From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

doi:10.1016/j.jsbmb.2015.05.005

Cited by 50 publications

(64 citation statements)

References 136 publications

(175 reference statements)

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“…The bidirectional interaction between ER and RTK pathways frequently conferred resistance to single-drug treatment of endocrine therapy or HER2-targeted therapy. PI3K/AKT/mTOR signaling contained multiple components (e.g., AKT) involved in these processes (3)(4)(5)9). Compared with expression profiling of the reference samples in transcriptional or translational levels ( Fig.…”

Section: Distinct Trastuzumab Response In Coh-sc1 and Coh-sc31 Pdxsmentioning

confidence: 99%

“…Activation of estrogen receptor alpha (ERa) promotes the growth of HR þ tumors. HR þ /HER2 À patients are treated with endocrine therapies, such as aromatase inhibitors (AI) and ERa antagonists (1)(2)(3). HER2 belongs to receptor tyrosine kinase (RTK) family.…”

Section: Introductionmentioning

confidence: 99%

“…A combination of HER2-targeting agents and chemotherapies is recommended for HER2 þ advanced breast cancer (4). HR þ /HER2 þ breast cancer is heterogeneous and bears the concurrent activity of ER and HER2 (3)(4)(5)(6). The HR þ status implies that the ER pathway plays a critical role in directing the clinical features of HR þ /HER2 þ breast cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical studies show that the addition of anti-HER2 therapies significantly improves the clinical outcomes of HR þ /HER2 þ patients treated with AIs (8). Clinical and laboratory studies also suggest that cross-talk between the ER and RTK signaling pathways plays a critical role in resistance to endocrine therapies and anti-HER2 agents in HR þ /HER2 þ breast cancers (3,5). The molecular mechanisms of acquired and de novo resistance to anti-HER2 agents vary in different biological contexts.…”

Section: Introductionmentioning

confidence: 99%

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Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR+/HER2+ Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant

Hsu

Kanaya

et al. 2018

Clinical Cancer Research

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Section: Distinct Trastuzumab Response In Coh-sc1 and Coh-sc31 Pdxsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR+/HER2+ Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant

Hsu

Kanaya

et al. 2018

Clinical Cancer Research

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“…They are ER positive, although often at lower levels compared with HER2-negative tumors. [95][96][97] Tumors from this subtype have a higher expression of such genes as GATA3, BCL2, and ESR1, and a higher frequency of GATA3 mutations. [13][14][15]75 Morphologically, they are mostly grade 2 to 3 tumors (often with low or negative PR), relapse early, show frequent nodal metastasis, and have a diminished response to endocrine therapy.…”

Section: Her2-positive Bcmentioning

confidence: 99%

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Tang¹,

Tse

2016

Archives of Pathology &Amp; Laboratory Medicine

131

109

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Context.-The pioneering works on molecular classification (MC) by Perou and Sorlie et al in the early 2000s using global gene expression profiling identified 5 intrinsic subtypes of invasive breast cancers (IBCs): luminal A, luminal B, normal breast-like, HER2-enriched, and basallike subtypes, each unique in incidence, survival, and response to therapy. Because the application of gene expression profiling in daily practice is not economical or practical at the present time, many investigators have studied the use of immunohistochemical (IHC) surrogates as a substitute for determining the MC of IBC.Objective.-To discuss the continuing efforts that have been made to develop clinically significant and readily available IHC surrogates for the MC of IBC.Data Sources.-Data were obtained from pertinent peer-reviewed English-language literature.Conclusions.-The most commonly used IHC surrogates are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), dividing IBC into luminal, HER2, and triple-negative subtypes. The addition of Ki-67, cytokeratin 5, and epidermal growth factor receptor (EGFR) separates luminal B from luminal A subtypes, and basal-like subtype from triple-negative breast cancer. More recently, biomarkers such as androgen receptor and p53 have been shown to further stratify these molecular subtypes. Although many studies of IHC-based MC have shown clinical significance similar to gene expression profiling-defined MC, its critical limitations are: (1) a lack of standardization in terminology, (2) a lack of standardization in biomarkers used for each subtype, and (3) the lack of a uniform cutoff for each biomarker. A panel of IHC surrogates for each subtype of IBC is proposed.

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Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes

et al. 2022

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ImportanceEvidence suggests that patients with human epidermal growth factor receptor 2–positive (ERBB2+ [formerly HER2+]) metastatic breast cancer (MBC) have different clinical characteristics and outcomes according to their hormone receptor (HR) status. The place of endocrine therapy (ET) for patients with HR+/ERBB2+ is still not clearly defined in this setting.ObjectiveTo evaluate the association of HR status and first-line inclusion of ET with outcomes among patients with ERBB2+ MBC.Design, Setting, and ParticipantsThis cohort study was an analysis of clinical data from the French clinical Epidemiological Strategy and Medical Economics (ESME) cohort, including patients with MBC who started treatment between 2008 and 2017. The last date of follow-up was June 18, 2020. Data were analyzed from May 2021 to May 2022.ExposuresPatients were treated with first-line ERBB2-targeted therapy and either chemotherapy (CT) with or without ET or ET alone. For the study of the association of maintenance ET with outcomes, we included patients treated with first-line ERBB2-targeted therapy with CT and with or without maintenance ET.Main Outcomes and MeasuresMedian overall survival (OS) and median first-line progression-free survival (PFS) were reported using the Kaplan-Meier method. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Multivariable analysis included age at MBC, time to MBC, number of metastatic sites, type of metastases, and Eastern Cooperative Oncology Group performance status.ResultsAmong 4145 women with ERBB2+ MBC, 2696 patients had HR+ (median [IQR] age, 58.0 [47.0-67.0] years) and 1449 patients had HR– (56.0 [47.0-64.0] years) tumors. The median OS for patients with HR+ vs HR− tumors was 55.9 months (95% CI, 53.7-59.4 months) vs 42.0 months (95% CI, 38.8-45.2 months), confirmed in multivariable analysis (hazard ratio, 1.40; 95% CI, 1.26-1.56; P &lt; .001). The median PFS for patients with HR+ vs HR− tumors was 12.2 months (95% CI, 11.5-12.9 months) vs 9.8 months (95% CI, 9.2-11.0 months; P = .01), and the HR was 1.15 (95% CI, 1.06-1.26; P &lt; .001). In multivariable analysis, no significant difference was found in OS or PFS for 1520 patients treated with ERBB2-targeted therapy with CT and with or without ET vs 203 patients receiving ERBB2-targeted therapy with ET, regardless of type of ERBB2-targeted therapy (trastuzumab or trastuzumab with pertuzumab). This result was confirmed by matching patients using a propensity score. Using the time-dependent ET variable among patients with ERBB2-targeted therapy with CT, those with maintenance ET had significantly better PFS (hazard ratio, 0.70; 95% CI, 0.60-0.82; P &lt; .001) and OS (hazard ratio, 0.47; 95% CI, 0.39-0.57; P &lt; .001).Conclusions and RelevanceThese results suggest that ET-containing first-line regimens may be associated with benefits among a subgroup of patients with HR+/ERBB2+ MBC.

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From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

Cited by 50 publications

References 136 publications

Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR+/HER2+ Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant

Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR+/HER2+ Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes

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