Summary
The relationship of changes in3H-thymidine labelling index (TLI) induced by primary chemotherapy to tumor response and relapse rate in 36 patients with previously untreated locally advanced breast cancer (LABC) was analyzed. All patients received primary chemotherapy (3 cycles FAC), followed by mastectomy and subsequent adjuvant chemotherapy (3 FAC alternated with 3 CMF). Tumor TLI was evaluated immediately prior to primary chemotherapy and at the time of mastectomy. Median pretreatment TLI was used to discriminate between tumors with a high or low proliferative rate. Clinical objective response to primary chemotherapy was 83% in patients with high TLI and 56% for those with low pretreatment TLI (p = 0.06). Primary chemotherapy induced a ≥ 50% reduction of the proliferative rate in 83% and 39% of the tumors with high and low pretreatment TLI, respectively (p = 0.006). Patients were classified into 4 groups according to TLI values both before and after primary chemotherapy: patients who remained in the high TLI group after primary FAC had the highest response rate (100%) and the lowest 2-year relapse rate (20%). These data suggest that: a) improved response to aggressive cytotoxic treatment occurs in tumors with high TLI at diagnosis; b) there is a significant correlation between TLI changes induced by primary chemotherapy and pretreatment proliferative activity; c) patients who remain in the high TLI group after primary chemotherapy are more likely to benefit from subsequent adjuvant systemic therapy.
This is a preview of subscription content, log in via an institution to check access.
References
Courdi A, Héry M, Dahan E, Gioanni J, Abbes M, Monticelli J, Ettore F, Moll J-L, Namer M: Factors affecting relapse in node-negative breast cancer. A multivariate analysis including the labeling index. Eur J Cancer Clin Oncol 25: 351–356, 1989
Meyer JS, Province M: Proliferative index of breast carcinoma by thymidine labeling: prognostic power independent of stage, estrogen and progesterone receptor. Breast Cancer Res Treat 12: 191–204, 1988
Silvestrini R, Daidone MG, Valagussa P, Salvadori B, Rovini D, Bonadonna G: Cell kinetics as a prognostic marker in locally advanced breast cancer. Cancer Treat Rep 71: 375–379, 1987
Silvestrini R, Daidone MG, Valagussa P, Di Fronzo G, Mezzanotte G, Bonadonna G: Cell kinetics as a prognostic indicator in node-negative breast cancer. Eur J Cancer Clin Oncol 25: 1165–1171, 1989
Tubiana M, Pejovic MH, Chavaudra N, Contesso G, Malaise EP: The long-term prognostic significance of the thymidine labelling index in breast cancer. Int J Cancer 33: 441–445, 1984
Daidone MG, Silvestrini R, Valentinis B, Ferrari L, Bartoli C: Changes in cell kinetics induced by primary chemotherapy in breast cancer. Int J Cancer 47: 380–383, 1991
Spyratos F, Briffod M, Tubiana-Hulin M, Andrieu C, Mayras C, Pallud C, Lasry S, Rouëssé J: Sequential cytopunctures during preoperative chemotherapy for primary breast carcinoma. Cancer 69: 470–475, 1992
Braunschweiger PG, Poulakos L, Schiffer LM:In vitro labeling and gold activation autoradiography for determination of labeling index and DNA synthesis time of solid tumors. Cancer Res 36: 1748–1753, 1976
Drewinko B, Patchen M, Yang L-Y, Barlogie B: Differential killing efficacy of twenty antitumor drugs on proliferating and nonproliferating human tumor cells. Cancer Res 41: 2328–2333, 1981
Weichselbaum RR, Hellman S, Piro AJ, Nove JJ, Little JB: Proliferation kinetics of a human breast cancer linein vitro following treatment with 17β-estradiol and 1-β-D-arabinofuranosylcytosine. Cancer Res 38: 2339–2342, 1978
Conte PF, Alama A, Bertelli G, Canavese G, Carnino F, Catturich A, Di Marco E, Gardin G, Jacomuzzi A, Monzeglio C, Mossetti C, Nicolin A, Pronzato P, Rosso R: Chemotherapy with estrogenic recruitment and surgery in locally advanced breast cancer: clinical and cytokinetic results. Int J Cancer 40: 490–494, 1987
Conte PF, Alama A, Rubagotti A, Chiara S, Nicolin A, Nicolò G, Rosso R, Gaddi M, Ghiringhello B, Tomao S, Foglia G, Ragni N: Cell kinetics in ovarian cancer. Relationship to clinicopathologic features, responsiveness to chemotherapy, and survival. Cancer 64: 1188–1191, 1989
Conte PF, Gardin G, Pronzato P, Miglietta L, Rosso R, Amadori D, Gentilini P, Monzeglio C, Gallotti P, Demicheli R, Brema F, Sismondi P, Miccoli P, Lanfranco C, Minuto F, Barreca A, Del Monte P:In vivo manipulation of human breast cancer growth by estrogens and growth hormone: kinetic and clinical results. J Steroid Biochem Molec Biol 37: 1103–1108, 1990
Remvikos Y, Beuzeboc P, Zajdela A, Voillemot N, Magdelénat H, Pouillart P: Correlation of pretreatment proliferative activity of breast cancer with response to cytotoxic chemotherapy. J Natl Cancer Inst 81: 1383–1387, 1989
Sulkes A, Livingston RB, Murphy WK: Tritiated thymidine labeling index and response in human breast cancer. J Natl Cancer Inst 62: 513–515, 1979
Conte PF, Fraschini G, Alama A, Nicolin A, Corsaro E, Canavese G, Rosso R, Drewinko B: Chemotherapy following estrogen-induced expansion of the growth fraction of human breast cancer. Cancer Res 45: 5926–5930, 1985
Meyer JS, Hixon B: Advanced stage and early relapse of breast carcinomas associated with high thymidine labeling indices. Cancer Res 39: 4042–4047, 1979
Conte PF, Gardin G, Pronzato P, Alama A, Nicolin A, Bertelli G, Amoroso D, Rosso R: Tumor proliferative activity and prognosis of locally advanced breast cancer patients treated with neo-adjuvant chemotherapy. In: Jacquillat C, Weil M, Khayat D (eds) Neo-Adjuvant Chemotherapy. Inserm (Vol 169), Paris, 1988, pp 241–244
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gardin, G., Alama, A., Rosso, R. et al. Relationship of variations in tumor cell kinetics induced by primary chemotherapy to tumor regression and prognosis in locally advanced breast cancer. Breast Cancer Res Tr 32, 311–318 (1994). https://doi.org/10.1007/BF00666008
Issue Date:
DOI: https://doi.org/10.1007/BF00666008