Spectrum of MAP3K1 mutations in breast cancer is luminal subtype‑predominant and related to prognosis

The article presents the experience of 19 Russian medical institutions on the use of eribulin in combination with trastuzumab in various treatment lines of metastatic HER2+ breast cancer in routine clinical practice. Aim. The main objective of this retrospective observational study was to evaluate the efficacy and tolerability of eribulin and trastuzumab combo in HER2+ breast cancer patients pretreated with anthracyclines and taxanes. The analysis included 60 patients who received at least 2 cycles of eribulin in combination with trastuzumab. 2 patients (3.3%) received treatment as the 1st line, as the 2nd 14 (23.3%), as the 3rd 16 (26.7%), and as the 4th and more 28 (46.7%). Materials and methods. Complete response was achieved in 2 (3.3%) patients, partial response in 9 (15%), stable disease in 33 (55%), stabilization for more than 6 months in 11 (18.3%), disease progression was detected in 16 (26.7%) patients. The objective response rate was 18.3% in the whole group, the clinical benefit rate 36.7%. Results. The objective response rate in the group of the luminal subtype (ER/PR+HER2+) was 26.9%, in HER2-overexpressed subtype (ER-PR-HER2+) 8.8% and 64.7%, respectively, disease progression was recorded 2.3 times more often 35.3% versus 15.5% in the luminal subtype group. The median progression-free survival in patients with HER2+ breast cancer was 4.95 months (95% confidence interval CI 3.048.29 months), in luminal subtype 6.38 months (95% CI 3.338.54 months), in non-luminal 4.44 months (95% CI 2.47.96 months); p=0.306. The treatment was well tolerated, the spectrum of adverse events corresponded to the eribulin toxicity profile. Conclusions. The uniqueness of this study lies in the fact that on a large clinical material from the standpoint of real clinical practice, a very promising treatment regimen that is not used routinely in a number of countries has been studied, its effectiveness and satisfactory tolerance have been confirmed.

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The chemoresistant population of luminal subtype human breast cancer cells expresses a basal phenotype.

10.1158/0008-5472.sabcs-42 ◽

2009 ◽

Cited By ~ 2

Author(s):

P Kabos ◽

WW Dye ◽

A Elias ◽

KB Horwitz ◽

CA Sartorius

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Luminal Subtype ◽

Basal Phenotype

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FOXA1 Expression in Breast Cancer—Correlation with Luminal Subtype A and Survival

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-07-0122 ◽

2007 ◽

Vol 13 (15) ◽

pp. 4415-4421 ◽

Cited By ~ 150

Author(s):

Sunil Badve ◽

Dmitry Turbin ◽

Mangesh A. Thorat ◽

Akira Morimiya ◽

Torsten O. Nielsen ◽

...

Keyword(s):

Breast Cancer ◽

Luminal Subtype ◽

Subtype A ◽

Foxa1 Expression

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Long-term prognostic factors of node-negative invasive breast cancer of luminal subtype: A comparison between histologic grades and molecular markers including Ki-67 and HER2.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.e11050 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. e11050-e11050

Author(s):

M. Ono ◽

H. Tsuda ◽

C. Shimizu ◽

K. Yonemori ◽

M. Ando ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Markers ◽

Prognostic Factors ◽

Invasive Breast Cancer ◽

Ki 67 ◽

Node Negative ◽

Luminal Subtype ◽

Subtype A

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Comparison of molecular (BluePrint+MammaPrint) and pathological subtypes for breast cancer among the first 800 patients from the EORTC 10041/BIG 3-04 (MINDACT) trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1022 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1022-1022

Author(s):

