Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up.

Opportunities to study the natural history of ductal carcinoma in situ are rare. A few studies of incompletely excised lesions in the premammographic era, retrospectively recognized as ductal carcinoma in situ, have demonstrated a proclivity for local recurrence in the original site. The authors report a follow-up study of 45 women with low-grade ductal carcinoma in situ treated by biopsy only, recognized retrospectively during a larger review of surgical pathology diagnoses and original histological slides for 26 539 consecutive breast biopsies performed at Vanderbilt, Baptist and St Thomas Hospitals in Nashville, TN from 1950 to 1989.

A multistage genetic association study identifies breast cancer risk loci at 10q25 and 16q24.

Background: Heritable risk for breast cancer includes an increasing number of common, low effect risk variants. We conducted a multistage genetic association study in a series of independent epidemiologic breast cancer study populations to identify novel breast cancer risk variants.

Methods: We tested 1,162 SNPs of greatest nominal significance from stage I of the Cancer Genetic Markers of Susceptibility breast cancer study (CGEMS; 1,145 cases, 1,142 controls) for evidence of replicated association with breast cancer in the Nashville Breast Cohort (NBC; 599 cases, 1,161 controls), the Collaborative Breast Cancer Study (CBCS; 1,552 cases, 1,185 controls), and BioVU Breast Cancer Study (BioVU; 1,172 cases, 1,172 controls).

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions: evidence against a precursor role.

Background: Columnar cell lesions are frequently associated with atypical ductal hyperplasia, lobular neoplasia, and tubular carcinoma, and have been suggested as a precursor lesion for low-grade carcinomas. However, in long-term follow-up studies, columnar cell lesions are associated with only a slight increase in later breast cancer development. If columnar cell lesions are precursor lesions, one would expect subsequent cancers to develop at the same site as the biopsy and to be preferentially of low grade.

Estrogen metabolism and exposure in a genotypic-phenotypic model for breast cancer risk prediction.

Background: Current models of breast cancer risk prediction do not directly reflect mammary estrogen metabolism or genetic variability in exposure to carcinogenic estrogen metabolites.

Methods: We developed a model that simulates the kinetic effect of genetic variants of the enzymes CYP1A1, CYP1B1, and COMT on the production of the main carcinogenic estrogen metabolite, 4-hydroxyestradiol (4-OHE(2)), expressed as area under the curve metric (4-OHE(2)-AUC). The model also incorporates phenotypic factors (age, body mass index, hormone replacement therapy, oral contraceptives, and family history), which plausibly influence estrogen metabolism and the production of 4-OHE(2).

A multistage association study identifies a breast cancer genetic locus at NCOA7.

Estrogen metabolism and growth factor signaling pathway genes play key roles in breast cancer development. We evaluated associations between breast cancer and tagging single-nucleotide polymorphisms (SNP) of 107 candidate genes of these pathways using single allele- and haplotype-based tests. We first sought concordance of associations between two study populations: the Nashville Breast Cohort (NBC; 510 cases, 988 controls), and the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer study (1,145 cases, 1,142 controls).

Protein phosphatase 2A subunit gene haplotypes and proliferative breast disease modify breast cancer risk.

Background: Protein phosphatase 2A (PP2A) is a major cellular phosphatase and plays key regulatory roles in growth, differentiation, and apoptosis. Women who are diagnosed with benign proliferative breast disease are at increased risk for the subsequent development of breast cancer.

Methods: The authors evaluated genetic variation of PP2A holoenzyme subunits for their potential contribution to breast cancer risk.

Heritable variation of ERBB2 and breast cancer risk.

Amplification of the epithelial growth factor receptor gene ERBB2 (HER2, NEU) in breast cancer is associated with a poor clinical prognosis. In mammary gland development, this receptor plays a role in ductal and lobuloalveolar differentiation. We conducted a systematic investigation of the role of genetic variation of the ERBB2 gene in breast cancer risk in a study of 842 histologically confirmed invasive breast cancer cases and 1,108 controls from the Shanghai Breast Cancer Study.

Histologic associations and long-term cancer risk in columnar cell lesions of the breast: a retrospective cohort and a nested case-control study.

Background: Mammary columnar cell lesions with atypia have been receiving increased scrutiny in view of their association with atypical hyperplasia (AH) and carcinoma. However, the few retrospective outcome studies performed have failed to establish an increased risk for recurrence or carcinoma on long-term follow-up.

Methods: The authors evaluated the overall cancer risk for 1261 biopsies with columnar cell lesions (CCL) in 4569 women from the Nashville Breast Cohort who were biopsied between 1969 and 1988.

Excellent survival, cancer type, and Nottingham grade after atypical lobular hyperplasia on initial breast biopsy.

Background: Atypical lobular hyperplasia (ALH) is associated with a 10% to 20% risk of subsequent invasive carcinoma, primarily in the ipsilateral breast. Nottingham grading, special tumor types, and survival after invasive cancer diagnosis were analyzed consistently for the first time.

Methods: A longitudinal follow-up study of 252 women who underwent 261 benign surgical biopsies between 1950 and 1985 with a diagnosis of ALH was undertaken.

Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies.

Background: Radial scars (RS) are benign breast lesions that have been implicated as independent risk factors for invasive breast carcinoma (IBC).

Methods: A retrospective cohort study of 9556 women who underwent biopsy between 1950-1986 and enrolled in the Nashville Breast Cohort was performed to investigate the association between RS in a benign breast biopsy and the risk of IBC. The risk associated with RS and coexistent proliferative disease (PD) was assessed adjusting for age at biopsy using a Cox hazards regression analysis with time-dependent covariates.

Adenomyoepithelioma: clinical, histologic, and immunohistologic evaluation of a series of related lesions.

