David W. Kinne

Medullary carcinoma of the breast: a clinicopathologic study with 10 year follow-up.

Primary breast carcinomas from 192 patients treated between 1955 and 1965 for medullary carcinoma or duct carcinoma with medullary features were reviewed and reclassified using strictly defined pathologic criteria. Tumors that fulfilled requirements for medullary carcinoma were identified in 57 patients. Another 79 tumors that varied slightly from these criteria were termed “atypical” medullary carcinoma and 56 were characterized as nonmedullary carcinoma. When compared with the patients with nonmedullary infiltrating duct carcinoma, patients with medullary carcinoma had a significantly higher survival rate at 10 years, (84% vs. 63%), similar frequency of axillary lymph node metastases, and a more favorable prognosis when nodal metastases were present. Within the medullary carcinoma group, patients had a significantly better survival rate if their primary tumors were smaller than 3 cm in diameter. The average size of medullary carcinomas was 2.9 cm and that of nonmedullary carcinomas, 4.0 cm. Bilaterality was not more common in patients with medullary carcinoma, but the interval between diagnosis of the tumors was twice as long when one lesion was medullary (8.8 years) than when both were infiltrating duct carcinomas (4.6 years). Bilaterality was significantly more common among patients with medullary carcinoma who had a positive family history. The medullary lesion was most often the second one to be diagnosed. The 79 patients with atypical medullary carcinoma had a 10‐year survival rate of 74%. Patients in this group whose tumors had a sparse lymphoid infiltrate had a relatively poor prognosis. Intraductal carcinoma at the periphery of the lesion was not associated with a less favorable prognosis. It was concluded that intraductal carcinoma was consistent with the diagnosis of medullary carcinoma if all other criteria for the diagnosis were satisfied. With these exceptions we were unable to draw any firm conclusions about favorable or unfavorable effects of other morphologic features on survival in the group with atypical medullary carcinoma. Until further study of this group reveals that some or all of the lesions form a distinct clinicopathologic entity they are best included under the heading of infiltrating duct carcinoma. When the criteria described in this report were used, medullary carcinoma proved to be a specific lesion associated with a significantly better prognosis than ordinary infiltrating duct carcinoma.

Pathological prognostic factors in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma: a study of 644 patients with median follow-up of 18 years.

Prognostic factors have been examined in 644 patients with tumor-node-metastasis (TNM) stage T1 breast carcinoma treated by mastectomy and followed for a median of 18.2 years. Overall, 148 patients (23%) died of recurrent breast carcinoma. Eighteen (3%) were alive with recurrent disease and 478 (74%) were alive or died of other causes without recurrence. Unfavorable clinicopathologic features were larger tumor size (1.1 to 2.0 cm v less than or equal to 1 cm), perimenopausal menstrual status, the number of axillary lymph node metastases, poorly differentiated grade, presence of lymphatic tumor emboli (LI) in breast tissue near the primary tumor, blood vessel invasion (BVI), and an intense lymphoplasmacytic reaction around the tumor. Median survival after recurrence for the entire series was 2 years. This was not significantly influenced by tumor size, the number of axillary nodal metastases, the type of treatment for recurrence, or the interval to recurrence. The proportions surviving 5 and 10 years after recurrence were 17% and 5%, respectively. Among T1N0M0 cases, the chance of a local recurrence was 2.8% within 20 years. Median survival of T1N0M0 cases after local recurrence (4.5 years) was significantly longer than after systemic recurrence (1.5 years). A similar trend (3.7 v 2.0 years), not statistically significant, was seen in T1N1M0 patients, who had a 6.5% chance of local recurrence within 20 years. Median survival following systemic recurrence detected 10 or more years after diagnosis in T1N0M0 and in T1N1M0 patients was significantly longer than the median survival for systemic recurrences found in the first decade of follow-up. This difference did not apply following local recurrence in either T1N0M0 or T1N1M0 cases. It is evident that patients with T1 breast carcinoma can be subdivided into differing prognostic groups and this must be taken into account when considering the role of adjuvant chemotherapy for stage I disease. Systemic adjuvant treatment may prove to be beneficial for patients with unfavorable prognostic factors, while women with an especially low risk for recurrence (eg, T1N0M0 tumor 1.0 cm or less) might be spared such treatment.

