Quality of life in MAP.3 (Mammary Prevention 3): a randomized, placebo-controlled trial evaluating exemestane for prevention of breast cancer.

Purpose: Exemestane, a steroidal aromatase inhibitor, reduced invasive breast cancer incidence by 65% among 4,560 postmenopausal women randomly assigned to exemestane (25 mg per day) compared with placebo in the National Cancer Institute of Canada (NCIC) Clinical Trials Group MAP.3 (Mammary Prevention 3) trial, but effects on quality of life (QOL) were not fully described.

Patients And Methods: Menopause-specific and health-related QOL were assessed by using the four Menopause-Specific Quality of Life Questionnaire (MENQOL) domains and the eight Medical Outcomes Study Short Form Health Survey (SF-36) scales at baseline, 6 months, and yearly thereafter.

Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial.

Background: Exemestane can prevent breast cancer in postmenopausal women. Because of potential widespread use, we examined the safety of exemestane on bone health.

Methods: In this nested safety substudy of the MAP.

Biological Markers Predictive of Invasive Recurrence in DCIS.

DCIS is a heterogeneous group of non-invasive cancers of the breast characterized by various degrees of differentiation and unpredictable propensity for transformation into invasive carcinoma. We examined the expression and prognostic value of 9 biological markers with a potential role in tumor progression in 133 patients with pure DCIS treated with breast conserving surgery alone, between 1982-2000. Histology was reviewed and immunohistochemical staining was performed.

Triple-negative breast cancer: clinical features and patterns of recurrence.

Purpose: To compare the clinical features, natural history, and outcomes for women with "triple-negative" breast cancer with women with other types of breast cancer.

Experimental Design: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative.

Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: correlation with disease stage.

The biological and clinical significance of circulating tumor cells (CTC) in the peripheral blood of breast cancer patients is not known. To study this question, we used a direct visualization assay to correlate the number of CTC with disease stage and progression. The CTC were enriched from the nucleated cell fraction by filtration and enumerated visually following immunostaining with anti-cytokeratin 8 (CK8) antibody CAM 5.

Prophylactic bilateral mastectomy: patterns of practice.

Background: Many women who are at an elevated risk of developing breast carcinoma choose prophylactic mastectomy to decrease their risk. We conducted a population-based study to review the indications for, and patterns of practice of prophylactic mastectomy in Ontario, Canada, since 1991.

Methods: A medical chart review was conducted at 33 hospitals that were identified as having conducted at least one prophylactic mastectomy.

RT-PCR amplification of CK19 mRNA in the blood of breast cancer patients: correlation with established prognostic parameters.

We optimized the assay for detection of cytokeratin 19 (CK19) mRNA by the reverse transcriptase-polymerase chain reaction (RT-PCR) in blood as an index of circulating tumor cells in breast cancer patients. The limit of detection of < 1 MCF7 tumor cells per 10(6) peripheral blood leukocytes (PBL) was achieved in mixing experiments. We did not detect CK19 mRNA in control bloods (0/30) or in the blood of patients with benign breast disease (0/15).

Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk.

Numerous studies have examined the relationship between organochlorines and breast cancer, but the results are not consistent. In most studies, organochlorines were measured in serum, but levels in breast adipose tissue are higher and represent cumulative internal exposure at the target site for breast cancer. Therefore, a hospital-based case-control study was conducted in Ontario, Canada to evaluate the association between breast cancer risk and breast adipose tissue concentrations of several organochlorines.

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

Purpose: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN.

Combined fine-needle aspiration, physical examination and mammography in the diagnosis of palpable breast masses: their relation to outcome for women with primary breast cancer.

Objective: To examine the combined and individual predictive values of fine-needle aspiration (FNA), physical examination (PE) of the breast and mammography (the "triple test") in diagnosing breast cancer in relation to the results of open surgical biopsy.

Design: A study of the records of patients who received both FNA and open surgical biopsy for the same palpable breast lump. The results of diagnostic assessment and open surgical biopsy were categorized as positive or negative.

Characteristics of local recurrence following lumpectomy for breast cancer.

We report the clinical characteristics and treatment of local breast relapse in our breast cancer patients who were initially managed with breast conservation surgery (lumpectomy) alone. A retrospective study was conducted of 366 patients who were treated since 1977. The clinical, pathological, and treatment data regarding the primary tumor and the recurrences (91) were reviewed.

