ERBB2 L755S

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Colorectal Adenocarcinoma1
ERBB2 L755S	Fluorouracil + Leucovorin + TrastuzumabCombination	Predictive	C	Does Not Support Sensitivity Response	3	accepted	EID4955 Patient was a 35 year old male who was treated with pseudoadjuvant FOLFOX chemotherapy. Patient relapsed and was found to have an ERBB2 L755S kinase domain mutation along with mutations in APC and BRA… (full text at CIViC) PMID 27626067 · Aung et al., 2016 · Open in CIViC	civic
Lung Non-Small Cell Carcinoma1
ERBB2 L755S	Trastuzumab Deruxtecan	Predictive	A	Supports Sensitivity Response	2	submitted	EID12233 In the phase 2 DESTINY-Lung02 trial, 152 metastatic NSCLC patients harbouring mutations in ERBB2 (HER2) were treated with the HER2 antibody-drug-conjugate (ADC) trastuzumab deruxtecan (5.4 mg/kg or 6.…

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Colorectal Adenocarcinoma1

ERBB2 L755S

Fluorouracil + Leucovorin + TrastuzumabCombination

Predictive

Does Not Support Sensitivity Response

accepted

EID4955

Patient was a 35 year old male who was treated with pseudoadjuvant FOLFOX chemotherapy. Patient relapsed and was found to have an ERBB2 L755S kinase domain mutation along with mutations in APC and BRA… (full text at CIViC)

PMID 27626067 · Aung et al., 2016 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma1

ERBB2 L755S

Trastuzumab Deruxtecan

Predictive

Supports Sensitivity Response

submitted

EID12233

In the phase 2 DESTINY-Lung02 trial, 152 metastatic NSCLC patients harbouring mutations in ERBB2 (HER2) were treated with the HER2 antibody-drug-conjugate (ADC) trastuzumab deruxtecan (5.4 mg/kg or 6.…

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
376035	-	-	—	Neoplasm	somatic	1	—	clinvar

Variation

Clinical significance

Review status

Stars

Conditions

Origin

Submitters

Last evaluated

Source

376035

—

Neoplasm

somatic

—

clinvar

Malignant Breast Neoplasm3
ERBB2 L755S	Canertinib	Predictive	D	Supports Sensitivity Response	3	submitted	EID10022 A series of HER2 (ERBB2) mutations (G309A, D769H, D769Y, V777L, P780ins, V824I, R678Q, R896C, del755-759, and L755S) were functionally characterized and tested for sensitivity to lapatinib or neratini… (full text at CIViC) PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic
ERBB2 L755S	Lapatinib	Predictive	D	Supports Resistance	5	accepted	EID241 The L755S mutation was shown to confer resistance to lapatinib in MCF10A cell lines retrovirally transduced with wildtype or mutant ERBB2. PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic
ERBB2 L755S	Neratinib	Predictive	D	Supports Sensitivity Response	5	accepted	EID283 The L755S mutation showed mild response to neratinib in MCF10A cell lines retrovirally transduced with wildtype or mutant ERBB2. PMID 23220880 · Bose et al., 2013 · Open in CIViC	civic

Malignant Breast Neoplasm3

ERBB2 L755S

Canertinib

Predictive

Supports Sensitivity Response

submitted

EID10022

A series of HER2 (ERBB2) mutations (G309A, D769H, D769Y, V777L, P780ins, V824I, R678Q, R896C, del755-759, and L755S) were functionally characterized and tested for sensitivity to lapatinib or neratini… (full text at CIViC)

PMID 23220880 · Bose et al., 2013 · Open in CIViC

civic

ERBB2 L755S

Lapatinib

Predictive

Supports Resistance

accepted

EID241

The L755S mutation was shown to confer resistance to lapatinib in MCF10A cell lines retrovirally transduced with wildtype or mutant ERBB2.

PMID 23220880 · Bose et al., 2013 · Open in CIViC

civic

ERBB2 L755S

Neratinib

Predictive

Supports Sensitivity Response

accepted

EID283

The L755S mutation showed mild response to neratinib in MCF10A cell lines retrovirally transduced with wildtype or mutant ERBB2.

PMID 23220880 · Bose et al., 2013 · Open in CIViC

civic

Malignant Colon Neoplasm1
ERBB2 L755S	Lapatinib + Neratinib + TrastuzumabCombination	Predictive	D	Supports Sensitivity Response	4	accepted	EID1176 Colon cancer patient derived xenografts with HER2 mutations are sensitive to HER2 targeted drugs and the greatest tumor reduction was seen with the combination of a tyrosine kinase inhibitor with tras… (full text at CIViC) PMID 26243863 · Kavuri et al., 2015 · Open in CIViC	civic

Malignant Colon Neoplasm1

ERBB2 L755S

Lapatinib + Neratinib + TrastuzumabCombination

Predictive

Supports Sensitivity Response

accepted

EID1176

Colon cancer patient derived xenografts with HER2 mutations are sensitive to HER2 targeted drugs and the greatest tumor reduction was seen with the combination of a tyrosine kinase inhibitor with tras… (full text at CIViC)

