In 1976 we began a randomized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors less than or equal to 4 cm in size. The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor. Women were randomly assigned to total mastectomy, segmental mastectomy alone, or segmental mastectomy followed by breast irradiation. All patients had axillary dissections, and patients with positive nodes received chemotherapy. Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy, with or without breast irradiation, resulted in disease-free, distant-disease-free, and overall survival at five years that was no worse than that after total breast removal. In fact, disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy (P = 0.04), and overall survival after segmental mastectomy, with or without radiation, was better than overall survival after total mastectomy (P = 0.07, and 0.06, respectively). A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years, as compared with 72.1 per cent of those receiving no radiation (P less than 0.001). Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free (P less than 0.001), although both groups received chemotherapy. We conclude that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm, provided that margins of resected specimens are free of tumor.

We conducted a randomized, double-blind, placebo-controlled trial of postoperative therapy with tamoxifen (10 mg twice a day) in 2644 patients with breast cancer, histologically negative axillary nodes, and estrogen-receptor-positive (greater than or equal to 10 fmol) tumors. No survival advantage was observed during four years of follow-up (92 percent for placebo vs. 93 percent for tamoxifen; P = 0.3). There was a significant prolongation of disease-free survival among women treated with tamoxifen, as compared with those receiving placebo (83 percent vs. 77 percent; P less than 0.00001). This advantage was observed in both the patients less than or equal to 49 years old (P = 0.0005) and those greater than or equal to 50 (P = 0.0008), particularly in the former, among whom the rate of treatment failure was reduced by 44 percent. Multivariate analysis indicated that all subgroups of patients benefited. Tamoxifen significantly reduced the rate of treatment failure at local and distant sites, tumors in the opposite breast, and the incidence of tumor recurrence after lumpectomy and breast irradiation. The benefit was attained with a low incidence of clinically appreciable toxic effects. The magnitude of the improvement obtained does not preclude the need for future trials in which patients given tamoxifen could serve as the control group in an evaluation of potentially better therapies. Tamoxifen treatment is justified in patients who meet the eligibility criteria of the present study and who refuse to participate in those trials. Since patients with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not eligible for this study, no information is available to indicate that such patients should receive tamoxifen.

The current findings completely affirm the validity of our original observations indicating the appropriateness of grouping primary breast cancer patients into those with negative, 1 to 3, or ≫4 positive nodes. Results, however, reveal that there is a risk in combining all patients with ≫4 positive nodes into a single group. Since there was a 25% greater disease‐free survival and an 18% greater survival in those with 4 to 6 than in those with ≫13 positive axillary nodes, such a unification may provide misleading information regarding patient prognosis, as well as the worth of a therapeutic regimen when compared with another from a putatively similar patient population. Of particular interest were findings relating the conditional probability, i.e., the hazard rate, of a treatment failure or death each year during the 5‐year period following operation to nodal involvement with tumor. Whereas the hazard rate for those with negative, or 1 to 3 positive nodes, was relatively low and constant, in those with ≫4 positive nodes the risk in the early years was much greater, but by the fifth year it was similar to that occurring when 1‐3 nodes were involved, and not much different from negative node patients. The same pattern existed whether 4 to 6 or ≫13 nodes were positive. When the current findings are considered relative to other factors with predictive import, it is concluded that nodal status still remains the primary prognostic discriminant.