Predictive value of nuclear DNA content in breast cancer in relation to clinical and morphologic factors. A retrospective study of 227 consecutive cases

Abstract

The predictive value of nuclear DNA content in breast cancer in relation to clinical and morphologic factors was studied in 227 consecutive cases of invasive breast adenocarcinomas with follow-up periods of 8 to 13 years. The results show that, with the use of Cox multivariate analysis nuclear DNA content provided significant prognostic information additional to that given by all other clinical and histomorphologic variables taken together. This fact indicates that the DNA content of breast cancer cells reflects biological properties, associated with the malignant behavior of the tumor, other than those determining the stage of the disease. Nuclear DNA content was strongly correlated to histopathologic grading of the ductal carcinomas, with poorly differentiated tumors more likely to be aneuploid. On the other hand, no clear correlation was found to exist between nuclear DNA content and axillary node status, indicating that these two factors are independent prognostic parameters. It is noteworthy that DNA content provided additional prognostic information within both the node-negative and node-positive patient groups. In summary, the results shown here indicate that nuclear DNA content, as an objective biological marker of tumor aggressiveness, can significantly improve our prognostic capabilities within the currently designated stages.

DNA flow cytometric analysis of primary operable breast cancer. Relation of ploidy and S-Phase fraction to outcome of patients in NSABP B-04

“…In the 16 reports relating ploidy and SPF to patient outcome, it was difficult to ascertain follow-up time in several. 19, 22 The followup times were 5 years or less in most of the studies14. 15,17,23,24,26,[28][29][30] and 5 to 8 years in four.20,21,2s,27 Our study reports findings through 10 years, and all patients were studied for more than 10 years.…”

Characterisation of breast fine-needle aspiration biopsies by centrosome aberrations and genomic instability

“…A number of prospective and retrospective studies revealed DNA aneuploid breast carcinomas as following a more malignant course than DNA diploid breast carcinomas do (Auer et al, 1980(Auer et al, , 1984Fallenius et al, 1988b). Recently, we have shown that aneuploid breast cancers can be subdivided into a genomically stable and unstable group by their proportion of cells with nonmodal DNA content values in the respective cytometrical DNA histograms, where the stable group proved to have a more favourable prognosis (Kronenwett et al, 2004).…”

c-erbB-2 oncogene as a prognostic marker in breast cancer

“…Hunts for new prognostic factors have considered variables such as oestrogen receptor (ER) status (Fisher et al, 1988) or the use of flow cytometry to determine ploidy and S-phase fraction (Clark et al, 1989;Fallenius et al, 1988). Publication of preliminary papers by Sainsbury et al (1987) and by Slamon et al (1987) showing that patients with over expression of the epidermal growth factor receptor (EGFR) or amplification of the c-erbB-2 oncogene had a poor prognosis, has drawn attention to the evaluation of oncogenes and growth factors as potential prognostic markers.…”