We have studied the genomic organization of the c-myc locus (MYC) from 121 human primary breast carcinomas. Two types of alterations were observed: (i) the c-myc protooncogene appeared to be amplified 2-to 15-fold in 38 (32%) of the carcinoma DNAs and (ii) a non-germ-line c-myc-related fragment of variable size was detected in 5 primary breast carcinoma DNAs. With three exceptions, all the tumors containing a genetic alteration of the c-myc locus were invasive ductal carcinomas. A significant correlation (P < 0.02) was observed between patients more than 50 years old and the presence of a genetically altered c-myc. Enhanced levels of c-myc RNA were observed in 10 of 14 breast carcinomas examined. The c-myc gene was genetically altered in 6 of these 10 tumors. The frequency with which the c-myc gene is altered and its correlation with age suggest that it may play a role in the development of breast carcinomas.Human breast cancer is a complex of neoplastic diseases that vary in histological appearance and biological behavior such as potential for invasiveness and metastasis (1). Several epigenetic factors may influence the development of malignant breast tumors, including hormonal status, age of the patient, frequency of successful pregnancies, and presence of hormone receptors on the tumor cells (2). In addition, certain families have a high incidence of breast cancer, which suggests an inherited predisposition to breast tumor development (3). At present, however, little information is available on the nature of the genetic changes that contribute to the development or progression of primary breast carcinomas.

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Care of cancer patients may be a source of considerable stress. As part of a large scale longitudinal study of the interaction of biological, psychological and environmental factors in determining patient outcome, the mental and physical health status of 37 members of the nursing staff of a cancer hospital was examined. The study identifies risk factors for stress, professional 'burn-out' and psychiatric morbidity. An assessment questionnaire also examined work time, work organization, relationships with colleagues, identification of stressful situations, and treatment of pain. Each subject completed three scales designed to measure stress and psychiatric morbidity: the Nursing Stress Scale, the Maslasch Burnout Inventory and the General Health Questionnaire. Item analysis suggested that stress is primarily related to inadequate training, lack of time to deal with the psychological component of care giving especially terminal care, and relationship difficulties with other medical staff. Multiple analysis of correspondence indicated that in the face of stress, risk factors for professional burnout are high psychiatric symptomatology, lack of information at the time of diagnosis, poor perceived health, relationship difficulties with patients and their families, and work uncertainties.

, et al.. Onset and relapse of psychiatric disorders following early breast cancer: a case-control study.: Mental health of primary breast cancer survivors.

The c-Ha-ras-1 locus in 104 breast cancer patients and 56 unaffected individuals was examined for allelic restriction fragment-length polymorphism. Four common and 16 rare alleles were detected in the combined populations. The distribution of common and rare alleles differed significantly between the two populations. The common restriction fragments represented 91% of the allele pool in the unaffected population. In breast cancer patients, these common alleles represented only 59% of the allele pool (P less than .001). More specifically, the frequency of two of the common fragments, the 6.5- and 8.0-kilobase alleles, was significantly diminished in the breast cancer population (P less than .001 and P less than .02, respectively). The frequency of rare c-Ha-ras-1 alleles and hence genotypes composed of two rare alleles was increased in the breast cancer population (P less than .001). One of the rare alleles had a significant (P less than .05) association with these breast cancer patients. These results suggest that genotype analysis of the c-Ha-ras-1 locus, in combination with other clinical parameters, may be of prognostic value in assessing the potential for cancer.

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In human skin, most studies have suggested a role of cfos or c-fos related genes in keratinocyte dierentiation. The aim of our work was to more directly address this question by transfecting more or less dierentiated keratinocyte cell lines (A431 and HaCaT) with constitutive expression vectors for c-Fos or c-Fos+c-Jun. Our results showed that c-Fos expression decreased keratinocyte growth, yet addition of c-Jun seemed to revert this c-Fos induced growth inhibition. Whereas no obvious dierentiation program was turned on by c-Fos or c-Fos+c-Jun expression in our tissular model, apoptotic ®gures were observed and con®rmed by in situ DNA fragmentation studies. These results do not rule out a role of c-Fos in keratinocyte dierentiation but may indicate that the cell lines we used have reached an irreversible state of transformation so that they no longer respond to dierentiation signals and rather die from apoptosis. These data add further evidence in favor of a role of c-Fos in epidermal homeostasis.

We have shown previously that fatty acid synthetase (FAS) is specifically induced by progestins in human breast cancer cell lines. To test the potential value of FAS as a clinical marker in breast diseases, we measured FAS expression in frozen sections of 22 benign and 27 malignant mammary tumors using in situ hybridization with the [35S]UTP alpha S-labeled FAS anti-sense mRNA. The hybridized RNA was quantified with an IMSTAR computerized image analyzer. We found FAS RNA in epithelial cells, but no labeling was detected in the connective tissue. In breast cancer, we found no correlation between FAS expression and estrogen receptor and progesterone receptor concentrations or status. However, the level of FAS was significantly (P less than .02) higher in premenopausal than in post-menopausal patients and increased with the grade of tumor differentiation (P less than .005 between the poorly and well-differentiated tumors). In benign mastopathies, high levels of FAS RNA were found in some cysts (mostly with apocrine metaplasia). In lobules, the FAS RNA level increased proportionally to the degree of proliferation determined by histological examination (P less than .015) and correlated with the H4 histone level measured in an adjacent section using in situ hybridization (r = 0.85, P less than .001). In ductal structures, a lower correlation (r = 0.64, P less than .01) was found between FAS and H4 RNA levels. We conclude that FAS RNA is overexpressed in some mammary tumors and may be useful in predicting high-risk mastopathies and less aggressive breast cancers.