Biologic and immunologic effects of preoperative trastuzumab for ductal carcinoma in situ of the breasta

Authors


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    The investigators are grateful to Aurora Madrigal, RN, and Rebekah Hubbard for assisting with patient accrual and processing of specimens and to Dr. David Jamieson for performing the cell-based ELISA for the quantification of trastuzumab.

Abstract

BACKGROUND:

Through this study, the authors sought to investigate the biologic and immunologic effects of preoperative trastuzumab in patients with ductal carcinoma in situ (DCIS) of the breast.

METHODS:

Patients with DCIS were enrolled in this open-label phase 2 trial and tested for HER2. Trastuzumab was given by intravenous infusion (8 mg/kg). The patients then had surgery 14 to 28 days after treatment. Tissue and peripheral blood samples were obtained before therapy and at the time of surgery to examine residual disease and immunologic response.

RESULTS:

Median age of the 69 enrolled patients was 53 years, mean mammographic size of the DCIS lesions was 5.2 ± 1.2 cm, and 24 patients (35%) were found to have HER2 overexpression/amplification (12 received trastuzumab and 12 untreated patients provided tissue for blinded, controlled biomarker analyses). No overt histologic evidence of response was noted. No significant change in mean pretherapy staining for Ki-67 (44.3 ± 3.4%) and cleaved caspase-3 (2.6 ± 0.8%) was noted when surgical specimens from drug-treated patient samples were compared with those not treated. Trastuzumab significantly augmented antibody-dependent cell mediated cytotoxicity (ADCC) in 100% of patients; this was demonstrated to be mediated through CD56+ degranulating natural killer cells (P < .01). One patient developed a significant anti-HER2 humoral CD4 T-cell response.

CONCLUSIONS:

Single-dose monotherapy with trastuzumab for patients with HER2-positive DCIS does not result in significant, clinically overt, histologic, antiproliferative, or apoptotic changes, but does result in the ability to mount ADCC mediated through natural killer cells and may also induce T-cell dependent humoral immunity. Further studies of trastuzumab for DCIS appear warranted. Cancer 2011. © 2010 American Cancer Society.

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