Abstract
The use of neo-adjuvant chemotherapy (often referred to as pre-operative or primary chemotherapy) represents a major change in the management of breast cancer as a systemic disease. Laboratory studies have shown that many anti-cancer agents with differing modes of action achieve cytotoxic effects by inducing apoptosis. In this study, we investigated the induction of apoptosis by neo-adjuvant chemotherapy in human breast cancer. The aim was to determine whether a correlation existed between post chemotherapy apoptotic index (AI) and clinical response and patients' survival. Our results indicate that apoptosis is induced by neo-adjuvant chemotherapy and that the response is variable. Our data show that post chemotherapy AI correlated with clinical response and increased patient survival, including both relapse (disease) free survival and overall survival. Post-neo-adjuvant chemotherapy AI levels in primary breast cancer may possibly predict an individual patient's overall response.
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References
Ellis PA, Smith IE: Primary chemotherapy for early breast cancer. Cancer Treat Rev 22: 437–50, 1996
Simpson-Herren L, Sanford AH, Holmquist JP: Effects of surgery on the cell kinetics of residual tumor. Cancer Treat Rep 60: 1740–1760, 1976
Meyn RE, Stephens LC, Hunter NR, Milas L: Induction of apoptosis in murine tumors by cyclophosphamide. Cancer Chemotherapy Pharmacol 33: 410–414, 1994
Gunduz N, Fisher B, Saffer EA: Effect of surgical removal on the growth and kinetics of residual tumor. Cancer Res 39: 3861–3865, 1979
Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E: Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res 49: 1996–2001, 1989
Fisher B, Saffer E, Rudock C, Coyle J, Gunduz N: Effect of local or systemic treatment prior to primary tumor removal on the production and response to a serum growth-stimulating factor in mice. Cancer Res 49: 2002–2004, 1989
Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV: Effect of pre-operative chemotherapy on local-regional disease inwomen with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15: 2483–2493, 1997
Hickman JA: Apoptosis induced by anticancer drugs. Cancer Metastasis Rev 11: 121–139, 1992
Ellis PA, Saccani-Jotti G, Clarke R, Johnston SR, Anderson E, Howell A, A'Hern R, Salter J, Detre S, Nicholson R: Induction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer. Int J Cancer 72: 608–613, 1997
Ellis PA, Smith IE, McCarthy K, Detre S, Salter J, Dowsett M: Pre-operative chemotherapy induces apoptosis in early breast cancer. Lancet 349: 849, 1997
Rasbridge SA, Gillet CE, Seymour AM, Patel K, Richards MA, Rubens RD, Millis RR: The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma. Br J Cancer 70: 335–341, 1994
Hayward JL: Assessment of response to therapy in advanced breast cancer. Br J Cancer 35: 113–117, 1977
Shao Z-M, Jiang M, Wu J, Han Q-X, Zhang T-Q, Shen Z-Z, Fontana JA: Identification of spontaneous programmed cell death during development of human breast cancer. Oncol Rep 3: 1133–1136, 1996
Shao Z-M, Jiang M, Wu J, Yu L-M, Han Q-X, Zhang T-Q, Shen Z-Z: Inhibition of apoptosis in human breast cancer and apoptosis in human breast cancer as related to prognosis. Oncol Rep 3: 1183–1186, 1996
Kute TE, Shao Z-M, Sugg NK, Long R, Russell GB, Case LD: Cathepsin D as a prognostic indicator for node-negative breast cancer patients using both immunoassays and enzymatic assays. Cancer Res 52: 5198–5203, 1992
Conte PF, Latreille J, Mauriac L, Calabresi F, Santos R, Campos D, Bonneterre J, Francini G, Ford JM: Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group. J Clin Oncol 14: 2552–2559, 1996
Scholl SM, Pierga JY, Asselain B, Beuzeboc P, Dorval T, Garcia-Giralt E, Jouve M, Palangie T, Remvikos Y, Durand J, et al.: Breast tumour response to primary chemotherapy predicts local and distant control as well as survival. Eur J Cancer 31A: 1969–1975, 1995
Fisher B, Mamounas EP: Pre-operative chemotherapy: a model for studying the biology and therapy of primary breast cancer. J Clin Oncol 13: 537–540, 1995
Bonadonna G, Valagussa P, Zucali R, Salvadori B: Primary chemotherapy in surgical resectable breast cancer. Ca Cancer J Clin 45: 227–243, 1995
Ferguson DJP, Anderson TJ: Morphological evalution of cell turnover in relation to the menstrual cycle in the ‘resting’ human breast. Br J Cancer 44: 177–181, 1981
Strange R, Li F, Suarer S, Burkhardt A, Friis RR: Apoptotic cell death and tissue remodelling during mouse mammary gland involution. Development 115: 49–58, 1992
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Shao, Zm., Li, J., Wu, J. et al. Neo-adjuvant chemotherapy for operable breast cancer induces apoptosis. Breast Cancer Res Treat 53, 263–269 (1999). https://doi.org/10.1023/A:1006194921139
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DOI: https://doi.org/10.1023/A:1006194921139