Randomized Trial of Black Cohosh for the Treatment of Hot Flashes Among Women With a History of Breast Cancer

PURPOSE Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients. PATIENTS AND METHODS Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits. RESULTS Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups. CONCLUSION Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.

Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up.

PURPOSE This study was undertaken to define prognostically favorable and unfavorable subgroups of node-negative breast carcinoma patients by employing conventional pathologic data. PATIENTS AND METHODS Seven hundred sixty-seven women with T1N0M0/T2N0M0 breast carcinoma treated consecutively from 1964 through 1970 by modified or radical mastectomy without systemic adjuvant therapy were analyzed at a median follow-up duration of 18 years. RESULTS Size and histologic type of the carcinoma were crucial discriminants of prognosis. We defined a prognostically favorable group of 219 patients (29%) with infiltrating duct or lobular carcinoma < or = 1.0 cm in diameter or special tumor types < or = 3.0 cm. This group had a relapse-free survival rate of 91% at 10 years and 87% at 20 years. The less favorable group (548 patients, 71%) with infiltrating duct or lobular carcinoma greater than 1.0 cm and special tumor types greater than 3.0 cm had relapse-free survival rates of 73% and 68% at 10 and 20 years, respectively. The frequency of nonmammary malignant neoplasms (NMMN) was similar to that of contralateral carcinoma. Deaths due to NMMN were seven times more frequent than deaths due to contralateral carcinoma. CONCLUSION Nearly 30% of these node-negative patients, identified on the basis of tumor size and type, had an extremely favorable prognosis. There is insufficient evidence to warrant the routine use of adjuvant therapy in this group unless new forms of treatment prove to be less toxic and/or more effective in enhancing relapse-free survival. Early detection of NMMN should be an important part of the follow-up of node-negative breast carcinoma patients.

Major Hepatic Resection Using Vascular Isolation and Hypothermic Perfusion

The technique and results of 29 major hepatic resections using the method of complete vascular isolation and hypothermic perfusion of the liver are reported. The method enables the surgeon to perform otherwise difficult or impossible resections through chilled bloodless hepatic parenchyma. Major intrahepatic vascular structures can thus be recognized and controlled readily under clear vision. Direct neoplastic involvement of, or tumor thrombi in the portal vein, hepatic vein or vena cava, can be successfully dealt with by appropriate surgical measures. The operative mortality was 10.3% for this series which included many tumors previously deemed unresectable. The technical detail and intraoperative physiologic monitoring crucial to success in the use of the method are described. It is hoped that with the widened scope of resectability afforded by this technique, and the use of adjuvant chemotherapy, the currently experienced low cure rates for hepatic cancer can be improved.

Angiosarcoma and other vascular tumors of the breast.

Vascular tumors of the breast, with the exception of perilobular hemangiomas, are generally considered to be malignant. The pathologic and clinical features of 40 patients with angiosarcoma of the breast and 12 with other vascular tumors of the breast were reviewed. Three general histologic patterns of growth were identified among the angiosarcomas and were found to correlate closely with prognosis. Whereas 10 of the 13 patients in histologic Group I were alive and free of disease with an average follow-up of nearly 6 years, only two of 16 Group III patients were free of disease, and 14 have died. The six Group II patients had a survival similar to those in Group I. In this series the disease-free survival at 3 years was 41% and at 5 years 33%, much better than that reported in previous reviews of mammary angiosarcoma. The data also indicated that adjuvant chemotherapy, specifically actinomycin D, is effective in some and possibly all patients with angiosarcoma of the breast. The 12 other vascular lesions had distinctly different morphologic features, a benign clinical course, and should probably not be viewed as angiosarcomas. However, total excision of all vascular lesions of the breast is essential in order to determine both the diagnosis and the appropriate therapy.

Male breast cancer: a clinicopathologic study of 97 cases.

