Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C). Gross respiratory tract lesions and standard lung and nasal sections were evaluated by light microscopy. A slight reduction of survival suggested that the HS level was at the maximum tolerated dose as commonly defined. Cigarette smoke exposure significantly increased the incidences of non-neoplastic and neoplastic proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas and carcinomas in females were: HS = 14%; LS = 6%; and C = 0%. These incidences represented minima because only standard lung sections and gross lesions were evaluated. Mutations in codon 12 of the K-ras gene occurred in 4 of 23 (17%) tumors. Three mutations were G to A transitions and one was a G to T transversion. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders). These results demonstrate that chronic whole-body exposure of rats to cigarette smoke can induce lung cancer.     

Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute's Surveillance, Epidemiology, and End Results database

BACKGROUND: Breast carcinomas in African-American patients appear to be more aggressive than in Caucasian patients due to multifactorial differences. METHODS: The authors compiled pathology data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database regarding stage, histologic grade, and estrogen receptor (ER) expression in breast carcinomas diagnosed in 197,274 African-American and Caucasian patients between 1990 and 2000, and the same information, along with nuclear grade, Ki-67, c-erb-B2, and p53 expression, in 2230 African-American and Caucasian patients diagnosed at Thomas Jefferson University Hospital between 1995 and 2002. Immunohistochemical markers were assayed in paraffin-embedded, formalin-fixed tissue stained with hematoxylin and eosin using antibodies to these proteins, with differences in expression analyzed by the chisquare test. RESULTS: In both databases, more African-American patients presented with advanced stage tumors and higher histologic (P < .001) and nuclear grade (P < .001) than Caucasian patients. African-American patients had less ER positivity (51.9% vs 63.1%; P < .001) but significantly higher Ki-67 (42.4% vs 28.7%; P < .001) and p53 expression (19.4% vs 13.1%; P < .05) than Caucasian patients with all stages of disease. In addition, the basal or "triple-negative" breast cancer phenotype was more common in African-American patients than in Caucasian patients (20.8% vs 10.4%; P < .0001), and was associated with higher histologic and nuclear grade (P < .0001). CONCLUSIONS: African-American patients with breast carcinomas are more likely than Caucasian patients to present with tumors that are of a later stage and higher grade, with higher Ki-67 expression and more ER negativity, thereby highlighting a greater need for early screening among African-American women. Molecular studies that may explain these differences, and correlations with survival, have been proposed to identify therapeutic targets.     

The effect of combined modality therapy on local control and survival

The systemic component of combined modality therapeutic programs has influenced both the selection of the approach to local control and survival in a number of tumor types. The more effective systemic therapy is against metastatic cancer by itself, the greater the impact on local control and survival. This observation is consistent with the invariable inverse relationship between curability and tumor cell number. For some common cancers, local control is good, but survival remains poor because of the inability to deal effectively with micrometastases. Improved systemic treatment is likely to have an impact on survival may shift local control measures, in some cases, to radiation therapy or lesser surgery without radiation therapy. There remains a substantial number of tumor types where both local control and survival is poor. In these tumors, improvement in local control by itself is not likely to improve survival because of the presence of micrometastases, but such improvements must occur before we can have a true evaluation of the systemic treatment of micrometastases in these tumors. The recent understanding that the metastatic process is under genetic control and the cloning of metastases genes offers a substantial opportunity to control this process and influence both local control and survival.