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Biomedical subjects

W D Dupont

Publications and source records attributed to W D Dupont.

At least 55 records · Page 3Linked to original sources
PubMed1994

Ductal carcinoma in situ of the breast with apocrine cytology: definition of a borderline category.

Papillary patterns of apocrine cells are frequent in benign breast biopsies and pose little diagnostic difficulty when the classic apocrine cytology is present. Dilemmas in diagnosis do occur, however, when the usual papillary patterns of hyperplastic apocrine epithelium are absent in hyperplastic lesion, particularly if it is extensive, presents more complex patterns, and/or lacks usual nuclear features. We classified lesions with nonclassic apocrine features into diagnostic categories to separate those with malignant potential from those that are truly benign. We selected 54 such cases sent in consultation over a 2-year period (1989 to 1991). We applied two sets of criteria: nuclear patterns (usual, borderline, and as seen in ductal carcinoma in situ) and extent of lesion (< mm, 4 to 8 mm, and > 8 mm). The cases were categorized into diagnostic groups defined by these criteria of extent of lesion and cytologic features. We believe that application of these criteria recognizing borderline features to unusual, apocrine lesions fosters reproducibility in diagnosis and thus predictability of clinical outcome. We found only 10 cases to fit into borderline categories after use of the two criteria. The clinical utility of this suggested diagnostic stratification will require follow-up studies for linkage of criteria to clinical outcomes.

Breast Neoplasms↗
PubMed1994

A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease.

A double-blind, randomized controlled trial over 5 years compared the safety, immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine significantly increased hemagglutination inhibition antibody titers. Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine. The efficacy of inactivated vaccine in preventing culture-positive influenza was 76% (95% confidence interval [CI], 58%-87%) for H1N1 disease and 74% (95% CI, 52%-86%) for H3N2; for cold-adapted vaccine, 85% (95% CI, 70%-92%) and 58% (95% CI, 29%-75%), respectively. The efficacy of inactivated vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69% (95% CI, 61%-76%) for H1N1 and 73% (95% CI, 65%-79%) for H3N2; for cold-adapted vaccine, 54% (95% CI, 44%-62%) and 32% (95% CI, 17%-44%), respectively. Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease.

Administration, Intranasal↗
PubMed1994

p53 mutations are confined to the comedo type ductal carcinoma in situ of the breast. Immunohistochemical and sequencing data.

BACKGROUND: Mutations in the p53 tumor suppressor gene have been identified in breast and many other carcinomas. It is not clear, however, when these mutations occur during breast carcinogenesis. Overexpression of 53 protein has been reported in some ductal carcinoma in situ (DCIS) lesions. To further study the overexpression of p53 in DCIS of the breast and correlate these findings with changes at the molecular level, we performed p53 immunostaining and direct sequencing in noncomedo and comedo DCIS. EXPERIMENTAL DESIGN: Archival blocks were obtained on cases of noncomedo DCIS, (including encysted, noninvasive papillary carcinoma) and comedo DCIS. Immunohistochemical staining with the p53 antibody DO7 was performed on all cases. Polymerase chain reaction (PCR) amplification of exons 5, 6, and 7 of the p53 gene was performed and the PCR products were directly sequenced. Four comedo DCIS cases that were p53 immunopositive were further screened for p53 mutations by PCR/single strand conformation polymorphism in exons 8 and 9 of the p53 gene. One of these cases showing a mobility shift was directly sequenced. RESULTS: We examined 39 lesions including comedo DCIS (N = 12) and noncomedo DCIS (N = 27), the latter including 17 encysted noninvasive papillary carcinomas. Immunostaining with DO7 was positive in 4 of 12 comedo DCIS lesions (33%) while all noncomedo lesions including encysted noninvasive papillary carcinomas were negative. Direct sequencing of PCR products confirmed wild-type DNA in exons 5 and 6 in all noninvasive papillary carcinomas, 3 randomly selected noncomedo DCIS lesions, and 4 p53 antibody-positive comedo DCIS lesions. In these latter 4 cases, wild-type DNA sequences were preserved in exon 7 for all cases. A single case had a conformational shift in exon 8 within the four cases screened in exons 8 and 9. Direct DNA sequencing of this exon revealed a G to A point mutation resulting in an arginine-to-histidine substitution at codon 273 of the protein. CONCLUSIONS: Our results suggest that mutant p53 protein accumulation in preinvasive lesions is limited to comedo (high grade) DCIS and that p53 positivity by immunohistochemistry does not correlate in all cases with specific p53 mutations in exons 5 to 9, the most highly conserved regions of this gene.

Aged↗
PubMed1993

Breast cancer risk associated with proliferative breast disease and atypical hyperplasia.

