Variant · Snv

PIK3CA H1047R

CI-VAR-00001873Explore in graph →NP_006209.2:p.His1047ArgNM_006218.3:c.3140A>GClinVar 13652 CIViC 107 rs121913279

Curated evidence

Evidence by cancer (43 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 1–43 of 43 evidence items across 12 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
Breast Tubular Carcinoma1
PIK3CA H1047R OR PIK3CA H1047L	(prognostic)	Prognostic	B	Supports Poor Outcome	1	accepted	EID3047 In a retrospective analysis of 32 Western Chinese female patients with invasive ductal breast cancer, PIK3CA H1047L (n=1) or H1047R (n=8) was associated with worse survival and increased incidence of … (full text at CIViC) PMID 28269754 · Cheng et al., 2017 · Open in CIViC	civic
Head and Neck Squamous Cell Carcinoma1
PIK3CA H1047R	Taselisib	Predictive	D	Supports Sensitivity Response	2	accepted	EID1465 The Cal-33 HNSCC cell line with H1047R mutation was found to have a low antiproliferative IC50 value for the alpha, gamma and delta isoform-specific PI3K inhibitor taselisib. Increasing taselisib conc… (full text at CIViC)

ClinVar

Clinical significance (1)

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

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
13652	Pathogenic	reviewed by expert panel	3	Carcinoma of colon; Hepatocellular carcinoma; Non-small cell lung carcinoma; Seborrheic keratosis; OVARIAN CANCER, EPITHELIAL, SOMATIC; Breast adenocarcinoma; CLOVES syndrome; Ovarian neoplasm; PIK3CA related overgrowth syndrome; Neoplasm; Rosette-forming glioneuronal tumor; MACRODACTYLY, SOMATIC; Lip and oral cavity carcinoma; Abnormal cardiovascular system morphology; Congenital macrodactylia; Megalencephaly-capillary malformation-polymicrogyria syndrome; CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC; CLAPO syndrome; Cerebrofacial Vascular Metameric Syndrome (CVMS); Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes; Segmental undergrowth associated with mainly venous malformation with capillary component; Segmental undergrowth associated with lymphatic malformation; Gastric cancer; Rare venous malformation; Breast carcinoma; Rare combined vascular malformation; Klippel-Trenaunay-like-Syndrome; PIK3CA-related disorder; PIK3CA-Related Overgrowth Spectrum Disorders; Nasopharyngeal carcinoma; Diffuse midline glioma, H3 K27M-mutant; Diffuse glioma, H3 G34 mutant; Neuroblastoma; Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; Cavernous lymphangioma; Cervical squamous cell carcinoma; Glioma; Colorectal cancer; Adenoid cystic carcinoma; Embryonal rhabdomyosarcoma

