DCIS of the breast: Are we over-diagnosing it? Are we over-treating it?

Leeper, Alexander; Dixon, J. Michael

doi:10.1016/j.maturitas.2010.12.008

Cited by 7 publications

(5 citation statements)

References 3 publications

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“…Ductal carcinoma in situ (DCIS) is the most common form of non‐invasive cancer of the breast, and constitutes a spectrum of proliferating malignant cells that are confined within the basement membrane of the ductal epithelium. As a consequence of widespread mammographic screening, DCIS today accounts for 20–25 per cent of newly diagnosed breast cancers, with more than 63 000 cases diagnosed annually in the USA.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ

Fancellu

Turner

Dixon

et al. 2015

British Journal of Surgery

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Section: Introductionmentioning

confidence: 99%

Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ

Fancellu

Turner

Dixon

et al. 2015

British Journal of Surgery

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“…High-grade DCIS is considered to progress more rapidly to invasive disease, but overall it is estimated that between one-third and half of DCIS diagnosed will progress to invasive breast cancer during a woman's lifetime (3). The frequency of DCIS has increased dramatically with the widespread use of mammographic screening, accounting now for 1 in 4 breast cancer diagnoses (3), contributing to recent concerns surrounding overdiagnosis and overtreatment within the breast screening setting (4,5). Indeed, the need to understand more about the biologic and molecular mechanisms underlying progression of DCIS to invasive disease and to generate robust risk stratification methods for patients with DCIS was highlighted in a recent NIH State-ofthe-Science conference on DCIS (3).…”

Section: Introductionmentioning

confidence: 99%

Altered Microenvironment Promotes Progression of Preinvasive Breast Cancer: Myoepithelial Expression of αvβ6 Integrin in DCIS Identifies High-risk Patients and Predicts Recurrence

Allen

Thomas

Clark

et al. 2014

Clinical Cancer Research

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Purpose: This study investigated the functional and clinical significance of integrin avb6 upregulation in myoepithelial cells of ductal carcinoma in situ (DCIS).Experimental Design: Archival samples of DCIS and DCIS with associated invasion (n ¼ 532) were analyzed for expression of avb6 by immunohistochemistry and ability to predict recurrence and progression assessedinanindependent,uniquecohortofDCIScaseswithlong-termfollow-up.Primarymyoepithelialcells and myoepithelial cell lines, with and without avb6 expression, were used to measure the effect of avb6 on growth and invasion of tumor cell lines in vitro and in a xenograft mouse model. Involvement of TGFb signaling was established using mink lung epithelial cell (MLEC) assay and antibody inhibition, and expression and activation of matrix metalloproteinase (MMP)-9 established by Real Time-PCR and zymography.Results: Expression of avb6 is significantly associated with progression to invasive cancer (P < 0.006) and with recurrence over a median follow-up of 114 months in a series of matched DCIS cases treated with local excision. We show that expression of avb6 drives myoepithelial cells to promote tumor cell invasion in vitro and enhances mammary tumor growth in vivo. The tumor-promoting effect of avb6-positive myoepithelial cells is dependent on TGFb-driven upregulation of MMP9 and can be abrogated by inhibiting this pathway.Conclusion: These findings indicate that altered myoepithelial cells in DCIS predict disease progression and recurrence and show that upregulation of avb6 on myoepithelial cells generates a tumor promoter function through TGFb upregulation of MMP-9. These data suggest that expression of avb6 may be used to stratify patients with DCIS. Clin Cancer Res; 20(2); 344-57. Ó2013 AACR.

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“…There has been growing concern that breast cancer screening may result in overdiagnosis and overtreatment of the disease (1). In the United States, around 60,000 cases of preinvasive ductal carcinoma in situ (DCIS) are diagnosed each year, accounting for 1 in 5 new breast cancer cases (American Cancer Society 2014, www.cancer.org/cancer/breastcancer/ detailedguide/breast-cancer-breast-cancer-types), for which the natural history remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

αvβ6 Expression in Myoepithelial Cells: A Novel Marker for Predicting DCIS Progression with Therapeutic Potential

2014

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The tumor microenvironment dynamically regulates the progression of cancer. In the breast, a unique component of the microenvironment is the myoepithelial cell. Normal myoepithelial cells act as "natural tumor suppressors"; however, more recent evidence suggests that these cells develop phenotypic changes, which may contribute to loss of tumor suppressor activity. We have shown that myoepithelial cells in a subset of preinvasive ductal carcinoma in situ (DCIS) upregulate expression of the integrin avb6, switching on tumor promoter activity through activation of TGFb and MMP9. This makes the tumor microenvironment more permissive to invasion, seen both in vitro and in vivo. In human tissue samples, increased myoepithelial avb6 expression correlated with increased risk of disease progression and recurrence. Current estimates suggest that as many as 50% of DCIS cases will never progress in the patient's lifetime, but there are no markers to predict the outcome of individual cases. The identification of avb6 in a subset of DCIS presents a unique way to stratify patients with DCIS into those who may or may not progress to more serious disease. As avb6 is not expressed on most normal adult tissues, this finding may also provide novel targets for therapy in this highrisk group. Cancer Res; 74(21); 5942-7. Ó2014 AACR.

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DCIS of the breast: Are we over-diagnosing it? Are we over-treating it?

Cited by 7 publications

References 3 publications

Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ

Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ

Altered Microenvironment Promotes Progression of Preinvasive Breast Cancer: Myoepithelial Expression of αvβ6 Integrin in DCIS Identifies High-risk Patients and Predicts Recurrence

αvβ6 Expression in Myoepithelial Cells: A Novel Marker for Predicting DCIS Progression with Therapeutic Potential

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