Heterogeneity Between Ducts of the Same Nuclear Grade Involved by Duct Carcinoma In Situ (DCIS) of the Breast.

Purpose: Nuclear grade of breast DCIS is considered during patient management decision-making although it may have only a modest prognostic association with therapeutic outcome. We hypothesized that visual inspection may miss substantive differences in nuclei classified as having the same nuclear grade. To test this hypothesis, we measured subvisual nuclear features by quantitative image cytometry for nuclei with the same grade, and tested for statistical differences in these features.

Effect of quantitative nuclear image features on recurrence of Ductal Carcinoma In Situ (DCIS) of the breast.

Background: Nuclear grade has been associated with breast DCIS recurrence and progression to invasive carcinoma; however, our previous study of a cohort of patients with breast DCIS did not find such an association with outcome. Fifty percent of patients had heterogeneous DCIS with more than one nuclear grade. The aim of the current study was to investigate the effect of quantitative nuclear features assessed with digital image analysis on ipsilateral DCIS recurrence.

Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment.

Background: Previously, 50% of patients with breast ductal carcinoma in situ (DCIS) had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments.

Methods: Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy.

The role of reexcision for positive margins in optimizing local disease control after breast-conserving surgery for cancer.

One of the most important factors associated with local recurrence after lumpectomy in breast cancer patients is the status of the surgical margin. Standard surgical practice is to obtain clear margins even if this requires a second surgical procedure. It is assumed that reexcision to achieve clear margins when positive margins are present at initial excision is as effective as complete tumor removal at a single procedure; however, the efficacy of reexcision in this context has not been well studied.

Biological significance of occult micrometastases in histologically negative axillary lymph nodes in breast cancer patients using the recent American Joint Committee on Cancer breast cancer staging system.

The biological significance of occult metastases in axillary lymph nodes of breast cancer patients is controversial. The purpose of the study was to determine the prognostic significance of occult micrometastases using the current American Joint Committee on Cancer (AJCC) staging system in a cohort of women with node-negative breast cancer, of whom 5% received adjuvant systemic therapy and who all had long-term follow-up. We studied a cohort of 214 consecutive histologically node-negative breast cancer patients with a median follow-up of 8 years.

Ascertaining prognosis for breast cancer in node-negative patients with innovative survival analysis.

Clinical decisions to administer adjuvant systemic therapy to women with early breast cancer require knowledge about baseline prognosis, which is only assessable in the absence of such adjuvant treatment, which most patients currently do receive. The Cox model is the standard tool for assessing the effect of prognostic factors; however, there may be substantive differences in the estimated prognosis obtained by the Cox model rather than a log-normal model. For more than 50 years, clinical breast cancer data for cohorts of patients have supported the choice of a log-normal model.

Prognostic factors affecting the natural history of node-negative breast cancer.

Purpose: We undertook a natural history investigation of a broad selection of prognostic factors in a cohort of women with node-negative breast cancer.

Patients And Methods: The cohort consisted of 415 consecutive histologic node-negative (T1-3, M0) patients, operated on for primary breast cancer at Women's College Hospital, Toronto, Canada, between 1977 and 1986. Only 7% of these patients were given adjuvant systemic therapy; further, for the 48% of women who underwent lumpectomy, only 29% received adjuvant radiotherapy to the breast.

Educating women about breast cancer. An intervention for women with a family history of breast cancer.

Objective: To evaluate an "information aid" for women with a family history of breast cancer.

Design: Before-after descriptive study.

Setting: Family practices in Ontario.

In situ duct carcinoma of the breast: clinical and histopathologic factors and association with recurrent carcinoma.

There has been a recent increase in the diagnosis of in situ duct carcinoma of the breast (DCIS) as a result of mammographic screening. DCIS is heterogeneous in appearance and likely in prognosis. There is no generally accepted model to predict progression to invasive carcinoma.

Pathologic Characteristics of Breast Cancer that Predict for Local Recurrence After Lumpectomy Alone.

Breast conservation surgery (BCS) plus irradiation has been shown to be equivalent to mastectomy in controlling ipsilateral breast cancer recurrence. The purpose of this study is to evaluate the factors that determine the rate of local recurrence in a group of patients treated with partial mastectomy without postoperative radiation, adjuvant hormonal therapy, or chemotherapy. We also assess the role of standard pathologic features, specifically lymphovascular invasion (LVI) in identifying high- and low-risk subsets of patients.

Low-dose IGF-I has no selective advantage over insulin in regulating glucose metabolism in hyperglycemic depancreatized dogs.

At supraphysiological levels, IGF-I bypasses some forms of insulin resistance and has been proposed as a therapeutic agent in the treatment of diabetes. Unfortunately, side effects of high-dose IGF-I (100-250 microg/kg) have precluded its clinical use. Low-dose IGF-I (40-80 microg/kg), however, shows minimal side effects but has not been systematically evaluated.

Factors associated with local breast cancer recurrence after lumpectomy alone: postmenopausal patients.

Background: We have been following a cohort of patients who underwent a lumpectomy without receiving adjuvant radiotherapy or adjuvant systemic therapy. We now report the experience of a postmenopausal subgroup.

Methods: The postmenopausal subgroup included 244 patients accrued between 1977 and 1986 and followed up.

Factors affecting distant disease-free survival for primary invasive breast cancer: use of a log-normal survival model.

Background: Invasive breast cancer is a frequently diagnosed disease that now comes with an ever expanding array of therapeutic management options. We assessed the effects of 20 prognostic factors in a multivariate context.

