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D L Page

Publications and source records attributed to D L Page.

At least 91 records · Page 5Linked to original sources
PubMed1996

Pathology of preinvasive and excellent-prognosis breast cancer.

This review of developments in breast cancer is targeted at two broad areas: 1) indicators of increased risk of sufficient magnitude to attain clinical significance (including precursors) and 2) indicators of good prognosis in invasive breast cancer. A specific and important group that appears in a somewhat intermediate position is the carcinomas in situ, particularly those of the ductal type. This area has attained great importance because of its continually increasing incidence in North America and elsewhere where mammography is used extensively. In addition to discussing in general the advancing subspeciation of these premalignant and low-malignant conditions, we also discuss advances in diagnostic techniques. This specifically relates to the great increase in the utilization of core needle biopsies under mammographic and ultrasonographic guidance.

Adenocarcinoma↗
PubMed1996

The role of pathology in premalignancy and as a guide for treatment and prognosis in breast cancer.

This review emphasizes tissue pathology and its practical relevance to patient management in premalignant breast disease and established breast cancer. The rationale and criteria for recognizing benign lesions that indicate a subsequent increased risk for cancer development are now well established, having been confirmed in several large epidemiologic studies. Our understanding of the heterogeneous nature of ductal carcinoma in situ (DCIS) continues to evolve. Recent efforts to classify DCIS into clinically meaningful categories underscore the central role of histopathology in the management of this disease. Through long term follow up studies, small examples of noncomedo DCIS treated by biopsy alone may predict local recurrence. Adequate surgical excision, however, avoids this possibility in the predominance of such cases. For invasive carcinomas, prognostic issues extend beyond predicting survival after local treatment. Now that the efficacy of systemic chemotherapy is established, the question is whether this therapy will be of use to a particular patient or group of similar patients. The list of possible clinically useful subcategories of prediction is growing and under active development. Prognostic factors that are in general use, having been repeatedly validated, particularly stage and histologic grade, as well as those that are emerging but in need of validation, are reviewed.

Breast Neoplasms↗
PubMed1996

Papillary apocrine change of the breast: associations with atypical hyperplasia and risk of breast cancer.

Micropapillary patterns of apocrine change in human female breasts are common histological findings. They have been identified as cancer associated and implicated as an indicator of cancer risk in a predictive manner. This study has stratified papillary apocrine change (PAC) into categories of increasing complexity using a combination of cytological and histological pattern rules. Cases (2,876) were identified in a review of 10,357 benign breast biopsies. Of 5966 women, 1613 and PAC and were followed for a median of 20 years after biopsy for the development of invasive carcinoma of the breast. There was a slight association with cancer risk elevation, but most of this disappeared when women with concurrent, specifically identified patterns of atypical hyperplasia (AH) were excluded from the groups with PAC. The resultant relative risk was only 1.2 after women with AH were excluded. Only 1% of the reviewed biopsies demonstrated highly complex patterns of PAC, and 20% of these had coexistent lesions of AH. Women with highly complex patterns of PAC without AH did experience a relative risk of 2.4 (95% confidence interval = 0.77-7.04) but without statistical significance. More than one-half of all PAC patterns occurred without concurrent foci of lesions of proliferative disease that are associated with a slight elevation of breast cancer risk (at least 1.5 times); when present without proliferative disease, there was no suggestion of later breast cancer risk for PAC.

Adult↗
PubMed1995

Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy.

BACKGROUND: The stratification of ductal carcinoma in situ (DCIS) of the human breast into prognostically relevant categories by size and histologic pattern is a current concern. Few studies have been able to follow women after the identification of any type of DCIS when they have had biopsy only. METHODS: This is an extension of a follow-up study of a group of 28 women with small, noncomedo ductal carcinomas in situ that were excised by biopsy only, published in 1982. All these women have now been successfully followed for an average of almost 30 years. RESULTS: The overall risk of development of invasive carcinoma for these women over almost 30 years is nine times that of the general population (95% confidence interval, 4.7-17). This is similar to the 11-fold elevation in relative risk that was determined after about 15 years of follow-up. All invasive carcinomas have developed in the same area in the same breast. There were two women in whom invasive carcinoma developed between 20 and 30 years after initial biopsy. One other woman had an extensive noncomedo DCIS that was identified 25 years after her initial biopsy, but had no evidence of invasive disease. CONCLUSIONS: The natural history of small, noncomedo DCIS can last over at least 2 decades, with invasive carcinoma developing at the same site in which DCIS was previously discovered in a significant percentage of women (broadly, between 25%-50%). This is quite different from the natural history of comedo DCIS or any type of DCIS treated purposefully by surgery alone.

