Abstract
The prognostic value of proliferative activity and its relationship with steroid hormone receptors and histopathological grade have been demonstrated for breast cancers. However, nothing is known about the underlying mechanisms. In order to understand the chronology of the appearance of increased proliferative activities, we used a series of 760 consecutive breast cancers for which we had obtained S-phase fractions (SPFs) by DNA flow cytometry. When the absolute difference from a DNA index of 1.00 was compared to SPFs, a significant positive correlation was obtained (r=0.39, p<0.0001), indicating that the probability of observing a high SPF increases when tumors progressively deviate from diploidy. A highly significant correlation was observed for the hyperploid group when hypertetraploid tumors were excluded, as the SPFs increased progressively as the DNA indices decreased from 2.00 to 1.30. This observation suggested a relationship with the evolution of chromosomal abnormalities as determined by cytogenetic analysis. Indeed, in a subset of 52 cases for which sufficient metaphases were available, there was a highly significant correlation between the SPF values and the proportion of rearranged chromosomes in the tumor cells (r=0.60, p<0.0001). When SPFs were separated into low or high using the median value (4.5%), a correlation also existed with the genetic evolution, since they increased from diploidy to hypodiploidy and then, after endoreduplication, from tetraploidy towards triploidy, as determined by the chromosome counts. Our results substantiate the relationship between proliferative activity and steroid hormone receptors which follow the same model. Therefore, it seems probable that the high proliferative activity of breast cancers indicates a state of genetic evolution which in turn may explain the prognostic significance.
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Clark GM, McGuire WL, Hubay CA, Pearson OH, Marshall JS: Progesterone receptor as a prognostic factor in stage II breast cancer. N Engl J Med 309: 1343–1346, 1983
Fisher B, Redmond CK, Wickerham DL, Rockette HE, Brown A,et al.: Relation of estrogen and/or progesterone receptor content of breast cancer to patient outcome following adjuvant chemotherapy. Breast Cancer Res Treat 3: 355–364, 1983
Vollenweider-Zerargui L, Barrelet L, Wong Y, Lemarchand-Beraud T, Gomez F: The predictive value of estrogen and progesterone concentrations on the clinical behavior of breast cancer in women. Cancer 57: 1171–1175, 1986
Nicholson S, Sainsbury JRC, Halcrow P, Kelly P, Angus B, Wright C, Henry J, Farndon JR, Harris AL: Epidermal growth factor (EGFr); results of a 6 year follow-up in operable breast cancer with emphasis on the node negative subgroup. Br J Cancer 63: 146–150, 1991
Slamon DJ, Clark GM, Wong SG,et al. Human breast cancer: correlation of relapse and survival with the amplification of the HER-2/neu oncogene. Science 235: 177–182, 1987
Silvestrini R, Daidone MG, Valagussa P,et al. Cell kinetics as a prognostic indicator in node-negative breast cancer. Eur J Cancer Clin Oncol 25: 1165–1171, 1989
Spyratos F, Maudelonde T, Brouillet JP,et al. Cathepsin D: an independent prognostic factor for metastasis of breast cancer. Lancet 2: 1115–1118, 1989
Tandon AK, Clark GM, Chamness GC,et al. Cathepsin D and prognosis in breast cancer. N Engl J Med 322: 297–302, 1990
Dressler LG, Bartow SA: DNA flow cytometry in solid tumors: practical aspects and clinical applications. Seminars in Diagnostic Pathology 6: 55–72, 1990
McGuire WL, Tandon AK, Allred DC, Chamness GC, Clark GM: How to use prognostic factors in axillary node-negative breast cancer patients. J Natl Cancer Inst 82: 1006–1015, 1990
Dutrillaux B, Gerbault-Seureau M, Remvikos Y, Zafrani B, Prieur M: Breast cancer genetic evolution: I. Data from cytogenetics and DNA content. Breast Cancer Res Treat 19: 245–255, 1991
Gerbault-Seureau M, Viehl P, Dutrillaux B: Recurrent HSR in the centromeric region of chromosome 8 in breast cancer. Ann Genet 30: 146–151, 1987
Dutrillaux B, Gerbault-Seureau M, Zafrani B: Characterization of chromosomal anomalies in human breast cancer. Cancer Genet Cytogenet 49: 203–217, 1990
Remvikos Y, Viehl P, Padoy E, Benhiayia B, Voillemot N, Magdelenat H: Breast cancer proliferation on cytological samples: a study by flow cytometry of S-phase fractions and BrdU incorporation. Br J Cancer 64: 501–507, 1991
Remvikos Y, Gerbault-Seureau M, Viehl P, Zafrani B, Magdelénat H, Dutrillaux B: Relevance of DNA ploidy as a measure of genetic deviation: a comparison of flow cytometry and cytogenetic data in 25 cases of human breast cancer. Cytometry 9: 612–618, 1988
Vindelov L, Christensen I, Nissen M: A detergent trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3: 323–327, 1983
Magdelénat H, Laine-Bidron C, Merle S, Zajdela A: Estrogen and progestin receptor assay in fine needle aspirates of breast cancer: methodological aspects. Eur J Cancer Clin Oncol 23: 425–429, 1987
Magdelenat H, Merle S, Zajdela A: Enzyme immunoassay of estrogen receptors in fine needle aspirates of breast tumors. Cancer Res 47: 4265s-4267s, 1987
Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–366, 1957
Tubiana M, Pejovic MH, Koscielny S,et al. Growth rate, kinetics of tumor cell proliferation and long-term outcome in human breast cancer. Int J Cancer 44: 17–22, 1989
Kallioniemi OP, Blanco G, Alavaikko M,et al. Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S-phase fraction. Cancer 62: 2183–2190, 1988
Magdelenat H, Gerbault-Seureau M, Lainé-Bidron C, Prieur M, Dutrillaux B: Genetic evolution of breast cancer: II. Relationship with estrogen and progesterone receptor expression. Breast Cancer Res Treat 22: 119–127, 1992
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Remvikos, Y., Gerbault-Seureau, M., Magdelénat, H. et al. Proliferative activity of breast cancers increases in the course of genetic evolution as defined by cytogenetic analysis. Breast Cancer Res Tr 23, 43–49 (1992). https://doi.org/10.1007/BF01831474
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DOI: https://doi.org/10.1007/BF01831474