HER2-Positive Breast Carcinoma12
PIK3CA H1047R	Capivasertib + LapatinibCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1506 The HER2 breast cancer cell line KPL4 with PIK3CA H1047R shows sub-optimal responses to trastuzumab and lapatinib, and was used to establish mouse xenografts. Treatment of mice with monotherapy of AZD… (full text at CIViC) PMID 22294718 · Davies et al., 2012 · Open in CIViC	civic
PIK3CA H1047R	Capivasertib + TrastuzumabCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1505 Tumor xenografts in mice were established with the KPL4 HER2 positive breast cancer cell line with PIK3CA H1047R mutation. KPL4 has suboptimal responses to trastuzumab and lapatinib. Xengraft treatmen… (full text at CIViC) PMID 22294718 · Davies et al., 2012 · Open in CIViC	civic
PIK3CA H1047R	Dactolisib	Predictive	D	Does Not Support Resistance	4	accepted	EID6206 This preclinical study tested the sensitivity of HER2-positive breast cancer cell line BT-474 (heterozygous for PIK3CA K111N) retrovirally transduced with PIK3CA H1047R to NVP-BEZ235 (dactolisib; a du… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC	civic
PIK3CA H1047R	Dactolisib + TrastuzumabCombination	Predictive	D	Supports Sensitivity Response	2	submitted	EID8182 In a preclinical study, efficacy of trastuzumab and NVP-BEZ235 (dactolisib) 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
PIK3CA H1047R	Everolimus + FulvestrantCombination	Predictive	C	Supports Sensitivity Response	2	accepted	EID1623 Case report of a 44-year-old patient with recurrent HER2-positive breast cancer. The primary tumor was HR positive; however, the metastatic tumor was HR negative. The patient was resistant to classica… (full text at CIViC) PMID 27445490 · Sun et al., 2016 · Open in CIViC	civic
PIK3CA H1047R	Lapatinib	Predictive	D	Supports Resistance	3	accepted	EID6202 This preclinical study tested, in vitro, the resistance to lapatinib (an anti-HER2 drug) of HER2-positive breast cancer cell lines (BT474 and SKBR3) retrovirally transduced with H1047R. The study foun… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC	civic
PIK3CA H1047R	Dactolisib + LapatinibCombination	Predictive	D	Does Not Support Resistance	3	submitted	EID6205 This preclinical study tested the sensitivity to lapatinib and NVP-BEZ235 (dactolisib; a dual PI3K/mTOR inhibitor) of a HER2-positive breast cancer cell line (BT474) retrovirally transduced with PIK3C… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC	civic
PIK3CA H1047R	Lapatinib + TrastuzumabCombination	Predictive	D	Supports Resistance	4	accepted	EID6204 In a preclinical study, efficacy of lapatinib and trastuzumab was evaluated in vitro against HER2 amplified breast cancer cell line BT474 (heterozygous for PIK3CA K111N) retrovirally transduced with P… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC	civic
PIK3CA H1047R	Pictilisib	Predictive	D	Supports Sensitivity Response	4	accepted	EID2096 This preclinical study tested the efficacy on several breast cancer cell lines of GDC-0941 (pictilisib), a selective inhibitor of all four isoforms of class I PI3-kinases at a range of IC50 values. Se… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
PIK3CA H1047R	Trastuzumab	Predictive	D	Supports Resistance	3	accepted	EID6203 This preclinical study tested the effect of trastuzumab (an anti-HER2 drug) on HER2-positive breast cancer cell lines (BT474 and SKBR3) retrovirally transduced with H1047R. The study found that the H1… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC	civic
PIK3CA H1047R	Trastuzumab	Predictive	D	Supports Resistance	2	accepted	EID8548 As part of a pre-clinical experiment, the efficacy of trastuzumab was evaluated against various HER2 positive cell lines. CC1954 and KPL-4 cell lines expressing PIK3CA H1047R were associated with resi… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC	civic
PIK3CA H1047R	Trastuzumab Emtansine	Predictive	D	Does Not Support Resistance	3	accepted	EID2103 As 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. HCC1954 and KPL-4 cell lines expre… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC	civic

HER2-Positive Breast Carcinoma12

PIK3CA H1047R

Capivasertib + LapatinibCombination

Predictive

Supports Sensitivity Response

accepted

EID1506

The HER2 breast cancer cell line KPL4 with PIK3CA H1047R shows sub-optimal responses to trastuzumab and lapatinib, and was used to establish mouse xenografts. Treatment of mice with monotherapy of AZD… (full text at CIViC)