Giuseppe Viale ◽

Leen Slaets ◽

Femke De Snoo ◽

Laura J. van 't Veer ◽

Emiel J. Rutgers ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Decision ◽

Luminal A ◽

Luminal Subtype ◽

Cancer Subtypes ◽

Luminal B ◽

Treatment Decision Making ◽

Main Driver ◽

Micro Array ◽

Treatment Plans

1022 Background: Biology has become the main driver of breast cancer therapy. Intrinsic biological subtypes by gene expression profiling have been identified. Pathology can be used to define surrogates of these subtypes but these are not always concordant, which may lead to different treatment plans. We investigated the concordance between BluePrint (BP) + MammaPrint (MP) (micro array based) breast cancer subtypes and pathological surrogates (based on ER, PR, HER2, and Ki67). Contrary to the Perou gene set (evolved into PAM50), BluePrint was trained using pathological data. Methods: Using available data (centrally assessed pathology and genomic) from the MINDACT pilot phase (Rutgers et al 2011) 621 tumors were analyzed. Two pathology classifications were used: one with 4 categories and one with 5 categories (Goldhirsch et al 2011). Based on BP 3 subtypes are formed: Luminal, HER2 and Basal. The Luminal subtype is further split into Luminal A (MP low risk) and Luminal B (MP high risk). Results: See table. Conclusions: All pathological Basal cases are BP Basal, apart from 1 BP HER2 case. Of the BP Basal cases, 15 are not pathological Basal: 1 is Luminal A, 11 are Luminal B (of which 8 are IHC ER/PR borderline (≥1% and < 10%)) and 3 are HER2. All pathological Luminal (A & B) that are BP HER2 are HER2- by TargetPrint. 25 of the 26 pathological HER2+ that are BP Luminal A are ER+. Most discordant cases are seen within the Luminal subtype, indicating that Ki67 discriminates Luminal A vs. B differently than MammaPrint does. The observed subtype discrepancies reveal potential important impact for treatment-decision making. MINDACT will provide important information. [Table: see text]

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Potential Benefits of Neoadjuvant Chemotherapy in Clinically Node-Positive Luminal Subtype− Breast Cancer

Journal of Breast Cancer ◽

10.4048/jbc.2019.22.e35 ◽

2019 ◽

Vol 22 (3) ◽

pp. 412 ◽

Cited By ~ 2

Author(s):

Hyung Suk Kim ◽

Tae Kyung Yoo ◽

Woo Chan Park ◽

Byung Joo Chae

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Luminal Subtype ◽

Node Positive ◽

Potential Benefits ◽

Clinically Node Positive

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IPH-926 lobular breast cancer cells are triple-negative but their microarray profile uncovers a luminal subtype

Cancer Science ◽

10.1111/cas.12276 ◽

2013 ◽

Vol 104 (12) ◽

pp. 1726-1730 ◽

Cited By ~ 8

Author(s):

Matthias Christgen ◽

Robert Geffers ◽

Hans Kreipe ◽

Ulrich Lehmann

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Triple Negative ◽

Lobular Breast Cancer ◽

Luminal Subtype ◽

Microarray Profile

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Rare steroid receptor-negative basal-like tumorigenic cells in luminal subtype human breast cancer xenografts

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0706216105 ◽

2008 ◽

Vol 105 (15) ◽

pp. 5774-5779 ◽

Cited By ~ 94

Author(s):

K. B. Horwitz ◽

W. W. Dye ◽

J. C. Harrell ◽

P. Kabos ◽

C. A. Sartorius

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Steroid Receptor ◽

Human Breast ◽

Luminal Subtype ◽

Tumorigenic Cells ◽

Breast Cancer Xenografts

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piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.641052 ◽

2021 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Xin Ding ◽

Ya Li ◽

Jinhui Lü ◽

Qian Zhao ◽

Yuefan Guo ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Stem Cell ◽

Cancer Cells ◽

Cancer Biology ◽

Breast Cancer Cells ◽

Dna Methyltransferases ◽

Luminal Breast Cancer ◽

Stem Cell Markers ◽

Luminal Subtype

Cancer stem cells (CSCs) are believed to be the main source of cancer relapse and metastasis. PIWI-interacting small non-coding RNAs (piRNAs) have been recently recognized to be relevant to cancer biology. Whether and how piRNAs regulate human CSCs remain unknown. Herein, upregulation of piR-823 was identified in tested luminal breast cancer cells, especially in the luminal subtype of breast CSCs. Enforced expression or targeted knockdown of piR-823 demonstrated its oncogenic function in regulating cell proliferation and colony formation in MCF-7 and T-47D breast cancer cells. In addition, piR-823 induced ALDH (+) breast CSC subpopulation promoted the expression of stem cell markers including OCT4, SOX2, KLF4, NANOG, and hTERT, and increased mammosphere formation. Tail vein injection of magnetic nanoparticles carrying anti-piR-823 into the mammary gland of tumor-burdened mice significantly inhibited tumor growth in vivo. DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B were demonstrated to be the downstream genes of piR-823, which regulate gene expression by maintaining DNA methylation. piR-823 increased the expression of DNMTs, promoted DNA methylation of gene adenomatous polyposis coli (APC), thereby activating Wnt signaling and inducing cancer cell stemness in the luminal subtype of breast cancer cells. The current study not only revealed a novel mechanism through which piRNAs contribute to tumorigenesis in breast cancer by regulating CSCs, but also provided a therapeutic strategy using non-coding genomes in the suppression of human breast cancer.

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