The low nuclear grade breast neoplasia family

Rakha, Emad A.

doi:10.1016/j.mpdhp.2011.12.004

Cited by 11 publications

(4 citation statements)

References 35 publications

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“…While classical lobular neoplasia and ADH were both most frequently seen in association with high-grade DCIS (53% of the total cases with lobular neoplasia as the only other atypical lesion and 39% of the total cases with ADH alone), this is a reflection of high-grade DCIS being the most frequently reported grade. As part of the low nuclear grade neoplasia family, 24 it is not surprising that additional atypias were proportionately more frequently associated with intermediate-or low-grade DCIS (12% of total of lobular neoplasia and 21% of ADH) compared with high-grade DCIS (4% of lobular neoplasia and 3% of ADH). In a further 111 patients, both ADH and lobular in situ neoplasia were present along with the DCIS, again more commonly seen with low-grade DCIS (4% of low-grade DCIS cases) than in intermediate-(1%) or high-grade disease (<1%).…”

Section: Discussionmentioning

confidence: 99%

Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project

et al. 2020

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Background The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes. Methods This was a national, prospective cohort study of DCIS diagnosed during 2003–2012. Results Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of high-grade disease increased (from 60 to 65%), low-grade DCIS decreased (from 10 to 6%) and mean size increased (from 21.4 to 24.1 mm). Mastectomy was more common for high-grade (36%) than for low-grade DCIS (15%). Few (6%) patients treated with breast-conserving surgery (BCS) had a surgical margin <1 mm. Of the 9191 women diagnosed in England (median follow-up 9.4 years), 7% developed DCIS or invasive malignancy in the ipsilateral and 5% in the contralateral breast. The commonest ipsilateral event was invasive carcinoma (n = 413), median time 62 months, followed by DCIS (n = 225), at median 37 months. Radiotherapy (RT) was most protective against recurrence for high-grade DCIS (3.2% for high-grade DCIS with RT compared to 6.9% without, compared with 2.3 and 3.0%, respectively, for low/intermediate-grade DCIS). Ipsilateral DCIS events lessened after 5 years, while the risk of ipsilateral invasive cancer remained consistent to beyond 10 years. Conclusion DCIS pathology informs patient management and highlights the need for prolonged follow-up of screen-detected DCIS.

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Section: Discussionmentioning

confidence: 99%

Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project

et al. 2020

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“…The existence of a low-grade breast neoplasia family has been put forward (40); this family of lesions encompassed most well-established precursors of ER-positive breast cancers (flat epithelial atypia, atypical ductal hyperplasia and atypical lobular hyperplasia) and low-grade lobular and ductal in situ and invasive carcinomas (41). These lesions share a common immunophenotype (ER-positive, HER2-negative, high molecular weight cytokeratin-negative and low KI67 proliferation fraction) and genetic signature (highly recurrent PIK3CA mutations/1q gain/16q loss) (38).…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family

et al. 2017

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Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1–13) and 4.0 (1–7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12, or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions harboring frequent TP53 somatic mutations, and likely represent low-grade forms of triple-negative disease with no/minimal metastatic potential, of which a subset has the potential to progress to high-grade triple-negative breast cancer.

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“…Because of their frequent coexistence and similar pattern of genetic alterations (eg, PIK3CA mutations and deletions of 16q and gains of 1q 97,99 ), lowgrade ER-positive nonobligate precursors and invasive carcinomas have been grouped together under the term lowgrade breast neoplasia family. 97,100 Progression from lowgrade ER-positive to high-grade ER-positive lesions is supported by the high frequency of the aforementioned genetic signature in ER-positive high-grade carcinomas. 97,99 Nonetheless, such progression is not limited to ER-positive lesions, and the ER-negative branch may be histologically and genetically more diverse than the ERpositive one.…”

Section: Evolutionary Pathways In Tn Disease Of the Breastmentioning

confidence: 99%

The Spectrum of Triple-Negative Breast Disease

Geyer

Pareja

Weigelt

et al. 2017

The American Journal of Pathology

142

101

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Triple-negative breast cancer is viewed clinically as an aggressive subgroup of breast cancer. In fact, most triple-negative breast cancers are poor-prognosis tumors with a complex genomic landscape. However, triple-negative disease is vastly heterogeneous, encompassing multiple entities with marked genetic, transcriptional, histologic, and clinical differences, with neoplasms in this group ranging from low to high grade. Among the less common low-grade triple-negative lesions, two large subgroups, both with a rather indolent behavior, can be distinguished: a low-grade triple-negative breast neoplasia family, which includes nonobligate precursors of triple-negative breast cancer, and, despite being low-grade, harbors the complex genomic landscape of usual triple-negative breast cancer, and the salivary gland-like tumors of the breast, lacking all the cardinal molecular features of conventional triple-negative breast cancer and underpinned by specific fusion genes or hotspot mutations, which may be of diagnostic and possibly therapeutic utility. Progression to high-grade triple-negative breast cancer likely occurs in both subgroups but at different rates. In this review, we describe the heterogeneity of triple-negative disease, focusing on the histologic and molecular features of the low-grade lesions. Recognition that triple-negative breast cancer is an operational term and that triple-negative disease is heterogeneous and includes low-grade forms driven by distinct sets of genetic alterations is germane to the successful implementation of precision medicine.

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The low nuclear grade breast neoplasia family

Cited by 11 publications

References 35 publications

Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project

Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project

Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family

The Spectrum of Triple-Negative Breast Disease

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