Circulating autoantibodies in patients with fibrocystic disease of the breast.

Antinuclear, parietal-cell, smooth-muscle, mitochondrial, and adrenal antibodies were determined in the blood serum of 110 patients with fibrocystic disease of the breast and of 102 healthy blood donors by indirect immunofluorescence. Thirty-eight percent of the patients had detectable autoantibodies compared to 16% of the controls (P less than 0.001). Significant differences were found in the incidence of parietal-cell and smooth-muscle autoantibodies between the patients and controls. In addition, more than one autoantibody was detected in the serum of a significantly larger number of patients than controls. The findings indicate that an immunologic mechanism is involved in the pathogenesis of fibrocystic disease of the breast.

Multicentricity in breast cancer. A study of 366 cases.

A total of 366 consecutive modified radical mastectomy specimens were studied for determination of multicentricity. The authors found that 187 samples (49.1%) were multicentric. Ten specimens contained in situ carcinoma without an infiltrating component; eight of them were multicentric. Multicentricity was correlated with various laboratory and clinical features, including patient age, tumor size, histologic type of breast cancer, tumor grade, presence and values of estrogen and progesterone receptors, the amount of solid tissue in the breast, and the family history. The data were organized in eight independent dimensions, four ordinal and four cardinal. Correlation analysis was applied to a cross tabulation supplemented with other statistical tests. The authors found that the factors related to multicentricity were the age of the patient, the size and the histologic type of the tumor, levels of the progesterone receptors more than 50 fmol/mg of protein, and the amount of solid tissue in the breasts. Tumor grade, estrogen receptors levels, and family history were not related to multicentricity. It was concluded that multicentricity is a frequent property of breast cancer. It is more common in young and perimenopausal women. Multicentricity occurs in small tumors but is, more common in larger ones.

Prognosis of mammary carcinoma in young women.

One hundred and sixty-two women with carcinoma of the breast, age 40 years or younger, were treated from 1950 to 1969. Mammary cancer is not uncommon in this age group. The 5 year survival rate among our operable patients was about 50 percent. The 5 year survival rate among patients 20 to 35 years of age was slightly higher than that in patients 36 to 40 years old. In stage B and more advanced breast cancer in young women, the outlook was poorer than in women 41 years and older. When axillary involvement is present during gestation or in the immediate postpartum period, the prognosis is especially poor. Young women have an unusually high proportion (35 percent) of low-grade, infrequently metastasizing tumors, such as medullary, intraductal, papillary, and lobular carcinomas. The presence of cancer in the axillary nodes at operation is the most important factor affecting prognosis in mammary cancer. From this study we can see no reason to consider carcinoma of the breast in young women a more lethal disease than that seen in their older counterparts.

Changes of chromosomes 1, 3, 6, and 11 in metastatic effusions arising from breast and ovarian cancer.

This cytogenetic study deals with cell material obtained from 15 pleural fluids from 11 patients with breast cancer and 27 ascitic fluids from 16 patients with ovarian cancer; in addition, 8 pleural, 5 ascitic, and 1 pericardial fluid from patients with tuberculosis, liver cirrhosis, and heart insufficiency, were studied. Using mainly direct methods, as well as short-term cell cultures, the chromosome spreads were GTG-banded. Cancerous biopsies showed a plethora of numerical and structural chromosome anomalies and exhibited broad aneuploidy. Chromosomes participating more often in numerical and structural aberrations were 1, 3, 6, 7, 8, 9, 11, 12, and 17. This study provides further cytogenetic evidence for the involvement of these chromosomes in breast and ovarian malignancy.

A feasibility study of 1-h paclitaxel infusion in patients with solid tumors.

