Nm23 expression in breast ductal carcinomas: a ten year follow-up study in a uniform group of node-negative breast cancer patients.

The nm23 gene was originally identified in murine melanoma cell lines as a putative metastasis suppressor gene. 1a a limited number of studies in breast carcinomas nm23 mRNA and/or protein levels were found to correlate inversely with lymph node metastases, and positively with the survival of patients. Using a monoclonal antibody to nm23-Hl protein we have examined the immunohistochemical expression of nm-23 in breast ductal carcinomas of 44 lymph node-negative patients with similar tumor pathologic features. The mean follow-up period of the patients was 138 months. Thirty two out of 44 tumors (72%) disclosed high immunohistochemical expression of nm23 protein and 12 (28%) low or negative expression. No correlation was observed between nm23 expression and the relapse or death rate of the patients. Similarly, no association was found between nm23 protein levels and estrogen receptor status or p53 protein. Our results do not seem to agree with the proposed antimetastatic property of nm23 protein, and indicate that its immunohistochemical determination has no prognose significance in the management of node-negative breast cancer patients.

Prognostic significance of apoptosis related proteins Bcl-2 and Bax in node-negative breast cancer patients.

In this immunohistochemical study we investigated the expression of Bcl-2 and Bax apoptosis related proteins in node-negative breast carcinomas. The results were correlated with the recurrence rate of the patients. In order to avoid the influence of the most important tumor prognostic parameters we selected two groups of node negative breast ductal carcinomas that were grade II according to Bloom and Richardson classification, had a diameter of 1-3 cm but differed in clinical outcome: 44 of the patients had a 10 year disease-free survival while 46 developed metastatic disease in the same period of time. Bcl-2 and to a lesser degree Bax expression were inversely related with distant metastases (Pbcl-2 = 0.007, Pbax = 0.03). Combined analysis of Bax/Bcl-2 expression in relation to clinical outcome showed that the absence of both factors was more strongly associated with the development of distant metastases (P = 0.006, Ptrend = 0.001). Our findings indicate that Bcl-2 and Bax apoptosis-related proteins are good indicators of prognosis in node-negative breast cancer patients, and their combined absence, suggestive of serious deregulation of the apoptotic process, may contribute to the biologic aggressiveness of the tumors.

Tumor angiogenesis in node-negative breast cancer: relationship with relapse free survival.

There is growing evidence that angiogenesis plays an important role in the biologic aggressiveness of breast cancer. using immunohistochemical methods, several studies have shown a worse prognosis for those patients with tumors with high angiogenic activity. The aim of this study was to correlate the microvessel density with relapses in node-negative breast cancer patients who exhibited homogeneous pathologic features. The study was based on 52 women with primary invasive ductal carcinoma graded according to Bloom and Richardson classification as group II. All patients were node-negative and had a tumor 1-3 cm in diameter. Twenty six patients had a 10 year relapse free survival while the other group of 26 patients showed tumor recurrences in the same time interval. Microvessels were highlighted immunohistochemically using an antibody for Factor VIII which is an endothelial marker. Vascular density was quantified at the richest in vessels part of the tumor through an ocular eyepiece equipped with a grid with 100 subdivisions at a 400 x magnification. The vascular density counts ranged from 16 to 230 per grid field. For the relapse-free group the mean value was 35 whereas for the group with recurrences, the mean value of vessel density was 68. This difference proved to be statistically significant, and suggests that angiogenesis is closely associated with early relapse in primary breast cancer. Such results are found in the majority of the retrospective studies and show that angiogenesis is an important new prognostic indicator in early-stage breast carcinoma. This marker should be further evaluated in order to demonstrate whether adjuvant therapies with angiogenesis inhibitors could improve the prognosis of those patients at high risk, e.g., those with highly vascularized tumors.

Prognostic variables in greek patients with stage II breast cancer: a Hellenic Cooperative Oncology Group study.

