Stress, depression, the immune system, and cancer

The links between the psychological and physiological features of cancer risk and progression have been studied through psychoneuroimmunology. The persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis in the chronic stress response and in depression probably impairs the immune response and contributes to the development and progression of some types of cancer. Here, we overview the evidence that various cellular and molecular immunological factors are compromised in chronic stress and depression and discuss the clinical implications of these factors in the initiation and progression of cancer. The consecutive stages of the multistep immune reactions are either inhibited or enhanced as a result of previous or parallel stress experiences, depending on the type and intensity of the stressor and on the animal species, strain, sex, or age. In general, both stressors and depression are associated with the decreased cytotoxic T-cell and natural-killer-cell activities that affect processes such as immune surveillance of tumours, and with the events that modulate development and accumulation of somatic mutations and genomic instability. A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to new clinical and treatment strategies.     

Inflammatory breast cancer: the disease, the biology, the treatment

Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy.     

Tobacco, alcohol, diet, occupation, and carcinoma of the esophagus

Information on occupation, smoking, food and beverage consumption, and medical history were compared between 275 incident cases of carcinoma of the esophagus and 275 neighborhood controls who were matched to the cases on age (within 5 years), race, and sex. Tobacco use, mainly cigarette smoking, was a significant risk factor for carcinoma of the esophagus. Ex-smokers of cigarettes showed a reduced risk relative to those who continued to smoke, and current smokers of two or more packs per day displayed a higher risk than those who smoked less. Alcohol consumption was another significant risk factor for carcinoma of the esophagus; there was a highly significant trend with average daily dose of ethanol. Relative to controls, cases also consumed significantly more fried bacon or ham, less fresh fruits and raw vegetables, and were more likely to prefer white than whole grain bread. Finally, there was a significant association between carcinoma of the esophagus and long-term occupational exposure to metal dust; this association was largely confined to the lower one-third section of the esophagus.     

Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide in the treatment of small cell carcinoma of the ovary

This report presents five adolescent girls and adult women with small cell carcinoma of the ovary (SCCO) who were treated with a polychemotherapy regimen consisting of vinblastine, cisplatin, cyclophosphamide, bleomycin, Adriamycin (doxorubicin), and etoposide (VPCBAE). Two patients had Stage IA, one Stage IIC, and two Stage IIIA disease. Initial therapy consisted of unilateral salpingo-oophorectomy in two cases and total abdominal hysterectomy and bilateral salpingo-oophorectomy in three cases. Three patients remained clinically free of disease after six courses of VPCBAE and the two patients who had measurable pelvic disease before the administration of chemotherapy had objective responses. Four patients died of disease from 11 to 18 months after initial laparotomy. One patient is alive and disease-free at 29 months. The VPCBAE combination appears to be effective in select cases of SCCO. A study of the efficacy of VPCBAE in a larger group of patients with SCCO seems to be indicated.     

Intensity-modulated radiation therapy: the inverse,the converse,and the perverse

Intensity-modulated radiation therapy (IMRT) is a refinement of current radiotherapy techniques rather than a major breakthrough. The term IMRT includes several different techniques that all share with classical arc therapy the principle of using multiple fields to reduce the dose to normal tissues, but integrating to a higher dose throughout the tumor volume itself. This paper reviews not only the putative upside but also the downside of the development of IMRT. Theoretical, practical, and cost considerations, both positive and negative, are discussed. There are several issues to be considered, but the most important perversely predict a significant increase in radiation-induced neoplasms, resulting not only from larger volumes of tissue exposed to more modest but still mutagenic doses, but also from a significant increase in total body dose from leakage, because the beam is typically on for a considerably longer period of time than is conventional. A plea is made for radiation oncologists to maintain a strong biologic and cellular orientation as oncology rapidly becomes more molecular in its orientation.     

Diet, cancer, and the lipidome.

The potential for dietary fat to interfere with the development of breast cancer by delaying its occurrence makes the identification of defined molecules a mandatory step in cancer prevention. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, biomarkers of past lipid intake such as the fatty acid composition of white adipose tissue have been used. When considered separately, candidate fatty acids identified as favorable on the basis of their association with breast cancer risk have usually led to inconsistent results in animal intervention studies. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions which finally determines the lipidome, the lipid profile that is found in individuals. This article presents a reappraisal of the role of the lipid profile through a comprehensive reanalysis of adipose tissue fatty acid composition obtained in patients with benign or malignant breast tumors as well as in experimental animals during dietary interventions. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low omega6/omega3 fatty acid ratio was associated with breast cancer protection. This lipidome may become the template for identifying breast cancer risk related to diet, and for designing proper dietary modifications to delay the occurrence of breast cancer, although the universality of the findings cannot be assessed from a single study.     

Social inequalities in the incidence and case fatality of cancers of the lung,the stomach,the bowels,and the breast

Objective  In order to examine health inequalities in terms of incidences and case fatalities in a German health insurance population. Lung cancer, stomach cancer, intestinal carcinoma, and breast cancer were considered. Social differentiation was depicted by income and occupational position in order to examine which one is more strongly associated with incidence and case fatality. Methods  Analyses were performed using data from a statutory health insurance (n = 170,848). Incomes were divided into quintiles, and subjects were grouped according to occupational status. Results  For lung cancer incidence a gradient between the highest and the lowest 20% of the income distribution emerged. The relative risk of the lowest category was RR = 7.03, for occupational position the figure was RR = 6.98. For stomach cancer the relative risks were RR = 5.33 for income and RR = 7.11 for occupational position. For intestinal carcinoma only income was significantly related with incidence (RR = 4.37 for the lowest 20% of the income distribution), and for breast cancer incidence no social inequalities were found. For case fatality increased relative risks emerged for lung cancer, but only for income. Conclusions  Income and occupational position were associated with cancer incidence with the exception of breast cancer. Apart from lung cancer, case fatalities were unrelated to measures of social differentiation.