The therapeutic response of ER+/HER2− breast cancers differs according to the molecular Basal or Luminal subtype

Bertucci, François; Finetti, Pascal; Gonçalvès, Anthony; Birnbaum, Daniel

doi:10.1038/s41523-020-0151-5

Cited by 32 publications

(35 citation statements)

References 74 publications

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“…Among the HR‐positive cases with an overall response of 11%, those reclassified as Basal‐like achieved pCR of 32% 112 . Recently, the analysis of a large in silico meta‐dataset of gene expression results ( n = 5342) reinforced previous results reporting chemotherapy response rates of 32% (27/85) for Basal‐like and 9% (42/452) for the Luminal subtype among HR+ patients 145 . Interestingly, expression profiles positioned reclassified HR+/Basal‐like group between the HR‐positive/Luminal and HR‐negative/Basal‐like subtype, suggesting that a different cell‐of‐origin should be considered for this group.…”

Section: Clinical Implications Of Classification Discordancementioning

confidence: 70%

“…Supportive of this is a finding that most genes associated with endocrine sensitivity were also found associated with chemotherapy resistance 148 . Conversely, in these retrospective studies, non‐Luminal subtypes present within HR‐positive disease showed lesser benefit from adjuvant hormone therapy, suggesting estrogen‐independency of these tumors 137,145,148 . The activation of EGFR has been recently identified as a resistance mechanism to endocrine therapy and may be responsible for poorer endocrine therapy responsiveness of HER2‐Enriched portion of HR‐positive patients 149 .…”

Section: Clinical Implications Of Classification Discordancementioning

confidence: 89%

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Molecular intrinsic versus clinical subtyping in breast cancer: A comprehensive review

2020

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Breast cancer is a heterogeneous disease manifesting diversity at the molecular, histological and clinical level. The development of breast cancer classification was centered on informing clinical decisions. The current approach to the classification of breast cancer, which categorizes this disease into clinical subtypes based on the detection of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki67, is not ideal. This is manifested as a heterogeneity of therapeutic responses and outcomes within the clinical subtypes. The newer classification model, based on gene expression profiling (intrinsic subtyping) informs about transcriptional responses downstream from IHC single markers, revealing deeper appreciation for the disease heterogeneity and capturing tumor biology in a more comprehensive way than an expression of a single protein or gene alone. While accumulating evidences suggest that intrinsic subtypes provide clinically relevant information beyond clinical surrogates, it is imperative to establish whether the current conventional immunohistochemistry‐based clinical subtyping approach could be improved by gene expression profiling and if this approach has a potential to translate into clinical practice.

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Section: Clinical Implications Of Classification Discordancementioning

confidence: 70%

Section: Clinical Implications Of Classification Discordancementioning

confidence: 89%

Molecular intrinsic versus clinical subtyping in breast cancer: A comprehensive review

2020

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“…Molecular signatures based on gene expression pattern include hormonal receptors such as androgen receptor (AR), estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and progesterone receptor (PR). Molecular subtypes can predict baseline prognosis, distant relapse-free survival and therapeutic decision-making strategies [6][7][8][9][10][11][12][13][14]. Docetaxel (DOCE) is a taxane derivate used in BC and PC.…”

Section: Introductionmentioning

confidence: 99%

Co-Adjuvant Therapy Efficacy of Catechin and Procyanidin B2 with Docetaxel on Hormone-Related Cancers In Vitro

Núñez-Iglesias

Novío

García

et al. 2021

IJMS

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Prostate (PC) and breast cancer (BC) are heterogeneous hormonal cancers. Treatment resistance and adverse effects are the main limitations of conventional chemotherapy treatment. The use of sensitizing agents could improve the effectiveness of chemotherapeutic drugs as well as obviate these limitations. This study analyzes the effect of single catechin (CAT), procyanidin B2 (ProB2) treatment as well as the co-adjuvant treatment of each of these compounds with docetaxel (DOCE). We used PC- and BC-derived cell lines (PC3, DU-145, T47D, MCF-7 and MDA-MB-231). The short and long-term pro-apoptotic, anti-proliferative and anti-migratory effects were analyzed. RT-qPCR was used to discover molecular bases of the therapeutic efficacy of these compounds. ProB2 treatment induced a two- to five-fold increase in anti-proliferative and pro-apoptotic effects compared to single DOCE treatment, and also had a more sensitizing effect than DOCE on DU145 cells. Regarding BC cells, ProB2- and CAT-mediated sensitization to DOCE anti-proliferative and pro-apoptotic effects was cell-independent and cell-dependent, respectively. Combined treatment led to high-efficacy effects on MCF-7 cells, which were associated to the up-regulation of CDKN1A, BAX, caspase 9 and E-cadherin mRNA under combined treatment compared to single DOCE treatment. CAT and ProB2 can enhance the efficacy of DOCE therapy on PC and BC cells by the sensitizing mechanism.

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“…Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. 1 The most common morphological type is invasive breast carcinoma of no special type (IBC NST), whose molecular subtypes are characterized by three main phenotypes: luminal (estrogen receptor– and/or progesterone receptor–positive), HER2-overexpressing, and triple-negative. 2 The molecular subtype is associated with the metastatic potential of breast cancer cells: the luminal tumor subtypes have a lower malignant progression rate and a better response to pharmacotherapy compared to those of the HER2-overexpressing subtype and triple-negative subtype of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Cytokines in various molecular subtypes of breast cancer

Autenshlyus

Davletova

Вараксин

et al. 2021

Int J Immunopathol Pharmacol

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Introduction Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown. Methods We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where “mitogens” means “polyclonal activators” (PA): phytohemagglutinin p, phytohemagglutinin M, concanavalin A, and Escherichia coli lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells. Results The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower “stimulation index of polyclonal activators” (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype. Conclusion Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.

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The therapeutic response of ER+/HER2− breast cancers differs according to the molecular Basal or Luminal subtype

Cited by 32 publications

References 74 publications

Molecular intrinsic versus clinical subtyping in breast cancer: A comprehensive review

Molecular intrinsic versus clinical subtyping in breast cancer: A comprehensive review

Co-Adjuvant Therapy Efficacy of Catechin and Procyanidin B2 with Docetaxel on Hormone-Related Cancers In Vitro

Cytokines in various molecular subtypes of breast cancer

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