PMID 26243863 · Kavuri et al., 2015 · Open in CIViC

civic

Malignant Colorectal Neoplasm1
ERBB2 L755S	Cetuximab	Predictive	D	Supports Resistance	3	accepted	EID4519 In an in vitro study, NCI-H508 cell lines expressing an ERBB2 L755S mutation demonstrated resistance to cetuximab treatment (IC50 > 200 ug/mL) compared with NCI-H508 cells expressing ERBB2 wild type (… (full text at CIViC) PMID 26243863 · Kavuri et al., 2015 · Open in CIViC	civic

Malignant Colorectal Neoplasm1

ERBB2 L755S

Cetuximab

Predictive

Supports Resistance

accepted

EID4519

In an in vitro study, NCI-H508 cell lines expressing an ERBB2 L755S mutation demonstrated resistance to cetuximab treatment (IC50 > 200 ug/mL) compared with NCI-H508 cells expressing ERBB2 wild type (… (full text at CIViC)

PMID 26243863 · Kavuri et al., 2015 · Open in CIViC

civic

Malignant Neoplasm1
ERBB2 L755S	Lapatinib	Predictive	D	Supports Resistance	2	accepted	EID3004 Cell proliferation analysis of Ba/F3 cells expressing ERBB2-L755S showed IC50 value of >2000nM, and was considered as lapatinib-resistant. PMID 22046346 · Kancha et al., 2011 · Open in CIViC	civic

Malignant Neoplasm1

ERBB2 L755S

Lapatinib

Predictive

Supports Resistance

accepted

EID3004

Cell proliferation analysis of Ba/F3 cells expressing ERBB2-L755S showed IC50 value of >2000nM, and was considered as lapatinib-resistant.

PMID 22046346 · Kancha et al., 2011 · Open in CIViC

civic

Pancreatic Ductal Adenocarcinoma2
ERBB2 L755S	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID11557 HPNE cells infected with lentiviral vectors containing the variant did show significant phosphorylation of ERBB2 (Supplementary Figure 1) compared to WT (Figure 2A and B). The variant also exhibits an… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic
ERBB2 L755S AND KRAS G12D	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID11558 KRAS G12D-transformed HPNE cells with lentiviral vectors containing the variant significantly increased colony formation in number and size in soft agar compared to infected HPNE cells with the varian… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic

Pancreatic Ductal Adenocarcinoma2

ERBB2 L755S

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID11557

HPNE cells infected with lentiviral vectors containing the variant did show significant phosphorylation of ERBB2 (Supplementary Figure 1) compared to WT (Figure 2A and B). The variant also exhibits an… (full text at CIViC)

PMID 31046123 · Li et al., 2020 · Open in CIViC

civic

ERBB2 L755S AND KRAS G12D

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID11558

KRAS G12D-transformed HPNE cells with lentiviral vectors containing the variant significantly increased colony formation in number and size in soft agar compared to infected HPNE cells with the varian… (full text at CIViC)

PMID 31046123 · Li et al., 2020 · Open in CIViC

civic

Triple-Negative Breast Carcinoma1
ERBB2 L755S	Capecitabine + NeratinibCombination	Predictive	C	Supports Sensitivity Response	2	submitted	EID8055 This patient originally presented in the clinic with an ER+, PR-, and HER2- mass on the left breast and bone metastasis. Family history showed negative germline mutations in BRCA1/2. Patient responded… (full text at CIViC) PMID 26358790 · Ben-Baruch et al., 2015 · Open in CIViC	civic

Triple-Negative Breast Carcinoma1

ERBB2 L755S

Capecitabine + NeratinibCombination

Predictive

Supports Sensitivity Response

submitted

EID8055

This patient originally presented in the clinic with an ER+, PR-, and HER2- mass on the left breast and bone metastasis. Family history showed negative germline mutations in BRCA1/2. Patient responded… (full text at CIViC)

PMID 26358790 · Ben-Baruch et al., 2015 · Open in CIViC

civic

HER2 Negative Breast Cancer1unmapped disease
ERBB2 L755S	(prognostic)	Prognostic	C	Supports Better Outcome	2	submitted	EID8015 Though limited to one case, Ben-Beruch et al provide compelling evidence individuals with HER2 mutations regardless of HER2 IHC status may benefit from neratinib alone or in combination. Case study of… (full text at CIViC) PMID 26358790 · Ben-Baruch et al., 2015 · Open in CIViC	civic

HER2 Negative Breast Cancer1unmapped disease

ERBB2 L755S

(prognostic)

Prognostic

Supports Better Outcome

submitted

EID8015

Though limited to one case, Ben-Beruch et al provide compelling evidence individuals with HER2 mutations regardless of HER2 IHC status may benefit from neratinib alone or in combination. Case study of… (full text at CIViC)

PMID 26358790 · Ben-Baruch et al., 2015 · Open in CIViC

civic

Evidence by cancer (12 items)

Clinical significance (1)