The independent effects of several patient, tumor and treatment-related prognostic factors on relapse-free survival (RFS) and overall survival (OS) were assessed by Cox multivariate regression analysis in 988 Greek patients with stage II breast cancer. At a median follow-up time of 83 (range 3.3-131+) months and after the evaluation of all patients together, the number of positive axillary nodes (p < 0.0001), tumor size (p = 0.0024) and tumor grade (p = 0.0008) were identified as significant prognostic factors for RFS. Also, the number of positive nodes (p < 0.0001), tumor size (p = 0.0002) and ER status (p = 0.0001) were found to be significant for OS. These short-term prognostic variables are similar to those reported for this group of patients in other European countries and in the USA.

Diet and breast cancer: a case-control study in Greece.

A case-control study of the role of diet in the etiology of breast cancer was conducted in Athens, Greece. There are reasons to believe that the diet of the Greek population is characterized by greater heterogeneity than that in most countries where such studies have been undertaken. The case series consisted of 120 consecutive patients with histologically confirmed breast cancer admitted to either of two teaching hospitals over a 12-month period. The controls were 120 patients admitted to a teaching hospital for trauma and orthopedic conditions during the same period. Dietary histories concerning the frequency of consumption of 120 foods and drinks were obtained by interview. Cases reported significantly less frequent consumption of vegetables as a group and, within that group, specifically of cucumber, lettuce and raw carrot. After adjustment for potential external confounding variables and for confounding between food categories, the odds ratio for persons in the highest quintile of vegetable consumers, relative to those in the lowest quintile, was 0.09 with 95% confidence limits 0.03-0.30. That is to say, the lowest quintile of vegetable consumers had about 10 times the breast cancer risk of the highest quintile. For a score based on consumption of only the 3 specified salad items the odds ratio over the extreme quartiles was 0.12 (0.05-0.32). There was no association with consumption of fats and oils, alcohol or coffee, and no significant association with any other major food category (including alcohol and coffee) after adjustment for confounding variables.

Risk of breast cancer among Greek women in relation to nutrient intake.

A case-control study of the role of diet in the cause of breast cancer was conducted in Athens, Greece. The case series consisted of 120 consecutive patients with histologically confirmed breast cancer admitted to either of two teaching hospitals over a 12-month period. The controls were 120 patients admitted to a teaching hospital for trauma and orthopedic conditions during the same period. Dietary histories concerning the frequency of consumption of 120 foods and drinks were obtained by interview. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a selected typical portion size for each specified food item by the frequency that the food was used per month and summing these estimates for all food items. Cases reported significantly less frequent consumption of vitamin A after controlling for total caloric intake, potential external confounding variables and other nutrients associated with breast cancer risk. The odds ratio estimated for consumption of vitamin A equal to the value of the 90th centile versus consumption equal to the value of the 10th centile was 0.46 with 90% confidence limits 0.26-0.82. There was no evidence that high intake of dietary fat increases the risk of breast cancer.

Pre- and postoperative chemoendocrine treatment with or without postoperative radiotherapy for locally advanced breast cancer.

From July, 1978 to September, 1981, 184 patients with localy advanced breast cancer (T3; T4a-b; any N; M0) regardless of their hormonal receptor status, entered a trial to evaluate the contribution of radiotherapy when added to an intensive preoperative chemoendocrine regimen. Seventy-eight patients were ultimately disqualified. All patients underwent sequentially: (1) two cycles of chemotherapy: Day 1--Oncovin 1.4 mg/m2, cyclophosphamide 350 mg/m2, Adriamycin 30 mg/m2; Day 2--methotrexate 20 mg/m2, 5-fluorouracil 350 mg/m2 (in addition, antiestrogens were given to postmenopausal patients); (2) mastectomy with complete axillary dissection combined with oophorectomy in patients before and one year after menopause; (3) radiotherapy randomly to one-half of the patients; and (4) ten additional chemotherapy cycles as above, with antiestrogens to all patients. No serious local sequellae were encountered from mastectomy or radiotherapy, but complications of chemotherapy were numerous, particularly in irradiated patients. One death due to toxicity occurred after preoperative chemotherapy. The results to date suggest that in irradiated patients metastases may become enhanced and that their local disease is not more effectively controlled than in patients not having radiotherapy. Two factors may have been largely responsible for the differences observed between the two groups: the delay of chemotherapy in irradiated patients and the sustained immunosuppression known to occur after mediastinal radiotherapy.