The optimal schedule for paclitaxel administration has not yet been determined. This phase I/II study was carried out to evaluate the safety of paclitaxel administration by 1-h infusion in the outpatient setting. A total of 43 patients with advanced pretreated malignancies (18 breast, 18 ovarian, and 7 non-small-cell lung cancers) received at least 2 cycles of paclitaxel given at 175 mg/ m2 in a single dose by 1-h i.v. infusion. This protocol was repeated every 21 days. All patients were premedicated as follows: promethazine given i.m. at 50 mg, dexamethasone given at 16 mg in 250 ml normal saline by i.v. infusion for 20 min and ranitidine given i.v. at 50 mg in 250 ml normal saline over 15 min, all premedication being carried out 1 h before the paclitaxel infusion. In a total of 156 cycles, only 1 patient presented with a hypersensitivity reaction (grade 2 urticaria in 1 cycle) and another patient developed transient facial flushing (in 1 cycle: this was resolved by slowing of the infusion rate) on this schedule of paclitaxel administration. Other adverse side effects were usually mild and well tolerated. Alopecia was universal; myelosuppression was uncommon because our patients were supported with granulocyte colony-stimulating factor (G-CSF, lenograstim) given at 34 IU/day in the presence of a neutrophil count of < 500 microliters; neutropenia was seen in 50/156 (32%) cycles and was mild. Neurotoxicity was the most serious adverse effect, and all patients experienced mild to severe neuro-muscular toxicity, mainly in the form of peripheral sensorimotor neuropathy and myalgias. In conclusion, 1-h paclitaxel administration is safe and reduces the duration of treatment, making its use more convenient and easy in the outpatient setting. A prospective comparison of 1-h versus 3-h paclitaxel infusion in terms of efficacy and toxicity is the subject of our current randomized study.

Carcinosarcoma of the submandibular salivary gland.

We report a rare case of submandibular salivary gland carcinosarcoma ('true' malignant mixed tumour) which occurred in a 77-year-old man. Microscopic examination showed a neoplasm comprised of sarcomatous elements (chondrosarcoma, rhabdomyosarcoma and osteosarcoma) with tabular salivary ductal adenocarcinoma. A short review of the literature is also presented and the poor prognosis of these tumours, in spite of complete surgical removal and additional radiation therapy and chemotherapy, is discussed.

Autoimmune thyroid disease in women with breast carcinoma.

AIMS: Estimation of prevalence of autoimmune thyroid disorders in Greek breast cancer patients (prospective study). METHODS: The prevalence of autoimmune thyroiditis was estimated in 310 Greek breast cancer patients, in 100 women with benign breast disease and in 190 women without any breast disease, by submitting them to clinical examination, ultrasound thyroid evaluation, serum thyroid antibody determination and fine needle aspiration (FNA) of the thyroid gland. RESULTS: Autoimmune thyroiditis was found in 136/310 (43.9%) breast cancer women: 95 were diagnosed by positive autoantibodies, 19 had positive FNA findings and 22 had both positive autoantibodies and positive FNA findings. In 117 cases, thyroid autoantibodies were positive (37.7% whereas the control groups had respective rates of 19% and 18.4% autoantibody positivity). CONCLUSIONS: There is evidence of high incidence of autoimmune thyroiditis in Greek breast cancer patients, increasing in relation to cancer stage.

Nitric oxide and peroxynitrite production by human erythrocytes: a causative factor of toxic anemia in breast cancer patients.