Methods: We accrued clinical data for 156 consecutive patients with stage 1-3 primary invasive breast cancer who were diagnosed in 1989-1990 at the Henrietta Banting Breast Center, and followed to 1995.

Assessment of treatment for patients with primary ductal carcinoma in situ in the breast.

Background: Current mammographic technology has resulted in increased detection of ductal carcinoma in situ (DCIS). It is necessary to assess which patients presenting with DCIS are good candidates for breast conservation and which of these patients should receive adjuvant radiation.

Methods: We accrued clinical data for 124 patients with a primary diagnosis of DCIS from 1979 through 1994.

Primary breast cancer in the elderly.

Objectives: With respect to breast cancer in the elderly, to define "old" in the context of comorbidity and physiologic rather than chronologic age. In addition, after discussion of factors influencing decisions regarding screening, stage at presentation and treatment decisions, to present an approach to the treatment of primary breast cancer in the elderly, taking into account quality of life, expected outcomes and cost-effectiveness.

Data Sources: A review of the medical literature from 1980 to 1996, using the MEDLINE database and 2 relevant studies from The Henrietta Banting Breast Centre Research Programme at Women's College Hospital, Toronto.

Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors.

Background: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment.

Alternative multivariate modelling for time to local recurrence for breast cancer patients receiving a lumpectomy alone.

Certain prognostic factors (patient and/or tumour characteristics) may be associated with low (or high) risk for local recurrence. Patients with these characteristics could be candidates for less (or more) adjuvant therapy or a less (or more) aggressive surgical approach. However, the assessment of many factors can be problematic with the standard multivariate technique-a Cox proportional hazards model and step-wise regression.

An improved statistical approach: can it clarify the role of new prognostic factors for breast cancer?

Recently, there has been a proliferation of new biomarkers, some of which may lead to an improved prognostic index or may influence treatment selection. However, there are methodological and statistical issues that require attention in assessing the role and use of these prognostic factors. Between 1977 and 1986, 1097 primary breast cancer patients were accrued for multidisciplinary research at the Henrietta Banting Breast Centre, Women's College Hospital; follow-up to 1990 is complete for 96% of the patients.

Factors associated with local breast cancer recurrence after lumpectomy alone.

Background: The purpose was to determine the rate of local breast relapse in patients with breast cancer uniformly treated with partial mastectomy but without postoperative radiotherapy and without systemic adjuvant therapy. We also systematically examined the factors associated with local recurrence to determine whether a low-risk subgroup existed.

Methods: A retrospective review of a prospectively followed (median, 8 years) cohort of 293 patients was performed.

Clinical behavior of untreated axillary nodes after local treatment for primary breast cancer.

Background: The purpose of this study was to examine the rate of axillary failure in patients with primary breast cancer treated without axillary dissection or radiation and to determine what factors may be associated with axillary failure.

Methods: We studied 112 patients with invasive breast cancer treated for primary disease with breast-conserving surgery without axillary dissection or radiation to the breast or axilla, accrued between 1977 and 1986. Data for these patients were prospectively gathered for a research database and reviewed retrospectively to determine axillary failure.

A moderate decline in specific activity does not lead to an underestimation of hepatic glucose production during a glucose clamp.

We have previously shown that modeling errors lead to underestimation of hepatic glucose production (HGP) during glucose clamps when specific activity (SA) declines markedly. We wished to assess whether the failure to keep SA constant substantially affects calculation of HGP during insulin infusion when glucose requirements to maintain the glucose clamp are moderate. Therefore, 150-minute hyperinsulinemic (5.

An investigation of cut-points for primary breast cancer oestrogen and progesterone receptor assays.

Oestrogen and progesterone receptor (ER and PgR) assay values are frequently used in medical decision-making for breast cancer patients. We have proposed statistical standardization of receptor assay values to improve inter-laboratory comparability, and now report the use of standardized log units (SLU) to investigate the effects of ER and PgR cut-points on time to first recurrence outside the breast (DFS). Between 1980 and 1986, there were 678 primary breast cancer patients treated at the Henrietta Banting Breast Centre (HBBC).

The Henrietta Banting Breast Centre database: a model for clinical research utilizing a hospital-based inception cohort.

The cohort study design has been used successfully in clinical cancer research. Cohorts, however, are valuable only if they produce results which are valid and generalizable. Some hospital-based inception cohorts satisfy both these requirements and may thus be useful research tools.

Intracerebroventricular administration of somatostatin octapeptide counteracts the hormonal and metabolic responses to stress in normal and diabetic dogs.

Intracerebroventricular (ICV) injection of carbachol elicits hormonal and metabolic responses similar to moderate stress. In normal dogs, ICV carbachol stimulated marked counterregulatory hormone release, but altered plasma glucose only marginally because the marked increment in glucose production (Ra) was almost matched by the increment of utilization (Rd), even though plasma insulin was unchanged. In alloxan-diabetic dogs, Rd did not match Ra and plasma glucose increased substantially.

Insulin-like growth factor-I and insulin have no differential effects on glucose production and utilization under conditions of hyperglycemia.

We have previously shown that in moderately hyperglycemic depancreatized dogs, a glucose-lowering infusion of insulin-like growth factor-I (IGF-I) increased glucose utilization and lactate more, and suppressed glucose production and lipolysis less, than an equipotent glucose-lowering dose of insulin. Similar differences have been observed by others in nondiabetic and diabetic rats. To determine whether the decline in glycemia was important in detecting differential effects of IGF-I and insulin on glucose turnover, IGF-I (0.