Molecular Subtype
HER2-Positive Breast Carcinoma
CI-CAN-00007795Explore in graph →
140 active trials3 approved drugs93 evidence items
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Molecular Subtype
CI-CAN-00007795Explore in graph →
Variants & evidence
117 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|
| BIRC5 Overexpression1 | |||||||
| Trastuzumab | Predictive | B | Supports Resistance | 4 | accepted | EID144913 HER2 breast cancer patients were treated with trastuzumab and then trastuzumab + docetaxel prior to surgery. Pretreatment biopsies and post-treatment surgical samples were obtained, and microarray … (full text at CIViC) PMID 23204226 · Chakrabarty et al., 2013 · Open in CIViC | civic |
| ZNF880 Fusion1 | |||||||
| Pyrotinib | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID11215Case report describing a 34-year-old female patient without a family history of breast cancer. After a radical mastectomy, histopathology revealed an invasive ductal carcinoma HER2 positive (FISH). Sh… (full text at CIViC) PMID 33371069 · Yue et al., 2020 · Open in CIViC | civic |
| ERBB2 Amplification34 | |||||||
| A66 | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1381Pharmacologic (A66; p110alpha specific inhibitor) or genetic (cre-mediated knockout) ablation of the p110alpha PI3K isoform reduced tumor growth and tumor formation, respectively, in athymic mice tran… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC | civic |
| Afatinib | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID1012LUX-Breast 1 is a phase 3 trial (NCT01125566) which enrolled 508 patients with metastatic HER2 positive BC who had progressed after adjuvant or first-line trastuzumab. It was thought that the wider ra… (full text at CIViC) PMID 26822398 · Harbeck et al., 2016 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID961A phase II study involving adult female patients, >=18 years, with stage IIIB or IV HER2-positive (by IHC and/or in situ fluorescence) metastatic breast cancer. All patients were previously treated wi… | |
| ERBB2 Overexpression1 | |||||||
| Trastuzumab Emtansine | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID4840Trastuzumab emtansine has its indication for patients with HER2-positive metastatic breast cancer after therapy with Trastuzumab and Taxane, approval based on PFS and preliminary OS data. EMILIA was a… (full text at CIViC) PMID 28526536 · Diéras et al., 2017 · Open in CIViC | civic |
| ERBB2 V777L1 | |||||||
| Trastuzumab + Trastuzumab EmtansineSubstitutes | Predictive | C | Supports Resistance | 3 | submitted | EID5817In a cohort of 205 Her2-receptor amplified breast cancers, 20 experienced recurrence after trastuzumab therapy. Of the 20 recurrent cases, only six patients had metastatic sites, excluding brain metas… (full text at CIViC) PMID 27900589 · Hirotsu et al., 2017 · Open in CIViC | civic |
| ERBB3 Overexpression1 | |||||||
| Trastuzumab Emtansine | Predictive | B | Does Not Support Resistance | 2 | accepted | EID8707In a phase 3 clinical trial (NCT00829166), metastatic HER-2 amplified breast cancer patients whose tumors harbored higher than median levels of ERBB3 mRNA treated with ado-trastuzumab emtansine (T-DM1… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC | civic |
| ERBB4 EXPRESSION2 | |||||||
| (prognostic) | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID1961Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased trastuzumab-induced HER4 nuclear translocation and enhanced trastuzumab response… (full text at CIViC) PMID 25153719 · Mohd Nafi et al., 2014 · Open in CIViC | civic |
| Trastuzumab | Predictive | D | Supports Resistance | 2 | accepted | EID868siRNA knockdown of HER4 or inhibition with neratinib enhanced trastuzumab response in breast cancer cell lines. PMID 25153719 · Mohd Nafi et al., 2014 · Open in CIViC | civic |
| FCGR2A H167R1 | |||||||
| Trastuzumab | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID10881325 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy from the N9831 clinical trial were analyzed. There was no statistical difference in disease-free survival between tr… (full text at CIViC) PMID 24989892 · Norton et al., 2014 · Open in CIViC | civic |
| FCGR3A F212V1 | |||||||
| Trastuzumab | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID10871325 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy from the N9831 clinical trial were analyzed. There was no statistically significant difference in disease-free survi… (full text at CIViC) PMID 24989892 · Norton et al., 2014 · Open in CIViC | civic |
