Pathologic Findings in Contralateral Reduction Mammaplasty Specimens in Patients with Breast Cancer

Ramakrishnan, Rathi; Bhandare, Deepa; Fine, Neil A.; Khan, Seema A.; Lal, Aseem; Nayar, Ritu

doi:10.1111/j.1075-122x.2005.00059.x

Cited by 3 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and may harbour neoplasms or pathological atypia [57][58][59][60]. Likewise, normal tissue adjacent to tumor may be significantly impacted by factors released near the tumor microenvironment.…”

Section: The Use Of Normal Breast Tissue In Cancer Researchmentioning

confidence: 99%

“…This suggests that the normal controls used were un-dissected breast tissues consisting mostly of fat. Further, data by others have demonstrated that suboptimal comparators such as reduction mammoplasties or adjacent normal tissue is fraught with problems that include benign neoplasia and pathological atypia [57][58][59][60], altered gene expression [61,62], altered epigenetic markers [63], and loss of heterozygosity [64,65]. Some have recently used cell separation techniques to separate ductal epithelium from stroma using live fresh biopsied tissues.…”

Section: Chapter 4: Summarymentioning

confidence: 99%

See 1 more Smart Citation

Abstract PD01-08: Decoding the Transcriptional Landscape of Triple-Negative Breast Cancer Using Next-Generation Whole Transcriptome Sequencing

Radovich¹,

Clare²,

Sledge³

et al. 2010

Cancer Research

View full text Add to dashboard Cite

Milan Radovich DECODING THE TRANSCRIPTIONAL LANDSCAPE OF TRIPLE-NEGATIVE BREAST CANCER USING NEXT GENERATION WHOLE TRANSCRIPTOME SEQUENCING Triple-negative breast cancers (TNBCs) are negative for the expression of estrogen (ER), progesterone (PR), and HER-2 receptors. TNBC accounts for 15% of all breast cancers and results in disproportionally higher mortality compared to ER & HER2positive tumours. Moreover, there is a paucity of therapies for this subtype of breast cancer resulting primarily from an inadequate understanding of the transcriptional differences that differentiate TNBC from normal breast. To this end, we embarked on a comprehensive examination of the transcriptomes of TNBCs and normal breast tissues using next-generation whole transcriptome sequencing (RNA-Seq). By comparing RNAseq data from these tissues, we report the presence of differentially expressed coding and non-coding genes, novel transcribed regions, and mutations not previously reported in breast cancer. From these data we have identified two major themes. First, BRCA1 mutations are well known to be associated with development of TNBC. From these data we have identified many genes that work in concert with BRCA1 that are dysregulated suggesting a role of BRCA1 associated genes with sporadic TNBC. In addition, we observe a mutational profile in genes also associated with BRCA1 and DNA repair that lend more evidence to its role. Second, we demonstrate that using microdissected normal epithelium maybe an optimal comparator when searching for novel therapeutic targets for TNBC. Previous studies have used other controls such as reduction mammoplasties, adjacent normal tissue, or other breast cancer subtypes, which may be sub-optimal and have lead to identifying ineffective therapeutic targets. Our data vii suggests that the comparison of microdissected ductal epithelium to TNBC can identify potential therapeutic targets that may lead to be better clinical efficacy. In summation, with these data, we provide a detailed transcriptional landscape of TNBC and normal breast that we believe will lead to a better understanding of this complex disease.

show abstract

Section: The Use Of Normal Breast Tissue In Cancer Researchmentioning

confidence: 99%

Section: Chapter 4: Summarymentioning

confidence: 99%

Abstract PD01-08: Decoding the Transcriptional Landscape of Triple-Negative Breast Cancer Using Next-Generation Whole Transcriptome Sequencing

Radovich¹,

Clare²,

Sledge³

et al. 2010

Cancer Research

View full text Add to dashboard Cite

show abstract

Breast Cancer and Reduction Mammoplasty

Jansen¹,

Ghere²,

Lee

et al. 2009

Mastopexy and Breast Reduction

View full text Add to dashboard Cite

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

Radovich

Clare

Atale

et al. 2013

Breast Cancer Res Treat

View full text Add to dashboard Cite

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER−,PR−,HER2−). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90% of TNBCs revealing an over-expressed central network. In conclusion, Use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

show abstract

Pathologic Findings in Contralateral Reduction Mammaplasty Specimens in Patients with Breast Cancer

Cited by 3 publications

References 13 publications

Abstract PD01-08: Decoding the Transcriptional Landscape of Triple-Negative Breast Cancer Using Next-Generation Whole Transcriptome Sequencing

Abstract PD01-08: Decoding the Transcriptional Landscape of Triple-Negative Breast Cancer Using Next-Generation Whole Transcriptome Sequencing

Breast Cancer and Reduction Mammoplasty

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

Contact Info

Product

Resources

About