PMID 22294718 · Davies et al., 2012 · Open in CIViC

Malignant Breast Neoplasm9
PIK3CA E542K OR PIK3CA E545K OR PIK3CA H1047R	FAC Regimen + FEC RegimenSubstitutes	Predictive	B	Does Not Support Resistance	3	accepted	EID6191 This study of 140 patients with stage II-III breast cancer assessed the response of patients with PIK3CA mutations to 6 months of preoperative chemotherapy. Exons 1, 9, and 20 of PIK3CA were screened… (full text at CIViC) PMID 18371219 · Liedtke et al., 2008 · Open in CIViC	civic
PIK3CA H1047R	(prognostic)	Prognostic	B	Supports Better Outcome	2	accepted	EID2097 Prognostic significance of PIK3CA mutations was evaluated in a retrospective study of 590 patients with surgically resected invasive breast cancer. Patients whose tumors harbored PIK3CA H1047R (n=88, … (full text at CIViC) PMID 19671852 · Kalinsky et al., 2009 · Open in CIViC	civic
PIK3CA H1047R	(prognostic)	Prognostic	B	Supports Better Outcome	2	accepted	EID2100 In Japanese invasive breast cancer patients, PIK3CA mutation was associated with improved relapse-free survival (p < .05). PMID 17202311 · Maruyama et al., 2007 · Open in CIViC	civic
PIK3CA H1047R	Izorlisib	Predictive	D	Supports Sensitivity Response	4	accepted	EID314 Breast cancer cell lines with H1047R mutation showed increased sensitivity to CH5132799 than cells with wild-type PIK3CA gene. PMID 21558396 · Tanaka et al., 2011 · Open in CIViC	civic
PIK3CA H1047R	PI-103	Predictive	D	Supports Sensitivity Response	1	submitted	EID8010 As part of a preclinical study, the efficacy of PI-103 was evaluated for several cell lines of breast cancer. Sensitivity and resistance was categorized as less than and more than an IC50 of 1umol/L, … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
PIK3CA H1047R	Pictilisib	Predictive	D	Supports Sensitivity Response	2	accepted	EID2102 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
PIK3CA H1047R	Trastuzumab	Predictive	B	Supports Resistance	—	submitted	EID2101 In unilateral breast cancer patients, PIK3CA mutation was associated with improved local recurrence-free survival. PMID 17575221 · Pérez-Tenorio et al., 2007 · Open in CIViC	civic
PIK3CA H1047R OR PIK3CA H1047Y OR PIK3CA H1047L	Alpelisib + FulvestrantCombination	Predictive	A	Supports Sensitivity Response	5	accepted	EID7318 In a phase 3 trial, patients with hormone receptor positive, HER2 receptor negative breast were allocated to alpelisib plus fulvestrant or placebo plus fulvestrant. Patients were enrolled into two coh… (full text at CIViC) PMID 31091374 · André et al., 2019 · Open in CIViC	civic
PIK3CA H1047R OR PIK3CA H1047Y OR PIK3CA H1047L OR PIK3CA H1047D OR PIK3CA H1047I OR PIK3CA H1047N OR PIK3CA H1047P OR PIK3CA H1047Q OR PIK3CA H1047T	Fulvestrant + Inavolisib + PalbociclibCombination	Predictive	A	Supports Sensitivity Response	3	accepted	EID12533 The phase III INAVO120 trial (NCT04191499) in 325 patients with endocrine-resistant, PIK3CA-mutated HR⁺/HER2⁻ locally advanced or metastatic breast cancer evaluated inavolisib plus palbociclib and ful… (full text at CIViC) PMID 40845250 · Wedam et al., 2025 · Open in CIViC	civic

