DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients

Abstract

Several potential prognostic factors are available today for patients with breast cancer, and many more are being identified and studied. To evaluate the clinical utility of these factors, it will be necessary to measure them on a large number of patients, and then follow these patients so that multivariate survival analyses can be performed. The Oncology Research Network was established in 1986 by the University of Texas Health Science Center at San Antonio and Nichols Institute Reference Laboratories in order to evaluate the clinical utility of new prognostic factors for patients with primary breast cancer. The first generation of prognostic factors included steroid receptors, along with DNA ploidy and S-phase fraction determined by flow cytometry. Currently, laboratory results have been obtained from more than 127,000 patients, and follow-up information is available on a subset of more than 25,000 of these patients. S-phase fraction was related to the ploidy status of the tumor. An increased incidence of aneuploidy and higher S-phase fractions were found in estrogen and progesterone receptor negative tumors, tumors from patients with positive axillary lymph nodes, tumors greater than 2 cm in diameter, and patients younger than 35 years of age. Preliminary survival analyses suggest that S-phase fraction and DNA ploidy, in combination with other prognostic factors, are powerful predictors of early disease relapse. The Oncology Research Network provides an important resource for examining the clinical significance of new laboratory assays and for expediting improvements in existing laboratory techniques.

Genotoxic stress leads to centrosome amplification in breast cancer cell lines that have an inactive G1/S cell cycle checkpoint

“…Deregulation of cell cycle checkpoints, development of genomic instability, and aneuploidy are hallmarks of breast cancer (Anbazhagan et al, 1991;Wenger et al, 1993;Gunther et al, 1997). Genomic instability represents a major problem in the management of breast cancer patients due to the generation of diverse tumor cell phenotypes, which in turn may facilitate the development of chemoresistance and tumor progression (Khong and Restifo, 2002;Pinto et al, 2003).…”

Stable ‘portrait’ of breast tumors during progression: data from biology, pathology and genetics

“…In a study of 127 000 breast tumors, about one-half were found to be diploid or near diploid, the others exhibiting various types of aneuploidy (Wenger et al 1993). In an analysis of 256 patients, 384 modal chromosome numbers were detected, ranging between 29 and 211; 74% of these modal numbers were between 41 and 50, 19% between 51 and 80.…”

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

“…These have repeatedly demonstrated that ERα-cancers have, on average, an increased proliferation rate compared to their ERα+ counterparts. [35][36][37] Increased proliferation rates are associated with a decreased time to relapse [38][39][40] and decreased overall survival. 41 Furthermore, the benefits of chemotherapy in terms of survival or response appear to be greatest for high growth rate tumors, 42,43 although results from some studies do not support this relationship.…”