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Postoperative chemo–endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor–positive stage II breast cancer

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Abstract

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer.

From 1988 to 1991, we studied the effects of postoperative adjuvant therapy for Japanese women with stage II breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER− tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT.

There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER− patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease–free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.0 1).

Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

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Authors and Affiliations

  1. Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka

    Keizo Sugimachi & Yoshihiko Maehara

  2. Department of Medical Informatics, Faculty of Medicine, Kyushu University, Fukuoka

    Kohei Akazawa

  3. National Kyushu Cancer Center Hospital, Fukuoka

    Yasuo Nomura

  4. Nagasaki Red Cross Hospital, Nagasaki

    Kazuyuki Eida

  5. Department of Surgery II, Kumamoto University Medical School, Kumamoto

    Michio Ogawa

  6. National Iwakuni Hospital, Yamaguchi

    Eiji Konaga

  7. Department of Surgery I, Okayama University Medical School, Okayama

    Noriaki Tanaka

  8. The Department of Surgery, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Hiroshima

    Tetsuya Toge

  9. Department of Surgery II, Hiroshima University School of Medicine, Hiroshima

    Kiyohiko Dohi

  10. National Beppu Hospital, Oita

    Shoichihi Noda

  11. Department of Surgery II, Kagawa Medical University, Kagawa

    Masazumi Maeda

  12. Department of Surgery II, School of Medicine, The University of Tokushima, Tokushima, Japan

    Yasumasa Monden

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  1. Keizo Sugimachi
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  13. Yasumasa Monden
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Sugimachi, K., Maehara, Y., Akazawa, K. et al. Postoperative chemo–endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor–positive stage II breast cancer. Breast Cancer Res Treat 56, 111–122 (1999). https://doi.org/10.1023/A:1006221425652

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