Summary
We studied cellular proliferation by measuring the tritiated thymidine labeling index (TLI) in slices of primary invasive breast carcinomas. Estrogen receptor (ER) and progesterone receptor (PgR) were measured by ligand-binding assay.
The TLI was a strong independent predictor of survival and relapse-free survival in women with or without axillary lymph nodal metastases and in American Joint Committee stage I. In operable node-negative women treated surgically, predicted survival at 5 years was 89 ± 4% (probability±standard error) for 81 patients with low TLI (⩽3%), 64 ± 7% for 101 with mid TLI (3.1 – 8%), and 66 ± 6% for 86 with high TLI (>8%) (P = 0.001). Probabilities of survival for patients with positive axillary nodes were 79 ± 6% for 86 with low, 71 ± 7% for 71 with mid, and 52 ± 6% for 89 with high TLI (P = 0.0002). In stage I patients (tumor diameter not exceeding 2 cm), 5-year survival probabilities were 93 ± 4% in 70 with low, 72 ± 8% in 43 with mid, and 58 ± 10% in 35 with high TLI, (P = 0.0005). The TLI was predictive for survival and relapse-free survival within subgroups positive and negative for ER and positive for PgR (P<0.05) in stage I patients, and a predictive trend was observed in the PgR-negative subgroup (P = 0.16). TLI also predicted within different categories of vascular invasion and nuclear grade.
A stepwise Cox proportional hazards model selected TLI, number of positive axillary lymph nodes, and maximum diameter of the breast carcinoma as independent variables predictive of relapse, and added ER as a fourth variable for prediction of survival.
Article PDF
Avoid common mistakes on your manuscript.
References
Knight WA, Livingston RB, Gregory EJ, McGuire WL: Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37: 4669–4671, 1977
Clark GM, McGuire WL, Hubay CA, Pearson OH, Marshall JS: Progesterone receptors as a prognostic factor in Stage II breast cancer. N Engl J Med 309: 1343–1347, 1983
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
Meyer JS, Friedman E, McCrate MM, Bauer WC: Prediction of early course of breast carcinoma by thymidine labeling. Cancer 51: 1879–1886, 1983
Silvestrini R, Daidone MG, Gasparini G: Cell kinetics as a prognostic marker in node-negative breast cancer. Cancer 56: 1982–1987, 1985
Silvestrini R, Daidone MG, Di Fronzo G, Morabito A, Valagussa P, Bonadonna G: Prognostic implication of labeling index versus estrogen receptors and tumor size in node-negative breast cancer. Breast Cancer Res Treat 7: 161–169, 1986
American Joint Committee for Cancer Staging and End-Results Reporting. Manual for Staging of Cancer 1978. Whiting Press, Chicago, 1978, pp 101–107
Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U: Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 294: 405–410, 1976
Fisher B, Redmond C, Wolmark N, Wieand HS: Diseasefree survival at intervals during and following completion of adjuvant chemotherapy: the NSABP experience. Cancer 48: 1273–1280, 1981
Meyer JS, Connor RE:In vitro labeling of solid tissues with tritiated thymidine for autoradiographic detection of S-phase nuclei. Stain Tech 52: 185–195, 1977
Meyer JS, Bauer WC, Rao BR: Subpopulations of breast carcinoma defined by S-phase fraction, morphology, and estrogen receptor content. Lab Invest 39: 225–235, 1978
Meyer JS, Stevens SC, White WL, Hixon B: Estrogen receptor assay of carcinomas of the breast by a simplified dextran-charcoal method. Am J Clin Pathol 70: 655–664, 1978
Pichon MF, Milgrom E: Characterization and assay of progesterone receptor in human mammary carcinoma. Cancer Res 37: 464–471, 1977
Meyer JS, Prey MU, Babcock DS, McDivitt RW: Breast carcinoma cell kinetics, morphology, stage, and host characteristics. Lab Invest 54: 41–51, 1986
