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Common as well as unusual, heretofore unmentioned histopathologic features observed in 336 typical and 273 atypical medullary breast cancers from 6404 patients enrolled in various stage I and II protocols of the National Surgical Adjuvant Breast and Bowel Projects (NSABP) are presented. Both medullary types exhibited comparable pathologic findings, except for the infiltrative border and/or slight or absent tumor lymphoid infiltrate which by definition characterize the atypical form. Both also demonstrated a similar, high proclivity to be aneuploid, and to lack estrogen and progesterone receptors and nodal metastases. After appropriate statistical adjustments, survival (analyzed for 198 patients with typical and 149 with atypical medullary cancers) was found to be better for untreated, node-negative and node-positive patients treated with L-PAM + 5Fu who had typical medullary cancers than those with the NOS histologic type. The magnitude of this difference was 6% at 5 and 17% at 10 years post-operatively (cumulative odds = 1.81 with a 95% confidence interval of 1.08 - 3.3) for the former group, and 4% at 5 and 16% at 10 years (cumulative odds = 1.56 with a 95% confidence interval of 1.08 - 2.23) for the latter. Survival was comparable for patients with atypical medullary and NOS types in both situations. No clear difference in survival was found in untreated, positive node patients with the 3 histologic types examined, although the sample sizes in this subset were relatively small. This information as well as other pertinent considerations indicate that the prognosis of typical medullary cancer is not as 'good' as previously perceived. It is also concluded that there is insufficient evidence at present to exclude the atypical medullary variant as a histologic type of breast cancer.

Investigation of the biologic significance of delay between biopsy and mastectomy was performed upon women with invasive carcinoma of the breast in protocol four of the NSABP. Since the period of delay was two weeks or less in approximately 75 per cent, no comment concerning the possible effects of longer periods can be made. Life table analyses failed to reveal any difference in ten year survival rates between patients undergoing radical mastectomy management by the one and two step procedures. Similarly, no difference in adjusted ten year survival rate was observed between women managed by the two step procedure who did or did not have residual tumor identified in the mastectomy specimen after the first step or biopsy. Importantly, the clinical or pathologic stages, sizes of tumor or histologic grades were similar in women managed by the one and two step procedures minimizing selection bias. The material used also allowed for study of the possible causative role of biopsy of the breast on the development of sinus histiocytosis in regional axillary lymph nodes. No difference in degree or types of this nodal reaction could be discerned in the lymph nodes of the mastectomy specimens obtained from patients who had undergone the one and two step procedures. This finding indicates that nodal sinus histiocytosis is indeed related to the neoplastic process, albeit in an undefined manner, rather than the trauma of biopsy per se as has been suggested. These results do not invalidate the use of the one step procedure in the management of patients with carcinoma of the breast. Indeed, it is highly likely that it will be commonly used now that breast-conserving operations appear to represent a viable alternative modality for the primary surgical treatment of carcinoma of the breast. Yet, it is apparent that the one step procedure will be performed for technical and practical rather than biologic reasons.