Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era

Shee, Kevin; Muller, Kristen E.; Marotti, Jonathan D.; Miller, Todd W.; Wells, Wendy A.; Tsongalis, Gregory J.

doi:10.1016/j.ajpath.2018.08.020

Cited by 18 publications

(17 citation statements)

References 94 publications

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“…Surgical excision, radiation, and endocrine therapy have become the standard treatment options to reduce the risk of disease progression, even for patients that would otherwise never evolve to IBC [34]. Traditionally, histological grade and hormone receptor status have been used to stratify DCIS patients according to their risk of recurrence and/or progression to IBC [35]. Collagen and smooth muscle actin layer remain uninterrupted in Cav-1/STAT5a dKO mice mammary ducts following estrogen treatment.…”

Section: Discussionmentioning

confidence: 99%

“…For each experimental group, immunofluorescence was performed in triplicate on mammary glands derived from 3 independent mice. AGING However, these features alone cannot reliably predict which DCIS lesions will progress to an invasive phenotype [1,35]. As such, there is an unmet need to further understand the molecular pathways involved in DCIS progression.…”

Section: Discussionmentioning

confidence: 99%

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Essential role of STAT5a in DCIS formation and invasion following estrogen treatment

Dees

Pontiggia

Jasmin

et al. 2020

Aging

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Ductal carcinoma in situ (DCIS) is one of the earliest stages of breast cancer (BCa). The mechanisms by which DCIS lesions progress to an invasive state while others remain indolent are yet to be fully characterized and both diagnosis and treatment of this pre-invasive disease could benefit from better understanding the pathways involved. While a decreased expression of Caveolin-1 (Cav-1) in the tumor microenvironment of patients with DCIS breast cancer was linked to progression to invasive breast cancer (IBC), the downstream effector(s) contributing to this process remain elusive. The current report shows elevated expression of Signal Transducer and Activator of Transcription 5a (STAT5a) within the DCIS-like lesions in Cav-1 KO mice following estrogen treatment and inhibition of STAT5a expression prevented the formation of these mammary lesions. In addition, STAT5a overexpression in a human DCIS cell line (MCF10DCIS.com) promoted their invasion, a process accelerated by estrogen treatment and associated with increased levels of the matrix metalloproteinase-9 (MMP-9) precursor. In sum, our results demonstrate a novel regulatory axis (Cav-1STAT5aMMP-9) in DCIS that is fully activated by the presence of estrogen. Our studies suggest to further study phosphorylated STAT5a (Y694) as a potential biomarker to guide and predict outcome of DCIS patient population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Essential role of STAT5a in DCIS formation and invasion following estrogen treatment

Dees

Pontiggia

Jasmin

et al. 2020

Aging

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“…Whether the absence of a readily identifiable dividing line is due to the limited resolution of our diagnostic techniques or results from a true continuum from one extreme to the other is unclear. It remains to be seen whether biomarkers will enable differentiation . For example, hormone‐positive human epidermal growth factor receptor 2 (HER2) negative subtypes of early breast cancer generally have an excellent prognosis with hormone therapy alone, avoiding the side effects of chemotherapy.…”

Section: Key Pointsmentioning

confidence: 99%

Precision medicine in an imprecise and complex world: Magic bullets, hype, and the fuzzy line between health and disease

Aron

2019

Evaluation Clinical Practice

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“…Development of sensitive and specific molecular diagnostics that can be used in conjunction with more traditional pathologic evaluation to identify low-risk patients will require a more complete understanding of the pathobiology of this neoplastic breast lesion. In this issue, Shee et al 26 discuss existing molecular biomarkers for precision medicine approaches to DCIS management and approaches to identification of new biomarkers for DCIS. With effective biomarkers and biomarker-based molecular assays, overtreatment of breast DCIS might be avoided by identifying the patients who are most likely to progress to invasive cancer (or, conversely, are unlikely to undergo disease progression).…”

Section: The Clinical Challenge Of Breast Dcismentioning

confidence: 99%

“…With effective biomarkers and biomarker-based molecular assays, overtreatment of breast DCIS might be avoided by identifying the patients who are most likely to progress to invasive cancer (or, conversely, are unlikely to undergo disease progression). 26…”

Section: The Clinical Challenge Of Breast Dcismentioning

confidence: 99%

Breast Ductal Carcinoma in Situ

Coleman

2019

The American Journal of Pathology

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This special Breast Ductal Carcinoma in Situ Theme Issue of The American Journal of Pathology includes four reviews covering major topics related to breast ductal carcinoma in situ (DCIS), which is a major health problem for women in the United States and worldwide. A focus on breast DCIS is warranted given its common occurrence, generally accepted precursor-product relationship with invasive breast cancer, and the need to treat DCIS patients appropriately to minimize the risk of progression to invasive disease. With an expanded understanding of the basic mechanisms that contribute to the development of DCIS and its progression to invasive breast cancer, key molecular pathways and effector molecules can be identified and exploited as biomarkers and in personalized approaches for treatment of the DCIS patient.

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Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era

Cited by 18 publications

References 94 publications

Essential role of STAT5a in DCIS formation and invasion following estrogen treatment

Essential role of STAT5a in DCIS formation and invasion following estrogen treatment

Precision medicine in an imprecise and complex world: Magic bullets, hype, and the fuzzy line between health and disease

Breast Ductal Carcinoma in Situ

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