma. Cancer 89:2145-2152, 2000[CrossRef][Medline]

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