From 1949 through 1976, 97 men have been treated at Memorial Hospital for primary operable breast cancer. Seven per cent had intraductal carcinoma. Of the patients with invasive carcinoma 30% were pathologic stage I, 54% stage II, and 16% stage III. Fourty-six per cent had pathologically negative axillary lymph nodes. The most common type of tumor was infiltrating duct carcinoma. Fourty per cent of the patients had microscopic gynecomastia. None of the eight patients with intraductal or intracystic carcinoma died of cancer. Survival of the entire group of men with invasive carcinoma was 40% after ten years. The ten-year survival for men with negative nodes was 79%, for men with positive nodes 11%. Comparison with a series of 304 women with breast cancer operated on at Memorial Hospital in 1960 revealed no difference with regard to incidence of positive axillary lymph nodes or stage of disease. There was, however, a significantly lower survival rate for men. This poorer prognosis was limited to those men with pathologically positive axillary nodes.

Obesity at Diagnosis of Breast Carcinoma Influences Duration of Disease-free Survival

OBJECTIVE To study disease-free survival at 10 years in relation to obesity at the time of diagnosis. DESIGN A prospective study of consecutively treated patients with primary breast cancer. SETTING Memorial Sloan-Kettering Cancer Center, New York. PATIENTS Nine hundred twenty-three women treated by mastectomy and axillary dissection. MAIN RESULTS Women who were obese (25% or more over optimal weight for height) at the time of primary breast cancer treatment were at significantly greater risk for recurrence (42%) compared with nonobese patients (32%) 10 years after diagnosis (P less than 0.01). In multivariate analyses, obesity remained a statistically significant prognostic factor after controlling for measured tumor size, number of positive axillary lymph nodes, age at diagnosis, and adjuvant chemotherapy with a hazard ratio of 1.29 (95% CI, 1.0 to 1.67). When analyses were restricted to the 557 patients free of lymph node metastases, the hazard ratio of recurrence associated with obesity was 1.59 (CI, 1.06 to 2.39); 32% of obese patients developed recurrent disease compared with 19% of nonobese women. CONCLUSIONS Obesity at the time of diagnosis is a significant prognostic factor that may limit the reduction in breast cancer mortality attainable through detection at an early stage of disease. Because obesity and the risk for breast cancer increase with age, interventions that encourage weight control may influence breast cancer survival rates.

Axillary micro- and macrometastases in breast cancer. Prognostic significance of tumor size

Recurrence and survival data at 10 years were examined for 147 women with single axillary lymph node metastases found in a modified radical or standard radical mastectomy. The cases were identified through a review of all patients with primary operable breast cancer treated at Memorial Hospital from 1964 to 1970. The patients were stratified into groups according to size of the primary tumor and of the metastatic deposit (micro < 2 mm; macro > 2 mm) as well as level of the positive node. In the entire series, there was a significantly poorer prognosis among those patients with single macrometastases (30/ 77 patients: 39% recurrence rate) when compared with those having micrometastases (17/70 patients: 24% recurrence rate). A major prognostic difference emerged after stratification by tumor size. Within the first six years of the follow-up period, T| patients with negative nodes and those with single micro-metasteses had similar survival curves, significantly better than those with macrometastases. However, at 12 years, the survival rate of those patients with either a micro- or macrometastasis was nearly identical, and significantly worse than for those patients with negative lymph nodes. On the other hand, among women with primary tumors 2.1–5.0 cm (T2), patients with negative lymph nodes or single micrometastases had survival curves that did not differ significantly throughout the course of the follow-up period. Both had an outcome significantly better than observed for patients with macrometastases. These findings have important implications for our understanding of the clinical behaviour of breast cancer and for the stratification of patients entered into randomized treatment trials

Discontinuous or "skip" metastases in breast carcinoma. Analysis of 1228 axillary dissections.

Patterns of axillary lymph node metastases were analyzed in 1228 recently performed modified, radical, and extended radical mastectomies. In these specimens the position or level of lymph nodes was designated intraoperatively by the surgeon. No lymph node metastases were found in 720 (58) of the specimens while the remainder (508 or 41%) had at least one affected lymph node. The distribution of involvement by level showed progressive spread from level I to III as the number of positive lymph nodes increased. Discontinuous or “skip” metastases not following this pattern occurred in 1.6% of all cases and 3% of those with lymph node metastases (95% confidence interval, 1–5%). Half of those with “skip” metastases had tumor limited to level II. The presence of “skip” metastases was not related to the size, location in the breast, or histologic type of the primary tumor. It is apparent that the potential risk from “skip” metastases is not great and that this should not be a major consideration in therapeutic decisions. The risk is likely to be negligible for women treated by axillary dissections that include level II.