| FGFR4 Overexpression1 | |||||||
| Dovitinib + FGF/VEGF Receptor Tyrosine Kinase Inhibitor, PD173074Substitutes | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID5828ERBB2-positive breast cancer cell lines including MDA-MB-361 and MDA-MB-453 were found to display outlier expression of FGFR4. Targeting FGFR4 in FGFR4 overexpressing ERBB2-positive breast cancer samp… (full text at CIViC) PMID 24124571 · Li et al., 2013 · Open in CIViC | civic |
| PIK3CA Amplification3 | |||||||
| Dactolisib + TrastuzumabCombination | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8272In a preclinical study, efficacy of NVP-BEZ235 (dactolisib) and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirally induced PI… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + Lapatinib + TrastuzumabCombination | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8273In a preclinical study, efficacy of NVP-BEZ235 (dactolisib), lapatinib, and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirall… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + LapatinibSubstitutes | Predictive | ||||||
| PIK3CA C420R3 | |||||||
| Pictilisib | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID2078This preclinical study tested the efficacy on several HER2 amplified breast cancer cell lines of GDC-0941 (pictilisib), a selective inhibitor of all four isoforms of class I PI3-kinases at a range of … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC | civic |
| Trastuzumab | Predictive | D | Supports Resistance | 2 | accepted | EID8549As part of a pre-clinical experiment, the efficacy of trastuzumab was evaluated against various HER2 positive cell lines. EFM-192A cell line expressing PIK3CA C420R was associated with resistance to t… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC | civic |
| Trastuzumab Emtansine | Predictive | D | Does Not Support Resistance | 3 | accepted | EID2346As part of a pre-clinical experiment, the efficacy of ado-trastuzumab emtansine (T-DM1) was compared to that of trastuzumab against various HER2 positive cell lines. EFM-192A cell line expressing PIK3… | |
Data updated 11 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
PMID 22418700 · Lin et al., 2012 · Open in CIViC
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| 〃 | Predictive | B | Supports Sensitivity Response | 3 | rejected | EID1010With multiple mechanisms of HER reprogramming thought to be behind trastuzumab resistance, including increased expression of ErbB members, afatinib, which broadly and irreversibly targets ErbB recepto… (full text at CIViC) PMID 22418700 · Lin et al., 2012 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1011This Phase II trial (LUX-Breast 3 - NCT01441596) compared afatinib, afatinib plus vinorelbine, or investigator's choice of treatment. 121 patients with HER2 overexpressing breast cancer with CNS recu… (full text at CIViC) PMID 26596672 · Cortés et al., 2015 · Open in CIViC | civic |
| Afatinib + Lapatinib + TrastuzumabSubstitutes | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID887In this phase 2 trial, treatment-naive, ERBB2-positive (by IHC) breast cancer patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to afatinib (n = 10), lapatinib (n = 8), or t… (full text at CIViC) PMID 25537159 · Rimawi et al., 2015 · Open in CIViC | civic |
| Afatinib + TrastuzumabCombination | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1013Trastuzumab resistance is thought to consist of multiple compensatory mechanisms involving ErbB family members such as increased signaling through ErbB family heterodimers. The irreversible TKI afati… (full text at CIViC) PMID 25370464 · Ring et al., 2015 · Open in CIViC | civic |
| Capecitabine + LapatinibCombination | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1132This Phase III trial took patients with locally advanced or metastatic HER2 (ERBB2) positive breast cancer that had progressed on prior trastuzumab treatment. Patients were given capecitabine (n=161)… (full text at CIViC) PMID 17192538 · Geyer et al., 2006 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1007In light of results showing increased PFS using mAB plus TKI in heavily pretreated patients, the efficacy of trastuzumab plus lapatinib in a neoadjuvant setting with untreated stage II or IIIA HER2 po… (full text at CIViC) PMID 22493419 · Guarneri et al., 2012 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1009This Phase III study (EGF104900) was motivated by preclinical and other data demonstrating synergistic activity between lapatinib and trastuzumab against HER2 positive breast cancer (BC) cells. In th… (full text at CIViC) PMID 20124187 · Blackwell et al., 2010 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1439In a randomized open label phase 3 study (NCT00553358), women with HER2 positive primary breast cancer treated with lapatinib plus trasuzumab had higher rates of pathological complete responses than s… (full text at CIViC) PMID 22257673 · Baselga et al., 2012 · Open in CIViC | civic |
