Subtype
Breast Adenocarcinoma
CI-CAN-00002035Explore in graph →
686 active trials9 approved drugs104 evidence items
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Subtype
CI-CAN-00002035Explore in graph →
Variants & evidence
141 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 K111N1 | ||||||||
| Trastuzumab Emtansine | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 3 | accepted | EID2866As part of a pre-clinical experiment, the efficacy of ado-trastuzumab emtansine (T-DM1) was evaluated against various HER2 positive cell lines. BT-474 cell line expressing PIK3CA K111N was associated … (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC | civic |
| PIK3CA K111N + PTEN UnderexpressionPIK3CAPTEN7 | ||||||||
| Dactolisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID8276In a preclinical study, efficacy of dactolisib monotherapy was evaluated in vitro against HER2 amplified human breast cancer cell line BT474 (heterozygous for PIK3CA K111N) with shRNA-induced PTEN exp… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8283In a preclinical study, efficacy of NVP-BEZ235 (dactolisib) and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with shRNA-induced PTEN expr… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | |
| PIK3CA Mutation8 | ||||||||
| 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 | ||||||||
| 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 | ||||||||
| PTEN Expression1 | ||||||||
| 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 |
| PTEN Loss11 | ||||||||
| 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 CarcinomaALIAS | 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 | civic |
| PTPN12 Loss-of-function1 | ||||||||
| Crizotinib + SunitinibCombination | Triple-Negative Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID6931Cancer-associated mutation of PTPN12 or reduced PTPN12 protein leads to aberrant activity of several tyrosine kinase receptors (MET, PDGFRβ, EGFR, and others). Restoring PTPN12 protein levels restrain… (full text at CIViC) PMID 29578538 · Nair et al., 2018 · Open in CIViC | civic |
| RB1 Loss-of-function3 | ||||||||
| Checkpoint Kinase Inhibitor AZD7762 | Triple-Negative Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12330A drug screen of triple-negative breast cancer (TNBC) cell lines found several therapies to be synthetically lethal with RB1 loss of function. Cell lines with endogenous expression of RB1 (BT20, MB453… (full text at CIViC) PMID 29386107 · Witkiewicz et al., 2018 · Open in CIViC | civic |
| Gemcitabine | Triple-Negative Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID12329A drug screen of triple-negative breast cancer (TNBC) cell lines found several therapies to be synthetically lethal with RB1 loss of function. Cell lines with endogenous expression of RB1 (BT20, MB453… (full text at CIViC) PMID 29386107 · Witkiewicz et al., 2018 · Open in CIViC | civic |
| Volasertib | ||||||||
| TACSTD2 T256R1 | ||||||||
| Sacituzumab Govitecan | Triple-Negative Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 3 | submitted | EID12265TROP2 T256R mutation alters the plasma membrane localization and cell-surface binding of hRS7, the humanized antibody incorporated into Sacituzumab Govitecan (SG). The TROP2 T256R encoded protein was … (full text at CIViC) PMID 34404686 · Coates et al., 2021 · Open in CIViC | civic |
| High2 | ||||||||
| Immune Checkpoint Inhibitor | Triple-Negative Breast CarcinomaALIAS | Predictive | E | Supports N/A | 3 | submitted | EID12950This review synthesizes current preclinical, translational, and clinical evidence evaluating tumor mutational burden (TMB) as a predictive biomarker for immune checkpoint inhibitor (ICI) response in t… (full text at CIViC) PMID 41249701 · Das et al., 2025 · Open in CIViC | civic |
| 〃 | Triple-Negative Breast CarcinomaALIAS | Predictive | E | Supports Sensitivity Response | 2 | accepted | EID13213TMB is being investigated as a predictive biomarker for response to immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC). TMB is defined as the number of somatic mutations per m… (full text at CIViC) PMID 41249701 · Das et al., 2025 · Open in CIViC | civic |
| TOP1 -122fs + TOP1 E418K1 | ||||||||
| Sacituzumab Govitecan | Triple-Negative Breast CarcinomaALIAS | Predictive | C | Supports Resistance | 3 | submitted | EID12266TOP1 E418K mutation and TOP1 122fs contribute to acquired resistance to Sacituzumab Govitecan (SG) therapy through alterations in the drug target TOP1. The patient, a 42-year-old female with metastati… (full text at CIViC) PMID 34404686 · Coates et al., 2021 · Open in CIViC | civic |
| ORC1 Mutation + XRCC3 MutationXRCC3ORC11 | ||||||||
| Cisplatin | Triple-Negative Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11716In this study, the sensitivity to Cisplatin (a platinum-based drug) was studied in XRCC3 knockout, and ORC1 mutant PDX models. A role of XRCC3 loss in cisplatin sensitivity was reported in the study. … (full text at CIViC) PMID 37029129 · Ter Brugge et al., 2023 · Open in CIViC | civic |
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.
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| Lapatinib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID8275In a preclinical study, efficacy of trastuzumab monotherapy was evaluated in vitro against HER2 amplified human breast cancer cell line BT474 (heterozygous for PIK3CA K111N) with shRNA-induced PTEN ex… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Dactolisib + LapatinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Resistance | 2 | accepted | EID8278In a preclinical study, efficacy of NVP-BEZ235 (dactolisib; a dual PI3K/mTOR inhibitor) and lapatinib combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 (h… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8277In a preclinical study, efficacy of lapatinib and trastuzumab combination therapy was evaluated in vitro against HER2 amplified breast cancer cell line BT474 with shRNA-induced PTEN expression loss. A… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID8274In a preclinical study, efficacy of trastuzumab monotherapy was evaluated in vitro against HER2 amplified human breast cancer cell line BT474 (heterozygous for PIK3CA K111N) with shRNA-induced PTEN ex… (full text at CIViC) PMID 19010894 · Eichhorn et al., 2008 · Open in CIViC | civic |
| 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 |
| 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 |
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| 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 |
| Trastuzumab | 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 |
| 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 |
| 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 |
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| PI3Ka/Di | 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 |
| 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 |
| 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 |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Resistance | 2 | accepted | EID1383A large-scale RNAi genetic sereen in HER2 overexpressing breast cancer cell line BT-474 was performed to discover genes whose loss induced trastuzumab resistance. The most prominently enriched gene in… (full text at CIViC) PMID 17936563 · Berns et al., 2007 · Open in CIViC | civic |
| Trastuzumab Emtansine | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Does Not Support Resistance | 3 | accepted | EID8706In a phase 3 clinical trial (NCT00829166), metastatic HER-2 amplified breast cancer patients whose tumors had decreased, slightly decreased, or absent PTEN expression (assessed by IHC) treated with ad… (full text at CIViC) PMID 26920887 · Baselga et al., 2016 · Open in CIViC | civic |
| PI3K/BET Inhibitor LY294002 + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1455Knockdown of PTEN in trastuzumab sensitive HER2 breast cancer BT474 cells induced trastuzumab resistance. PTEN null cells treated with PI3K inhibitor LY294002 also did not show substantial inhibition,… (full text at CIViC) PMID 15324695 · Nagata et al., 2004 · Open in CIViC | civic |
| Triple-Negative Breast CarcinomaALIAS |
| Predictive |
| D |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID12331A drug screen of triple-negative breast cancer (TNBC) cell lines found several therapies to be synthetically lethal with RB1 loss of function. Cell lines with endogenous expression of RB1 (BT20, MB453… (full text at CIViC) PMID 29386107 · Witkiewicz et al., 2018 · Open in CIViC |
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