Molecular phenotypes of DCIS predict overall and invasive recurrence

Williams, Kathryn E; Barnes, N. L. P.; Cramer, Angela; Johnson, R.J.; Cheema, K.; Morris, Julie; Howe, Miles; Bundred, Nigel

doi:10.1093/annonc/mdv062

Cited by 102 publications

(89 citation statements)

References 27 publications

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“…Although HER2 overexpression is implicated in the pathogenesis of breast cancer (89–91), HER2 is more commonly overexpressed in patients with DCIS (∼27%-56%) (8,12,18) when compared with invasive breast cancer (∼11%-20%) (85,86) (Table 1). The underlying reason why HER2, which is considered to be an important driver of breast cancer (91), is more highly expressed in noninvasive disease, is unclear.…”

Section: Her2mentioning

confidence: 99%

The Conundrum of Genetic “Drivers” in Benign Conditions

Kato

Lippman

Flaherty

et al. 2016

JNCI J Natl Cancer Inst

130

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Advances in deep genomic sequencing have identified a spectrum of cancer-specific passenger and driver aberrations. Clones with driver anomalies are believed to be positively selected during carcinogenesis. Accumulating evidence, however, shows that genomic alterations, such as those in BRAF, RAS, EGFR, HER2, FGFR3, PIK3CA, TP53, CDKN2A, and NF1/2, all of which are considered hallmark drivers of specific cancers, can also be identified in benign and premalignant conditions, occasionally at frequencies higher than in their malignant counterparts. Targeting these genomic drivers can produce dramatic responses in advanced cancer, but the effects on their benign counterparts are less clear. This benign-malignant phenomenon is well illustrated in studies of BRAF V600E mutations, which are paradoxically more frequent in benign nevi (∼80%) than in dysplastic nevi (∼60%) or melanoma (∼40%-45%). Similarly, human epidermal growth factor receptor 2 is more commonly overexpressed in ductal carcinoma in situ (∼27%-56%) when compared with invasive breast cancer (∼11%-20%). FGFR3 mutations in bladder cancer also decrease with tumor grade (low-grade tumors, ∼61%; high-grade, ∼11%). “Driver” mutations also occur in nonmalignant settings: TP53 mutations in synovial tissue from rheumatoid arthritis and FGFR3 mutations in seborrheic keratosis. The latter observations suggest that the oncogenicity of these alterations may be tissue context–dependent. The conversion of benign conditions to premalignant disease may involve other genetic events and/or epigenetic reprogramming. Putative driver mutations can also be germline and associated with increased cancer risk (eg, germline RAS or TP53 alterations), but germline FGFR3 or NF2 abnormalities do not predispose to malignancy. We discuss the enigma of genetic “drivers” in benign and premalignant conditions and the implications for prevention strategies and theories of tumorigenesis.

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Section: Her2mentioning

confidence: 99%

The Conundrum of Genetic “Drivers” in Benign Conditions

Kato

Lippman

Flaherty

et al. 2016

JNCI J Natl Cancer Inst

130

View full text Add to dashboard Cite

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“…On the other hand, in IBC and DCIS proliferation rate evaluated by Ki67 imunostain recorded different values from low to high rates and it is usualy correlated with tumor grade [30]. Recently, a high KI67 index proved to be an independed prognostic factor, those patients having a high risk for recurrence as IBC [31] HER2neu oncoprotein is one of the four memberes of HER family and plays and important role in cellular growth [32]. If for IBC, the negative impact on prognosis of HER2neu overexpresion is well establised, its role is still debate in DCIS [33].…”

Section: Discussionmentioning

confidence: 99%

Morphopathological and immunohistochemical features of a pure mucinous breast carcinoma – Case report

Aşchie

Bălțătescu

Cozaru

et al. 2016

ARS Medica Tomitana

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Pure mucinous carcinoma is a rare special type of breast carcinoma with a 2% incidence and it is usualy asociated with a good prognosis. It must distingished from the mixed subtype of mucinos breast carcinoma, which has an invasive non-mucinous component in more than 10% of the tumor and change the favourable outcome of the first subtype. In this report we present a case of a premenopausal woman with a lump in right breast wich histopathologically proved to be a pure mucinous carcinoma associated with high grade ductal carcinoma in situ. Immunohistochemical and ancillary studies demonstrate a great heterogeneity of the neoplastic cells, with different molecular profile for each component of the tumor. The presence of ductal carcinoma in situ with a different imunophenotype from pure mucinous carcinoma rise the ipothesis of a different tumor cell biology which may change clincal evolution.

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“…A more targeted approach to the use of adjuvant therapies following breast conservation for DCIS is also likely to be necessary if women are to receive optimal care. The adoption of molecular phenotyping using ER, HER-2 and Ki67 status [28] or commercially available techniques such as the recently validated Oncotype DX DCIS [29] may help effectively stratify patients and identify those at higher risk of recurrence who may benefit from the addition of adjuvant therapies and those who may be effectively managed by local excision alone. The management of DCIS is an evolving field; identifying areas of uncertainty, developing trials to address these and encouraging clinicians to recruit their patients into new and on-going studies will therefore be necessary if the current controversies are to be addressed and the care for patients improved This study has demonstrated previously significant variability in the current management of DCIS across the UK.…”

Section: Follow-upmentioning

confidence: 99%