Cancer Family
Malignant Breast Neoplasm
CI-CAN-00000227Explore in graph →
Top-level2,628 active trials43 approved drugs310 evidence items
- NCIt
- C9335
- ICD-10
- C50
- DOID
- 1612
- Other
- 2 more codes
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Cancer Family
CI-CAN-00000227Explore in graph →
Variants & evidence
464 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| PIK3CA K111N + PTEN UnderexpressionPIK3CAPTEN1 | ||||||||
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 2 | accepted | EID8279In a preclinical study, efficacy of NVP-BEZ235 (dactolisib; a dual PI3K/mTOR inhibitor) and trastuzumab combination therapy was evaluated in vitro against HER2 amplified human breast cancer cell line … (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| PIK3CA Mutation18 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Better Outcome | 3 | accepted | EID2025Prognostic significance of PIK3CA mutations was evaluated in a retrospective study of 590 patients with surgically resected invasive breast cancer. Patients with tumors harboring PIK3CA mutations (n=1… (full text at CIViC) PMID 19671852 · Kalinsky et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Prognostic | B | Supports Better Outcome | 3 | accepted | EID6188This was a Swedish study of 270 breast tumors removed from patients with unilateral operable breast cancer, and either lymph node metastases or a tumor diameter >30mm. PIK3CA missense mutations were f… (full text at CIViC) PMID 17575221 · Pérez-Tenorio et al., 2007 · Open in CIViC | civic |
| Alpelisib + FulvestrantCombination | Malignant Breast Neoplasm | Predictive | A | |||||
| AKT1 Mutation + PIK3CA Mutation + PTEN MutationPIK3CAPTENAKT11 | ||||||||
| Capivasertib + FulvestrantCombination | Malignant Breast Neoplasm | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID12020In 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 |
| ESR1 Mutation + PIK3CA Mutation + RB1 MutationPIK3CARB1ESR11 | ||||||||
| Fulvestrant + PalbociclibCombination | Malignant Breast Neoplasm | Predictive | B | Supports Resistance | 3 | accepted | EID12045In this phase III trial (PALOMA-3), patients with ER+, HER2- advanced breast cancer were treated with CDK4/6 inhibitors. Patients were randomized to receive palbociclib plus fulvestrant (P+F) or place… (full text at CIViC) PMID 30206110 · O'Leary et al., 2018 · Open in CIViC | civic |
| PIK3CA N345D + PIK3CA N345H + PIK3CA N345I + PIK3CA N345K + PIK3CA N345S + PIK3CA N345T + PIK3CA N345Y1 | ||||||||
| Fulvestrant + Inavolisib + PalbociclibCombination | Malignant Breast Neoplasm | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID12538The 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 |
| PIK3CA Overexpression4 | ||||||||
| Dactolisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8269In a preclinical study, efficacy of NVP-BEZ235 (dactolisib) monotherapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with retrovirally induced PIK3CA amplification. Auth… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8268In a preclinical study, efficacy of lapatinib monotherapy was evaluated in vitro against HER2 amplified breast cancer cell lines (BT474 and SKBR3) with retrovirally induced PIK3CA expression. Authors … (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | ||||||||
| PIK3CA Q546E + PIK3CA Q546R1 | ||||||||
| Alpelisib + FulvestrantCombination | Malignant Breast Neoplasm | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7316In 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 K111E + PIK3CA K111N + PIK3CA K111R + PIK3CA Q546E + PIK3CA Q546H + PIK3CA Q546K + PIK3CA Q546L + PIK3CA Q546P + PIK3CA Q546R1 | ||||||||
