Relationships of S-phase fraction of breast carcinoma in relapse to duration of remission, estrogen receptor content, therapeutic responsiveness, and duration of survival.

The fractions of tumor cells in S phase (DNA synthesis) were measured by in vitro thymidine labeling and autoradiography in 48 breast carcinomas after relapse. The S-phase fractions (SPF's), expressed as S-phase cells/100 cells, had a lognormal distribution with a geometric mean of 6.5 and a median of 7.4. Paired SPF measurements on the primary and relapsed breast carcinomas of 14 patients showed that the SPF usually increased over time. The SPF after relapse correlated negatively with the interval between primary therapy and relapse and with duration of survival after relapse. Low SPF's were associated with older age, minimal nuclear anaplasia, and estrogen receptor positivity, but SPF was the only variable that could be shown to have independent prognostic significance. Therefore, the prognostic powers of the estrogen receptor status and nuclear grade appear to result from their correlations with the SPF. Either low SPF or presence of estrogen receptor predicted response to hormonal therapy.