Abstract
We analysed 170 histological samples of invasive ductal breast cancer from years 1988-91 by computerized nuclear morphometry, to find objective and quantitative thresholds for nuclear grade. Based on Kaplan-Meier curves reflecting survival and recurrence of disease and univariate analysis by Cox's regression, optimal thresholds were determined for features related to nuclear size and size variation. In our material, with mean follow-up time of 5 years 9 months, the determined thresholds for nuclear profile area (32 microm2 and 47 microm2), nuclear diameter (6.4 microm and 7.4 microm) and mean shortest nuclear axis (4.8 microm and 6.4 microm) best separated the cases with favourable, intermediate and unfavourable course of disease. In this material from the era of mammography and adjuvant therapy, the mean shortest nuclear axis was found to be a significant prognostic factor, with a risk ratio (RR) exceeded only by that of tumour size (RRs 2.9- and 3.5-fold respectively). The results suggest that morphometric grading criteria can be developed for application in Bloom-Richardson grading and in the Nottingham Prognostic Index.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aaltomaa S., Lipponen P., Eskelinen M., Alhava E., Syrjänen K. Nuclear morphometry and mitotic indexes as prognostic factors in breast cancer. Eur J Surg. 1991 May;157(5):319–324. [PubMed] [Google Scholar]
- Aaltomaa S., Lipponen P., Eskelinen M., Kosma V. M., Marin S., Alhava E., Syrjänen K. Comparison of classic and quantitative prognostic factors in hormone receptor-positive and hormone receptor-negative female breast cancer. Am J Surg. 1993 Mar;165(3):307–311. doi: 10.1016/s0002-9610(05)80831-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Baak J. P., Kurver P. H., De Snoo-Niewlaat A. J., De Graef S., Makkink B., Boon M. E. Prognostic indicators in breast cancer--morphometric methods. Histopathology. 1982 May;6(3):327–339. doi: 10.1111/j.1365-2559.1982.tb02727.x. [DOI] [PubMed] [Google Scholar]
- Baak J. P., Van Dop H., Kurver P. H., Hermans J. The value of morphometry to classic prognosticators in breast cancer. Cancer. 1985 Jul 15;56(2):374–382. doi: 10.1002/1097-0142(19850715)56:2<374::aid-cncr2820560229>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
- CUTLER S. J., EDERER F. Maximum utilization of the life table method in analyzing survival. J Chronic Dis. 1958 Dec;8(6):699–712. doi: 10.1016/0021-9681(58)90126-7. [DOI] [PubMed] [Google Scholar]
- Dalton L. W., Page D. L., Dupont W. D. Histologic grading of breast carcinoma. A reproducibility study. Cancer. 1994 Jun 1;73(11):2765–2770. doi: 10.1002/1097-0142(19940601)73:11<2765::aid-cncr2820731119>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
- Davis B. W., Gelber R. D., Goldhirsch A., Hartmann W. H., Locher G. W., Reed R., Golouh R., Säve-Söderbergh J., Holloway L., Russell I. Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Cancer. 1986 Dec 15;58(12):2662–2670. doi: 10.1002/1097-0142(19861215)58:12<2662::aid-cncr2820581219>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- 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]
- Frierson H. F., Jr, Wolber R. A., Berean K. W., Franquemont D. W., Gaffey M. J., Boyd J. C., Wilbur D. C. Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma. Am J Clin Pathol. 1995 Feb;103(2):195–198. doi: 10.1093/ajcp/103.2.195. [DOI] [PubMed] [Google Scholar]
- Henson D. E., Ries L., Freedman L. S., Carriaga M. Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. Cancer. 1991 Nov 15;68(10):2142–2149. doi: 10.1002/1097-0142(19911115)68:10<2142::aid-cncr2820681010>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- Kairisto V., Poola A. Software for illustrative presentation of basic clinical characteristics of laboratory tests--GraphROC for Windows. Scand J Clin Lab Invest Suppl. 1995;222:43–60. doi: 10.3109/00365519509088450. [DOI] [PubMed] [Google Scholar]
