Tumor nuclear grade, estrogen receptor, and progesterone receptor : their value alone or in combination as indicators of outcome following adjuvant therapy for breast cancer

Previous reports by us have shown that the outcome of breast cancer patients who have received systemic adjuvant therapy is influenced by tumor estrogen or progesterone receptor (ER or PR) content or by nuclear grade. This publication provides information regarding the relative merit of those three markers. Findings from patients receiving L-PAM plus 5-FU (PF) or PF plus tamoxifen (PFT) indicate that the disease-free survival and survival within each regimen was almost identical when related to either ER, PR, or nuclear grade. Those having tumors with either of the receptors greater than or equal to 10 fmol or a good nuclear grade had a better outcome through five postoperative years than did those with ER or PR 0-9 fmol or poor nuclear grade. The magnitude of the difference was similar for each of the three discriminants. Since they were found to be of equal predictive value, one marker might well serve as a substitute for another. Cox regression analyses, however, clearly indicate that ER, PR, and nuclear grade have an independent influence on outcome and that a more accurate assessment of outcome is obtained when more than one marker is employed. Thus, information should be obtained on as many markers as possible. This conclusion is supported by observations presented which indicate that nuclear grade in combination with either or both of the receptors is a better predictor than either marker alone and that, as indicated by life table probability values and relative odds ratios, an increasing number of favorable tumor prognostic indicators results in a better patient outcome particularly in PFT-treated patients. A possible explanation is considered for why the separation of receptor/nuclear grade categories is more orderly and pronounced in PF-treated patients receiving tamoxifen than in those given PF alone.