Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Nov;74(9):1469–1478. doi: 10.1038/bjc.1996.567

Prospective evaluation of prognostic factors in operable breast cancer.

R A Hawkins 1, A L Tesdale 1, M E Killen 1, W J Jack 1, U Chetty 1, J M Dixon 1, M J Hulme 1, R J Prescott 1, M A McIntyre 1, W R Miller 1
PMCID: PMC2074769  PMID: 8912547

Abstract

In 215 patients with operable breast cancer (T1-T3, N0-1, M0) and no other or previous cancer, presenting to a single breast unit, sufficient tumour was available for the prospective determination of four putative biochemical markers of prognosis: oestrogen receptor (ER) activity, cathepsin D (cath D), epidermal growth factor receptor (EGFR) activity and cyclic AMP-binding proteins (c-AMP-b). There were significant inter-relationships between ER and EGFR (r = -0.26), c-AMP-b and cath D (r = +0.32) and ER and c-AMP-b (r = +0.14). After follow-up (median 36.2 months), a total of 55 recurrences (18 locoregional only) and 35 deaths were recorded. By univariate analysis, up to 10 of 18 biochemical, clinical and histopathological variables of potential prognostic value were significantly related to disease-free interval or death, but by multivariate analysis only oestrogen receptor concentration and node status contributed significantly to risk of both distant recurrence/death; in addition, tumour size made a small contribution to the risk for a distant recurrence only. Only two parameters, tumour grade and ER concentration, were significantly related to risk of locoregional recurrence by univariate analysis, but by multivariate analysis, only tumour grade was important. It is concluded that tumour ER concentration, axillary nodal status and tumour grade remain as the most important prognostic factors in the early years after presentation of operable breast cancer, with a minor influence of tumour size. At this time, the prognostic significance of quantitative measurements of ER concentration, carefully controlled for the quality of both assay and tumour specimen, is probably greater than is generally appreciated. We have yet to identify other factors, which add significantly to the short-term prognostic value of these key features.

