Variant · Snv

PIK3CA C420R

CI-VAR-00000311Explore in graph →NP_006209.2:p.Cys420ArgNM_006218.3:c.1258T>CClinVar 31945 CIViC 931 rs121913272

Curated evidence

Evidence by cancer (7 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 1–7 of 7 evidence items across 4 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
HER2-Positive Breast Carcinoma3
PIK3CA C420R	Pictilisib	Predictive	D	Supports Sensitivity Response	3	accepted	EID2078 This 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
PIK3CA C420R	Trastuzumab	Predictive	D	Supports Resistance	2	accepted	EID8549 As 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

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
31945	Pathogenic	criteria provided, multiple submitters, no conflicts	2	CLOVES syndrome; Ovarian neoplasm; PIK3CA related overgrowth syndrome; CLAPO syndrome; Abnormal cardiovascular system morphology; Capillary malformation; Segmental undergrowth associated with lymphatic malformation; Rare combined vascular malformation; Cowden syndrome; Neoplasm; Colorectal cancer; PIK3CA-related disorder; Neuroblastoma; Diffuse midline glioma, H3 K27M-mutant; Medulloblastoma WNT activated; IDH-wildtype glioblastoma; Immature ovarian teratoma; Colon adenocarcinoma

Malignant Breast Neoplasm2
PIK3CA C420R	Alpelisib + FulvestrantCombination	Predictive	A	Supports Sensitivity Response	4	accepted	EID11275 In this randomized, phase III trial, 572 patients with HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously underwent randomization, including 341 patients w… (full text at CIViC) PMID 31091374 · André et al., 2019 · Open in CIViC	civic
PIK3CA R88Q OR PIK3CA C420R OR PIK3CA M1043V OR PIK3CA M1043I OR PIK3CA M1043T	Fulvestrant + Inavolisib + PalbociclibCombination	Predictive	A	Supports Sensitivity Response	3	accepted	EID12539 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 Breast Neoplasm2

PIK3CA C420R

Alpelisib + FulvestrantCombination

Predictive

Supports Sensitivity Response

accepted

EID11275

In this randomized, phase III trial, 572 patients with HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously underwent randomization, including 341 patients w… (full text at CIViC)

PMID 31091374 · André et al., 2019 · Open in CIViC

civic

PIK3CA R88Q OR PIK3CA C420R OR PIK3CA M1043V OR PIK3CA M1043I OR PIK3CA M1043T

Fulvestrant + Inavolisib + PalbociclibCombination

Predictive

Supports Sensitivity Response

accepted

EID12539

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 Neoplasm1
PIK3CA C420R	Cetuximab	Predictive	C	Does Not Support Resistance	3	accepted	EID1999 One patient participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had a tumor which harbored PIK3CA C420R and was wildtype for KRAS, BRAF and … (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic

Malignant Colorectal Neoplasm1

PIK3CA C420R

Cetuximab

Predictive

Does Not Support Resistance

accepted

EID1999

One patient participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had a tumor which harbored PIK3CA C420R and was wildtype for KRAS, BRAF and … (full text at CIViC)

PMID 20619739 · De Roock et al., 2010 · Open in CIViC

civic

HER2 Negative Breast Cancer1unmapped disease
PIK3CA C420R	Capivasertib + FulvestrantCombination	Predictive	A	Supports Sensitivity Response	2	submitted	EID12183 In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC) PMID 37256976 · Turner et al., 2023 · Open in CIViC	civic

HER2 Negative Breast Cancer1unmapped disease

PIK3CA C420R

Capivasertib + FulvestrantCombination

Predictive

Supports Sensitivity Response

submitted

EID12183

In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC)

PMID 37256976 · Turner et al., 2023 · Open in CIViC

civic