DNA flow cytometric analysis of primary operable breast cancer. Relation of ploidy and S-phase fraction to outcome of patients in NSABP B-04.
Between 1971 and 1974, 1665 women with primary operable breast cancer were randomized into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial (B-04) conducted to evaluate the effectiveness of several different regimens of surgical and radiation therapy. No systemic therapy was given. Cells from archival paraffin-embedded tumor tissue taken from 398 patients were analyzed for ploidy and S-phase fraction (SPF) using flow cytometry. Characteristics and outcome of patients with satisfactory DNA histograms were comparable to those from whom no satisfactory cytometric studies were available. In patients with diploid tumors (43%), the mean SPF was 3.4% +/- 2.3%; in the aneuploid population (57%), the SPF was 7.9% +/- 6.3%. Only 29.9% +/- 17.3% of cells in aneuploid tumors were aneuploid. Diploid tumors were more likely than aneuploid tumors to be of good nuclear grade (P less than 0.001) and smaller size (P equals 0.03). More tumors with high SPF were of poor nuclear grade than were tumors with low SPF (P equals 0.002). No significant difference in 10-year disease-free survival (P equals 0.3) or survival (P equals 0.1) was found between women with diploid or aneuploid tumors. Patients with low SPF tumors had a 13% better disease-free survival (P equals 0.0006) than those with a high SPF and a 14% better survival (P equals 0.007) at 10 years than patients with high SPF tumors. After adjustment for clinical tumor size, the difference in both disease-free survival and survival between patients with high and low SPF tumors was only 10% (P equals 0.04 and 0.08, respectively). Although SPF was found to be of independent prognostic significance for disease-free survival and marginal significance for survival, it did not detect patients with such a good prognosis as to preclude their receiving chemotherapy. The overall survival of patients with low SPF was only 53% at 10 years. These findings and those of others indicate that additional studies are necessary before tumor ploidy and SPF can be used to select patients who should or should not receive systemic therapy.
Fisher
B
B
National Surgical Adjuvant Breast and Bowel Project Headquarters, Pittsburgh, PA 15261.
Gunduz
N
N
Costantino
J
J
Fisher
E R
ER
Redmond
C
C
Mamounas
E P
EP
Siderits
R
R
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D011003:Ploidies; D011379:Prognosis; D011446:Prospective Studies; D016196:S Phase; D016019:Survival Analysis
D004273:DNA, Neoplasm