High-dose toremifene as first-line treatment of metastatic breast cancer resistant to adjuvant aromatase inhibitor: A multicenter phase II study

Sawaki,Masataka; Wada,Masaki; Sato,Yasuyuki; Mizuno,Yutaka; Kobayashi,Hironobu; Yokoi,Kazuki; Yoshihara,Motoi; Kamei,Keitaro; Ohno,Mototsugu; Imai,Tsuneo

doi:10.3892/ol.2011.449

High-dose toremifene as first-line treatment of metastatic breast cancer resistant to adjuvant aromatase inhibitor: A multicenter phase II study

Authors:
- Masataka Sawaki
- Masaki Wada
- Yasuyuki Sato
- Yutaka Mizuno
- Hironobu Kobayashi
- Kazuki Yokoi
- Motoi Yoshihara
- Keitaro Kamei
- Mototsugu Ohno
- Tsuneo Imai
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Affiliations: Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, Japan, Department of Surgery, Komaki Municipal Hospital, Komaki, Aichi, Japan, Department of Breast and Endocrine Surgery, Nagoya Medical Center, Nagoya, Aichi, Japan, Department of Endocrine Surgery, Fujita Health University, Toyoake, Aichi, Japan, Department of Surgery, Okazaki Municipal Hospital, Okazaki, Aichi, Japan, Department of Surgery, Toyohashi Municipal Hospital, Toyohashi, Aichi, Japan, Department of Surgery, Ogaki Municipal Hospital, Ogaki, Gifu, Japan, Department of Breast and Endocrine Surgery, Gifu Prefectural Tajimi Hospital, Gifu, Japan
Published online on: October 19, 2011 https://doi.org/10.3892/ol.2011.449
Pages: 61-65

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Abstract

There is currently no standardized therapy available for metastatic breast cancer in patients with aromatase inhibitor (AI)-resistant breast cancer. We conducted a prospective study to examine the efficacy and safety of high-dose toremifene (TOR) treatment for the first-line treatment of metastatic breast cancer following AI adjuvant therapy. A multicenter phase II study was designed (Registry no.: UMIN000000489). Inclusion criteria comprised hormone-responsive postmenopausal women who had received adjuvant AI postoperatively for >1 year and had relapsed during the treatment or within 12 months of completion of adjuvant therapy. Treatment comprised oral intake of 120 mg TOR once a day. The primary endpoint was objective response rate (ORR). The secondary endpoints were evaluations of clinical benefit (CB), progression-free survival (PFS) and toxicity. A total of 13 patients were enrolled. ORR was 7.7% (1/13) [95% CI, 0.2-36.0%]. In total, 7 patients (53.8%) had stable disease (SD), 5 of whom were long SD, and 5 patients (38.5%) experienced progressive disease (PD). The CB rate was 46.2% (6/13) [95% CI, 19.2-74.9%]. The median time to PFS was 5.9 months. No serious adverse events were observed. Patients with HER2-positive disease exhibited marginally poorer PFS (p=0.08). Patients with PD had a relatively short duration of AI treatment in contrast to responders, who had a longer period of AI treatment (p=0.02). High-dose TOR as a first-line treatment following AI adjuvant therapy was effective and well tolerated. A longer duration of adjuvant AI therapy and negative HER2 overexpression may, with further studies, be beneficial as positive predictive factors for the effectiveness of TOR treatment.

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