Full text

PDF
1469

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman D. G. Categorising continuous variables. Br J Cancer. 1991 Nov;64(5):975–975. doi: 10.1038/bjc.1991.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BLOOM H. J., RICHARDSON W. W. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957 Sep;11(3):359–377. doi: 10.1038/bjc.1957.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BROWN J. B., BULBROOK R. D., GREENWOOD F. C. An evaluation of a chemical method for the estimation of oestriol, oestrone and oestradiol-17 beta in human urine. J Endocrinol. 1957 Nov;16(1):41–48. doi: 10.1677/joe.0.0160041. [DOI] [PubMed] [Google Scholar]
  4. Barker S., Panahy C., Puddefoot J. R., Goode A. W., Vinson G. P. Epidermal growth factor receptor and oestrogen receptors in the non-malignant part of the cancerous breast. Br J Cancer. 1989 Nov;60(5):673–677. doi: 10.1038/bjc.1989.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Cardiff R. D. Cathepsin D and breast cancer: useful? Hum Pathol. 1994 Sep;25(9):847–848. doi: 10.1016/0046-8177(94)90001-9. [DOI] [PubMed] [Google Scholar]
  7. Castiglioni T., Merino M. J., Elsner B., Lah T. T., Sloane B. F., Emmert-Buck M. R. Immunohistochemical analysis of cathepsins D, B, and L in human breast cancer. Hum Pathol. 1994 Sep;25(9):857–862. doi: 10.1016/0046-8177(94)90003-5. [DOI] [PubMed] [Google Scholar]
  8. Cho-Chung Y. S., Bodwin J. S., Clair T. Cyclic AMP-binding proteins: inverse relationship with estrogen-receptors in hormone-dependent mammary tumor regression. Eur J Biochem. 1978 May;86(1):51–60. doi: 10.1111/j.1432-1033.1978.tb12283.x. [DOI] [PubMed] [Google Scholar]
  9. Cren H., Lechevrel C., Roussel G., Goussard J. Evolution of immunoreactivity of monoclonal antibodies H222 and/or D547 used in the detection of breast cancer estrogen receptors. Varying reactivity of receptor isoforms. J Steroid Biochem Mol Biol. 1991 Oct;39(4A):519–527. doi: 10.1016/0960-0760(91)90246-2. [DOI] [PubMed] [Google Scholar]
  10. Dixon J. M., Page D. L., Anderson T. J., Lee D., Elton R. A., Stewart H. J., Forrest A. P. Long-term survivors after breast cancer. Br J Surg. 1985 Jun;72(6):445–448. doi: 10.1002/bjs.1800720614. [DOI] [PubMed] [Google Scholar]
  11. Fisher E. R., Anderson S., Redmond C., Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project protocol B-06. 10-year pathologic and clinical prognostic discriminants. Cancer. 1993 Apr 15;71(8):2507–2514. doi: 10.1002/1097-0142(19930415)71:8<2507::aid-cncr2820710813>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  12. Foekens J. A., Portengen H., van Putten W. L., Trapman A. M., Reubi J. C., Alexieva-Figusch J., Klijn J. G. Prognostic value of receptors for insulin-like growth factor 1, somatostatin, and epidermal growth factor in human breast cancer. Cancer Res. 1989 Dec 15;49(24 Pt 1):7002–7009. [PubMed] [Google Scholar]
  13. Gasparini G., Bevilacqua P., Pozza F., Meli S., Boracchi P., Marubini E., Sainsbury J. R. Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer. Br J Cancer. 1992 Nov;66(5):970–976. doi: 10.1038/bjc.1992.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hawkins R. A., Black R., Steele R. J., Dixon J. M., Forrest A. P. Oestrogen receptor concentration in primary breast cancer and axillary node metastases. Breast Cancer Res Treat. 1981;1(3):245–251. doi: 10.1007/BF01806264. [DOI] [PubMed] [Google Scholar]
  15. Hawkins R. A., Killen E., Whittle I. R., Jack W. J., Chetty U., Prescott R. J. Epidermal growth factor receptors in intracranial and breast tumours: their clinical significance. Br J Cancer. 1991 Apr;63(4):553–560. doi: 10.1038/bjc.1991.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hawkins R. A., White G., Bundred N. J., Dixon J. M., Miller W. R., Stewart H. J., Forrest A. P. Prognostic significance of oestrogen and progestogen receptor activities in breast cancer. Br J Surg. 1987 Nov;74(11):1009–1013. doi: 10.1002/bjs.1800741118. [DOI] [PubMed] [Google Scholar]
  17. Haybittle J. L., Blamey R. W., Elston C. W., Johnson J., Doyle P. J., Campbell F. C., Nicholson R. I., Griffiths K. A prognostic index in primary breast cancer. Br J Cancer. 1982 Mar;45(3):361–366. doi: 10.1038/bjc.1982.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Henry J. A., McCarthy A. L., Angus B., Westley B. R., May F. E., Nicholson S., Cairns J., Harris A. L., Horne C. H. Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer. An immunohistochemical study. Cancer. 1990 Jan 15;65(2):265–271. doi: 10.1002/1097-0142(19900115)65:2<265::aid-cncr2820650214>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  19. Humeniuk V., Hawkins R. A., Prescott R. J., Roberts M. M., Stewart H. J., Forrest A. P. Oestrogen receptors and primary breast cancer. Aust N Z J Surg. 1982 Aug;52(4):408–414. doi: 10.1111/j.1445-2197.1982.tb06020.x. [DOI] [PubMed] [Google Scholar]
