PROGNOSTIC INDICATORS INCLUDING DNA HISTOGRAM TYPE, RECEPTOR CONTENT, AND STAGING RELATED TO HUMAN-BREAST CANCER-PATIENT SURVIVAL

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44 (9), 4187-4196
Abstract
Primary tumors from breast cancer patients were evaluated for the biochemical presence of 3 steroid cytosolic receptors and by DNA histogram analysis using flow cytometry. These parameters were compared with the histological and staging diagnoses and the patients'' survival over a 36-mo. period. A total of 74 patients with primary breast tumors were evaluated. The breast samples invariably demonstrated a peak population of diploid G0/1 cells which contained 2C amounts of DNA, as determined by mixing experiments using normal human breast tissues or trout erythrocytes as fixed standards. The tumors were classified into 5 DNA histogram types based on their DNA index distributions established by flow cytometry. These results showed that 21% of the tumors were diploid and indistinguishable from the diploid population of normal breast cells, 8% were hypodiploid, 11% were hypertetraploid, 8% were multiploid and the remaining 52% were hyperdiploid. The DNA index values varied from 0.78 (hypodiploid) to 2.60 (hypertetraploid). The percentages of S-phase cells were lowest in the diploid and hypertetraploid tumors and highest in the hypodiploid tumors. Among the 24 patients who died during the 36-mo. follow-up, 92% (22 of 24) were classified in one of the aneuploid groups. Three high-risk groups identified on the basis of survival after 36 mo. were distinguished: hypodiploid (50% survival); multiploid (43% survival); and hyperdiploid (50% survival). Rates of survival in the diploid and hyperdiploid groups were 87 and 71%, respectively. The hypodiploid group was distinguished by having the lowest mean estrogen cytosolic receptor value [26 .+-. 13 (SD) fmol/mg], progesterone cytosolic receptor value (13 .+-. 15 fmol/mg) and androgen cytosolic receptor value (< 1 .+-. 1 fmol/mg). The diploid tumors had some of the highest receptor values, with mean estrogen cytosolic receptor value equal to 102 .+-. 114 fmol/mg, progesterone cytosolic receptor value equal to 74 .+-. 110 fmol/mg, and androgen cytosolic receptor value equal to 65 .+-. 80 fmol/mg. The lowest survival rates (17% after 36 mo.) occurred in patients over 67 yr of age who had aneuploid tumors, compared to 100% survival in patients over 67 yr of age with diploid tumors. The value of using flow cytometry and steroid receptor values as supplements to histopathology for the characterization of subgroups of mammary cancer patients is thus demonstrated. The ability to identify patients with a good prognosis compared to those at high risk of recurrence and death will be valuable in the design of future prospective treatment studies.