Summary
A prospective randomised clinical trial in patients with node-negative, fast-proliferating breast cancer was initiated in January 1990 to verify the feasibility and reliability of a 3H-thymidine (3H-Tdr) autoradiographic assay in a prospective and consecutive series of node-negative patients and the therapeutic effect of adjuvant chemotherapy in patients with node-negative breast cancer and high tumour proliferative activity. Node-negative patients with a high 3H-Tdr Labelling Index (3H-Tdr-LI) were randomised to receive either no further treatment or combination chemotherapy consisting of fluorouracil, epirubicin plus cyclophosphamide (FEC) for 6 cycles. The autoradiographic assay was performed in 307 of 317 patients (97%) and was evaluable in 291 of 317 patients (92%). A total of 176 patients with a high 3H-Tdr-LI entered the clinical randomised study: 91 in the FEC arm and 85 in the control arm. Patient groups were fairly well balanced regarding the most important clinical and pathological characteristics. In total, 530 FEC cycles have been administered with an actual dose intensity of 90%. Patients receiving FEC demonstrated leucopenia in 35% of cases, alopecia in 70%, and loss of menses in premenopausal patients in an age-dependent manner. Patients are still being entered into the study.
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Baak JPA, van Diest PJ, Ariens AT, van Beek MWPM, Bellot SM, et al. The Multicenter Morphometric Mammary Carcinoma Project (MMMCP). A nationwide prospective study on reproducibility and prognostic power of routine quantitative assessments in The Netherlands. Pathology Research Practice 185: 664–670, 1989
Bonadonna G, Valagussa P, Moliterni A, Buzzoni R, Zambetti M, et al. Milan adjuvant and neoadjuvant studies in Stage I and II resectable breast cancer. In Salmon SE (Ed.) Adjuvant therapy of cancer: IV Proceedings of the 6th International Conference of the Adjuvant Therapy of Cancer, 7–10 March 1990, Tucson, Arizona, pp. 169–173, W.B. Saunders Co., Philadelphia, 1990
Clark GM, Mathieu MC, Owens MA, Dressler LG, Eude L, et al. Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients. Journal of Clinical Oncology 10: 428–432, 1992
Hery M, Gioanni J, Lalanne CM, Namer M, Courdi A. The DNA labeling index: a prognostic factor in node-negative breast cancer. Breast Cancer Research and Treatment 9: 207–211, 1987
Italian Multicenter Breast Study with Epirubicin. Phase III randomised study of fluorouracil, epirubicin, and cyclophosphamide vs fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. Journal of Clinical Oncology 6: 976–982, 1988
McGuire WL, Tandon AK, Allred DC, Chamness GC, Clark GM. How to use prognostic factors in axillary node-negative breast cancer patients. Journal of the National Cancer Institute 82: 1006–1015, 1990
Meyer JS, Province M. Proliferative index of breast carcinoma by thymidine labeling: prognostic power independent of stage, estrogen and progesterone receptors. Breast Cancer Research and Treatment 12: 191–204, 1988
Paradiso A, Mangia A, Rodrigues de Gesus ML, Vairo M, Fusilli S, et al. Intratumor proliferative activity heterogeneity of primary breast cancer determined by 3H-thymidine labeling index. British Journal of Cancer. Submitted for publication, 1993
Paradiso A, Tommasi S, Mangia A, Lorusso V, Simone G, et al. Tumor proliferative activity, progesterone receptor status, estrogen receptor level and clinical outcome of estrogen-positive advanced breast cancer. Cancer Research 50: 2958–2962, 1990
Piffanelli A, Pelizzola D, Giovannini G, Catozzi L, Faggioli L, et al. Characterization of laboratory working standards for quality control of immunometric and radiometric estrogen receptor assays. Clinical evaluation of breast cancer biopsies. Tumori 75: 550–556, 1989
Sertoli MR, Pronzato P, Rubagotti A, Queirolo P, Catturich A, et al. A randomized study of perioperative chemotherapy in primary breast cancer. In Salmon SE (Ed.) Adjuvant therapy of cancer: IV Proceedings of the 6th International Conference of the Adjuvant Therapy of Cancer, 7–10 March 1990, Tucson, Arizona, pp. 196–203, W.B. Saunders Co., Philadelphia, 1990
Silvestrini R, De Lena M, Paradiso A, on behalf of SICCAB. Feasibility and reproducibility of the 3H-thymidine labeling index in breast cancer. Cell Proliferation 24: 437–445, 1991
Silvestrini R, Daidone MG, Valagussa P, Di Fronzo G, Mezzanotte G, et al. Cell kinetics as a prognostic indicator in node-negative breast cancer. European Journal of Cancer and Clinical Oncology 25: 1165–1171, 1989
Tubiana M, Pejovic MH, Koscielny S, Chavaudra M, Malaise E. Growth rate, kinetics of tumor cell proliferation and long-term outcome in human breast cancer. International Journal of Cancer 44: 17–22, 1989
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Paradiso, A., Mangia, A., Barletta, A. et al. Randomised Clinical Trial of Adjuvant Chemotherapy in Patients with Node-Negative, Fast-Proliferating Breast Cancer. Drugs 45 (Suppl 2), 68–74 (1993). https://doi.org/10.2165/00003495-199300452-00011
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DOI: https://doi.org/10.2165/00003495-199300452-00011