| Fulvestrant + Inavolisib + PalbociclibCombination | Malignant Breast Neoplasm | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID12536The 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 |
| PIK3CA Q546R1 | ||||||||
| (oncogenic) | Malignant Breast Neoplasm | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID7723Recurrent PIK3CA mutations detected in breast cancer were evaluated by in vitro and in vivo growth and transformation assays. The PIK3CA mutation Q546R was found in 16 samples from COSMIC. Expression … (full text at CIViC) PMID 26627007 · Dogruluk et al., 2015 · Open in CIViC | civic |
| PIK3CA C420R + PIK3CA M1043I + PIK3CA M1043T + PIK3CA M1043V + PIK3CA R88Q1 | ||||||||
| Fulvestrant + Inavolisib + PalbociclibCombination | Malignant Breast Neoplasm | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID12539The 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 |
| PIK3CA Rare Mutation2 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Better Outcome | 2 | accepted | EID2042Prognostic significance of PIK3CA mutations was evaluated in a retrospective study of 590 patients with surgically resected invasive breast cancer. Tumors harboring rare PIK3CA mutations (N345K: 2.4%,… (full text at CIViC) PMID 19671852 · Kalinsky et al., 2009 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Prognostic | B | Supports Better Outcome | 2 | rejected | EID8915Prognostic significance of PIK3CA mutations was evaluated in a retrospective study of 590 patients with surgically resected invasive breast cancer. Tumors harboring rare PIK3CA mutations (N345K: 2.4%,… (full text at CIViC) PMID 19671852 · Kalinsky et al., 2009 · Open in CIViC | civic |
| PIK3R1 Mutation1 | ||||||||
| MTOR Kinase Inhibitor PP242 | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1612Sensitivity to mTORC1/2 inhibitor PP242 was assessed in a panel of breast cancer cell lines with various mutation backgrounds. PTEN and PIK3CA mutations were heavily represented in the panel. However,… (full text at CIViC) PMID 21358673 · Weigelt et al., 2011 · Open in CIViC | civic |
| PSMD4 Amplification1 | ||||||||
| Talazoparib | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4834Current randomized Phase III trials of PARPi in metastatic breast cancer are limited to patients with BRCA1/2 mutations, no biomarker of PARPi beyond BRCA status is available. we created a cell line (… (full text at CIViC) PMID 28316110 · Fejzo et al., 2017 · Open in CIViC | civic |
| PTEN Expression2 | ||||||||
| Everolimus + FulvestrantCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | C | Supports Resistance | 1 | accepted | EID1624Case 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 |
| Trastuzumab | Malignant Breast Neoplasm | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID955Trastuzumab was more effective in cell lines (SKBR3 vs. drug-resistant SKBR3/R) and 17 patient samples that exhibit elevated PTEN expression (by IHC). PMID 16404430 · Fujita et al., 2006 · Open in CIViC | civic |
| PTEN Loss14 | ||||||||
| Alpelisib | Malignant Breast Neoplasm | Predictive | D | Supports Resistance | 4 | accepted | EID716A case report described a responder to PI3K inhibitor BYL719 for a tumor with PIK3CA E542K mutation. After partial response for 9.5 months, resistance developed. Sequencing in this and other patients … (full text at CIViC) PMID 25409150 · Juric et al., 2015 · Open in CIViC | civic |
| Dactolisib + Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8280In 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 shRNA-induc… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Everolimus | HER2-Positive Breast Carcinoma | |||||||
Data updated 14 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.
