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In order to aid in the identification of a group of breast cancer patients at high risk of recurrence in whom the possible value of adjuvant chemotherapy might be most readily demonstrable, the authors reviewed the clinicopathologic features of 74 women with infiltrating, Stage I, estrogen receptor-negative breast carcinoma. They found significant correlations between short-term recurrence (within 2 years) and extensive necrosis (P less than 0.005), anaplastic tumor nuclear morphology (P less than 0.01), a positive family history of breast carcinoma (P less than 0.05), diffuse hyperplasia of axillary lymph nodes (P less than 0.05), and young age (P less than 0.05). Twenty percent of all patients experienced recurrence within 2 years, while recurrence was noted in 32% of patients with highly pleomorphic nuclei, 38% of those with extensive necrosis, and 45% of those with a positive family history. Recurrence was noted in 55% of the small number of patients with both anaplastic nuclear morphology and a positive family history. These apparent risk factors for early recurrence may be helpful in prospectively selecting patients most eligible to receive adjuvant chemotherapy.

Metastatic behavior of neuroblastic tumors was analyzed to determine whether the secondary distribution of tumor was random, or whether the pattern of metastases was predictable and related to tumor type. The authors reviewed the 64 patients subjected to complete autopsy who had metastases from a neuroblastoma, retinoblastoma, medulloblastoma, or pinealoblastoma. The organ and tissue distribution of metastases was recorded in relation to location of primary tumor, type of therapy, survival, and presence of central nervous system metastases. Data were analyzed using chi-square contingency tables, correlation coefficients, and cluster analysis. The results indicate that: (1) the development of central nervous system metastases from neuroblastoma correlates with the pattern of extracentral nervous system metastases; (2) the pattern of tumor metastases is altered by chemotherapy and/or radiation; and (3) regardless of the site of origin, neuroblastic tumors behave in a uniform manner with a nonrandom metastatic distribution in particular tissues within the central nervous system. Cluster analysis demonstrated patterns of neuroblastoma tumor metastases which were consistent with both Hutchison and Pepper syndromes. The findings suggest that a random distribution, as might be secondary to blood flow, does not account for metastatic patterns, but rather that there are preferential patterns of growth, possibly reflecting trophic tendencies in neoplasms.

Heterogeneity of malignant neoplasms is a recognized phenomenon now, but the implications of this with respect to the responsiveness of carcinomas to different modes of therapy are not known. To examine this question, we reviewed the clinical and pathologic features of 85 autopsied patients with small cell carcinoma of the lung. Patients who were treated with chemotherapy plus radiation survived significantly longer than all other patients (P less than 0.005), but there were no significant differences in the mean number of metastatic sites or overall tumor burden at autopsy. Patients who were treated with chemotherapy only had significantly more frequent (P less than 0.05) and more extensive (P less than 0.005) metastases to the leptomeninges, more frequent metastases to other sites within the lungs (P less than 0.05), and less frequent metastases to the adrenal glands (P less than 0.01) and pancreas (P less than 0.05). The patients who were treated with radiation only had more extensive metastases to the adrenal glands (P less than 0.005), and more frequent metastases to the pancreas (P less than 0.001), colon (P less than 0.01), and cerebral white matter (P less than 0.05). The patients who were treated with both chemotherapy and radiation had more frequent and more extensive metastases to the gastrointestinal tract (P less than 0.05) and serosal surfaces (P less than 0.01), but not to any site within the central nervous system (CNS). The latter suggests that prophylactic treatment of the CNS may not be necessary to prolong survival when patients are treated with both chemotherapy and radiation. The results also suggest that although chemotherapy and radiation may prolong survival in patients with small cell carcinoma of the lung, these forms of treatment change the biologic behavior of the tumors by eliminating certain clones that are distinguishable by their metastatic patterns.

The responsiveness of prostate cancer to treatment with estrogen has been recognized for over 40 years, but whether the effect is mediated by diminished tumor growth or reduction in metastatic spread is not known. To answer this question the authors reviewed the clinical and pathologic features of 89 patients with metastatic prostate cancer after autopsy. Sixty-three percent of the patients studied were black. Patients treated with estrogen survived somewhat longer (0.05 less than P less than 0.10), but they had significantly greater numbers of metastatic sites (P less than 0.001) and greater overall tumor burden (P less than 0.001), with significantly increased frequencies of metastases to the liver, adrenal gland, bone, lymph nodes, large bowel, lungs, serosal surfaces, ureters, and central nervous system (CNS) (all P less than 0.05 or lower) compared with patients who had not been treated with estrogen. However, patients not treated with estrogen more frequently died from other causes (P less than 0.001). When the patients who died from other causes were excluded from the data analysis, there were no significant differences in the number of metastatic sites between patients who received estrogen therapy and those who did not, and the only remaining significant difference in the distribution of metastases was that patients who received estrogen treatment had more frequent metastases to the adrenal cortex and CNS (P less than 0.05). These observations were corroborated by cluster analysis of the metastatic patterns. Cluster analysis also identified a subset of predominantly (67%) black patients who developed distant metastases without much local spread of tumor. This suggests that tumor behavior in this group was less predictable than for the other patients in whom disease appeared to progress from Stage A to Stage D as expected. The authors conclude that estrogen therapy may prolong survival by slowing the rate of tumor growth rather than by inhibiting the metastatic progression of prostate cancer or destroying selective populations of tumor cells.