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OBJECTIVE--Metformin has been associated with a reduction in breast cancer risk and may improve survival after cancer through direct and indirect tumor-suppressing mechanisms. The purpose of this study was to [...]

Substantial observational epidemiological evidence exists that physical activity and weight control are associated with decreased risk of postmenopausal breast cancer. Uncertainty remains regarding several aspects of these associations, including the effect of possible confounding factors on these associations. We present the rationale and design for two randomized controlled trials that can help resolve this uncertainty. In a 5-year prevention trial conducted among women at high risk of breast cancer, the primary endpoint would be breast cancer incidence. For a comparable survivorship trial, the primary endpoint would be the disease-free interval and secondary endpoints would be breast cancer recurrence-free interval, second primary breast cancer, and total invasive plus in situ breast cancer. A set of inclusion and exclusion criteria is proposed for both trials. Intervention goals are the same for both trials. Goals for the weight control intervention would be, for women whose body mass index (BMI) is greater than 25 kg/[m.sup.2], to lose 10% of body weight and, for women whose BMI is less than or equal to 25 kg/[m.sup.2], to avoid weight gain. The goal for the physical activity intervention would be to achieve and maintain regular participation in a moderate-intensity physical activity program for a total of 150-225 minutes over at least 5 days per week. Sample size calculations are based on alternative assumptions about hazard ratio, adherence, follow-up duration, and power and are presented for the primary prevention and survivorship trials. Although both studies could enhance our understanding of breast cancer etiology and benefit public health, practical considerations, including smaller sample size, ease of recruitment, and reduced likelihood of early termination, favor the survivorship trial at this time.

Measurement of health-related quality-of-life (HRQOL) in randomized clinical trials in breast cancer has become common. In this review, we take stock of the contribution that HRQOL measurement in breast cancer clinical trials makes to clinical decision making regarding selection of optimal treatment. A series of MEDLINE searches was conducted to identify all randomized trials in breast cancer that included self-reported HRQOL or psychosocial outcomes. A total of 256 citations were identified that included HRQOL or psychosocial outcomes in breast cancer patients, and 66 of these involved randomized clinical trials of treatment. These 66 reports of breast cancer clinical trials of treatment are discussed in this review. Forty-six of the trials evaluated biomedical interventions, and 20 evaluated psychosocial interventions. Among the biomedical trials, eight trials evaluated HRQOL in primary management of breast cancer, seven trials evaluated HRQOL in adjuvant therapy of breast cancer patients, 20 trials involved metastatic breast cancer, eight trials involved symptom control/supportive care, and three trials evaluated different approaches to investigation or follow-up of breast cancer patients. Among the psychosocial trials, 13 trials evaluated HRQOL in adjuvant therapy of breast cancer patients, and their partners or spouses, six trials involved metastatic breast cancer, and one trial focused on symptom control. We found that the contribution of HRQOL measurement to clinical decision making depended on the clinical setting. In primary management of breast cancer, where medical outcomes of several treatment options are equivalent, HRQOL measurement provided added information for clinical decision making beyond that of traditional medical outcomes. In trials in the adjuvant setting, HRQOL measurement did not influence clinical decision making. In metastatic disease, HRQOL outcomes provided little information beyond that obtained from traditional medical outcomes, including toxicity. In the symptom control/supportive care setting, results of HRQOL questionnaires targeting specific symptoms (e.g., emesis) guided treatment decisions. In psychosocial intervention trials, psychosocial and/or HRQOL measurements often provided the only outcome information; therefore, selection of instruments that captured attributes likely to be altered by the intervention was essential. Until results of ongoing trials in breast cancer are available, caution is recommended in initiating new HRQOL studies unless treatment equivalency is expected, or unless the HRQOL questions target unique or specific issues that can only be addressed through patient self-report, including outcomes of psychosocial interventions.

Stanley ambled into the interview room for his 3 o'clock appointment, sliding the box of smokes back into his pocket and looking across at me expectantly. As usual, he kept [...]