A comparison of all-subset Cox and accelerated failure time models with Cox step-wise regression for node-positive breast cancer.

Clinical studies usually employ Cox step-wise regression for multivariate investigations of prognostic factors. However, commercial packages now allow the consideration of accelerated failure time models (exponential, Weibull, log logistic, and log normal), if the underlying Cox assumption of proportional hazards is inappropriate. All-subset regressions are feasible for all these models.

Benign and malignant breast disease: the relationship between women's health status and health values.

The study purpose was to determine whether differences in the weights assigned to various dimensions of health by 90 women in three subgroups (benign breast disease, breast cancer receiving chemotherapy, and breast cancer receiving other therapies) were associated with differences in self-reported health status in these dimensions. Two methods, one direct and the other indirect, were used to elicit values for mobility, depression, and social support. Two different scales also provided self-reports of health status in each of these dimensions.

Effect of stress on glucoregulation in physiology and diabetes.

To examine the glucoregulatory responses to stress and their impact on diabetes, we used the following models of stress: A) Hypoglycemia; B) Epinephrine infusion; C) intracerebroventricular (ICV) injection of carbachol, an analog of acetylcholine. A) Hypoglycemia induces release of all counterregulatory hormones. During acute hypoglycemia, glucose production increases initially mainly due to glucagon release but eventually also due to a very large increment in catecholamines.

Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs.

The effects of equipotent glucose-lowering doses of insulinlike growth factor I (IGF-I) and insulin on tracer-determined glucose kinetics and several metabolites were compared in 14 experiments (7 in each group) in fasted, totally depancreatized dogs. This model prevented variations in insulin secretion induced by IGF-I and permitted evaluation of the effects of IGF-I on extrapancreatic glucagon. Steady-state moderate hyperglycemia (9.

Paradoxical reduction in pancreatic glucagon with normalization of somatostatin and decrease in insulin in normoglycemic alloxan-diabetic dogs: a putative mechanism of glucagon irresponsiveness to hypoglycemia.

In alloxan-diabetic (A-D) dogs, plasma glucagon does not increase when glycemia is decreased by insulin. Therefore, as in insulin-dependent diabetes mellitus (IDDM), increased glucose utilization is not matched by an increase in hepatic production. To explore further the abnormal effects of insulin on regulation of pancreatic glucagon, we studied content and morphology of pancreatic hormones in six normal (N) dogs, five hyperglycemic A-D (HD) dogs, and in four A-D dogs where normoglycemia was maintained by insulin (ND).

Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy.

21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen.

Regulation of glucose turnover during exercise in pancreatectomized, totally insulin-deficient dogs. Effects of beta-adrenergic blockade.

To examine whether glucose metabolic clearance increases and whether catecholamines influence glucose turnover during exercise in total insulin deficiency, 24-h fasted and insulin-deprived pancreatectomized dogs were studied before and during exercise (60 min; 100 m/min; 10% slope) with (n = 8) and without (n = 8) propranolol infusion (PI, 5 micrograms/kg-min). Exercise with or without PI was accompanied by four and fivefold increments in norepinephrine and epinephrine respectively, while glucagon (extrapancreatic) fell slightly. Basal plasma glucose and FFA concentrations and rates of tracer-determined (3[3H]glucose) hepatic glucose production (Ra) and total glucose clearance (including urinary glucose loss) were 459 +/- 24 mg/dl, 1.

Elevated somatostatin in pancreatic islets of adrenalectomized dogs.

We have observed both hyperglucagonemia and hypoinsulinemia in adrenalectomized (Adx) dogs. To determine whether these hormonal alterations are related to changes in distribution of islet hormones in the pancreas, we examined the concentration and total mass of insulin, glucagon, and somatostatin in the head, body, and tail of the pancreas by immunoassay and immunocytochemistry. We studied 6 normal dogs, 5 Adx dogs deprived of cortisol for 24 h (Adx I) and 5 for 48-72 h (Adx II).

Extrapancreatic glucagon in control of glucose turnover in depancreatized dogs.

Depancreatized dogs have plasma immunoreactive glucagon (IRG), which is of gastric origin and is immunologically indistinguishable from pancreatic glucagon. The effects of extrapancreatic IRG on the tracer-determined rate of glucose production were examined to establish whether this hormone contributes to the hyperglycemia observed in six conscious, depancreatized dogs after insulin withdrawal. The dogs were initially maintained normoglycemic with an intraportal insulin infusion.