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. 1998 Sep;78(6):812–815. doi: 10.1038/bjc.1998.584

A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.

J Sjöström 1, S Krajewski 1, K Franssila 1, E Niskanen 1, V M Wasenius 1, S Nordling 1, J C Reed 1, C Blomqvist 1
PMCID: PMC2062970  PMID: 9743306

Abstract

The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m(-2)), epirubicin (60 mg m(-2)) and cyclophosphamide (500 mg m(-2)) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. TTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.

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Selected References

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  1. Blomqvist C., Elomaa I., Rissanen P., Hietanen P., Nevasaari K., Helle L. Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration. J Clin Oncol. 1993 Mar;11(3):467–473. doi: 10.1200/JCO.1993.11.3.467. [DOI] [PubMed] [Google Scholar]
  2. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
  3. Hietanen P., Blomqvist C., Wasenius V. M., Niskanen E., Franssila K., Nordling S. Do DNA ploidy and S-phase fraction in primary tumour predict the response to chemotherapy in metastatic breast cancer? Br J Cancer. 1995 May;71(5):1029–1032. doi: 10.1038/bjc.1995.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Krajewski S., Blomqvist C., Franssila K., Krajewska M., Wasenius V. M., Niskanen E., Nordling S., Reed J. C. Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res. 1995 Oct 1;55(19):4471–4478. [PubMed] [Google Scholar]
  5. Krajewski S., Bodrug S., Gascoyne R., Berean K., Krajewska M., Reed J. C. Immunohistochemical analysis of Mcl-1 and Bcl-2 proteins in normal and neoplastic lymph nodes. Am J Pathol. 1994 Sep;145(3):515–525. [PMC free article] [PubMed] [Google Scholar]
  6. Krajewski S., Krajewska M., Shabaik A., Miyashita T., Wang H. G., Reed J. C. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol. 1994 Dec;145(6):1323–1336. [PMC free article] [PubMed] [Google Scholar]
  7. Niskanen E., Blomqvist C., Franssila K., Hietanen P., Wasenius V. M. Predictive value of c-erbB-2, p53, cathepsin-D and histology of the primary tumour in metastatic breast cancer. Br J Cancer. 1997;76(7):917–922. doi: 10.1038/bjc.1997.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Remvikos Y., Beuzeboc P., Zajdela A., Voillemot N., Magdelénat H., Pouillart P. Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy. J Natl Cancer Inst. 1989 Sep 20;81(18):1383–1387. doi: 10.1093/jnci/81.18.1383. [DOI] [PubMed] [Google Scholar]
  9. Ro J., Sahin A., Ro J. Y., Fritsche H., Hortobagyi G., Blick M. Immunohistochemical analysis of P-glycoprotein expression correlated with chemotherapy resistance in locally advanced breast cancer. Hum Pathol. 1990 Aug;21(8):787–791. doi: 10.1016/0046-8177(90)90046-8. [DOI] [PubMed] [Google Scholar]
  10. Sjöström J., Blomqvist C. Predictive factors for response to cytotoxic treatment in advanced breast cancer: a review. Acta Oncol. 1996;35 (Suppl 5):84–90. doi: 10.3109/02841869609083978. [DOI] [PubMed] [Google Scholar]
  11. Verrelle P., Meissonnier F., Fonck Y., Feillel V., Dionet C., Kwiatkowski F., Plagne R., Chassagne J. Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma. J Natl Cancer Inst. 1991 Jan 16;83(2):111–116. doi: 10.1093/jnci/83.2.111. [DOI] [PubMed] [Google Scholar]

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