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1958
Kalbfleish JD, Prentice RL: The Statistical Analysis of Failure Time Data. John Wiley & Sons, New York, 1980
Cox DR, Oates D: Analysis of Survival Data. Chapman and Hall, London, 1984
Gilchrist KW, Kalish L, Gould VE, Hirschl S, Imbriglia JE, Levy WM, Patchefsky AS, Penner DW, Pickren J, Roth JA, Schinella RA, Schwartz IS, Wheeler JE: Interobserver reproducibility of histopathological features in stage II breast cancer. An ECOG Study. Breast Cancer Res Treat 5: 3–10, 1985
Meyer JS, Lee JY: Relationships of S-phase fraction of breast carcinoma in relapse to duration of remission, estrogen receptor content, therapeutic responsiveness, and duration of survival. Cancer Res 40: 1890–1896, 1980
Steel GG: Cell loss as a factor in the growth of human tumours. Eur J Cancer 3: 381–387, 1967
Steel GG: Cytokinetics of Neoplasia. In: Holland JF, Frei E III, (eds) Cancer Medicine. Lea & Febiger, Philadelphia, 1982, pp 177–189
Meyer JS: Growth and cell kinetic measurements in human tumors. Path Annu 16(2): 53–81, 1981
Fisher B, Slack N, Katrych D, Wolmark N: Ten year follow-up results of patients with carcinoma of the breast in a cooperative clinical trial evaluating surgical adjuvant chemotherapy. Surg Gynec Obstet 140: 528–534, 1975
Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP: Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer 45: 2917–2924, 1980
McGuire WL, Clark GM, Dressler LG, Owens MA: Role of steroid hormone receptors as prognostic factors in primary breast cancer. NCI Monogr 1: 19–23, 1986
Sears HF, Janus C, Levy W, Hopson R, Creech R, Grotzinger P: Breast cancer without axillary metastases. Are there high-risk biologic subpopulations? Cancer 50: 1820–1827, 1982
Stewart JF, Rubens RD, Millis RR, King RJB, Hayward JL: Steroid receptors and prognosis in operable (stage I and II) breast cancer. Eur J Cancer Clin Oncol 19: 1381–1387, 1983
Vollenweider-Zerargui L, Barrelet L, Wong Y, Lemarchand-Beraud T, Gomez F: The predictive value of estrogen and progesterone receptors' concentrations on the clinical behavior of breast cancer in women. Clinical correlation on 547 patients. Cancer 57: 1171–1180, 1986
Aamdal S, Bormer O, Jorgensen O, Host H, Eliassen G, Kaalhus O, Ing DR, Pihl A: Estrogen receptors and longterm prognosis in breast cancer. Cancer 53: 2525–2529, 1984
Howat JMT, Barnes DM, Harris M, Swindell R: The association of cytosol oestrogen and progesterone receptors with histological features of breast cancer and early recurrence of disease. Brit J Cancer 47: 629–640, 1983
Clark GM, Osborne CK, McGuire WL: Estrogen receptor status and tumor size identify a subgroup from 1461 nodenegative breast cancer patients at high risk for recurrence and death. J Clin Oncol, 1987, in press
Meyer JS: Potential value of cell kinetics in management of cancers of unknown origin. In: Fer MF, Greco FA, Oldham RK, (eds) Poorly Differentiated Neoplasms and Tumors of Unknown Origin. Grune and Stratton, Orlando, 1986, pp 519–539
Land H, Parada LF, Weinberg RA: Cellular oncogenes and multistep carcinogenesis. Science 222: 771–778, 1983
Slamon DJ, diKernion JB, Verma IM, Cline MJ: Expression of cellular oncogenes in human malignancies. Science 224: 256–262, 1984
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177–182, 1987
Meyer JS, McDivitt RW: Reliability and stability of the thymidine labeling index of breast carcinoma. Lab Invest 54: 160–164, 1986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Meyer, J.S., Province, M. Proliferative index of breast carcinoma by thymidine labeling: Prognostic power independent of stage, estrogen and progesterone receptors. Breast Cancer Res Tr 12, 191–204 (1988). https://doi.org/10.1007/BF01805940
Issue Date:
DOI: https://doi.org/10.1007/BF01805940