A high-fat diet may contribute to cyclic mastopathy. This condition is characterized by breast swelling, tenderness and pain during the last phase of the menstrual cycle. Researchers measured blood levels of fat in 34 women with severe cyclic mastopathy and 29 women without this condition. The women with cyclic mastopathy had elevated blood levels of high-density lipoprotein cholesterol during the symptomatic phase compared to the other women. Their dietary fat intake was also greater at all times compared to the other group.

Women who experience breast abnormalities at certain times of their menstrual cycle may also experience more severe premenstrual syndrome (PMS). Researchers compared 34 women with severe abnormal breast symptoms to 29 women with normal breast symptoms during one menstrual cycle. Women with abnormal breast symptoms were more likely to seek medical attention for breast lumpiness and breast problems. They received mammograms, breast biopsies, and breast needle aspirations more often than did women with normal breast symptoms. Women with breast abnormalities had more severe PMS including water retention, emotional and behavior changes, and lack of concentration.

A retrospective review of data on patients entered on two limited small cell lung cancer studies of the National Cancer Institute of Canada (BR.3 and BR.6) was undertaken to determine [...]

This article examines methods to identify and classify woman abusers among the prison population, focusing on the need for batterer screening and treatment in US prisons. Topics include the personality and behavioral aspects of men who use physical violence against women.

Previously published at www.cmaj.ca He sits expectantly, eyes fixed on me. The wall clock ticking over his head reminds us both that he needs to be on his way. I [...]

Coronary artery bypass grafting is a surgical procedure to restore the circulation of blood through the coronary arteries, those which nourish the heart, by the removal of areas of obstruction due to atherosclerosis, or hardening of the arteries. All too often these areas again become obstructed by the presence of blood clots. By the 10th year following their 'bypass' operation as many as 40 to 50 percent of all patients experience re-closure of their coronary vessels. The current report describes the preliminary results of the injection of urokinase, a thrombolytic or clot-breaking therapy, into the area of the blockage through a catheter (a tube) inserted into a peripheral vein and passed through the circulatory system. In all three patients chest pain occurred six to eight hours after the initiation of the urokinase infusion and was related to changes in the electrocardiogram (ST elevation). Following the urokinase infusion the patients underwent an additional X- ray examination (angiogram) to view the vessels of the heart. All three patients had some break-down of their clots, but significant stenosis remained. The evidence suggests that there is risk of precipitating a myocardial infarction when attempts are made to inject urokinase by catheter. This risk appears to be related to the incomplete removal of the clot and the possibility that small fragments of it may block small blood vessels of the heart muscle itself (microembolization). Before this method is applied further, the risks and the possible benefits need to be more completely researched.

Background: Breast carcinomas occurring in carriers of BRCA1 gene mutations may have a distinctly different pathway of molecular pathogenesis from those occurring in noncarriers. Data from murine models implicate loss of p53 (also known as TP53) gene function as a critical early event in the malignant transformation of cells with a BRCA1 mutation. Therefore, breast tumors from BRCA1 mutation carriers might be expected to exhibit a high frequency of p53 mutations. This study examined the frequency of p53 mutations in the breast tumors of Ashkenazi Jewish carriers and noncarriers of BRCA1 mutations. Methods: Tumor DNA from carriers and noncarriers of BRCA1 mutations was screened for mutations in exons 4 through 10 of the p53 gene by use of the polymerase chain reaction and single-strand conformation polymorphism (SSCP) analysis of the amplified DNA. Direct sequencing was performed on gene fragments that showed altered mobility in SSCP analysis. Results: Mutations in the p53 gene were detected in 10 of 13 tumors from BRCA1 mutation carriers versus 10 of 33 tumors from noncarriers (two-sided P = .007). The p53 mutations were distributed throughout exons 4 through 10 and included both protein-truncating and missense mutations in both groups. Conclusions: A statistically significantly higher frequency of p53 mutations was found in breast tumors from carriers of BRCA1 mutations than from noncarriers, which adds to the accumulating evidence that loss of p53 function is an important step in the molecular pathogenesis of BRCA1 mutation-associated breast tumors. This finding may have implications for understanding phenotypic differences and potential prognostic differences between BRCA1 mutation-associated hereditary breast cancers and sporadic cancers. [J Natl Cancer Inst 1999;91:469-73]