| Neratinib | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID761Oral neratinib showed objective response rates of 24 and 56% respectively in prior-trastuzumab (n=63) and trastuzumab-naive (n=64) cohorts in a Phase II trial. As for the primary endpoint, the 16-week… (full text at CIViC) PMID 20142587 · Burstein et al., 2010 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8072A panel of HER2 positive breast cancer cell lines (n=12) displayed greater sensitivity to Neratinib (HKI-272) compared to triple negative breast cancer cell lines (n=15, p=.0002) and luminal breast ca… (full text at CIViC) PMID 24009064 · Canonici et al., 2013 · Open in CIViC | civic |
| 〃 | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8073Two HER2 positive breast cancer cells lines were 480-times more sensitive to Neratinib (HKI-272) compared to a HER2 negative breast cancer cell line (MDA-MB-435) as indicated by decreased proliferatio… (full text at CIViC) PMID 15173008 · Rabindran et al., 2004 · Open in CIViC | civic |
| Capecitabine + NeratinibCombination | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID8048A phase III clinical trial (NALA, NCT01808573) with a randomized parallel design of 621 patients evaluated the combination therapy of Neratinib plus capecitabine (N+C) (307 pts.) vs. Lapatinib plus ca… (full text at CIViC) | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID8050A Phase II clinical trial (NCT00741260 ) assessed the safety and efficacy of Neratinib plus capecitabine in the treatment of HER2 positive breast cancer patients. Of the 72 patients in this study, 65 … (full text at CIViC) PMID 25287822 · Saura et al., 2014 · Open in CIViC | civic |
| Neratinib + TrastuzumabSequential | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID1113In this two arm, Phase III study (NCT00878709) of the efficacy of a 12 month course of the TKI neratinib after trastuzumab-based adjuvant therapy of early stage HER2-positive breast cancer was assesse… (full text at CIViC) PMID 26874901 · Chan et al., 2016 · Open in CIViC | civic |
| Docetaxel + Pertuzumab + TrastuzumabCombination | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID1077CLEOPATRA (NCT00567190) was a Phase III, randomized and double-blind, placebo-controlled study of 808 patients with HER2-positive metastatic breast cancer. Patients were HER2-positive by IHC3+ or FIS… (full text at CIViC) PMID 25693012 · Swain et al., 2015 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1437In a randomized phase 3 trial, HER2 positive metastatic breast cancer patients given first-line treatment of pertuzumab plus trastuzumb plus docetaxel experienced improved progression free survival (1… (full text at CIViC) PMID 22149875 · Baselga et al., 2012 · Open in CIViC | civic |
| Pictilisib | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1380The HER2/Neu mammary tumor mouse model MMTV-NeuT was employed to demonstrate dependence of HER2 tumor formation on PIK3 p110alpha isoform. MMTV-NeuT mice were crossed with floxed p110alpha mice. Diass… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC | civic |
| Tgx 221 | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID1382Treatment of cells obtained from MMTV-NeuT mouse mammary tumors with the p110beta selective inhibitor TGX-221 showed significant but minimal reductions in lipid kinase activity and negligible reductio… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC | civic |