In the present study we demonstrated that human erythrocytes possess a NO synthase (NOS) that can be activated by oxidative stress and Ca2+ accumulation to produce nitric oxide (NO), and that this activation could be involved in the pathogenesis of toxic anaemia in breast cancer patients. By causing oxidative stress in human erythrocytes with hydrogen peroxide (H2O2) (100 microM), or by increasing the intracellular calcium concentration using various doses (up to 100 microM) of the calcium ionophore A23187, a gradual increase in both NO and peroxynitrite (ONOO-) release that was inhibited by N-monomethyl-L-arginine (L-NMMA) (1mM) was observed. Time-dependent experiments using hemolysates showed a linear rise of NO production which was elevated by 60% in the presence of superoxide dismutase (SOD) (100 U). NOS isolated from hemolysates was constitutively expressed and was dependent on NADPH, Ca2+/calmodulin, tetrahydrobiopterin and flavins. In reconstitution experiments, when purified NOS, isolated from erythrocytes, was added to purified soluble guanylate cyclase (sGC), isolated from endothelial cells, in the presence of the appropriate cofactors and substrates, a linear increase in cGMP production at various concentrations (up to 50 microM) of H2O2 was observed. Furthermore, it was shown that erythrocytes from breast cancer patients were subjected to higher oxidative stress by ONOO- (100 microM), with a consequential increase of membrane rigidity, than erythrocytes from healthy individuals. Such mechanic changes may result in shortening of the lifespan of erythrocytes, a feature of toxic anemia in cancer patients.

Alterations of the 16q22.1 and 16q24.3 chromosomal loci in sporadic invasive breast carcinomas: correlation with proliferative activity, ploidy and hormonal status of the tumors.

BACKGROUND: Breast cancer is characterized by complex genetic alterations found in multiple chromosomal regions, most commonly losses of 17p, 16q, 8p and others. A number of tumor suppressor genes mapped on these loci have been investigated in mammary tumors, whereas other gene products are of unclear function and await identification. MATERIALS AND METHODS: We analyzed the loss of heterozygosity (LOH) of two chromosomal loci: a. 16q24.3 using the genetic markers D16S303, D16S3026 and D16S3407 and b. 16q22.1, the locus of E-cadherin gene, using the microsatelite markers D16S503, D16S752 and D16S512, in a series of 63 sporadic invasive breast carcinomas consisting of 56 ductal, 4 lobular and 3 tumors of mixed type. Our findings were correlated with proliferative activity, ploidy and hormonal status of the tumors. RESULTS: Fourteen (22.2%) tumors demonstrated LOH of 16q24.3. Allelic imbalance of the 16q22.1 locus was found in 19 of 61 informative cases (31%) and commonly coexisted with LOH of 16q24.3. A significant association was observed between LOH of D16S752 and the absence of progesterone receptors in tumor cells (p = 0.005). CONCLUSIONS: LOH of 16q24.3 and 16q22.1 are frequent genetic alterations in breast cancer and they do not seem to correlate with tumor cell proliferation or ploidy. The statistical association between LOH of 16q24.3 and progesterone receptors need to be further investigated in larger series.

The prognostic value of alpha-thymosins in breast cancer.

The prognosis of breast cancer is of major clinical importance and several histopathological, biochemical and immunological variables have been reported to be useful prognostic factors. In the present study, we investigated the clinical significance of the levels of alpha-thymosins in relation to established prognostic factors, both in breast cancer and non-malignant breast lesions, alpha-thymosin levels were measured in breast tissue extracts by specific radioimmunoassays (RIAs) developed for human prothymosin alpha (ProT alpha) and parathymosin alpha (ParaT alpha) and were found to be significantly higher (up to 17.2-fold) in malignant but not in benign breast lesions, as compared to the values of the neighbouring tissues. When alpha-thymosin levels of the tumor samples were correlated with various known prognostic parameters a statistically significant correlation (p < 0.05) was observed between the levels of ProT alpha in malignant tissues to the grade of cancer and the lymph node status of the patient. An association between ProT alpha levels with increase in risk of death from breast cancer was also noticed. These results suggest that the expression of alpha-thymosins in human breast cancer a) depends on the proliferation status of the tumor, b) associates with established prognostic factors describing the metastatic potential of the tumor and c) is related to the overall survival of the patient. The fact that such relationships hold only for cancer tissues encourages the future use of alpha-thymosins as potent prognostic factors in breast cancer.

Surgical management of diseases of the adolescent female breast: a clinicopathologic study.