Malignant Colorectal Neoplasm10
PIK3CA H1047R	Unspecified therapy	Predictive	C	Supports N/A	2	submitted	EID7219 The PCR-RFLP method had a capability to detect as litter as 0.4 % of mutation, and revealed 16.3 % of the PIK3CA H1047R mutation in 86 CRC tissues.A positive association between the PIK3CA H1047R muta… (full text at CIViC) PMID 27405731 · Li et al., 2016 · Open in CIViC	civic
PIK3CA H1047R	Aspirin	Predictive	B	Supports Sensitivity Response	—	rejected	EID2108 In a study of 413 patients with colorectal cancer who were taking aspirin since diagnosis, the frequency of PIK3CA mutations was 17% (70/413). In 530 patients with colorectal cancer not using aspirin,… (full text at CIViC) PMID 23094721 · Liao et al., 2012 · Open in CIViC	civic
PIK3CA H1047R	Aspirin	Predictive	B	Supports Sensitivity Response	—	submitted	EID2109 Phosphatidylinositol 3-kinase (PIK3CA) is composed of an 85kDa regulatory subunit and a 110kDa (p110alpha) catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which u… (full text at CIViC) PMID 9742087 · Klippel et al., 1998 · Open in CIViC	civic
PIK3CA H1047R	Cetuximab	Predictive	B	Supports Resistance	—	submitted	EID3731 Rectal cancer patients with PIK3CA mutations showed a higher risk of local recurrence (HR:3.5; 95% CI:1.3-9.3, P=0.013, univariate analysis; HR:3.4, 95% CI:1.2-9.2, P=0.017, multivariate analysis) com… (full text at CIViC) PMID 19903786 · He et al., 2009 · Open in CIViC	civic
PIK3CA H1047R	Cetuximab	Predictive	C	Supports Resistance	—	rejected	EID3728 In colorectal cancer patients treated with salvage cetuximab therapy in combination with chemotherapy, PIK3CA mutations were associated with reduced progression-free survival (2.5mo vs. 3.9mo, HR:2.1,… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
PIK3CA H1047R	Cetuximab + IrinotecanCombination	Predictive	C	Supports Resistance	3	accepted	EID3841 Five patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored PIK3CA H1047R (exon 21), were wildtype for KRAS,… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
PIK3CA H1047R	Cetuximab + PanitumumabSubstitutes	Predictive	B	Does Not Support Resistance	2	accepted	EID258 In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS PIK3CA and PTEN we… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
PIK3CA H1047R	Cetuximab + PanitumumabSubstitutes	Predictive	C	Supports Resistance	2	accepted	EID388 In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS PIK3CA and PTEN we… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
PIK3CA H1047R	Vemurafenib	Predictive	D	Supports Resistance	3	accepted	EID3733 In an in vitro study, a RKO cell line expressing BRAF V600E (a known vemurafenib sensitizing mutation) and PIK3CA H1047R co-mutation demonstrated reduced sensitivity to vemurafenib treatment. Resistan… (full text at CIViC) PMID 22180495 · Yang et al., 2012 · Open in CIViC	civic
PIK3CA H1047R	Akt Inhibitor MK2206 + VemurafenibCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID8364 Resistance of RKO cells, which harbor BRAF V600E (a known vemurafenib sensitizing mutation) and PIK3CA H1047R, to vemurafenib monotherapy was abrogated by the addition of pan-AKT inhibitor MK-2206 in … (full text at CIViC) PMID 22180495 · Yang et al., 2012 · Open in CIViC	civic

Malignant Head and Neck Neoplasm4
PIK3CA H1047R	Alpelisib	Predictive	D	Supports Sensitivity Response	1	accepted	EID1401 In a panel of head and neck cancer cell lines, 2 lines containing the PIK3CA mutation H1047R (Detroit562 and SNU-1076) were more sensitive to growth inhibition (IC50 1.10 and 6.82) by the PI3Kalpha sp… (full text at CIViC) PMID 25550549 · Keam et al., 2015 · Open in CIViC	civic
PIK3CA H1047R	Cetuximab + DactolisibCombination	Predictive	D	Supports Sensitivity Response	2	accepted	EID1363 Xenografts from one head and neck cancer cell line (CAL-33) with a PIK3CA H1047R mutation were more sensitive to the combined inhibition of PI3K/mTOR and EGFR with BEZ-235 and cetuximab (N=9) than cet… (full text at CIViC) PMID 23619167 · Lui et al., 2013 · Open in CIViC	civic
PIK3CA H1047R	Dactolisib	Predictive	D	Supports Sensitivity Response	1	accepted	EID1361 Lentiviral transduction of PIK3CA H1047R mutation into head and neck cancer cell line SCC25 led to increased sensitivity to PI3K/mTOR inhibition with BEZ235 compared to unmanipulated cells (IC50 value… (full text at CIViC) PMID 25855885 · Wirtz et al., 2015 · Open in CIViC	civic
PIK3CA H1047R	Dactolisib	Predictive	D	Supports Sensitivity Response	2	accepted	EID1362 Two head and neck cancer cell lines with PIK3CA H1047R mutation were more sensitive to PI3K/mTOR inhibition with BEZ-235 (NVP-BEZ235, Dactolisib) than two wild type cell lines in vitro. One cell line … (full text at CIViC) PMID 23619167 · Lui et al., 2013 · Open in CIViC	civic