Subtype
Breast Carcinoma
CI-CAN-00000594Explore in graph →
872 active trials12 approved drugs113 evidence items
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Subtype
CI-CAN-00000594Explore in graph →
Variants & evidence
156 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 |
|---|---|---|---|---|---|---|---|---|
| AKT3 Overexpression1 | ||||||||
| Pan-AKT Kinase Inhibitor GSK690693 | Triple-Negative Breast CarcinomaALIAS | Predictive | E | Supports Sensitivity Response | 4 | accepted | EID1923AKT3 was found to be preferentially required for the proliferation and tumor growth of TNBC. It was found to be upregulated in a set of TNBC cell lines compared to other breast cancer types. Depletion… (full text at CIViC) PMID 24335962 · Chin et al., 2014 · Open in CIViC | civic |
| BIRC5 Overexpression1 | ||||||||
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 4 | accepted | EID144913 HER2 breast cancer patients were treated with trastuzumab and then trastuzumab + docetaxel prior to surgery. Pretreatment biopsies and post-treatment surgical samples were obtained, and microarray … (full text at CIViC) PMID 23204226 · Chakrabarty et al., 2013 · Open in CIViC | civic |
| BRAF G469E1 | ||||||||
| Trametinib | Breast Ductal Carcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID7861Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in non-V600 BRAF mutant tumors. 32 patients were eligible and received therapy with trametinib. Of these 1 patient had a confir… (full text at CIViC) PMID 31924734 · Johnson et al., 2020 · Open in CIViC | civic |
| BRCA1 Loss-of-function1 | ||||||||
| Olaparib | Triple-Negative Breast CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11216Report of OlympiA (NCT02032823), a randomized, double-blind, placebo-controlled study of 1836 patients with HER2-negative breast cancer with germline pathogenic or likely pathogenic mutations in BRCA1… (full text at CIViC) PMID 34081848 · Tutt et al., 2021 · Open in CIViC | civic |
| BRCA1 Mutation2 | ||||||||
| Carboplatin + CisplatinSubstitutes | Triple-Negative Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1684In an evaluation of 77 patients, those who had BRCA1/2 germline mutations (n=11) had an increase response rate to cisplatin when compared to those without germline mutations (54.5% versus 19.7%; P=0.0… (full text at CIViC) PMID 25847936 · Isakoff et al., 2015 · Open in CIViC | civic |
| Olaparib | Triple-Negative Breast CarcinomaALIAS | Predictive | B | Supports Resistance | 3 | accepted | EID1775In a study of 26 patients with breast cancer, 10 patients were BRCA-positive and 16 patients were BRCA-negative. Regardless of BRCA status, none showed objective response when treated with olaparib. PMID 21862407 · Gelmon et al., 2011 · Open in CIViC | civic |
| BRCA1 Mutation + BRCA2 MutationBRCA2BRCA11 | ||||||||
| Olaparib | Breast Carcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12763In the breast carcinoma cohort of the phase II TAPUR trial (NCT02693535), patients with BRCA1/2 alterations treated with olaparib (26 evaluable) had 1 CR (BRCA2 loss), 11 PR (BRCA1 n=5, BRCA2 n=4, BRC… (full text at CIViC) PMID 41100773 · Al Baghdadi et al., 2025 · Open in CIViC | civic |
| BRCA2 Loss-of-function1 | ||||||||
| Olaparib | Triple-Negative Breast CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11217Report of OlympiA (NCT02032823), a randomized, double-blind, placebo-controlled study of 1836 patients with HER2-negative breast cancer with germline pathogenic or likely pathogenic mutations in BRCA1… (full text at CIViC) PMID 34081848 · Tutt et al., 2021 · Open in CIViC | civic |
| BRCA2 Mutation2 | ||||||||
| Carboplatin + CisplatinSubstitutes | Triple-Negative Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1685In an evaluation of 77 patients, those who had BRCA1/2 germline mutations (n=11) had an increase response rate to cisplatin when compared to those without germline mutations (54.5% versus 19.7%; P=0.0… (full text at CIViC) PMID 25847936 · Isakoff et al., 2015 · Open in CIViC | civic |
| Olaparib | Triple-Negative Breast CarcinomaALIAS | Predictive | B | Does Not Support Sensitivity Response | 3 | accepted | EID1776In a study of 26 patients with breast cancer, 10 patients were BRCA-positive and 16 patients were BRCA-negative. Regardless of BRCA status, none showed objective response when treated with olaparib. PMID 21862407 · Gelmon et al., 2011 · Open in CIViC | civic |
| CBLC EXPRESSION1 | ||||||||
| Olaparib | Breast Carcinoma | Predictive | D | Supports Resistance | 2 | accepted | EID805The E3 ubiquitin ligase, CBLC, was identified as a candidate biomarker for olaparib sensitivity in a siRNA screen and further validated in-vitro in two breast carcinoma cell lines (MCF7 and HS578T). I… (full text at CIViC) PMID 25883215 · Frankum et al., 2015 · Open in CIViC | civic |
| CD274 Amplification1 | ||||||||
| Durvalumab | Triple-Negative Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12054Sensitivity to durvalumab was tested in patients with triple-negative breast cancer (TNBC) harbouring CD274 gain/amplification. CD274 amplifications were noted in 42% (n=23) of the TNBC samples. Patie… (full text at CIViC) PMID 33462450 · Bachelot et al., 2021 · Open in CIViC | civic |
| CDK12 Loss-of-function1 | ||||||||
