Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors.

PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83). CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.

Changes in the findings of dynamic MRI by preoperative CAF chemotherapy for patients with breast cancer of stage II and III: pathologic correlation.

Preoperative neoadjuvant chemotherapy is essential for treatment of patients with breast cancer who have a large tumor mass and/or regional lymph node involvement, in terms of both tumor shrinkage and further improvement of the survival rate. In order to safely perform breast-conservation treatment for these patients, a detailed diagnostic procedure for precisely evaluating the therapeutic response is needed. Dynamic magnetic resonance imaging (MRI) is thought to be important in the evaluation of responses to neoadjuvant therapy in patients with considerably large tumors, however, few studies have detailed the changes, as depicted by dynamic MRI, that can be expected with neo-adjuvant chemotherapy. The purpose of this study was to document the changes that occur in response to neoadjuvant chemotherapy and to correlate them with the pathological findings observed in the surgical specimen. The study was performed at Kochi Medical School Hospital from 1995 to 1998. The series consisted of 31 patients with stage II and III breast cancer. Prior to and after 1-5 courses of neoadjuvant chemotherapy, dynamic MRI examinations were performed. Eight of the time-intensity curves for the 10 grade 1a tumors flattened during neoadjuvant chemotherapy, while two remained the same. Six of the curves flattened for the 14 grade 1b tumors, 7 remained the same, and one spiked. And for the seven grade 2 tumors, two of the curves flattened and five remained the same (p=0.0340). In the five grade 1 tumors, the mean after/before normalized peak signal intensity ratio was 0.42+/-0.22. In the 18 grade 2 and 8 grade 3 tumors, the mean normalized signal intensity ratios were 0.59+/-0.28, 0.88+/-0.10, respectively (p<0.05). In the 15 tumors that showed shrinkage of the linear enhancement during neo-adjuvant chemotherapy, 10 had no remarkable intraductal spreading and 9 had a negative surgical margin. In the 16 tumors that had no shrinkage of the linear enhancement during chemotherapy, 13 had remarkable intraductal spreading and 12 had a positive surgical margin (p<0.05). It is concluded that dynamic MRI is a valuable tool for determining tumor response and predicting a positive surgical margin. Breast-conservation treatment can be performed for these patients by meticulous assessment using such detailed diagnostic procedures after local tumor control by combined chemotherapy with high dose-intensity.

Enhancement of BOP-induced pancreatic carcinogenesis in selenium-fed Syrian golden hamsters under specific dietary conditions.

We measured the effects of dietary selenium (Se) on pancreatic cancer induced in Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine (BOP). The animals were fed six experimental diets that contained different combinations of the following: 0.1, 2.5, or 5.0 ppm Se from sodium selenite or 2.5 ppm Se from D,L-selenomethionine in either a low (6.0%)- or high (24.4%)-fat diet. Se treatment was begun four weeks before BOP treatment, and the high-fat diet was fed from one week after the last BOP treatment. No evidence for inhibition of pancreatic cancer by Se was observed; in fact, with some experimental conditions, high-Se diets increased the pancreatic carcinoma yield. However, the dietary conditions needed for enhancement differed between the sexes. The male hamsters that received the high-fat diet containing 2.5 ppm Se had more carcinomas than did males given the 0.1 ppm Se level. Carcinoma yields in females did not differ between these diets. Females that received 2.5 ppm Se from D,L-selenomethionine had a greater pancreatic carcinoma yield that did those given 0.1 ppm Se diet. However, carcinoma yields did not differ in males fed these diets. Acinar cell nodule yields were generally reduced in hamsters given the high-Se diets, especially when Se levels in the high-fat diets were compared. Prefeeding 0.1 or 2.5 ppm Se did not influence the elution constants of pancreatic DNA from ductal cells, indicating no effect of Se on the repair of BOP-induced, single-strand breaks in DNA from these cells. Measurements in acinar cells suggested a more rapid repair of single-strand breaks in hamsters prefed 2.5 ppm Se than in those prefed 0.1 ppm Se.

The relationship of dietary selenium and breast cancer.

An inverse relationship exists between dietary selenium (Se) concentrations and the incidence of human breast cancer. The addition of Se to the diet has been shown to decrease the incidence of spontaneous murine mammary tumors. We compared the serum Se concentrations in breast cancer patients with those of women without breast cancer. Serum was collected from 35 women with breast cancer. Nineteen of these women had infiltrating ductal carcinoma and two had Paget disease of the nipple. Nine women had lymph nodal metastases at the time of mastectomy, four had definite evidence of metastatic disease when the blood samples were drawn, and the disease process of one patient was unclassified. Samples from 27 women known to be free of breast cancer were used as controls. The difference noted between the mean serum Se concentrations of breast cancer patients and controls were found to be significant.