One hundred thirteen evaluable patients with previously untreated stage III breast carcinoma were treated with three monthly cycles of cyclophosphamide (CYC), doxorubicin (DOX), 5-fluorouracil (5-FU), vincristine (VCR), and prednisone (PRED) (CAFVP). Subsequently, 91 (81%) were deemed operable. Patients were then randomized to receive surgery or radiotherapy (RT) to determine which of these modalities afforded better local tumor control. All patients also received 2 additional years of CAFVP in a further attempt to eradicate local disease and systemic micrometastases. Forty-one of the randomized patients have relapsed. Approximately half of the initial relapses in each arm were local. The overall duration of disease control was similar following either modality, with a median of 29.2 months for surgery patients and 24.4 months for RT patients. Similarly, there was no major difference in survival related to randomized treatment with an overall median of 39 months (median follow-up 37 months). Pre- or perimenopausal status and inflammatory disease were associated with shorter disease control and survival. Treatment was generally well tolerated and toxicity was acceptable. This study demonstrates that prolonged control of stage III breast carcinoma can be achieved with combined modality therapy in which cytotoxic chemotherapy precedes and follows treatment directly primarily at the breast tumor, using either surgery or RT. Nevertheless, new regimens must be designed if significant advances that may lead to the cure of this disease are to be achieved.

In 1971, the National Surgical Adjuvant Breast Project (NSABP) implemented a prospective randomized clinical trial to compare the worth of alternative treatments with radical mastectomy in women with primary operable breast cancer. Information has been obtained from 1,665 patients eligible for follow-up from 34 NSABP member institutions in Canada and the United States. Results from that trial, at present in its sixth year with patients on study for an average of 36 months, (26 to 62 months), fail to demonstrate an advantage for those who had a radical mastectomy. No significant difference in the treatment failure or survival has as yet been observed in clinically negative node patients who have been randomly managed by conventional radical mastectomy, total mastectomy with postoperative regional radiation or total mastectomy followed by axillary dissection of those patients who subsequently develop positive nodes. Similarly, there presently exists no difference between patients with clinically positive nodes treated by radical mastectomy o r by total mastectomy followed by radiation. Of particular interest is the observation that based upon findings from radical mastectomy patients, there may be as many as 40% of patients having a total mastectomy who had histologically positive nodes unremoved, to date only 15% have developed positive nodes requiring a n axillary dissection. The persistence of such a difference in incidence would have profound biological significance. The discovery that leaving behind positive axillary nodes has as yet not been influential in enhancing the incidence of distant metastases o r the overall proportion of treatment failures and that a disproportionate number of treatment failures in the total mastectomy group occurred in those patients who subsequently required axillary dissection provides reinforcement to the view that positive axillary lymph nodes are not the predecessor of distant tumor spread but are a manifestation of disseminated disease.comer 39:2827-2839,1977. HERE HAS EXISTED GREAT CONTROVERSYtional Surgical Adjuvant Breast Project T concerning the treatment of primary breast (NSABP), after almost a decade of planning cancer. Prompted by that uncertainty, the Na-initiated in August of 1971, a prospective ran-

Analysis of disease-free survival rates in 374 women with operable breast cancer revealed that pre-operative weight, particularly in combination with serum cholesterol, is a significant prognostic determinant. Overall, women weighing under 150 pounds had a significantly higher cumulative five-year disease-free survival rate (67%) compared with women weighing more (49%) (z = 2.2298, P = 0.026). Women with low serum cholesterol levels had better cumulative five-year disease-free survival (67%) than women with high serum cholesterol levels (58%) (z = 1.1008, P = 0.27). The combination of high weight and high serum cholesterol levels was associated with an extremely poor cumulative five-year disease-free survival (32%) compared with that observed for women in whom values of either, or both, variables were low (68%) (z = 3.7843, P = 0.0004). These patterns in disease-free survival persisted even after controlling for tumor stage. The findings indicate that weight and cholesterol, in addition to their previously reported effect on the risk of breast cancer development, influence significantly the subsequent course of the disease. Cancer 47:2222-2227. 1981. ECENT STUDIES support Haenszel's hypothesis'

A retrospective study evaluating five-year survival rates in relation to pretreatment lymphocyte counts was undertaken in 453 patients with breast carcinoma. Patients with early tumor stages had higher pretreatment lymphocyte counts than those with advanced tumors: five-year survival in patients with pretreatment counts above 2000 per mm3 was 87% in Stage I, 67% in Stage II, and 57% in Stage III, while the comparable figures in patients with lower counts were 82%, 51%, and 29%. The differences in five-year survival rates for Stage II and III were significant: z equals 1.6955, p equals 0.046 and z equals 1.8841, p equals 0.03. Similar differences were noted in the disease-free, five-year survival rates. The corresponding figures in the three tumor stages for patients with counts above 2000/mm3 were 80%, 63%, and 53%, while those for patients with lower counts were 74%, 44%, and 18%. The differences in Stage II and III were also statistically significant: z equals 1.8430, p equals 0.33 and z equals 2.592, p equals 0.005 respectively. The possibility that the presence of suppressant factors related to the thymus may influence levels of lymphocytes was evaluated. Comparison of pre-thymectomy and postthymectomy lymphocyte counts in a control group of patients who had thymectomy for myasthenia gravis revealed a gradual increase of lymphocytes following thymectomy. The increase was significant at the second year following thymectomy. These observations indicate that lymphocyte counts may serve as prognostic indicators in patients with breast cancer. Low lymphocyte counts may be related to the presence of suppressor substances.

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Analysis of five-year disease-free survival rates in 608 women with operable breast cancer revealed that the reproductive history is a significant prognostic determinant. Overall parous women had a significantly higher cumulative five-year disease-free survival rate (60%), compared to the nulliparous (46%) (z = 2.5, p = 0.012). Significant differences were also noted when gravidity in addition to parity was taken as the determinant. The corresponding disease-free survival rates were 61% and 50%, respectively (z = 1.98, p = 0.048). Five-year survival rates were influenced in a similar manner by these variables but the observed differences were less significant. The trend toward higher survival rates in parous and gravidae women were noted in all tumor stages but achieved statistical significance only in stage III. The findings indicate that parity and gravidity affect not only the risk of breast cancer development but also the subsequent course of the disease. Parity seems to be a strong risk and prognostic factor than gravidity.

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