Aged↗
PubMed1995

Mammary tumor suppression by transforming growth factor beta 1 transgene expression.

In cell culture, type alpha transforming growth factor (TGF-alpha) stimulates epithelial cell growth, whereas TGF-beta 1 overrides this stimulatory effect and is growth inhibitory. Transgenic mice that overexpress TGF-alpha under control of the mouse mammary tumor virus (MMTV) promoter/enhancer exhibit mammary ductal hyperplasia and stochastic development of mammary carcinomas, a process that can be accelerated by administration of the chemical carcinogen 7,12-dimethylbenz[a]anthracene. MMTV-TGF-beta 1 transgenic mice display mammary ductal hypoplasia and do not develop mammary tumors. We report that in crossbreeding experiments involving the production of mice carrying both the MMTV-TGF-beta 1 and MMTV-TGF-alpha transgenes, there is marked suppression of mammary tumor formation and that MMTV-TGF-beta 1 transgenic mice are resistant to 7,12-dimethylbenz[a]anthracene-induced mammary tumor formation. These data demonstrate that overexpression of TGF-beta 1 in vivo can markedly suppress mammary tumor development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Recurrent mammary carcinoma after local excision. A segmental problem.

BACKGROUND: The acceptance of local operative therapy for mammary carcinoma has stimulated scrutiny of specific techniques with the goals of minimizing the incidence of local recurrence while optimizing the cosmetic result. Intraductal spread of carcinoma has been established as a major factor in determining the rate of local recurrence after breast-conserving therapy for mammary carcinoma. The relationship of the anatomic location of a recurrent neoplasm to that of the primary tumor is likely to be instructive in evaluating the effectiveness of various proposed approaches to primary excision. METHODS: Using the tumor registry of a tertiary care medical center, the authors reviewed all patients with mammary carcinoma treated with primary local excision during a 9-year period (1984-1992; n = 86), and identified all patients who subsequently experienced local recurrence (n = 5). The pathologic anatomic findings in each case were reviewed carefully and correlated with clinical and mammographic data. RESULTS: The rate of local recurrence in this series was 5.8%, similar to that of Veronesi's "lumpectomy" group (7%). In all five patients, the recurrent lesion was located in the same breast quadrant, along a radius from the nipple to the edge of the breast disc that crossed the site of the initial lesion. CONCLUSION: Local recurrence of mammary carcinoma after breast-conserving operative therapy most often occurs within the same segment; it is therefore proposed that its incidence may be substantially reduced with the use of a primary excision technique (based on normal breast anatomy) that removes en bloc the dominant tumor mass and the associated (possibly diseased) duct system.

Adult↗
PubMed1995

Controversies in the local management of invasive and non-invasive breast cancer.

Since the recent acceptance of partial mastectomy (lumpectomy or segmentectomy) as equivalent to mastectomy for survival, design of the local management of breast cancers has centered around concerns of local recurrence. There has been wide acceptance of the tumorectomy or lumpectomy approach by most authors in North America, while in Italy, following the Milan trials, there has been a preference for a segmental or quadrantectomy approach. The latter preferentially includes more ductal tissue toward and distant from the nipple and has shown a local recurrence rate less than 50% as great as that seen with lumpectomy. Radiotherapy dosages and techniques are of concern as well. If extensive ductal carcinoma in situ is a determinant of local recurrence, and if DCIS spreads preferentially along ducts in a radial fashion, then the extent of DCIS is most likely to be preferentially arrayed toward the nipple as well as in tissue on the other side of a tumor mass away from the nipple--such has been our knowledge of the ramifications of the ductal tree, in a radial fashion around the nipple. Acceptable cosmesis after a segmental approach to excision may be more difficult to obtain, but has been acceptable in some groups of patients. We may soon see a situation in which the operation is tailored to the specifics of an individual patient. The size of a resection, based on an even margin around a tumor mass (lumpectomy) or the number of degrees subtended by the arc representing the peripheral aspect of a segmental excision will depend on the size of the dominant lesion being resected, the size of the breast and any available data concerning the likely extent of the lesion, with DCIS having a special concern.

Breast Neoplasms↗
PubMed1995

Immunolocalization of transforming growth factor-alpha in normal and diseased human gastric mucosa.

