Secretory Breast Carcinoma

Castillo, Marie Del; Chibon, Fréderic; Arnould́, Laurent; Croce, Sabrina; Ribeiro, Agnès; Pérot, Gaëlle; Hostein, Isabelle; Geha, Sameh; Bozon, Catherine; Garnier, Agnès; Laé, Marick; Vincent‐Salomon, Anne; MacGrogan, Gaëtan

doi:10.1097/pas.0000000000000487

Cited by 80 publications

(25 citation statements)

References 22 publications

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“…Interestingly, the salivary gland counterpart of breast secretory carcinoma (aka, mammary analogue secretory carcinoma) has only been recognized due to the identification of the specific fusion gene in lesions previously classified as unusual variants of salivary gland acinic cell carcinomas (44). In contrast to microglandular adenoses/atypical microglandular adenoses and breast acinic cell carcinomas, salivary gland-like tumors of the breast do not resemble conventional triple-negative breast cancers at the genetic level, harbor low levels of genetic instability with few copy number changes (12, 45) and do not harbor highly recurrent TP53 mutations (12). Although those lesions may also, albeit less frequently, progress to high-grade triple-negative breast cancers, there is evidence that those high-grade carcinomas also differ genetically from conventional triple-negative breast cancers (45, 46).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to microglandular adenoses/atypical microglandular adenoses and breast acinic cell carcinomas, salivary gland-like tumors of the breast do not resemble conventional triple-negative breast cancers at the genetic level, harbor low levels of genetic instability with few copy number changes (12, 45) and do not harbor highly recurrent TP53 mutations (12). Although those lesions may also, albeit less frequently, progress to high-grade triple-negative breast cancers, there is evidence that those high-grade carcinomas also differ genetically from conventional triple-negative breast cancers (45, 46). Previous observations based on histologic and immunohistochemical analyses have suggested a potential association between microglandular adenosis and adenoid cystic carcinomas (47).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…6,99 Recurrent 8q, 1q, 16pq, and 12p gains, along with 22q losses have been identified. 6,99,100 Del Castillo et al 6 have reported on a case of a lethal high-grade secretory carcinoma with fluorescence in situ hybridization-proven ETV6 rearrangement, which despite harboring a simple genome, displayed more gains and losses of entire chromosomes and chromosomal arms than lower-grade tumors. Further studies of secretory carcinomas with high-grade transformation are warranted to define their prognosis and molecular underpinning.…”

Section: Tnbcs: the Importance Of Histologic Subtypingmentioning

confidence: 96%

“…Although the vast majority of cases are low-grade TNBCs, cases of high-grade or with weak hormone receptor expression have been reported. 6 …”

Section: Tnbcs: the Importance Of Histologic Subtypingmentioning

confidence: 99%

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Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

et al. 2016

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Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

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NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS

Marino

Buono

Montella

et al. 2023

The Journal of Pathology CR

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Triple‐negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type‐agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for the selection of patients for targeted therapy. The main aim of our study was to investigate the frequency of NTRK aberrations, i.e. fusions, gene copy number gain, and amplification, in a series of TNBC using different methods. A total of 83 TNBCs were analyzed using pan‐TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real‐time polymerase chain reaction (RT‐PCR), and RNA‐based next‐generation sequencing (NGS). Of 83 cases, 16 showed pan‐TRK positivity although no cases had NTRK‐fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern consisting of one fusion signal and one/more single green signals, but all cases were negative for fusion by NGS and RT‐PCR testing. In addition, FISH analysis showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, and five cases with NTRK3 copy number gain, all negative for pan‐TRK IHC. Our data demonstrate that IHC has a high false‐positive rate for the detection of fusions and molecular testing is mandatory; there is no need to perform additional molecular tests in cases negativity for NTRK by IHC. In conclusion, the NTRK genes are not involved in fusions in TNBC, but both copy number gain and amplification are frequent events, suggesting a possible predictive role for other NTRK aberrations.

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Secretory Breast Carcinoma

Cited by 80 publications

References 22 publications

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

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

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS

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