BACKGROUND: Women with proliferative breast disease (PD) have been observed to have an increased risk of breast cancer. The authors evaluated the effect of PD on breast cancer risk in a case-control study among participants of the Breast Cancer Detection Demonstration Project (BCDDP). METHODS: More than 280,000 women were screened in the BCDDP at 29 centers. Study subjects were selected from BCDDP participants who underwent biopsy that revealed benign breast tissue. There were five BCDDP centers for which histologic slides were available on more than 85% of the benign biopsy specimens. Case patients for this study were the 95 women from these five centers who had breast cancer develop during follow-up. Two matched control patients who did not have breast cancer develop were selected for each case. The biopsy slides were reviewed by two pathologists who were blinded with regard to cancer outcome. RESULTS: Women with atypical hyperplasia (AH) had 4.3 times the breast cancer risk of women without PD (95% confidence interval [CI], 1.7-11). In women with PD lacking AH, the relative risk was 1.3 (95% CI, 0.77-2.2). A family history of breast cancer (FH) increased breast cancer risk 2.4 times (95% CI, 1.4-4.3). The joint occurrence of FH and AH had a strong synergistic effect on breast cancer risk. CONCLUSIONS: AH is a reliable marker of increased breast cancer risk among women undergoing breast biopsy.

Adult↗
PubMed1993

Diagnostic criteria and cancer risk of proliferative breast lesions.

Breast cancer risk assessment in women following a benign breast biopsy is a promising area with regard to intermediate endpoint determination, and has been particularly fostered by the consensus agreement concerning the risk attributed to specific diagnoses [1]. Several recent studies have largely verified this approach [2-4], and a recent report demonstrates general agreement among most expert pathologists regarding diagnostic criteria for these lesions [5]. However, in a limited number of cases, determining exact levels of risk for individual patients has been problematic as a result of a failure by pathologists to achieve consensus on diagnostic criteria for these same lesions. This situation has arisen primarily because it is much more tenable to disagree over subjective diagnostic criteria, than it is to argue with robustly supported epidemiological data. Without agreement on reproducible diagnostic criteria, widely promulgated consensus risk estimates for these specific histologic entities are no longer applicable. In addition, those individuals who choose different diagnostic criteria for proliferative breast lesions fail to realize that the terminology, epidemiological risk estimates, and diagnostic criteria used by Dupont and Page are inexorably linked. Since the publication of the consensus statement [1], those using the terms of "atypical ductal hyperplasia" and "atypical lobular hyperplasia" have by default accepted the diagnostic criteria of Dupont and Page. Therefore, surgical pathologists who desire to make use of the consensus risk estimates must familiarize themselves with diagnostic criteria for the various histologic entities that comprise proliferative disease of the breast as defined by Dupont and Page [6].(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1993

Anatomic indicators (histologic and cytologic) of increased breast cancer risk.

Anatomic indicators of increased breast cancer risk have regularly been identified as hyperplastic lesions, analogous to other body sites. Most of these have been shown to indicate a later increased risk anywhere in either breast and should thus be regarded as indicators or markers of increased risk. Unfortunately, these are largely identified incidentally to current methods of detection. Specific combined histologic and cytologic criteria for the definition of these lesions have been evaluated for both their reproducibility of diagnosis and outcome variables. Several studies agree that usual patterns of hyperplasia of at least moderate degree indicate an increased risk of later breast carcinoma between 1.5 and 2 times that of the general population. The specifically defined examples of atypical hyperplasia, lesions of relative rarity, are found in 4-5% of biopsies (depending upon method of detection) and recognize a risk in the range of 4-5 times that of the general population controlled for age and duration of follow-up. Thus, several cohort studies using comparable criteria for definition of the anatomic lesions have found similar clinical outcomes. Other approaches to histologic definition have produced a lesser degree of separation between the non "atypical" and other forms of hyperplasia. Although it is not clear whether we are dealing with continuous variables or discrete histologic/cytologic variables, it is clear that when combined criteria are used, a greater degree of predictability is obtained. Other related risk features include most predominantly family history, which when present with atypical hyperplasia indicates an increased risk beyond that of either alone. Other means of detection of these various lesions, such as fine needle aspiration cytology, have not been verified. True non-obligate precursors of breast cancer are probably confined to low grade and non-comedo ductal carcinomas of the breast.

Breast↗
PubMed1992

Analysis of the PvuII restriction fragment-length polymorphism and exon structure of the estrogen receptor gene in breast cancer and peripheral blood.