Sixty-three patients, ages 10 to 20 years with diseases of the breast were operated on during a 10 year period. A variety of pathologic entities were found. The most common were diagnoses fibroadenoma, cystic disease, and cellulitis with abscess formation. Malignancy was found in three patients: lobular carcinoma in situ in one, angiosarcoma in the second, and lymphosarcoma in the third.

Cushing's syndrome. Analysis of 18 cases.

Eighteen patients with Cushing's syndrome were analyzed retrospectively. Eleven patients had diffuse or adenomatous hyperplasia, 5 an adenoma and 3 a carcinoma. Iodocholesterol scanning provides considerable help in localization of the disease. Surgical treatment, while curative for benign cases, affects only slightly the course of malignant disease.

Prediction of malignancy in solitary thyroid nodules in a country with endemic goiter.

From January 1962 through October 1975, 455 patients with single thyroid nodules were operated on at King Paul Hospital. Malignancy was proved in forty-three patients. The overall incidence of carcinoma was 9.5 per cent. A higher incidence of cancer was found in patients less than ten years of age (40 per cent), between eleven and twenty years of age (20 per cent), and more than sixty-one years of age (17.4 per cent). Malignant nodules were more frequent in males (17.5 per cent) than in females (8.3 per cent). Radioactive iodine scanning does not distinguish benign from malignant nodule. Solitary thyroid nodules require operative excision supplemented with replacement therapy.

Use of artificial neural networks (computer analysis) in the diagnosis of microcalcifications on mammography.

INTRODUCTION/OBJECTIVE: The purpose of this study was to evaluate a computer based method for differentiating malignant from benign clustered microcalcifications, comparing it with the performance of three physicians. METHODS AND MATERIAL: Materials for the study are 240 suspicious microcalcifications on mammograms from 220 female patients who underwent breast biopsy, following hook wire localization under mammographic guidance. The histologic findings were malignant in 108 cases (45%) and benign in 132 cases (55%). Those clusters were analyzed by a computer program and eight features of the calcifications (density, number, area, brightness, diameter average, distance average, proximity average, perimeter compacity average) were quantitatively estimated by a specific artificial neural network. Human input was limited to initial identification of the calcifications. Three physicians-observers were also evaluated for the malignant or benign nature of the clustered microcalcifications. RESULTS: The performance of the artificial network was evaluated by receiver operating characteristics (ROC) curves. ROC curves were also generated for the performance of each observer and for the three observers as a group. The ROC curves for the computer and for the physicians were compared and the results are:area under the curve (AUC) value for computer is 0.937, for physician-1 is 0.746, for physician-2 is 0.785, for physician-3 is 0.835 and for physicians as a group is 0.810. The results of the Student's t-test for paired data showed statistically significant difference between the artificial neural network and the physicians' performance, independently and as a group. DISCUSSION AND CONCLUSION: Our study showed that computer analysis achieves statistically significantly better performance than that of physicians in the classification of malignant and benign calcifications. This method, after further evaluation and improvement, may help radiologists and breast surgeons in better predictive estimation of suspicious clustered microcalcifications and reduce the number of biopsies for non-palpable benign lesions.

Breast masses in young girls. Report of five cases.

The pubertal breast may be the seat of lesions comparable to those of the adult female breast. Of the five girls referred to in this report, aged 11 to 15 years, three had fibrocystic disease, one had a huge intracystic papilloma and the last one had multiple papillomas. The two girls with fibrocystic disease and the one girl with multiple papillomas had a family history of breast cancer which had appeared in their grandmothers. The possible relationship between the breast diseases of the two generations is discussed.

Amount and distribution of solid and fatty tissues in the female breast and their relationship to carcinoma.

