Differences in molecular features of triple‐negative breast cancers based on the age at diagnosis

159 Background: “Triple negative” has been used to characterize a subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. They are aggressive cancers with limited treatment options. It’s unknown if similar phenotype found in other cancer types, like endometrial cancer, harbor similar molecular alterations and prognosis. We aim to compare molecular features between TNEC and TNBC. Methods: A total of 3133 endometrial cancer samples were evaluated by Caris Life Sciences (Phoenix, AZ) from Mar, 2011 to Jul, 2014 by multiplatform profiling, which included a combination of sequencing (Sanger or NGS), protein expression (IHC), and/or gene amplification (CISH or FISH). 545 TNEC and 2049 TNBC were identified based on reported pathology and compared using Fisher exact tests. Results: Compared to an incidence of 15-20% TNBC in breast cancer, 17% (545/3133) TNEC was seen in our cohort, of which 13% were endometrioid, 22% serous, 26% carcinosarcoma, 7% clear cell, and 22% other. Compared with TNBC, TNEC showed 1.9 exonic mutations per case while TNBC showed 1.2 mutations per case. As shown in the table, AR expression is lower in TNEC than TNBC. TP53 mutation was common in both but more frequent in TNBC. While BRCA1/2 mutation rates were similar, low MGMT and ERCC1 were more common in TNEC, suggesting increased aberrant DNA repair. DNA synthesis protein expression was higher in TNEC including TS, RRM1, and TOPO2A, although TNBC had higher TOPO1. PD-1 expression was more common in TNEC suggesting immune pathway involvement. PI3K/AKT/mTor, MAPK and Wnt pathways were more involved in TNEC with greater PTEN, PIK3CA, FBXW7, KRAS and CTNNB1 mutations. Conclusions: Our study reveals significantly higher overall mutation rates in TNEC than TNBC, and specifically higher activations of multiple molecular pathways including PI3K/Akt/mTor, MAPK and Wnt. Further studies are warranted to validate these findings in clinical trials.

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Immune-related biomarkers in triple-negative breast cancer

Breast Cancer ◽

10.1007/s12282-021-01247-8 ◽

2021 ◽

Author(s):

Juan Zhang ◽

Qi Tian ◽

Mi Zhang ◽

Hui Wang ◽

Lei Wu ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Combined Treatment ◽

Tumor Infiltrating Lymphocytes ◽

Molecular Characteristics ◽

Immune Gene ◽

Breast Cancers ◽

Related Factors ◽

Molecular Features

AbstractBreast cancer is a commonly diagnosed female cancer in the world. Triple-negative breast cancer (TNBC) is the most dangerous and biologically aggressive subtype in breast cancer which has a high mortality, high rates of relapse and poor prognosis, representing approximately 15–20% of breast cancers. TNBC has unique and special biological molecular characteristics and higher immunogenicity than other breast cancer types. On the basis of molecular features, TNBC is divided into different subtypes and gets various treatments. Especially, immunotherapy becomes a promising and effective treatment to TNBC. However, not all of the TNBC patients are sensitive to immunotherapy, the need of selecting the patients suitable for immunotherapy is imperative. In this review, we discussed recent discoveries about the immune-related factors of TNBC, including tumor-infiltrating lymphocytes (TILs), programmed death-ligand protein-1 (PD-L1), immune gene signatures, some other emerging biomarkers for immunotherapy effectivity and promising biomarkers for immunotherapy resistance. In addition, we summarized the features of these biomarkers contributing to predict the prognosis and effect of immunotherapy. We hope we can provide some helps or evidences to clinical immunotherapy and combined treatment for TNBC patients.

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Triple-Negative Breast Cancer Histological Subtypes with a Favourable Prognosis

Cancers ◽

10.3390/cancers13225694 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5694

Author(s):

Gábor Cserni ◽

Cecily M. Quinn ◽

Maria Pia Foschini ◽

Simonetta Bianchi ◽

Grace Callagy ◽

...

Keyword(s):

Cell Carcinoma ◽

Working Group ◽

Triple Negative ◽

Metaplastic Carcinoma ◽

Classical Type ◽

Low Grade ◽

Breast Cancers ◽

Rare Tumour ◽

Molecular Features ◽

European Working

Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.

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P1-08-20: Parity Interferes with the Effect of Age at Diagnosis on the Frequency Breast Cancers Are Triple-Negative.

10.1158/0008-5472.sabcs11-p1-08-20 ◽

2011 ◽

Author(s):

V Vannevel ◽

O Brouckaert ◽

K Leunen ◽

F Amant ◽

P Berteloot ◽

...

Keyword(s):

Triple Negative ◽

Age At Diagnosis ◽

Breast Cancers ◽

Effect Of Age

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A Targetable Androgen Receptor–Positive Breast Cancer Subtype Hidden Among the Triple-Negative Cancers

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2014-0122-ra ◽

2014 ◽

Vol 139 (5) ◽

pp. 612-617 ◽

Cited By ~ 20

Author(s):

Damoun Safarpour ◽

Fattaneh A. Tavassoli

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Triple Negative ◽

Therapeutic Option ◽

Breast Cancer Subtype ◽

Growth Factor Receptor ◽

Data Sources ◽

Breast Cancers ◽

Breast Carcinomas ◽

Molecular Features

Context Triple-negative breast cancer (TNBC) is a subgroup of breast cancers that by definition lack expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). A diverse group of tumors, TNBC shares some morphologic and molecular features with basal-like breast cancer, a category of breast cancer defined by gene expression profiling. More likely to occur in young women and African Americans, TNBCs may exhibit aggressive behavior and are associated with poor prognosis despite their initial response to conventional chemotherapy. Because hormonal or HER2-targeted therapies are ineffective for these tumors, the main therapeutic option is systemic chemotherapy. Therefore, identification of new targets for therapy is urgently needed for this group. Objective To review and present recent literature along with our own experience regarding the clinical and morphologic characteristics and the prevalence of androgen receptor (AR) expression in TNBC, and to discuss the potential use of AR as a therapeutic target for AR+ TNBC. Data Sources Data sources are published articles from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusions AR is the most commonly expressed hormone receptor among all breast carcinomas, with a prevalence of 25% to 75% among TNBCs. Therefore, we strongly support the routine assessment of AR in TNBC, and preferably in all breast carcinomas.

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