The presence of estrogen receptor (ER) is a well-known predictor of clinical outcome in human breast cancer. We examined the ER gene in 26 primary breast cancers (14 ER-positive, 12 ER-negative) to determine if alterations of the gene are associated with the ER-negative status. In tumor biopsies and peripheral blood DNA obtained from the same patients we analyzed the ER exon structure using polymerase chain reaction amplification, restriction endonuclease digestion, and agarose gel electrophoresis. All blood and tumor samples, regardless of ER status, showed a complete set of eight exons of normal sizes, ruling out deletions or rearrangements of the ER gene in excess of +/- 20 nucleotides. Previous reports indicate that the two-allele ER PvuII polymorphism could be associated with ER expression in breast cancer (Hill et al., Cancer Res., 49: 145-148, 1989) as well as with patient age at time of tumor diagnosis (Parl et al., Breast Cancer Res. Treat., 14: 57-64, 1989). We localized the PvuII polymorphism in intron 1, 0.4 kilobase upstream of exon 2. Sequence analysis showed the polymorphism to result from a point mutation (T----C) at the fifth position of the restriction site (CATCTG). We determined the PvuII restriction fragment-length polymorphism genotype in 257 primary breast cancers and 140 peripheral blood DNA samples obtained from women without breast cancer. The results indicate that the PvuII polymorphism is not associated with ER content or patient age at tumor diagnosis.

Adult↗
PubMed1992

Indicators of increased breast cancer risk in humans.

Specific atypical histological patterns of epithelial hyperplasia (AH) indicate a medically relevant risk of breast cancer development in 5-10% of women with otherwise benign biopsies. This risk is about four times that of similar women, i.e., of the same age and at risk for the same length of time. These relative risks are not stable with time and fall 10-15 years after detection. Absolute risk for invasive breast cancer after AH is about 10% in 10-15 years after biopsy and is most certain for perimenopausal women. Proliferative disease without atypia predicts only a slight elevation of risk with a relative risk (RR) of 1.5 to 2 times that of the general population. There is such a strong interaction between family history and AH that it is relevant to consider women with atypical hyperplasia who have a positive family history (FH) of breast cancer separately from those who do not. The absolute risk of breast cancer development in women with AH without a FH was 8% in 10 years (RR about 4), whereas those with a positive family history experienced a risk of about 20% at 15 years (RR of about 10). This interaction of AH and FH has also been observed in other recent studies. Low replacement doses of conjugated estrogen after menopause do not further elevate risk beyond that identified by histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1992

Benign breast disease: indicators of increased breast cancer risk.

Assessment of cancer risk, particularly with a view toward targeting strategies for prevention, is a recent development. The future will see the garnering of more specific information about determinants of risk and their interaction with screening prevention and therapeutic modalities. We are not a full professional generation removed from a time when the question of malignancy in the breast was absolute, yes or no. Now special types of breast cancer are recognized that pose little threat to life, while some benign conditions indicate greatly increased risk of death from cancer. Comparisons of premalignant determinants in other organ systems indicate that cytologic, histologic, and metaplastic features may be more or less important in different organs. Their separate and combined analysis as predictors give a complex measure of tissue organization, which is often predictive of concurrent cancer and/or future cancer development. In proliferative breast disease, the markers of cancer risk may be classified into histologic categories of slightly, moderately, and markedly increased risk. In cases of slightly increased risk, the probability for cancer development is 1.5 to 2 times that of the general population; a moderately increased risk denotes that the likelihood of cancer development may be 4 to 5 times greater; a markedly increased risk has a predictive value of 9 to 10 times that of the general population.

Breast↗
PubMed1991

Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease.

We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC). Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC. Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time-dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia). We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain.

Adult↗
PubMed1991

Menopausal estrogen replacement therapy and breast cancer.

We conducted a meta-analysis of the literature concerning breast cancer and estrogen replacement therapy. The overall relative risk of breast cancer associated with this therapy was 1.07. However, the variation of the estimated risks among the studies was far greater than could plausibly be explained by chance alone. To explain this variation, we looked at the effects of type, duration, and dosage of treatment. Overall, women who took 0.625 mg/d or less of conjugated estrogens had a risk of breast cancer that was 1.08 times that of women who did not receive this therapy (95% confidence interval [CI], 0.96 to 1.2). The relative risks from these individual studies of low-dosage therapy did not differ significantly from each other. Women who took 1.25 mg/d or more of conjugated estrogens had a breast cancer relative risk of 2.0 or less in all studies. However, the variation in observed risks at this higher dosage was significant. This implies that other risk factors varied among these studies, making it difficult to estimate the overall risk associated with this dosage. The relative risk of breast cancer associated with estrogen replacement therapy among women with a history of benign breast disease was 1.16 (95% CI, 0.89 to 1.5). The combined results from multiple studies provide strong evidence that menopausal therapy consisting of 0.625 mg/d or less of conjugated estrogens does not increase breast cancer risk.

Breast Diseases↗
PubMed1990

Anatomic markers of human premalignancy and risk of breast cancer.