| Supports Sensitivity Response |
| 5 |
| accepted |
EID7313In 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 |
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| 〃 | Malignant Breast Neoplasm | Predictive | A | Supports Sensitivity Response | 5 | rejected | EID7317In 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 |
| Bazedoxifene + Palbociclib RegimenCombination | Breast Carcinoma | Predictive | B | Does Not Support Sensitivity Response | 4 | submitted | EID12619In a phase Ib/II trial of bazedoxifene 40 mg daily plus palbociclib 125 mg (NCT02448771; HR positive, HER2 negative breast carcinoma; n = 36), the regimen produced a 24 week clinical benefit rate of 3… (full text at CIViC) PMID 36215125 · Tsuji et al., 2022 · Open in CIViC | civic |
| Capecitabine + LapatinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 3 | accepted | EID8705In a phase 3 clinical trial (NCT00829166), metastatic HER-2 amplified breast cancer patients whose tumors harbored PIK3CA mutations treated with standard of care capecitabine and lapatinib combination… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC | civic |
| Capivasertib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1504HER2 overexpressing breast cancer cell lines with PIK3CA mutation BT474c (K111N) and HCC-1954 (H1047R) were used to establish mouse tumor xenografts. In BT474c xenografts, three dosing schedules of AZ… (full text at CIViC) PMID 22294718 · Davies et al., 2012 · Open in CIViC | civic |
| Everolimus | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1296Archival tumor samples from 549 patients from the BOLERO-1 and -3 trials were analyzed for alterations in the PI3K pathway using next-generation sequencing, immunohistochemistry (IHC) and Sanger seque… (full text at CIViC) PMID 27091708 · André et al., 2016 · Open in CIViC | civic |
| Everolimus + MTOR Kinase Inhibitor PP242Substitutes | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1610A panel of 31 breast cancer cell lines was tested for sensitivity to mTORC1 inhibitor everolimus and mTORC1/mTORC2 inhibitor PP242. Inhibitor concentrations for 50% survival fraction (SF50) were measu… (full text at CIViC) PMID 21358673 · Weigelt et al., 2011 · Open in CIViC | civic |
| Nab-paclitaxel | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 2 | submitted | EID13086Targeted NGS of 17 genes was utilized to assess alterations in pre-treatment tumour biopsy samples of HER2+ breast cancers from the prospective GeparSepto (G7) trial of anti-HER2 therapy (trastuzumab/… (full text at CIViC) PMID 41974716 · Van Mackelenbergh et al., 2026 · Open in CIViC | civic |
| Pertuzumab/Trastuzumab Regimen | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 3 | submitted | EID13085Targeted NGS of 17 genes was utilized to assess alterations in pre-treatment tumour biopsy samples of HER2+ breast cancers from the prospective GeparSepto (G7) trial of combination trastuzumab plus pe… (full text at CIViC) PMID 41974716 · Van Mackelenbergh et al., 2026 · Open in CIViC | civic |
| Palbociclib + Phosphatidylinositide 3-Kinase InhibitorCombination | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1607Three PIK3CA mutant breast cancer cell lines were rendered resistant to PI3K inhibitors (BYL719 or GDC-0941) by chronic exposure. Co-treatment of all three cell lines with PI3K inhibitor and CDK4/6 in… (full text at CIViC) PMID 25002028 · Vora et al., 2014 · Open in CIViC | civic |
| Phosphatidylinositide 3-Kinase Inhibitor + RibociclibCombination | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID1600Three PI3K mutant breast cancer cell lines were rendered resistant to PI3K inhibitors (BYL719 or GDC-0941), and a panel of 42 inhibitor compounds was tested on the cells for ability to resensitize the… (full text at CIViC) PMID 25002028 · Vora et al., 2014 · Open in CIViC | civic |
| Trastuzumab | Malignant Breast Neoplasm | Predictive | B | Supports Resistance | 3 | accepted | EID2087In retrospective study of 175 metastatic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation (E542K, E545K, or H1047R) was associated with a greater risk o… (full text at CIViC) PMID 21594665 · Razis et al., 2011 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 3 | accepted | EID2098In a retrospective study of 105 HER2-positive metastic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation (E542K, E545K, or H1047R) was associated with a … (full text at CIViC) PMID 21594665 · Razis et al., 2011 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 2 | accepted | EID1384The HER2 overexpressing breast cancer cell line BT-474 transduced with mutant PIK3CA H1047R demonstrated essentially normal proliferation under trastuzumab, while control cells showed negligible proli… (full text at CIViC) PMID 17936563 · Berns et al., 2007 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Predictive | C | Supports Resistance | — | rejected | EID2076In HER2-positive metastic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation was associated with an increased risk of progression (HR:2.50, 95% CI:1.35-4.… (full text at CIViC) PMID 21594665 · Razis et al., 2011 · Open in CIViC | civic |