| Olaparib + TalazoparibSubstitutes | Breast Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12571In micropapillary breast carcinoma and a subset of HER2-amplified breast cancers, genomic disruptions of CDK12 (out-of-frame rearrangements and breakpoints within the HER2 amplicon) were associated wi… (full text at CIViC) PMID 24395524 · Natrajan et al., 2014 · Open in CIViC | civic |
| CDK2 CYTOPLASMIC EXPRESSION1 | ||||||||
| Carboplatin + EribulinCombination | Triple-Negative Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID2969In a Phase 2 trial, HRD score, HR deficiency status, and cytoplasmic CDK2 predicted pathologic complete remission to neoadjuvant therapy with carboplatin and eribulin in early stage TNBC patients. PMID 26006067 · Kaklamani et al., 2015 · Open in CIViC | civic |
| ZNF880 Fusion1 | ||||||||
| Pyrotinib | HER2-Positive Breast CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID11215Case report describing a 34-year-old female patient without a family history of breast cancer. After a radical mastectomy, histopathology revealed an invasive ductal carcinoma HER2 positive (FISH). Sh… (full text at CIViC) PMID 33371069 · Yue et al., 2020 · Open in CIViC | civic |
| ERBB2 Amplification34 | ||||||||
| A66 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1381Pharmacologic (A66; p110alpha specific inhibitor) or genetic (cre-mediated knockout) ablation of the p110alpha PI3K isoform reduced tumor growth and tumor formation, respectively, in athymic mice tran… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC | civic |
| Afatinib | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID1012LUX-Breast 1 is a phase 3 trial (NCT01125566) which enrolled 508 patients with metastatic HER2 positive BC who had progressed after adjuvant or first-line trastuzumab. It was thought that the wider ra… (full text at CIViC) PMID 26822398 · Harbeck et al., 2016 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast Carcinoma | |||||||
| ERBB2 L755S1 | ||||||||
| Capecitabine + NeratinibCombination | Triple-Negative Breast CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID8055This 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 |
Data updated 15 minutes 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.
| Predictive |
| B |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID961A phase II study involving adult female patients, >=18 years, with stage IIIB or IV HER2-positive (by IHC and/or in situ fluorescence) metastatic breast cancer. All patients were previously treated wi… (full text at CIViC) PMID 22418700 · Lin et al., 2012 · Open in CIViC |
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| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | rejected | EID1010With multiple mechanisms of HER reprogramming thought to be behind trastuzumab resistance, including increased expression of ErbB members, afatinib, which broadly and irreversibly targets ErbB recepto… (full text at CIViC) PMID 22418700 · Lin et al., 2012 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1011This Phase II trial (LUX-Breast 3 - NCT01441596) compared afatinib, afatinib plus vinorelbine, or investigator's choice of treatment. 121 patients with HER2 overexpressing breast cancer with CNS recu… (full text at CIViC) PMID 26596672 · Cortés et al., 2015 · Open in CIViC | civic |
| Afatinib + Lapatinib + TrastuzumabSubstitutes | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID887In this phase 2 trial, treatment-naive, ERBB2-positive (by IHC) breast cancer patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to afatinib (n = 10), lapatinib (n = 8), or t… (full text at CIViC) PMID 25537159 · Rimawi et al., 2015 · Open in CIViC | civic |
| Afatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1013Trastuzumab resistance is thought to consist of multiple compensatory mechanisms involving ErbB family members such as increased signaling through ErbB family heterodimers. The irreversible TKI afati… (full text at CIViC) PMID 25370464 · Ring et al., 2015 · Open in CIViC | civic |
| Capecitabine + LapatinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1132This Phase III trial took patients with locally advanced or metastatic HER2 (ERBB2) positive breast cancer that had progressed on prior trastuzumab treatment. Patients were given capecitabine (n=161)… (full text at CIViC) PMID 17192538 · Geyer et al., 2006 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1007In light of results showing increased PFS using mAB plus TKI in heavily pretreated patients, the efficacy of trastuzumab plus lapatinib in a neoadjuvant setting with untreated stage II or IIIA HER2 po… (full text at CIViC) PMID 22493419 · Guarneri et al., 2012 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1009This Phase III study (EGF104900) was motivated by preclinical and other data demonstrating synergistic activity between lapatinib and trastuzumab against HER2 positive breast cancer (BC) cells. In th… (full text at CIViC) PMID 20124187 · Blackwell et al., 2010 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1439In a randomized open label phase 3 study (NCT00553358), women with HER2 positive primary breast cancer treated with lapatinib plus trasuzumab had higher rates of pathological complete responses than s… (full text at CIViC) PMID 22257673 · Baselga et al., 2012 · Open in CIViC | civic |
