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Risk factors for Luminal A ductal carcinoma in situ (DCIS) and invasive breast cancer in the Carolina Breast Cancer Study.

ABSTRACT: PURPOSE:Invasive breast cancers are thought to arise from in situ lesions, but some ductal carcinoma in situ (DCIS) are indolent with low likelihood of progressing to invasive carcinoma. Comparison of risk factor associations between DCIS and invasive disease may elucidate which factors influence early versus late stages of carcinogenesis. Therefore, we determined whether there were differences in risk factor profiles for screen-detected DCIS and invasive breast cancer among Luminal A lesions. METHODS:We conducted a case-control analysis using data from the Carolina Breast Cancer Study (1993-2001). Analyses were restricted to Luminal A tumors and screen-detected tumors among mammography-eligible women, to limit confounding by mode of detection (N = 108 DCIS; N = 203 invasive). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between risk factors and lesion type. RESULTS:In stratified analyses, we observed qualitative differences in the direction of association for ever smoking, obese BMI, high waist-to-hip-ratio (WHR), and ?10 years of oral contraceptive use between DCIS and invasive disease. Breastfeeding was inversely associated with invasive disease and was not associated with DCIS. Interaction tests for risk factor associations between Luminal A DCIS and invasive breast cancer were not statistically significant (p>0.05). CONCLUSIONS:Among Luminal A tumors, established breast cancer risk factors may exert stronger effects on progression of early lesions to invasive disease, with lesser effects on risk of DCIS.

SUBMITTER: Williams LA

PROVIDER: S-EPMC6347264 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Risk factors for Luminal A ductal carcinoma in situ (DCIS) and invasive breast cancer in the Carolina Breast Cancer Study.

Williams Lindsay A LA Casbas-Hernandez Patricia P Nichols Hazel B HB Tse Chiu Kit CK Allott Emma H EH Carey Lisa A LA Olshan Andrew F AF Troester Melissa A MA

PloS one 20190125 1

<h4>Purpose</h4>Invasive breast cancers are thought to arise from in situ lesions, but some ductal carcinoma in situ (DCIS) are indolent with low likelihood of progressing to invasive carcinoma. Comparison of risk factor associations between DCIS and invasive disease may elucidate which factors influence early versus late stages of carcinogenesis. Therefore, we determined whether there were differences in risk factor profiles for screen-detected DCIS and invasive breast cancer among Luminal A le ...[more]

PMID: 30682163

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Project description:Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the intrinsic molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients. Breast cancer samples, 31 pure DCIS patients, 36 IDC patients, 42 mixed and 6 normal.

Dataset Information

Risk factors for Luminal A ductal carcinoma in situ (DCIS) and invasive breast cancer in the Carolina Breast Cancer Study.

Publications

Risk factors for Luminal A ductal carcinoma in situ (DCIS) and invasive breast cancer in the Carolina Breast Cancer Study.

Similar Datasets

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