| Trastuzumab | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID1122HERA was a Phase III trial assessing application of trastuzumab in an extended adjuvant setting. Patients were HER2 positive with completely excised invasive BC, node positive or negative, and having… (full text at CIViC) PMID 16236737 · Piccart-Gebhart et al., 2005 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID528A randomized clinical trial of 469 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved time to disease progression, objective response rate, and duration … (full text at CIViC) PMID 11248153 · Slamon et al., 2001 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID529A randomized clinical trial of 186 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved overall survival, response rate, response duration, time to progres… (full text at CIViC) PMID 15911866 · Marty et al., 2005 · Open in CIViC | civic |
| Capecitabine + TrastuzumabCombination | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1133In this Phase III trial, trastuzumab-based treatment was assessed in women with locally advanced or metastatic HER2 positive breast cancer who had progressed on trastuzumab. Patients had 12 weeks or … (full text at CIViC) PMID 19289619 · von Minckwitz et al., 2009 · Open in CIViC | civic |
| Trastuzumab Emtansine | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1159The Phase III trial, TH3RESA (NCT01419197), was performed in patients with advanced HER2 breast cancer that was heavily pretreated. Patients were required to have prior exposure to trastuzumab and la… (full text at CIViC) PMID 24793816 · Krop et al., 2014 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1160The EMILIA study (NCT00829166) was a Phase II trial to assess the efficacy of trastuzumab emtansine (T-DM1, n=495) in comparison to lapatinib plus capecitabine (n=496), in treatment of advanced HER2 p… (full text at CIViC) PMID 23020162 · Verma et al., 2012 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1764In the single arm Phase II study (TDM4258g) breast cancer patients who had progressed on previous anti-HER2 therapy were given transtuzumab emtansine (T-DM1), a HER2 monoclonal antibody and antimicrot… (full text at CIViC) PMID 21172893 · Burris et al., 2011 · Open in CIViC | civic |
| 〃 | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1432In a randomized phase II study, first line treatment of HER2-positive metastatic breast cancer with trastuzumab emtansine (T-DM1) resulted in improved progression free survival and fewer serious adver… (full text at CIViC) PMID 23382472 · Hurvitz et al., 2013 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID1008This Phase III trial compared the activity of lapatinib vs. trastuzumab vs. sequential trastuzumab followed by lapatinib vs. lapatinib plus trastuzumab in an adjuvant treatment setting. 8381 women we… (full text at CIViC) PMID 26255196 · Zardavas et al., 2015 · Open in CIViC | civic |
| Neratinib + TrastuzumabSequential | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID8047Primarily based on the results from the phase III ExteNET clinical trial (Study 3004, NCT00878709), on July 17, 2017, the FDA approved neratinib (NERLYNX, HKI-272) for extended adjuvant therapy of adu… (full text at CIViC) PMID 29523624 · Singh et al., 2018 · Open in CIViC | civic |
| 〃 | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID8049The initial 2 year follow-up of the Phase III clinical trial (exteNET, NCT00878709) where early stage HER2 positive breast cancer patients underwent adjuvant trastuzumab therapy and then either receiv… (full text at CIViC) PMID 29146401 · Martin et al., 2017 · Open in CIViC | civic |
| Palbociclib + TrastuzumabCombination | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1561In a panel of 47 breast cancer cell lines, HER2 overexpressing cells were among those more sensitive to CDK4/6 inhibitor Palbociclib (PD0332991). In the trastuzumab sensitive cell line Bt474, palbocic… (full text at CIViC) PMID 19874578 · Finn et al., 2009 · Open in CIViC | civic |
| Pilaralisib + TrastuzumabCombination | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID1448In 5 trastuzumab resistant HER2 overexpressing breast cancer cell lines, combination of the pan-PI3K inhibitor XL147 (pilaralisib) and trastuzumab treatment induced cell death to similar or greater le… (full text at CIViC) PMID 23204226 · Chakrabarty et al., 2013 · Open in CIViC | civic |
| D |
| Supports Sensitivity Response |
| 2 |
| accepted |
EID8271This preclinical study tested the sensitivity of HER2-positive breast cancer cell line BT-474 (heterozygous for PIK3CA K111N) retrovirally transduced with wildtype PIK3CA to NVP-BEZ235 (dactolisib; a … (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC |
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PMID 26920887 · Baselga et al., 2016 · Open in CIViC
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