Abstract
Background. To evaluate the changes in the biological features of breast cancer cells induced by primary chemotherapy (PCT) and their possible relationship with the response to therapy, we performed an extensive immunohistochemical study before and after PCT. Patients and methods. PCT was administered to 29 women with breast cancer. On specimens obtained by tru-cut and post-chemotherapy surgery we analyzed the following parameters: histology, histologic grade, apoptotic index, hormone receptor levels, Ki67, PCNA, EGFr, bcl-2, p53, p170. The significance of the changes induced by PCT and their correlations with the type of response were evaluated. Results. Twelve patients achieved a partial response with PCT. No baseline biological parameter correlated with the type of response. After PCT we observed a significant increase in the apoptotic index (p = 0.000), PCNA (p=0.036), EGFr (p = 0.005), and p170 expression (p=0.001), regardless of the type of chemotherapy administered (anthracyclines, 25 cases, or CMF, 4 cases). Responder patients displayed a significant decrease in ER levels (p = 0.015), whereas in non responders there was an increase in PCNA (p=0.008) and EGFr expression (p=0.002). The apoptotic index and p170 expression rose after PCT regardless of the type of response. Conclusions. PCT induced significant variations in the phenotype of breast cancer cells. These changes might reflect the selection of new neoplastic clones with different biological properties and so could facilitate the choice of appropriate chemotherapy agents.
Similar content being viewed by others
References
Scholl SM, Fourquet A, Asselain B et al.: Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumors considered too large for breast conserving surgery: preliminary results of randomized trial: S6. Eur J Cancer 30A: 645-652, 1994
Fisher B, Rockette H, Robidoux A et al.: Effect of preoperative therapy for breast cancer on local regional disease: first report of NSABP B18. Proc Am Soc Clin Oncol 13: 64 (Abs 57), 1994
Fisher B, Wickerham DL: Preoperative systemic therapy for the treatment of primary breast cancer. In: Powles TJ, Smith IE (eds) Medical Management of Breast Cancer. London, UK, Martin Dunitz, 1991, pp 281-285
Bonadonna G, Veronesi U, Brambilla C et al.: Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst 82: 1539-1545, 1990
McGuire WL, Clark GM: Prognostic factors and treatment decision in axillary node negative breast cancer patients. N Engl J Med 326: 1756-1761, 1992
Chevallier B, Heintzmann F, Mosseri V et al.: Prognostic value of estrogen and progesterone receptors in operable breast cancer. Cancer 62: 2517-2524, 1988
Silvestrini R, Daidone MG, Valagussa P et al.: 3H-tymidine-labeling index as a prognostic indicator in node-positive breast cancer. J Clin Oncol 8: 1321-1326, 1990
Remvikos Y, Mosseri V, Zajdela A et al.: Prognostic value of S-phase fraction of breast cancer treated by primary radiotherapy or neo-adjuvant chemotherapy. Ann NY Acad Sci 698: 193-203, 1993
Wintzer HO, Zipfel I, Shulte J et al.: Ki67 immunostaining in human breast tumors and its relationship to prognosis. Cancer 67: 421-428, 1991
Gillett CE, Barnes DM, Camplejohn RS: Comparison of three cell cycle associated antigens as markers of proliferative activity and prognosis in breast carcinoma. J Clin Pathol 46: 1126-1128, 1993
Isola J, Visakorpi T, Holli K et al.: Association of overexpression of tumor suppressor protein p53 and rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst 84: 1109-1114, 1992
Tandon AK, Clark GM, Chamness GC et al.: HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7: 1120-1128, 1989
Sainsbury JRC, Malcolm AJ, Appleton DR et al.: Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol 38: 1225-1228, 1985
Silvestrini R, Veneroni S, Daidone MG et al.: The bcl-2 protein: A prognostic indicator strongly related to p53 protein in lymph node negative breast cancer patients. J Natl Cancer Inst 86: 499-504, 1994
Charpin C, Vielh P, Duffaud F et al.: Quantitative immunocytochemical assays of p-glycoprotein in breast carcinomas: Correlation to messenger RNA expression and to immunohistochemical prognostic indicators. J Natl Cancer Inst 86: 1539-1545, 1994
Contesso G, Saccani Jotti G, Bonadonna G: Tumor grade as prognostic factor in primary breast cancer. Eur J Cancer Clin Oncol 25: 403-409, 1989
Lipponen P, Aaltomaa S, Kosma VM et al.: Apoptosis in breast cancer as related to histopathological characteristics and prognosis. Eur J Cancer 30A: 2068-2073, 1994
Fisher B: Preoperative chemotherapy: A model for studying the biology and the therapy of primary breast cancer. J Clin Oncol 13: 537-540, 1995
Klijn JG, Berns EM, Foekens JA: Prognostic factors and response to therapy in breast cancer. Cancer Surv 18: 165-198, 1993
Wosikowski K, Saceda M, Martin MB et al.: Phenotypic changes associated with the development of multidrug resistance in human breast cancer cells. Proc Am Assoc Cancer Res 34: A133 (Abst), 1993
Nie NH, Hadlay-Hull C, Jenkins JG et al.: SPSS (Statistical Package for the Social Sciences). McGraw Hill, New York, 1979
Waller U: Giant nuclei after myleran therapy and splenic irradiation. Pathol Microbiol 23: 283-290, 1960
Kennedy S, Merino SJ, Swain S et al.: The effects of hormonal and chemotherapy on tumoral and non neoplastic breast tissue. Hum Pathol 21: 192-198, 1990
Skipper HE: Kinetics of mammary tumor cell growth and implications for therapy. Cancer 28: 1479-1499, 1971
Rainsbridge SA, Gillett CE, Seymour AM et al.: The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma. Brit J Cancer 70: 335-341, 1994
Clark GM: Prognostic and predictive factors. In: Harris JR, Lippman ME, Morrow M et al. (eds): Disease of the breast. Lipincott-Raven, Philadelphia, 1996, pp. 461-485
Baserga R: Growth regulation of the PCNA gene. J Cell Sci 98: 433-436, 1991
Chan WK, Poulsom R, Long QL et al.: Bcl-2 expression in invasive mammary carcinoma: Correlation with apoptosis, hormone receptors and p53 expression. J Pathol (Suppl) 169: 153A, 1993
Allred CD, Clark GM, Elledge R et al.: Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85: 200-206, 1993
Sainsbury J, Farndon J, Sherbet G et al.: Epidermal-growth-factor receptors and estrogen receptors in human breast cancer. Lancet i: 364-366, 1985
Murayama Y, Kurata S, Mishima Y: Regulation of human estrogen receptor gene, epidermal growth factor receptor gene, and oncogenes by estrogen and antiestrogen in MCF.7 cell. Cancer Detect Prev 13: 103-107, 1988
Baselga J, Mendelsohn J: The epidermal growth factor receptor as a target for therapy in breast carcinoma. Breast Cancer Res Treat 29: 127-138, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Frassoldati, A., Adami, F., Banzi, C. et al. Changes of biological features in breast cancer cells determined by primary chemotherapy. Breast Cancer Res Treat 44, 185–192 (1997). https://doi.org/10.1023/A:1005875002458
Issue Date:
DOI: https://doi.org/10.1023/A:1005875002458