| Trastuzumab Emtansine | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Does Not Support Resistance | 3 | accepted | EID8536In a phase 3 clinical trial (NCT00829166), metastatic HER-2 amplified breast cancer patients whose tumors harbored PIK3CA mutations treated with ado-trastuzumab emtansine (T-DM1; n=40) were associated… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC | civic |
| HER2-Positive Breast CarcinomaALIAS |
| Predictive |
| D |
| Supports Sensitivity Response |
| 2 |
| accepted |
EID8270In a preclinical study, efficacy of lapatinib and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell lines (BT474 and SKBR3) with retrovirally induced PIK… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC |
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| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID8267HER2-positive breast cancer cell lines (BT-474 and SKBR3) were retrovirally transduced with wildtype PIK3CA and treated with trastuzumab. PIK3CA overexpression diminished the growth inhibitory effects… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Predictive |
| B |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID1297Archival tumor samples from 549 patients from the BOLERO-1 and -3 trials were analyzed for alterations in the PI3K pathway using next-generation sequencing, immunohistochemistry (IHC) and Sanger seque… (full text at CIViC) PMID 27091708 · André et al., 2016 · Open in CIViC |
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| Everolimus + MTOR Kinase Inhibitor PP242Substitutes | Malignant Breast Neoplasm | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID1611In a panel of 31 breast cancer cell lines, 11 had loss of PTEN function. Cells were tested for sensitivity to mTORC1 inhibitor everolimus and mTORC1/2 inhibitor PP242, and no significant correlation w… (full text at CIViC) PMID 21358673 · Weigelt et al., 2011 · Open in CIViC | civic |
| PI-103 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 1 | accepted | EID8012As 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 |
| PI3Ka/Di | Malignant Breast Neoplasm | Predictive | D | Supports Resistance | 1 | submitted | EID8021As 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 |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 1 | accepted | EID8022As 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 |
| PI3Kbeta Inhibitor AZD8186 | Malignant Breast Neoplasm | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID711Breast and prostate cancer cell lines responsive to AZD8186 were enriched for PTEN deficiency. PMID 25398829 · Hancox et al., 2015 · Open in CIViC | civic |
| Pictilisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID2045This 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 |
| 〃 | Malignant Breast Neoplasm | Predictive | D | Does Not Support Sensitivity Response | 2 | accepted | EID2074This 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 |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 3 | accepted | EID1385A subgroup of HER2-positive breast cancer patients that received first-line trastuzumab treatment were assessed for PTEN loss via IHC of FFPE samples. 46 samples showed PTEN loss while 41 did not, and… (full text at CIViC) PMID 20813970 · Esteva et al., 2010 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Does Not Support Resistance | 3 | accepted | EID1386While some reports indicate PTEN loss is associated with resistance to trastuzumab, in a subgroup of HER2 breast cancer FFPE samples from patients receiving trastuzumab as later line therapy (second o… (full text at CIViC) PMID 20813970 · Esteva et al., 2010 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 2 | accepted | EID2035In a retrospective study of 111 HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapy, PTEN loss (as measured by IHC) was associated with shorter survival as measured … (full text at CIViC) PMID 21594665 · Razis et al., 2011 · Open in CIViC | civic |
| 〃 | Malignant Breast Neoplasm | Predictive | B | Supports Resistance | 2 | accepted | EID2043In a retrospective study of 182 metastatic breast cancer patients of mixed HER2 status treated with trastuzumab-based therapy, PTEN loss (as measured by IHC) was associated with a higher risk of death… (full text at CIViC) PMID 21594665 · Razis et al., 2011 · Open in CIViC | civic |