Premenopausal node-negative breast cancer: May adjuvant chemotherapy be indicated by the analysis of nuclear DNA dynamics?

Abstract

The management of premenopausal node-negative breast cancer patients is discussed controversially. Accurate cellular as well as biochemical markers are essential for this cancer group to identify high risk patients needing adjuvant chemotherapy. In the present study, flow cytometric DNA analysis (DNA-ploidy status, DNA-index, S-phase fraction, S+(G2+M)-phase fraction) and clinico-pathological variables (clinical stage, tumor size, receptor status, age, histological type and grade) as prognostic factors were determined on paraffin-embedded tumors to predict overall survival (OS) and disease-free survival (DFS). Median observation time was 6.1 years (n = 57). S+(G2+M)-phase fraction was the only flow cytometric DNA predictor of overall survival in the univariate analysis (log-rank test): As compared to the patients with lower S+(G2+M)-phase fraction (< or = 9.3%), patients with S+(G2+M)-phase fraction greater than 9.3% had shorter survival (P = 0.039). Of all the clinico-pathological parameters analyzed (univariate analysis), the survival time was found to be longer when estrogen- and/or progesterone-receptor status was positive (overall survival: P = 0.039; disease-free survival: P = 0.017) and the histological grade was low (overall survival: I + II vs III: P = 0.024; I vs II vs III: P = 0.046). In the multivariate analysis, receptor status was the strongest predictor for overall and disease-free survival. These results suggest that S+(G2+M)-phase fraction in premenopausal node-negative breast cancer could be an additional valuable prognostic factor to classify high risk breast cancer patients needing adjuvant chemotherapy.

DNA aneuploidy and breast cancer: a meta-analysis of 141,163 cases

“…From eight [ 7 , 9 – 11 , 16 , 22 , 26 , 33 ] studies using 50 years of age as a cut point, the RR of patients with aneuploidy tumor less than 50 years compared to those above 50 years old was 1.00 (95% CI, 0.91 to 1.11; P = 0.94; Figure 3H ). Likewise, pooled analysis of the studies [ 20 , 26 , 34 ] using 40 years as a cut point showed a similar result (RR = 0.99; 95% CI, 0.81 to 1.21; P = 0.92). Four studies [ 7 , 17 , 18 , 34 ] explored the aneuploidy frequency in premenopausal and postmenopausal women with BCs and our analysis demonstrated that aneuploidy was not significantly associated with menopausal status (RR = 1.02; 95% CI, 0.93 to 1.12; P = 0.66; sign test: P = 0.04).…”

“…Six studies [ 7 , 11 , 20 , 25 , 34 , 35 ] investigated the correlation between aneuploidy rate and tumor pTNM stages. This pooled analysis revealed that aneuploidy was significantly less frequent in patients with stage I BC compared to those with stages II-IV tumors (RR = 0.84; 95% CI, 0.74 to 0.96; P = 0.01, random-effects model; Figure 3A ; sign test: P = 1; RD = −0.12; 95% CI, −0.17 to −0.08; P < 0.00001, fixed- effect model).…”

“…Eight studies [ 7 , 9 , 10 , 20 , 22 , 33 – 35 ] provided data concerning the association between aneuploidy frequency and tumor grade. The meta-analysis revealed that aneuploidy was significantly more frequent in G2 tumors than in G1 tumors (RR = 1.58; 95% CI, 1.40 to 1.79; P < 0.00001, fixed-effect model; Figure 3D ; sign test: P = 0.074; RD = 0.21; 95% CI, 0.13 to 0.28; P < 0.00001, random-effects model).…”

“…Twelve studies [ 7 , 9 , 11 , 16 , 18 , 20 , 22 , 25 – 27 , 34 , 35 ] investigated the aneuploidy frequency in ER + and ER − BCs. The pooled analysis uncovered that aneuploidy was significantly more frequent in ER − tumors than in ER + tumors (RR = 1.32; 95% CI, 1.22 to 1.43; P < 0.00001; Figure 3G ; sign test: P = 0.04; RD = 0.18; 95% CI, 0.12 to 0.24; P < 0.00001) based on a random-effects model.…”

Progesterone Receptor A and B Isoforms in the Human Breast and Its Disorders

“…In this study, grade I and grade II are designated low grade (non-high grade), and grade III is considered to be high grade. 9,10) For grading of DCIS, the Van Nuys DCIS classification 11,12) was used. In this study, group 3 was designated as high grade, and the other two groups were designated as low grade (non-high grade).…”