  20. Jensen E. V. Estrogen receptors in hormone-dependent breast cancers. Cancer Res. 1975 Nov;35(11 Pt 2):3362–3364. [PubMed] [Google Scholar]
  21. Johnson M. D., Torri J. A., Lippman M. E., Dickson R. B. The role of cathepsin D in the invasiveness of human breast cancer cells. Cancer Res. 1993 Feb 15;53(4):873–877. [PubMed] [Google Scholar]
  22. Koenders P. G., Beex L. V., Kienhuis C. B., Kloppenborg P. W., Benraad T. J. Epidermal growth factor receptor and prognosis in human breast cancer: a prospective study. Breast Cancer Res Treat. 1993;25(1):21–27. doi: 10.1007/BF00662397. [DOI] [PubMed] [Google Scholar]
  23. Koenders P. G., Faverly D., Beex L. V., Bruggink E. D., Kienhuis C. B., Benraad T. J. Epidermal growth factor receptors in human breast cancer: a plea for standardisation of assay methodology. Eur J Cancer. 1992;28(2-3):693–697. doi: 10.1016/s0959-8049(05)80128-5. [DOI] [PubMed] [Google Scholar]
  24. Miller W. R., Elton R. A., Dixon J. M., Chetty U., Watson D. M. Cyclic AMP binding proteins and prognosis in breast cancer. Br J Cancer. 1990 Feb;61(2):263–266. doi: 10.1038/bjc.1990.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miller W. R., Senbanjo R. O., Telford J., Watson D. M. Cyclic AMP binding proteins in human breast cancer. Br J Cancer. 1985 Oct;52(4):531–535. doi: 10.1038/bjc.1985.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miller W. R., Watson D. M., Jack W., Chetty U., Elton R. A. Tumour cyclic AMP binding proteins: an independent prognostic factor for disease recurrence and survival in breast cancer. Breast Cancer Res Treat. 1993;26(1):89–94. doi: 10.1007/BF00682703. [DOI] [PubMed] [Google Scholar]
  27. Nicholson S., Sainsbury J. R., Needham G. K., Chambers P., Farndon J. R., Harris A. L. Quantitative assays of epidermal growth factor receptor in human breast cancer: cut-off points of clinical relevance. Int J Cancer. 1988 Jul 15;42(1):36–41. doi: 10.1002/ijc.2910420108. [DOI] [PubMed] [Google Scholar]
  28. Osborne C. K. Prognostic factors for breast cancer: have they met their promise? J Clin Oncol. 1992 May;10(5):679–682. doi: 10.1200/JCO.1992.10.5.679. [DOI] [PubMed] [Google Scholar]
  29. Paterson D. A., Anderson T. J., Jack W. J., Kerr G. R., Rodger A., Chetty U. Pathological features predictive of local recurrence after management by conservation of invasive breast cancer: importance of non-invasive carcinoma. Radiother Oncol. 1992 Nov;25(3):176–180. doi: 10.1016/0167-8140(92)90264-u. [DOI] [PubMed] [Google Scholar]
  30. Rochefort H. Cathepsin D in breast cancer. Breast Cancer Res Treat. 1990 Jul;16(1):3–13. doi: 10.1007/BF01806570. [DOI] [PubMed] [Google Scholar]
  31. Roger P., Montcourrier P., Maudelonde T., Brouillet J. P., Pages A., Laffargue F., Rochefort H. Cathepsin D immunostaining in paraffin-embedded breast cancer cells and macrophages: correlation with cytosolic assay. Hum Pathol. 1994 Sep;25(9):863–871. doi: 10.1016/0046-8177(94)90004-3. [DOI] [PubMed] [Google Scholar]
  32. Saez S., Cheix F., Asselain B. Prognostic value of estrogen and progesterone receptors in primary breast cancer. Breast Cancer Res Treat. 1983;3(4):345–353. doi: 10.1007/BF01807587. [DOI] [PubMed] [Google Scholar]
  33. Sainsbury J. R., Farndon J. R., Needham G. K., Malcolm A. J., Harris A. L. Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet. 1987 Jun 20;1(8547):1398–1402. doi: 10.1016/s0140-6736(87)90593-9. [DOI] [PubMed] [Google Scholar]
  34. Shek L. L., Godolphin W. Survival with breast cancer: the importance of estrogen receptor quantity. Eur J Cancer Clin Oncol. 1989 Feb;25(2):243–250. doi: 10.1016/0277-5379(89)90015-1. [DOI] [PubMed] [Google Scholar]
  35. Simon R., Altman D. G. Statistical aspects of prognostic factor studies in oncology. Br J Cancer. 1994 Jun;69(6):979–985. doi: 10.1038/bjc.1994.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Søreide J. A., Lea O. A., Kvinnsland S. Cytosol protein content and prognosis in operable breast cancer. Correlations with steroid hormone receptors and other prognostic factors. Breast Cancer Res Treat. 1991 Dec;20(1):25–32. doi: 10.1007/BF01833354. [DOI] [PubMed] [Google Scholar]
  37. Yamamoto H., Suzuki T. Prostaglandin-E2-induced activation of adenosine 3'-5' cyclic monophosphate-dependent protein kinases of a murine macrophage-like cell line (P388D1). J Immunol. 1987 Nov 15;139(10):3416–3421. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES