ERBB2 Amplification

CI-VAR-00000208Explore in graph →CIViC 306

Curated evidence

Evidence by cancer (100 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 51–100 of 100 evidence items across 20 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Non-Small Cell Carcinoma3
ERBB2 Amplification	Trastuzumab	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID1042 In this phase II trial a small group of patients with IHC2+ or IHC3+ HER2 NSCLC, in which primary platinum-based therapy had failed, were given either docetaxel or trastuzumab after which both groups … (full text at CIViC) PMID 14967075 · Lara et al., 2004 · Open in CIViC	civic
ERBB2 Amplification	Trastuzumab Emtansine	Predictive	D	Supports Sensitivity Response	4	accepted	EID1050 Efficacy of trastuzumab in HER2 overexpressing NSCLC remains unclear. In this study using a panel of NSCLC HER2 overexpressing cell lines, antiproliferative effects of trastuzumab emtansine (T-DM1) w… (full text at CIViC) PMID 24898067 · Cretella et al., 2014 · Open in CIViC

ClinVar

Clinical significance (0)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

Data not yet available

No ClinVar interpretation attached to this variant.

Lung Small Cell Carcinoma1
ERBB2 Amplification	Irinotecan + TrastuzumabCombination	Predictive	C	Supports Sensitivity Response	4	accepted	EID1044 This report details 2 case studies in relapsed HER2 positive SCLC. In the first case, a 50 pack-year patient showed intense non-mutant HER2 expression by IHC without DNA amplification, and had underg… (full text at CIViC) PMID 25601188 · Kinehara et al., 2015 · Open in CIViC	civic

Malignant Biliary Tract Neoplasm1
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Supports Sensitivity Response	2	accepted	EID5983 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Two of seven… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic

Malignant Breast Neoplasm12
ERBB2 Amplification	AKTi-1/2	Predictive	D	Supports Sensitivity Response	3	accepted	EID760 Xenografts established from breast cancer cell lines with ERBB2 amplification and PIK3CA mutation (BT474) or PIK3CA mutation alone (MCF7) were effectively inhibited in-vivo with an AKT1/2-inhibitor (A… (full text at CIViC) PMID 18725974 · She et al., 2008 · Open in CIViC	civic
ERBB2 Amplification	Capecitabine + LapatinibCombination	Predictive	A	Supports Sensitivity Response	4	submitted	EID11247 In a phase III, randomized, open-label trial, 408 women with HER2-positive, locally advanced or metastatic breast cancer that, after treatment with regimens that included an anthracycline, a taxane, a… (full text at CIViC) PMID 17192538 · Geyer et al., 2006 · Open in CIViC	civic
ERBB2 Amplification	Lapatinib + LetrozoleCombination	Predictive	A	Supports Sensitivity Response	4	submitted	EID11248 In a phase III, randomized, double-blind, controlled trial, 219 post-menopausal women with HER2-positive, histologically confirmed stage IIIB/IIIC or IV estrogen receptor-positive and/or progesterone … (full text at CIViC) PMID 19786658 · Johnston et al., 2009 · Open in CIViC	civic
ERBB2 Amplification	Lapatinib + TrastuzumabCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1006 In-vitro studies using ERBB2 over-expressing breast cancer cell lines BT474 and SKBR3 (with ERBB2 amplification) showed apoptosis under either labatinib or trastuzumab treatment. A marked synergistic… (full text at CIViC) PMID 16091755 · Xia et al., 2005 · Open in CIViC	civic
ERBB2 Amplification	Margetuximab	Predictive	A	Supports Sensitivity Response	5	accepted	EID11249 In this phase III, randomized, open-label trial, 536 patients with HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, with at least one being for metastatic disease. T… (full text at CIViC) PMID 33480963 · Rugo et al., 2021 · Open in CIViC	civic
ERBB2 Amplification	MTOR Kinase Inhibitor PP242	Predictive	D	Supports Sensitivity Response	2	accepted	EID1613 In a panel of 31 breast cancer cell lines with varied mutation backgrounds, 10 cell lines harbored HER2 (ERBB2) amplification. Sensitivity to the mTORC1/2 inhibitor PP242 was assessed, and 8/10 HER2 p… (full text at CIViC) PMID 21358673 · Weigelt et al., 2011 · Open in CIViC	civic
ERBB2 Amplification	PI3Ka/Di	Predictive	D	Does Not Support Sensitivity Response	1	submitted	EID8023 As part of a preclinical study, the efficacy of PI3KA/Di—a selective inhibitor for the α and δ subunits of class I PI3K—was evaluated for several cell lines of breast cancer. Sensitivity and resistanc… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
ERBB2 Amplification	Pictilisib	Predictive	D	Supports Sensitivity Response	3	accepted	EID2071 This preclinical study tested the efficacy of GDC-0941, a selective inhibitor of class I PI3K, on several cell lines of breast cancer. Sensitivity and resistance was categorized as less than and more … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
ERBB2 Amplification	Trastuzumab Deruxtecan	Predictive	B	Supports Sensitivity Response	4	submitted	EID7648 In a phase 1 trial, patients with HER2-positive breast cancer were treated with Trastuzumab Deruxtecan (DS-8201a). The response rate was 59.5% (66/111). PMID 31047803 · Tamura et al., 2019 · Open in CIViC	civic
ERBB2 Amplification	Capecitabine + Trastuzumab + TucatinibCombination	Predictive	A	Supports Sensitivity Response	5	submitted	EID11250 In this phase II, randomized, double-blinded, controlled study, 612 patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine. The… (full text at CIViC) PMID 31825569 · Murthy et al., 2020 · Open in CIViC	civic
ERBB2 Amplification AND CDK12 Amplification	Disitamab Vedotin + Trastuzumab Deruxtecan Regimen + Trastuzumab Emtansine RegimenSubstitutes	Predictive	B	Supports Sensitivity Response	3	submitted	EID12569 In a real-world cohort of metastatic breast cancer (n = 63; 30 HER2-positive, 33 HER2-low), patients received HER2-targeted antibody-drug conjugates (trastuzumab deruxtecan (68.25%), disitamab vedotin… (full text at CIViC) PMID 39806366 · Huang et al., 2025 · Open in CIViC	civic
ERBB2 Amplification AND YES1 Amplification	Neratinib	Predictive	D	Supports Resistance	3	submitted	EID12095 Neratinib-resistant cell lines were established by stepwise escalation method and high concentration method in breast cancer cell line BT-474 and lung cancer cell line H2170 with HER2 amplification. E… (full text at CIViC) PMID 31856375 · Takeda et al., 2020 · Open in CIViC	civic

Malignant Colorectal Neoplasm13
ERBB2 Amplification	(oncogenic)	Oncogenic	B	Supports Oncogenicity	4	submitted	EID11485 Altered human epidermal growth factor receptor 2 (HER2) signaling caused by genomic amplification of ERBB2 or mutations is oncogenic and has been observed in multiple cancer types. Based on the study,… (full text at CIViC) PMID 29338072 · Ross et al., 2018 · Open in CIViC	civic
ERBB2 Amplification	Afatinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID7807 Afatinib monotherapy was tested in patient-derived colorectal cancer (M051) mouse xenografts and gastric cancer cell-line (NCI-N87) mouse xenografts. Tumor shrinkage was observed and tumor volume was… (full text at CIViC) PMID 26296355 · Leto et al., 2015 · Open in CIViC	civic
ERBB2 Amplification	Cetuximab	Predictive	B	Supports Resistance	4	accepted	EID1686 A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC) PMID 22586653 · Bertotti et al., 2011 · Open in CIViC	civic
ERBB2 Amplification	Cetuximab	Predictive	B	Supports Resistance	4	accepted	EID1687 A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC) PMID 22586653 · Bertotti et al., 2011 · Open in CIViC	civic
ERBB2 Amplification	Cetuximab	Predictive	B	Supports Resistance	3	accepted	EID1993 We identified 142 patients with metastatic colorectal cancer whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF. All patients received cetuximab aft… (full text at CIViC) PMID 28223103 · Jeong et al., 2017 · Open in CIViC	civic
ERBB2 Amplification	Capecitabine + Cetuximab + OxaliplatinCombination	Predictive	B	Does Not Support Resistance	1	accepted	EID895 141 patients were analyzed for ERBB2 (HER2) positivity by FISH and/or IHC. Only 6 (4.3%) were ERBB2 positive. These patients did not show a difference in outcome after capecitabine, oxaliplatin and ch… (full text at CIViC) PMID 24146218 · Sclafani et al., 2013 · Open in CIViC	civic
ERBB2 Amplification	Cetuximab + PanitumumabSubstitutes	Predictive	B	Supports Resistance	2	accepted	EID1688 HER2 amplification (FISH) was assessed in 170 KRAS wt mCRC patients treated with cetuximab or panitumumab. HER2 copy number status was significantly correlated with response rate, PFS and OS. Patients… (full text at CIViC) PMID 23348520 · Martin et al., 2013 · Open in CIViC	civic
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Supports Sensitivity Response	3	accepted	EID7302 In an updated report of a part of the phase 2a MyPathway trial, 57 patients with treatment-refractory, metastatic colorectal cancer with HER2 amplification received pertuzumab and trastuzumab. Objecti… (full text at CIViC) PMID 30857956 · Meric-Bernstam et al., 2019 · Open in CIViC	civic
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Supports Sensitivity Response	3	accepted	EID11668 In this clinical study of 38 patients with colorectal cancer (CRC), 28 had CRC with ERBB2 amplification, and were treated with a combination of Pertuzumab and Trastuzumab. The DC rate in the patients … (full text at CIViC) PMID 36315917 · Gupta et al., 2022 · Open in CIViC	civic
ERBB2 Amplification	Trastuzumab Deruxtecan	Predictive	B	Supports Sensitivity Response	4	submitted	EID11321 In this open-label, phase II trial, 78 patients were enrolled in the study; for the 53 patients with HER2-positive tumours (cohort A), a confirmed objective response was reported in 24 patients (95% C… (full text at CIViC) PMID 33961795 · Siena et al., 2021 · Open in CIViC	civic
ERBB2 Amplification	Trastuzumab Emtansine	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID7585 In NCI-MATCH, patients with advanced solid tumors other than breast and gastro-esophageal tumors harboring ERBB2 amplification were treated with ad-trastuzumab emtansine (T-DM1). ERBB2 amplification w… (full text at CIViC) PMID 31504139 · Jhaveri et al., 2019 · Open in CIViC	civic
ERBB2 Amplification	Lapatinib + TrastuzumabCombination	Predictive	B	Supports Sensitivity Response	4	accepted	EID1689 Phase 2 study in 27 patients with HER2 positive (IHC, FISH), KRAS wt metastatic colorectal cancer refractory to standard of care received trastuzumab and lapatinib. After a median follow-up of 94 week… (full text at CIViC) PMID 27108243 · Sartore-Bianchi et al., 2016 · Open in CIViC	civic
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Supports Sensitivity Response	4	accepted	EID5981 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Thirty of 1… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic

Malignant Endometrial Neoplasm1
ERBB2 Amplification	Trastuzumab	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID1098 This phase II single arm study assessed trastuzumab monotherapy in HER2 positive endometrial cancers with tumor response as primary endpoint. Participants had stage III, IV or recurrent HER2 positive… (full text at CIViC) PMID 19840887 · Fleming et al., 2010 · Open in CIViC	civic

Malignant Esophageal Neoplasm1
ERBB2 Amplification	Ibrutinib	Predictive	D	Supports Sensitivity Response	3	submitted	EID6929 This study found the clinical BTK/ERBB2 kinase inhibitor, ibrutinib, downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle a… (full text at CIViC) PMID 28830912 · Chong et al., 2018 · Open in CIViC	civic

Malignant Gastric Neoplasm5
ERBB2 Amplification	Afatinib	Predictive	D	Supports Sensitivity Response	3	submitted	EID7808 Afatinib monotherapy was tested in patient-derived colorectal cancer (M051) mouse xenografts and gastric cancer cell-line (NCI-N87) mouse xenografts. Tumor shrinkage was observed and tumor volume was … (full text at CIViC) PMID 26296355 · Leto et al., 2015 · Open in CIViC	civic
ERBB2 Amplification	Chemotherapy + Pembrolizumab + TrastuzumabCombination	Predictive	A	Supports Sensitivity Response	4	submitted	EID11251 In this randomized, double-blind, placebo-controlled, Phase III trial, 264 patients were enrolled with histologically or cytologically confirmed diagnoses of previously untreated, locally advanced, un… (full text at CIViC) PMID 34912120 · Janjigian et al., 2021 · Open in CIViC	civic
ERBB2 Amplification	Trastuzumab	Predictive	A	Supports Sensitivity Response	4	submitted	EID11253 In this open-label, randomized, phase II trial, 187 patients with HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma that had progressed while they were receiving at least two pre… (full text at CIViC) PMID 32469182 · Shitara et al., 2020 · Open in CIViC	civic
ERBB2 Amplification	Trastuzumab Deruxtecan	Predictive	B	Supports Sensitivity Response	3	accepted	EID7647 In a phase 1 trial, 44 patients with HER2-positive gastric or gastroesophageal junction cancer previously treated with trastuzumab were treated with Trastuzumab Deruxtecan (DS-8201a). The response rat… (full text at CIViC) PMID 31047804 · Shitara et al., 2019 · Open in CIViC	civic
ERBB2 Amplification OR ERBB2 Overexpression	Chemotherapy + TrastuzumabCombination	Predictive	A	Supports Sensitivity Response	5	submitted	EID11255 In this phase 3, open-label, randomized controlled trial, 594 patients (584 in the primary analysis) with HER2-positive amplification or overexpression gastric or gastroesophageal junction adenocarcin… (full text at CIViC) PMID 20728210 · Bang et al., 2010 · Open in CIViC	civic

Malignant Lung Neoplasm1
ERBB2 Amplification AND YES1 Amplification	Neratinib	Predictive	D	Supports Resistance	3	submitted	EID12096 Neratinib-resistant cell lines were established by stepwise escalation method and high concentration method in breast cancer cell line BT-474 and lung cancer cell line H2170 with HER2 amplification. E… (full text at CIViC) PMID 31856375 · Takeda et al., 2020 · Open in CIViC	civic

Malignant Neoplasm1
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID12025 In this phase 2 clinical trial, 35 patients harbouring tumours with HER2 amplifications (copy number (CN) ≥7) were treated with a combination of trastuzumab and pertuzumab. Patients with breast/gastro… (full text at CIViC) PMID 38433347 · Connolly et al., 2024 · Open in CIViC	civic

Malignant Pancreatic Neoplasm2
BRAF V600E AND ERBB2 Amplification AND SMAD4 LOSS AND TP53 V218E	Bevacizumab + Lapatinib + Trametinib + TrastuzumabCombination	Predictive	C	Supports Sensitivity Response	3	submitted	EID11712 In this clinical trial, 18 patients with pancreatic cancer were recruited. In this case, the patient (74 y/F) with pancreatic cancer harboring, BRAF V600E, SMAD4 Loss, ERBB2 amplification, and, TP53 V… (full text at CIViC) PMID 36670111 · Shaya et al., 2023 · Open in CIViC	civic
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Supports Sensitivity Response	2	accepted	EID5985 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Two of nine … (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic

Malignant Salivary Gland Neoplasm1
ERBB2 Amplification	Trastuzumab Emtansine	Predictive	B	Supports Sensitivity Response	3	submitted	EID7856 In NCI-MATCH, patients with advanced solid tumors other than breast and gastro-esophageal tumors harboring ERBB2 amplification were treated with ad-trastuzumab emtansine (T-DM1). ERBB2 amplification w… (full text at CIViC) PMID 31504139 · Jhaveri et al., 2019 · Open in CIViC	civic

Malignant Uterine Neoplasm1
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID5986 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. None of the … (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic

Ovarian Mucinous Adenocarcinoma1
ERBB2 Amplification	Carboplatin + TrastuzumabCombination	Predictive	C	Supports Sensitivity Response	2	submitted	EID13137 Ovarian mucinous carcinoma responds poorly to paclitaxel and carboplatin, prompting interest in targeted therapy, and it resembles gastro-oesophageal adenocarcinoma, a tumour type in which HER2 (ERBB2… (full text at CIViC) PMID 20003286 · McAlpine et al., 2009 · Open in CIViC	civic

Pancreatic Adenocarcinoma1
ERBB2 Amplification	Afatinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID962 Afatinib was growth-inhibitory for three pancreatic cancer cell lines but cytotoxic only toward BxPC3 (KRAS wt) and Capan-2 (KRAS mut) cells, both of which express high levels of EGFR, ERBB2, and ERBB… (full text at CIViC) PMID 26668065 · Huguet et al., 2016 · Open in CIViC	civic

Pancreatic Ductal Adenocarcinoma1
ERBB2 Amplification	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID11563 The ERRB2 amplification effect in PDAC was studied through CAPAN1 cells and ERBB2-KO (knockout) CAPAN1 cells that were KO using CRISPR (Figure 4C, Supp Table 4), with a 90% reduction of ERBB2 compared… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic

Salivary Gland Carcinoma1
ERBB2 Amplification	Pertuzumab + TrastuzumabCombination	Predictive	B	Supports Sensitivity Response	2	accepted	EID5984 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Four of five… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic

Scrotal Paget Disease1
ERBB2 Amplification	Trastuzumab	Predictive	C	Supports Sensitivity Response	2	accepted	EID1693 A 71-year old male with metastatic extramammary Paget’s disease of the scrotum overexpressing Her2/neu was treated with trastuzumab, achieving a complete response. At 12 months, he maintains stable di… (full text at CIViC) PMID 25692060 · Barth et al., 2015 · Open in CIViC	civic

Transitional Cell Carcinoma1
ERBB2 Amplification	Afatinib	Predictive	B	Supports Sensitivity Response	2	submitted	EID7810 In this phase II trial, patients with metastatic platinum-refractory urothelial carcinoma (UC) received afatinib (40 mg/day). Among the 21 tumors, five of six patients (83.3%) with ERBB2 (HER2) and/or… (full text at CIViC) PMID 27044931 · Choudhury et al., 2016 · Open in CIViC	civic

Uterine Corpus Endometrial Carcinoma1unmapped disease
ERBB2 Amplification	Afatinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID886 Eight uterine cancer cell lines (four with ERBB2 amplification and four without) were treated with scalar concentrations of afatinib. Primary chemotherapy-resistant USC cell lines harbouring ERBB2 gen… (full text at CIViC) PMID 25268372 · Schwab et al., 2014 · Open in CIViC	civic