title: Shift in cytotoxic target from estrogen receptor-positive to estrogen receptor-negative breast cancer cells by trastuzumab in combination with taxane-based chemotherapy.
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.
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto 862-8505.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hayashi
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Kai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okumura
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Osako
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Arima
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
authors.forename: Reiki
authors.initials: R
authors.lastname: Nishimura