- Kronqvist P., Collan Y., Kuopio T., Kujari H. Nuclear morphometry in breast cancer: the influence of sampling rules and freezing of samples. Mod Pathol. 1995 Feb;8(2):187–192. [PubMed] [Google Scholar]
- Kronqvist P., Kuopio T., Collan Y., Horvath C., Tamm U. The reproducibility of nuclear morphometric measurements in invasive breast carcinoma. Anal Cell Pathol. 1997;15(1):47–59. doi: 10.1155/1997/402125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ladekarl M., Sørensen F. B. Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast. APMIS. 1993 Dec;101(12):895–903. doi: 10.1111/j.1699-0463.1993.tb00198.x. [DOI] [PubMed] [Google Scholar]
- Larsson L. G., Nyström L., Wall S., Rutqvist L., Andersson I., Bjurstam N., Fagerberg G., Frisell J., Tabár L. The Swedish randomised mammography screening trials: analysis of their effect on the breast cancer related excess mortality. J Med Screen. 1996;3(3):129–132. doi: 10.1177/096914139600300305. [DOI] [PubMed] [Google Scholar]
- Moss S. M., Ellman R., Coleman D., Chamberlain J. Survival of patients with breast cancer diagnosed in the United Kingdom trial of early detection of breast cancer. United Kingdom Trial of Early Detection of Breast Cancer Group. J Med Screen. 1994 Jul;1(3):193–198. doi: 10.1177/096914139400100312. [DOI] [PubMed] [Google Scholar]
- Pienta K. J., Coffey D. S. Correlation of nuclear morphometry with progression of breast cancer. Cancer. 1991 Nov 1;68(9):2012–2016. doi: 10.1002/1097-0142(19911101)68:9<2012::aid-cncr2820680928>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
- Robbins P., Pinder S., de Klerk N., Dawkins H., Harvey J., Sterrett G., Ellis I., Elston C. Histological grading of breast carcinomas: a study of interobserver agreement. Hum Pathol. 1995 Aug;26(8):873–879. doi: 10.1016/0046-8177(95)90010-1. [DOI] [PubMed] [Google Scholar]
- Robert N. J. Adjuvant therapy in breast cancer. Obstet Gynecol Clin North Am. 1994 Dec;21(4):693–707. [PubMed] [Google Scholar]
- Schöndorf H., Naujoks H. Determining the nuclear area in normal breast epithelia and in the nuclei of mammary carcinomas. J Cancer Res Clin Oncol. 1985;109(3):241–244. doi: 10.1007/BF00390363. [DOI] [PubMed] [Google Scholar]
- Stierer M., Rosen H., Weber R. Nuclear pleomorphism, a strong prognostic factor in axillary node-negative small invasive breast cancer. Breast Cancer Res Treat. 1992 Jan;20(2):109–116. doi: 10.1007/BF01834640. [DOI] [PubMed] [Google Scholar]
- Styblo T. M., Wood W. C. Adjuvant chemotherapy in the node-negative breast cancer patient. Surg Clin North Am. 1996 Apr;76(2):327–341. doi: 10.1016/s0039-6109(05)70442-4. [DOI] [PubMed] [Google Scholar]
- Tabàr L., Fagerberg G., Duffy S. W., Day N. E., Gad A., Gröntoft O. Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am. 1992 Jan;30(1):187–210. [PubMed] [Google Scholar]
- Uyterlinde A. M., Baak J. P., Schipper N. W., Peterse H. J., Meijer J. W., Vooys P. G., Matze E. Prognostic value of morphometry and DNA flow-cytometry features of invasive breast cancers detected by population screening: comparison with control group of hospital patients. Int J Cancer. 1991 May 10;48(2):173–181. doi: 10.1002/ijc.2910480204. [DOI] [PubMed] [Google Scholar]
- Zweig M. H., Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993 Apr;39(4):561–577. [PubMed] [Google Scholar]
- van der Linden H. C., Baak J. P., Lindeman J., Hermans J., Meyer C. J. Morphometry and breast cancer. II. Characterisation of breast cancer cells with high malignant potential in patients with spread to lymph nodes: preliminary results. J Clin Pathol. 1986 Jun;39(6):603–609. doi: 10.1136/jcp.39.6.603. [DOI] [PMC free article] [PubMed] [Google Scholar]