Patterns of DNA Ploidy and S-Phase Fraction Associated with Breast Cancer Survival in Blacks and Whites1

A significant survival difference between black and white breast cancer patients has been observed in the United States. Evaluation ofthe prognostic value of DNA ploidy and S-phase fraction (SPF) in black and white breast cancer patients may contribute to our understanding of the mechanisms of racial disparity in survival. A sample of 98 patients (50 blacks and 48 whites) who participated in the Black/White Cancer Survival Study was selected for DNA flow cytometry analysis. Patients were followed between 4.5 and 6.5 years. The impacts of DNA ploidy and SPF on breast cancer survival were examined. Kaplan-Meier survival curves, log rank statistics, and Cox proportional hazards regression were used for survival analyses. Black patients were more likely than white patients to have tumors with high SPF (P < 0.05), but there was no difference in DNA ploidy (P = 0.79). Because there were significant interactions of both DNA ploidy and SPF with race, survival was examined separately for blacks and whites. Significantly poorer survival was observed for white patients with class A ploidy (hypodiploidy, hypotetraploidy, and hypertetraploidy; P = 0.001) and with high SPF (P = 0.025). The elevated hazard ratios remained significant after adjusting for age and stage. Further adjustment for adjuvant therapy and histopathological characteristics of tumor reduced the hazard ratios of SPF to a nonsignificant level. No significant associations were found between survival and DNA ploidy or SPF among blacks. DNA ploidy and SPF are prognostic factors for breast cancer survival in white patients but not in Received 7/8/96; revised 12/1 3/96; accepted 1/24/97. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with I 8 U.S.C. Section 1734 solely to indicate this fact. This work was supported in part by National Cancer Institute Contract NO1-CN-45175 and by the Louisiana Cancer and Lung Trust Fund Board. 2 To whom requests for reprints should be addressed, at Department of Pathology, Box P5-1, 1901 Perdido Street, Louisiana State University Medical Center. New Orleans, LA 701 12. Phone: (504) 568-47 16: Fax: (504) 599-1278. blacks. This may have clinical implication in breast cancer management. INTRODUCTION A significant survival difference between black and white breast cancer patients has been observed in the United States ( I, 2). In addition to a more advanced stage of disease at diagnosis, several hypotheses have been proposed to explain the poor survival of blacks with breast cancer. These include a lower socioeconomic status, fewer cancer-directed treatments, limited access to health care, more prevalent comorbidity, and more aggressive types of tumors among blacks than whites (3-7). Analysis of tumor ploidy and SPF3 by DNA flow cytometry has been demonstrated to be a powerful technique in evaluating the DNA content and cell proliferation of breast cancer (8). Studies have shown SPF and DNA ploidy to be associated with breast cancer survival (9, 10). Therefore, evaluation of the prognostic value of DNA ploidy and SPF in black and white breast cancer patients may provide clues to the racial difference in survival. When the DNA ploidy was separated into diploidy and aneuploidy, inconsistent associations had been reported between DNA ploidy and survival (9, 1 1-14). A revised DNA ploidy classification which better predicts survival has been proposed (1 1 ). As a result, a more consistent pattern between DNA ploidy and survival was observed when DNA ploidy was classified by the DI (10-12, 15, 16). Diploidy, near-hyperdiploidy, and tetraploidy have been associated with a better survival (10, 12, 15), whereas a significantly poorer survival has been observed in breast cancer patients with hypodiploid, hypotetraploid, and hypertetraploid tumors (1 1 , 15, 16). Hypodiploidy and hypotetraploidy have been associated with large tumor size, high histological grade, and low expression of the ER and PR (15, 16). Hypertetraploid tumors tend to have large tumor size and advanced tumor stage ( I 1). A prognostic value has not been established yet for multiploid tumors (13). In contrast to DNA ploidy, high SPF has been widely accepted to be a significant indicator for breast cancer survival (13, 17, 18) and has been reported to be associated with nuclear grade, tumor size, ER, PR, lymph node metastasis, and age ( I 2, 15, 17). In this study, we examined the associations of DNA ploidy and SPF with known prognostic factors. We further investigated their impact on breast cancer survival and contribution to black/ white survival disparity. 3 The abbreviations used are: SPF. S-phase fraction: BAD. backgroundaggregate-debris; DI, DNA index; ER, estrogen receptor; HR. hazard ratio; PR, progesterone receptor. Research. on April 20, 2017. © 1997 American Association for Cancer clincancerres.aacrjournals.org Downloaded from 588 Ploidy, SPF, and Breast Cancer Survival by Race Table I Black/white distributions of selected pr ognostic factors amo ng all eligible subjects and study sample Prognostic factors All eligible subjects (%)