Biomarker Expression and Risk of Subsequent Tumors After Initial Ductal Carcinoma In Situ Diagnosis

Kerlikowske, Karla; Molinaro, Annette M.; Gauthier, Mona L.; Berman, Hal K.; Waldman, Fred; Bennington, James L.; Sánchez, Henry; Jimenez, Cynthia A.; Stewart, Kim; Chew, Karen; Ljung, Britt–Marie; Tlsty, Thea D.

doi:10.1093/jnci/djq101

Cited by 307 publications

(298 citation statements)

References 43 publications

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“…9,10,24,28 Additionally, Kepple et al 29 and Kerlikowske et al 30 found Her-2 positivity to be significantly associated with an increased risk of recurrence in DCIS. This correlates with findings in the previous study, in which Her-2 status was inversely related to bcl-2 status, a marker of low-grade breast neoplasms.…”

Section: Discussionmentioning

confidence: 99%

Prognostic markers and long-term outcomes in ductal carcinoma in situ of the breast treated with excision alone

Holmes

Lloyd

Chervoneva

et al. 2011

Cancer

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Section: Discussionmentioning

confidence: 99%

Prognostic markers and long-term outcomes in ductal carcinoma in situ of the breast treated with excision alone

Holmes

Lloyd

Chervoneva

et al. 2011

Cancer

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“…Kerlikowske et al (2010) have recently described an association between p16 Ink4a overexpression in breast ductal carcinoma in situ and the risk of subsequent DCIS or invasive cancer. In brief, p16 Ink4a overexpression together with a high ki67 and COX-2 overexpression was associated with progression to an invasive carcinoma, whereas p16 Ink4a overexpression with high ki67 but without COX-2 overexpression was associated with subsequent DCIS.…”

Section: Subcellular Location Of P16 Ink4a Overexpressionmentioning

confidence: 99%

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

et al. 2011

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p16 Ink4a is a protein involved in regulation of the cell cycle. Currently, p16 Ink4a is considered a tumor suppressor protein because of its physiological role and downregulated expression in a large number of tumors. Intriguingly, overexpression of p16 Ink4a has also been described in several tumors. This review attempts to elucidate when and why p16 Ink4a overexpression occurs, and to suggest possible implications of p16 Ink4a in the diagnosis, prognosis and treatment of cancer.

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“…This distinction has a critical impact on patient prognosis: whereas women with DCIS show no reduction in survival 5 y after diagnosis, those with invasive cancers have a 15-74% reduction in 5-y survival rates depending on the extent of tumor invasion at diagnosis (2). Given these observations, there is significant interest in finding genes that promote the invasive progression of early-stage tumors (3). Previous studies have sought molecular alterations present in invasive tumors but not DCIS, leading to the identification of hundreds of genomic and gene-expression alterations specifically associated with invasive cancers (4)(5)(6).…”

mentioning

confidence: 99%

SMARCE1 is required for the invasive progression of in situ cancers

Sokol

Feng

Jin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here, we show that SMARCE1 is required for the invasive progression of DCIS and other early-stage tumors. We show that SMARCE1 drives invasion by regulating the expression of secreted proteases that degrade basement membrane, an ECM barrier surrounding all epithelial tissues. In functional studies, SMARCE1 promotes invasion of in situ cancers growing within primary human mammary tissues and is also required for metastasis in vivo. Mechanistically, SMARCE1 drives invasion by forming a SWI/SNF-independent complex with the transcription factor ILF3. In patients diagnosed with early-stage cancers, SMARCE1 expression is a strong predictor of eventual relapse and metastasis. Collectively, these findings establish SMARCE1 as a key driver of invasive progression in early-stage tumors.T he past two decades have brought an exponential increase in the diagnosis of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). DCIS remains encapsulated within the ductal-lobular architecture of mammary epithelium; in contrast, invasive breast cancers have escaped this architecture by breaking through the basement membrane, a layer of ECM rich in collagen (IV) and laminins that separates epithelial tissues from the adjacent stromal microenvironment ( Fig. S1A) (1). This distinction has a critical impact on patient prognosis: whereas women with DCIS show no reduction in survival 5 y after diagnosis, those with invasive cancers have a 15-74% reduction in 5-y survival rates depending on the extent of tumor invasion at diagnosis (2). Given these observations, there is significant interest in finding genes that promote the invasive progression of early-stage tumors (3). Previous studies have sought molecular alterations present in invasive tumors but not DCIS, leading to the identification of hundreds of genomic and gene-expression alterations specifically associated with invasive cancers (4-6). However, it is unclear if genes that are amplified or up-regulated in invasive cancers also functionally drive DCIS invasion. In large part, the difficulty in addressing this question can be traced to a paucity of experimental systems that model cancer invasion within a microenvironment that faithfully replicates human breast tissue.The treatment of early-stage cancers remains an unresolved issue. Women with early-stage breast cancers-which include DCIS and stage I tumors that have not entered the lymph nodesare typically treated by lumpectomy followed by localized radiation. However, recurrence with metastasis occurs in a significant fraction of women with stage I cancers; if such tumors could be prospectively identified, it would be possible to preemptively adopt a more aggressive therapy. Conver...

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Biomarker Expression and Risk of Subsequent Tumors After Initial Ductal Carcinoma In Situ Diagnosis

Abstract: Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer, whereas histopathology information cannot.

Cited by 307 publications

References 43 publications

Prognostic markers and long-term outcomes in ductal carcinoma in situ of the breast treated with excision alone

Prognostic markers and long-term outcomes in ductal carcinoma in situ of the breast treated with excision alone

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

SMARCE1 is required for the invasive progression of in situ cancers

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