The study is based on 112 consecutive mastectomy specimens with carcinoma. Breasts were grossly divided into three basic types: solid, when showing a sizable cone of solid tissue (mammary tissue and fibrous stroma), fatty when almost completely replaced by fat, and intermediary types Ia and Ib. It appears that these types represent stages of an evolutionary process involving the anatomical structure of the breast during life. Mammary alterations gradually lead to lobular atrophy. Generalized lobular atrophy characterizes mainly fatty breasts. Lesions of fibrocystic disease are frequent in breasts of all types. In all three types of breast carcinomas were more frequently located in the outer portion of the breast. Rare locations of carcinomas are associated with the type of breast: a central location is more frequent in fatty, an inner location in intermediary and a diffuse in solid breasts. In fatty breasts irregular tumors are common while in solid breasts tumors without clear borders appear to develop. Multicentric carcinomas were much more frequent in solid breasts than in the other types of breasts. Most multicentric carcinomas are accompanied by multicentric carcinoma in situ. Infiltrative lobular and mixed (lobular-ductal) carcinomas are accompanied by lobular carcinoma in situ, lobular cancerization or both. In infiltrative ductal and the special types of carcinomas the histology of carcinoma in situ differs according to whether or not the infiltrative tumor is single or multicentric. The difference concerns the complete lack of lobular cancerization from cases with single infiltrative tumors.

Fibrocystic disease of the breast and HLA antigens.

One hundred and ten patients with fibrocystic disease of the breast and 200 controls were HLA typed with a panel of 100 antisera for A and B locus. The main finding was the decreased frequency of BW35 antigen among patients compared to the controls. The difference remained significant in patients with the fibrous type of the disease and in patients of the nulliparous group. In addition the last group of patients showed a significant increase of All antigen.

Functioning metastatic parathyroid carcinoma.

A case of 53-year-old woman with a parathyroid adenoma and a parathyroid carcinoma with functioning metastases to the lungs, mediastinum and pleura is reported. The administration of inorganic phosphate solution failed to control hypercalcemia. The therapeutic methods available to deal with metastases are discussed.

Medullary carcinoma of the thyroid gland.

Nine cases of medullary carcinoma of the thyroid gland (MTC) are reported. Four of the carcinomas were of the familial type. Five of the patients were men and four were women. Patient age ranged from 23 to 66 years, with a mean age of 40 years. The median age of the four patients with the familial MTC was 32 years. A total or a subtotal thyroidectomy was performed in four and five patients, respectively, associated with a modified neck dissection in six patients with involved cervical lymph nodules. An underlying pheochromocytoma of the left adrenal was excised in one patient prior to thyroidectomy. In all cases the parathyroid glands were identified, and in two cases of familial MTC, in which they were grossly enlarged, the parathyroid glands were removed. Four patients died as a result of their disease within 3 years, whereas patients are well 4 to 12 years after surgery. The best chance of cure lies in early diagnosis and an aggressive surgical removal of the primary tumor and any cervical metastases.

Bilateral breast cancer.

Seventy-eight confirmed cases of second primary breast cancer in the contralateral breast were encountered over a 22-year period in 1332 women with invasive breast cancer treated in our department. Tumors were grouped into those simultaneously detected in both breasts or within 6 months of each other (synchronous, 1.6%) and those detected within more than 6 months (metachronous, 4.2%). The mean interval between metachronous cancers was 117 months. Patients with bilateral tumors were more likely to have a family history of breast cancer than those with unilateral disease. Women with metachronous tumors tended to be younger when diagnosed with the first carcinoma as compared with those having unilateral or synchronous bilateral cancers. No differences were noticed in size and lymph node status between the first or second tumor of bilateral cases in comparison to patients with unilateral disease. Significantly more (P < 0.05) first metachronous tumors were found to be lobular invasive cancers. Histopathologic type of the first tumor was the same as the second in 62.8 per cent of all cases. Concordance of estrogen receptor status between bilateral tumors was 71.4 per cent. Our results indicate that the risk of developing, a contralateral breast cancer is related to the patient's age, family history of breast cancer, and lobular histology of the tumor.