Dramatic response to cyclin D–dependent kinase 4/6 inhibitor in refractory poorly differentiated neuroendocrine carcinoma of the breast

Shanks, Allison; Choi, Julia; Karur, Vinit

doi:10.1080/08998280.2018.1463041

Cited by 14 publications

(13 citation statements)

References 21 publications

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“…4,8,9,46,47 The molecular alterations (PIK3CA, TP53, RB1, CCND1) in breast NEC are common in invasive ER þ (luminal) ductal carcinomas of no-special-type suggesting potential relevance of cell cycle (CDK4/6 inhibitors) in isolated cases of this rare cancer. 48,49 There are also ongoing clinical trials with cell cycle inhibitors aimed to treat patients with lung and head/neck cancers harboring CCND1 amplification (trials: NCT03356223 and NCT02785939). Although FGFR inhibitors have been recently considered as a promising therapeutic option in breast cancer, the preliminary clinical data with FGFR inhibitors have yielded disappointing results.…”

Section: Ngs and Archer Fusion Resultsmentioning

confidence: 99%

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Vranić

Palazzo

Sanati

et al. 2019

Clinical Breast Cancer

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Neuroendocrine breast cancer lacks specific therapy, but similar common neuroendocrine carcinomas may offer guidance for therapy development. This study, for the first time, identified several biomarkers for targeted therapy approaches in patients with breast neuroendocrine carcinoma. Introduction: Neuroendocrine carcinoma (NEC) of the breast is a rare, special type of breast cancer, reportedly constituting 2% to 5% of all breast cancers. Although breast NEC does not have a specific targeted therapy, several new targeted therapies based on specific biomarkers were recently investigated in the NEC of lung and in other types of breast carcinoma, which may provide guidance to their feasibility in breast NEC. Materials and Methods: Twenty breast NECs were profiled for biomarkers of therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), histone deacetylase (H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 gene fusions) targeted inhibitors, alkylating agents (MGMT), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays. Results: Predictive expression of TROP-2, FOLR1, and H3K36Me3 were detected in different subsets of tumors and may pave the way for development of novel targeted therapies in some patients with breast NECs. There was no evidence of DLL3 expression, NTRK gene fusions, or MGMT hypermethylation. No biomarkers predictive of immune checkpoint inhibitor efficacy (programmed death-ligand 1 expression, tumor mutational burden, microsatellite instability) were identified. FGFR and CCND1 gene amplifications were detected in isolated cases. Conclusions: This study identified several potential targets for novel therapies in breast NEC, including farletuzumab and mirvetuximab soravtansine (FOLR1), sacituzumab govitecan (TROP-2), and HDAC inhibitors (H3K36Me3). In some cases, CCND1 gene amplification may indicate the usefulness of investigational therapies. The reported results should serve as an early indication of potential clinical relevance in selected patients with breast NEC.

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Section: Ngs and Archer Fusion Resultsmentioning

confidence: 99%

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Vranić

Palazzo

Sanati

et al. 2019

Clinical Breast Cancer

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“…A recent study suggested that menin has an essential role as a FOXA1 and GATA3-bound enhancer, leading to aggressive features of ERpositive breast cancers and probably also to aromatase inhibitor resistance via activating ESR1 mutations [42]. Furthermore, ESR1 was found to be mutated in a case study of an NEBC patient whose cancer did not respond to the commonly used platinum-based chemotherapy or hormone-based treatment [43]. The mutation was found when genotyping a patient's liver lesion that had been treated with the cyclin D-dependent kinase 4/6 inhibitor palbociclib.…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A

et al. 2018

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Objectives: Due to the rarity of breast carcinomas with neuroendocrine features (NEBC), the knowledge on their biology is very limited but the identification of their biology and prognostic factors is essential to evaluate both pathogenesis and possible targeted treatment options. We assessed the expression of the well-characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in NEBC. Methods: We assessed the immunohistochemical expression of neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive ductal carcinomas (IDC). Results: Nuclear and cytoplasmic TS, nuclear and cytoplasmic NSE, and nuclear p27 had significant overexpression in NEBC compared with IDC (for all, p < 0.01). In NEBC, cytoplasmic SSTR-2A expression was associated with excellent distant disease-free survival (p = 0.013), cytoplasmic menin expression with poorer relapse-free survival (p = 0.022), and nuclear p27 with longer breast cancer-specific survival (p = 0.022). Conclusions: There is a striking similarity in GEP-NET and NEBC regarding prognostic factors. GEP-NET and NEBC also appear to show similar expression patterns of the studied markers, while there are notable differences compared to IDC. Due to the wide expression of SSTR-2A, the treatment option with somatostatin analogs in NEBC should be evaluated.

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“…The addition of a cyclin-dependent kinase (CDK) 4/6 inhibitor to an aromatase inhibitor has significantly changed the prognosis of metastatic patients, both naïve and pre-exposed to ET, providing a great benefit in terms of PFS and, at least in some studies, in terms of OS [ 52 – 54 ]. Namely, the combination of palbociclib and fulvestrant has been used in the treatment of a patient affected from NEBC, with positive results [ 55 ]. The patient, affected by high-grade NEBC, was refractory to platinum-based chemotherapy as well as first-line hormonal treatment with tamoxifen and leuprolide, but showed a durable response to fulvestrant plus palbociclib.…”

Section: Methodsmentioning

confidence: 99%

Neuroendocrine breast carcinoma: a rare but challenging entity

Trevisi

Salvia²,

Lilleri

et al. 2020

Med Oncol

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Breast carcinoma with neuroendocrine differentiation, also known as neuroendocrine breast carcinoma (NEBC), includes a heterogeneous group of rare tumors, which account for 2–5% of all invasive breast carcinomas. Because of their low incidence, most of the current limited knowledge of these tumors derives from anecdotal case reports or small retrospective series. The diagnosis of NEBC is based on the presence of morphological features similar to gastrointestinal and lung NETs and neuroendocrine markers. NEBCs are usually hormone receptors positive and HER2 negative, but despite this luminal phenotype, most recent studies suggested that NEBC could be associated with worse prognosis compared to invasive breast cancer without neuroendocrine differentiation. Due to its rarity and lack of randomized data, there is little evidence to guide the choice of treatment, so NEBC is currently treated as any invasive breast carcinoma not-otherwise specified. Recently, attempts to molecularly characterize NEBC have been made, in order to provide new targets for a more personalized treatment of this uncommon entity.

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Dramatic response to cyclin D–dependent kinase 4/6 inhibitor in refractory poorly differentiated neuroendocrine carcinoma of the breast

Cited by 14 publications

References 21 publications

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A

Neuroendocrine breast carcinoma: a rare but challenging entity

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