Adenomyoepithelioma, strictly defined, is a proliferation of both epithelial and myoepithelial elements. The broad range of lesions that may fall under this umbrella, however, may be quite diverse. The diagnostic confusion surrounding this entity and its prognostic implications have led to a diagnosis by default as malignant and to overtreatment of some patients.

The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up.

Background: Opportunities to study the natural history of ductal carcinoma in situ (DCIS) are rare. A few studies of incompletely excised lesions in the premammographic era now recognized as DCIS have provided critical insights into its proclivity for local recurrence in the original site. At the time the biopsies in the current study were originally examined, small DCIS was not diagnosed and, by default, these women were treated by biopsy only.

Immunohistochemical expression of estrogen receptor in enlarged lobular units with columnar alteration in benign breast biopsies: a nested case-control study.

The prognostic and therapeutic implications of estrogen receptor (ER) status in breast cancer are well known. Whether ER status plays a role in benign breast lesions and the progression to malignancy has not been proven. Enlarged lobular units with columnar alteration (ELUCA), also known as unfolded lobular units, have been associated with mild elevations in subsequent breast cancer risk.

Breast cancer risk associated with estrogen receptor expression in epithelial hyperplasia lacking atypia and adjacent lobular units.

Estrogen is associated with many epidemiologic risk factors for invasive breast cancer. Cells that express estrogen receptors (ERs) in epithelial hyperplasia lacking atypia (EHLA) may influence breast cancer progression. We conducted a nested case-control study of 268 women with biopsy-confirmed EHLA to determine whether immunohistochemical expression of ERalpha in EHLA affects subsequent breast cancer risk.

Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study.

Background: Clinical decisions about atypical lobular hyperplasia are based on the belief that later invasive breast-cancer risk is equal in both breasts. We aimed to show laterality and subsequent risk implications of invasive breast cancer in women with atypical lobular hyperplasia.

Methods: We did a retrospective cohort study of 252 women who had undergone 261 benign surgical biopsies that showed atypical lobular hyperplasia from 1950 to 1985, as part of the Nashville Breast Studies.

Prognostic value of morphometry in patients with normal breast tissue or usual ductal hyperplasia of the breast.

Women with usual ductal hyperplasia have a relative risk of 1.6-1.9 of subsequent breast cancer development.

No elevation in long-term breast carcinoma risk for women with fibroadenomas that contain atypical hyperplasia.

Background: The authors previously showed that women with a fibroadenoma have a relative risk of invasive breast carcinoma of approximately 2.0 compared with women of similar age from the general population. This relative risk approaches 1.

Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in-situ and invasive carcinomas.

Aims: Loss of transforming growth factor beta type II receptor (TGFbeta-RII) expression has been associated with resistance to TGFbeta-mediated inhibition of cell proliferation and tumour progression. We investigated whether the expression of TGFbeta-RII is related to the progression of human breast cancer and whether there is a correlation between TGFbeta-RII expression and phenotypic markers of biological aggressiveness.

Methods And Results: Immunohistochemical methods were used to detect TGFbeta-RII in archival breast samples including benign proliferative lesions, ductal carcinoma in situ (DCIS) and invasive mammary carcinomas (IMC).

Transforming growth factor-beta and breast cancer risk in women with mammary epithelial hyperplasia.

Background: Transforming growth factors-beta (TGF-betas) regulate mammary epithelial cell division. Loss of expression of TGF-beta receptor II (TGF-beta-RII) is related to cell proliferation and tumor progression. Breast epithelial hyperplastic lesions lacking atypia (EHLA) are associated with a mild elevation in breast cancer risk.

Estrogen replacement therapy in women with a history of proliferative breast disease.

Background: Little information is available regarding the invasive breast carcinoma risk associated with estrogen replacement therapy (ERT) in women with histories of histologically defined breast lesions.

Methods: A retrospective cohort study of a consecutive series of women who underwent breast biopsies that proved to be benign between 1952-1978 was conducted. Follow-up data were obtained for 9494 women (87.

Potent antithrombin activity and delayed clearance from the circulation characterize recombinant hirudin genetically fused to albumin.

In this study we sought to extend the plasma half-life while maintaining the potent antithrombin activity of hirudin. We hypothesized that gene fusion of hirudin to albumin would result in the expression of a slowly cleared hirudin molecule. A hirudin variant 3 (HV3) cDNA was obtained by gene synthesis, while a 1,996-bp full-length rabbit serum albumin (RSA) cDNA was selected from a rabbit liver cDNA library.

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.

Long-term risk of breast cancer in women with fibroadenoma.

Background: Fibroadenomas are benign breast tumors that are commonly diagnosed in young women and are associated with a slight increase in the risk of breast cancer. These lesions vary considerably in their histologic characteristics. We assessed the correlation between the histologic features of fibroadenomas and the risk of subsequent breast cancer.

Molecular cloning and expression of rabbit heparin cofactor II: a plasma thrombin inhibitor highly conserved between species.

Heparin cofactor II (HCII), a circulating plasma protein that inhibits thrombin, is a member of the serine proteinase (serpin) family of proteins. The extent to which HCII structure is conserved across species lines was investigated, by obtaining cDNA clones encoding rabbit HCII. Overlapping clones corresponding to rabbit HCII were obtained by the combined use of hybridization screening of a rabbit liver cDNA library, and by rapid amplification of cDNA ends (RACE).

The UMLS Metathesaurus: representing different views of biomedical concepts.

The UMLS Metathesaurus is a compilation of names, relationships, and associated information from a variety of biomedical naming systems representing different views of biomedical practice or research. The Metathesaurus is organized by meaning, and the fundamental unit in the Metathesaurus is the concept. Differing names for a biomedical meaning are linked in a single Metathesaurus concept.