Shift in cytotoxic target from estrogen receptor-positive to estrogen receptor-negative breast cancer cells by trastuzumab in combination with taxane-based chemotherapy

Hayashi,Mitsuhiro; Kai,Kazuharu; Okumura,Yasuhiro; Osako,Tomofumi; Arima,Nobuyuki; Iwase,Hirotaka; Nishimura,Reiki

doi:10.3892/ol.2011.232

Shift in cytotoxic target from estrogen receptor-positive to estrogen receptor-negative breast cancer cells by trastuzumab in combination with taxane-based chemotherapy

Authors:
- Mitsuhiro Hayashi
- Kazuharu Kai
- Yasuhiro Okumura
- Tomofumi Osako
- Nobuyuki Arima
- Hirotaka Iwase
- Reiki Nishimura
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Affiliations: Department of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto 862-8505, Japan, Department of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan, Department of Clinical Pathology, Kumamoto City Hospital, Kumamoto 862-8505, Japan, Department of Breast and Endocrine Surgery, Faculty of Life Sciences, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860-8556, Japan
Published online on: January 11, 2011 https://doi.org/10.3892/ol.2011.232
Pages: 303-308

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Abstract

Trastuzumab has shown significant clinical benefits in patients with operable and metastatic HER2-positive breast cancer. However, the biological mechanism of the additional effect of trastuzumab administered in combination with conventional chemotherapy is poorly understood. We performed a retrospective analysis of 55 patients with HER2-positive breast cancer treated with anthracycline and taxane (chemotherapy alone; CT), or trastuzumab in combination with taxane-based chemotherapy (CT+T) for neoadjuvant chemotherapy. We determined the therapeutic efficacies [clinical (CR) and pathological complete responses (pCR)] and changes in the proportion of positive cells for each biomarker pre- to post-neoadjuvant chemotherapy for each treatment regimen. Clinical-CR and quasi-pCR rates defined as the absence of invasive tumors or only a few remaining invasive tumor cells were 6.9 and 31.0% in the CT group and 46.2 and 65.4% in the CT+T group, respectively. In the CT group, the proportion of estrogen receptor (ER)-/progesterone receptor (PgR)-positive cells decreased significantly following treatment (ER, 73.5 vs. 50.9%; P=0.02). Changes in the proportion of ER-/PgR-positive cells were not noted in the CT+T group (ER, 81.9 vs. 80.3%; P=0.61), although a relatively greater decrease in the proportion of Ki-67-positive cells was found in the CT+T group than that in the CT group (-26.5 vs. -13.7%). These findings indicate that CT+T inhibits ER-negative and Ki-67-positive breast cancer cells. In conclusion, trastuzumab sensitized ER-negative proliferative cells to cytotoxic chemotherapy. This finding may indicate an additional clinical effect of trastuzumab when administered in combination with conventional chemotherapy as neoadjuvant chemotherapy for HER2-positive breast cancer.

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