Roles for transforming growth factor-alpha (TGF alpha) in the stomach include cell migration and proliferation, inhibition of acid secretion, and cytoprotection. The authors have previously shown increased TGF alpha expression in rat gastric mucosa in response to acute gastric injury. They also have shown that TGF alpha immunoreactivity is increased in the gastric mucosa of four patients with Ménétrier's disease. To further characterize TGF alpha immunoreactivity in human gastric mucosa, the authors have performed immunohistochemical analysis with an anti-TGF alpha monoclonal antibody on human gastric biopsies (n = 25) showing either normal (n = 8), mild reactive/reparative change in common conditions with or without associated gastritis (n = 13), and exaggerated mucosal change in proliferative conditions (Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic polyps) (n = 17). All normal biopsies showed a predictable pattern of TGF alpha immunostaining, with significant positivity found only in foveolar cells at the luminal surface and parietal cells, sparing foveolar cells in the gastric pits, mucous neck cells and chief cells of the gastric glands. Three patients with mild foveolar hyperplasia without associated inflammation did not deviate from the normal pattern except in foci of reactive epithelial change. Ten of 11 patients with chronic active gastritis, in addition to this normal staining pattern, demonstrated significant immunoreactivity in deeper foveolar cells and mucous neck cells showing reactive epithelial changes, defined as the presence of nuclear enlargement and nucleolar prominence with or without mucin depletion. Three cases of ulceration with associated reactive epithelial changes also showed increased immunoreactivity. Furthermore, five cases of Ménétrier's disease with massive foveolar hyperplasia and minimal inflammation (MFH) and six cases with hypertrophic lymphocytic gastritis (HLG) have been studied, and both show full-thickness TGF alpha immunoreactivity restricted to the gastric epithelium. This pattern of staining is indistinguishable from that observed in two cases of hyperplastic polyps but differs significantly from that observed in cases of mild foveolar hyperplasia. These results further define patterns of TGF alpha immunostaining in normal, reactive/reparative and exaggerated proliferative human gastric biopsies, confirm participation of TGF alpha in the response to gastric mucosal injury, and provide additional support for a possible role for TGF alpha in the pathogenesis of proliferative gastric disorders including Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic gastric polyps.

Gastric Mucosa↗
PubMed1995

Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression.

We have characterized expression of the familial breast and ovarian cancer gene, BRCA1, in cases of non-hereditary (sporadic) breast cancer and analyzed the effect of antisense inhibition of BRCA1 on the proliferative rate of mammary epithelial cells. BRCA1 mRNA levels are markedly decreased during the transition from carcinoma in situ to invasive cancer. Experimental inhibition of BRCA1 expression with antisense oligonucleotides produced accelerated growth of normal and malignant mammary cells, but had no effect on non-mammary epithelial cells. These studies suggest that BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth whose function is compromised in breast cancer either by direct mutation or alterations in gene expression.

Alleles↗
PubMed1995

Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions.

The elucidation of molecular alterations that occur during human breast cancer progression may contribute to the development of preventative strategies. Using in situ hybridizations on a cohort of 94 biopsy lesions, quantitatively increased cyclin D mRNA expression levels were observed in only 18% of benign lesions, which confer no or slightly increased breast cancer risk, and 18% of premalignant atypical ductal hyperplasias, which confer a four to fivefold increase in breast cancer risk. The transition to carcinoma was accompanied by frequent cyclin D mRNA overexpression in 76% of low-grade ductal carcinomas in situ, 87% of higher grade comedo ductal carcinomas in situ and 83% of infiltrating ductal breast carcinomas. The data identify a molecular event that may separate benign and premalignant human breast lesions from any form of breast carcinoma.

Breast Neoplasms↗
PubMed1995

Pathology of preinvasive and excellent-prognosis breast cancer.

Little has been added in the past year to our knowledge of the premalignant lesions that have implications of increased subsequent cancer risk. However, studies of molecular biologic associations of these lesions are proceeding. The heterogeneous nature of ductal carcinoma in situ and its clinical implications continues to evolve. Several studies of ductal carcinoma in situ have confirmed that this entity extends in continuity within the breast whether associated with invasive carcinoma or not. Therapeutic stratification of ductal carcinoma in situ lesions depending on their grade and size is widely accepted, however, formal larger cooperative studies are necessary. Therapeutic use of histologic grading and recognizing special histologic subtypes continues to gain importance. Studies detailing the the use of grading as an additive measure of the predictiveness of staging, as well as documentation of interobserver agreement when fostered by rule-structured agreement, dominate the current literature on this subject. The use of stereotactically guided needle biopsy is rapidly gaining a broad consensus. Precise guidelines for management of borderline diagnoses are under development.

Breast Neoplasms↗