Epithelial hyperplasia of the breast carries an increased likelihood of carcinoma development, with most lesions best understood as markers of higher risk. The indication of increased cancer risk for more worrisome or complex histologic patterns has been supported in many studies. About 25% of women who underwent biopsies in the premammographic era had well-developed hyperplastic changes associated with an elevated risk of 1.5 to 2.0 times that of the general population when age and length of time of follow-up were considered. Somewhat fewer than 5% of women had specific patterns of atypical hyperplasia (AH) that approached the criteria of carcinoma in situ (CIS). These women with AH had a risk of cancer four to five times that of the general population, or about one half the risk associated with microscopic CIS. Only ductal CIS should be considered without question to be an intrinsic precancerous lesion because of its regular association with recurrence at the site of its initial diagnosis. Further studies indicated an appreciable interaction between AH and other nonanatomic risk factors, particularly a family history of breast cancer. Also, lower dosage estrogen replacement after menopause does not affect risk in any histologically defined group. The atypical hyperplastic lesions are more common in women undergoing biopsies on the indication of mammographic calcifications than because of palpable masses. The primary therapeutic implications of these premalignant lesions are intensified breast cancer surveillance and screening for these patients.

Breast↗
PubMed1990

Power and sample size calculations. A review and computer program.

Methods of sample size and power calculations are reviewed for the most common study designs. The sample size and power equations for these designs are shown to be special cases of two generic formulae for sample size and power calculations. A computer program is available that can be used for studies with dichotomous, continuous, or survival response measures. The alternative hypotheses of interest may be specified either in terms of differing response rates, means, or survival times, or in terms of relative risks or odds ratios. Studies with dichotomous or continuous outcomes may involve either a matched or independent study design. The program can determine the sample size needed to detect a specified alternative hypothesis with the required power, the power with which a specific alternative hypothesis can be detected with a given sample size, or the specific alternative hypotheses that can be detected with a given power and sample size. The program can generate help messages on request that facilitate the use of this software. It writes a log file of all calculated estimates and can produce an output file for plotting power curves. It is written in FORTRAN-77 and is in the public domain.

Case-Control Studies↗
PubMed1990

Premalignant conditions and markers of elevated risk in the breast and their management.

Most epithelial hyperplasias of the human breast indicate an increased likelihood of carcinoma development, and the majority are best understood as markers or indicators of higher risk. Prospective studies of women with hyperplasia biopsied in the premammographic era indicate that about 70 per cent of women had mild or no hyperplastic epithelial alterations and experienced no increase in the risk of subsequent carcinoma. About 25 per cent of women had well-developed hyperplastic changes associated with a risk 1.5 to 2.0 times that of the general population controlled for age and length of follow-up. Somewhat fewer than 5 per cent of women had specific patterns of atypical hyperplasia that approached the patterns of carcinoma in situ. The women with atypical hyperplasia had a risk of cancer four to five times that of the general population, or about half the risk associated with microscopic carcinoma in situ. Only ductal carcinoma in situ should be considered without question to be an intrinsically precancerous lesion because of its regular association with recurrence at the site of its initial diagnosis. No follow-up studies of comparable type involving women with mammographically detected lesions are as yet available. However, it is clear that the incidence of atypical hyperplasia is higher in mammographically directed biopsies. The principal therapeutic implication of these premalignant lesions is a need for intensified breast cancer surveillance and screening for these patients.

Breast↗
PubMed1989

Invasive breast cancer risk in women with sclerosing adenosis.

To assess sclerosing adenosis (SA) as an independent risk factor for subsequent invasive breast cancer (IBC), the authors reviewed 10,366 benign breast biopsy specimens (BB) obtained between 1950 and 1968 and identified 547 cases of SA meeting strict histologic criteria of expanded lobular units with whorled compressed acini. Of those women targeted for follow-up (3303, of whom 349 had SA), 84% were successfully followed for an average of 17 years. The relative risk for IBC among patients with SA regardless of the presence of atypical hyperplasia (AH) was 2.1. This risk decreased to 1.7 when patients with AH were excluded, and rose to 6.7 when only those patients with SA and AH were analyzed. The coexistence of a family history of IBC in a first-degree relative did not further elevate risk above that of SA alone when women with AH were excluded. Sclerosing adenosis was found to be positively associated with atypical lobular hyperplasia (ALH) as ALH was present in biopsy specimens with SA 2.7 times more frequently than in other biopsy specimens. Perimenopausal age, histologic calcification, and family history of IBC (FH) were also positively associated with SA. Sclerosing adenosis was most frequent in the perimenopausal period and had a weak association with family history of IBC. No association with atypical ductal hyperplasia (ADH) was identified. The authors conclude sclerosing adenosis represents an independent risk factor for subsequent invasive breast cancer apart from its association with ALH, and the risk (excluding patients with coexistent atypical hyperplasia) is in the range of 1.7, times thereby justifying inclusion of sclerosing adenosis as a component of a group of histopathologically defined lesions termed "proliferative breast disease without atypia" which implies a relative cancer risk of 1.5 to 2.0.

Breast Neoplasms↗