| Neratinib | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID761Oral neratinib showed objective response rates of 24 and 56% respectively in prior-trastuzumab (n=63) and trastuzumab-naive (n=64) cohorts in a Phase II trial. As for the primary endpoint, the 16-week… (full text at CIViC) PMID 20142587 · Burstein et al., 2010 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8072A panel of HER2 positive breast cancer cell lines (n=12) displayed greater sensitivity to Neratinib (HKI-272) compared to triple negative breast cancer cell lines (n=15, p=.0002) and luminal breast ca… (full text at CIViC) PMID 24009064 · Canonici et al., 2013 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8073Two HER2 positive breast cancer cells lines were 480-times more sensitive to Neratinib (HKI-272) compared to a HER2 negative breast cancer cell line (MDA-MB-435) as indicated by decreased proliferatio… (full text at CIViC) PMID 15173008 · Rabindran et al., 2004 · Open in CIViC | civic |
| Capecitabine + NeratinibCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID8048A phase III clinical trial (NALA, NCT01808573) with a randomized parallel design of 621 patients evaluated the combination therapy of Neratinib plus capecitabine (N+C) (307 pts.) vs. Lapatinib plus ca… (full text at CIViC) | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID8050A Phase II clinical trial (NCT00741260 ) assessed the safety and efficacy of Neratinib plus capecitabine in the treatment of HER2 positive breast cancer patients. Of the 72 patients in this study, 65 … (full text at CIViC) PMID 25287822 · Saura et al., 2014 · Open in CIViC | civic |
| Neratinib + TrastuzumabSequential | HER2-Positive Breast CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID1113In this two arm, Phase III study (NCT00878709) of the efficacy of a 12 month course of the TKI neratinib after trastuzumab-based adjuvant therapy of early stage HER2-positive breast cancer was assesse… (full text at CIViC) PMID 26874901 · Chan et al., 2016 · Open in CIViC | civic |
| Docetaxel + Pertuzumab + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID1077CLEOPATRA (NCT00567190) was a Phase III, randomized and double-blind, placebo-controlled study of 808 patients with HER2-positive metastatic breast cancer. Patients were HER2-positive by IHC3+ or FIS… (full text at CIViC) PMID 25693012 · Swain et al., 2015 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1437In a randomized phase 3 trial, HER2 positive metastatic breast cancer patients given first-line treatment of pertuzumab plus trastuzumb plus docetaxel experienced improved progression free survival (1… (full text at CIViC) PMID 22149875 · Baselga et al., 2012 · Open in CIViC | civic |
| Pictilisib | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1380The HER2/Neu mammary tumor mouse model MMTV-NeuT was employed to demonstrate dependence of HER2 tumor formation on PIK3 p110alpha isoform. MMTV-NeuT mice were crossed with floxed p110alpha mice. Diass… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC | civic |
| Tgx 221 | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID1382Treatment of cells obtained from MMTV-NeuT mouse mammary tumors with the p110beta selective inhibitor TGX-221 showed significant but minimal reductions in lipid kinase activity and negligible reductio… (full text at CIViC) PMID 22802530 · Utermark et al., 2012 · Open in CIViC | civic |
| Trastuzumab | HER2-Positive Breast CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID1122HERA was a Phase III trial assessing application of trastuzumab in an extended adjuvant setting. Patients were HER2 positive with completely excised invasive BC, node positive or negative, and having… (full text at CIViC) PMID 16236737 · Piccart-Gebhart et al., 2005 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID528A randomized clinical trial of 469 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved time to disease progression, objective response rate, and duration … (full text at CIViC) PMID 11248153 · Slamon et al., 2001 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID529A randomized clinical trial of 186 patients with previously untreated, HER2-positive, metastatic breast cancer demonstrated improved overall survival, response rate, response duration, time to progres… (full text at CIViC) PMID 15911866 · Marty et al., 2005 · Open in CIViC | civic |
| Capecitabine + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1133In this Phase III trial, trastuzumab-based treatment was assessed in women with locally advanced or metastatic HER2 positive breast cancer who had progressed on trastuzumab. Patients had 12 weeks or … (full text at CIViC) PMID 19289619 · von Minckwitz et al., 2009 · Open in CIViC | civic |
| Trastuzumab Emtansine | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1159The Phase III trial, TH3RESA (NCT01419197), was performed in patients with advanced HER2 breast cancer that was heavily pretreated. Patients were required to have prior exposure to trastuzumab and la… (full text at CIViC) PMID 24793816 · Krop et al., 2014 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1160The EMILIA study (NCT00829166) was a Phase II trial to assess the efficacy of trastuzumab emtansine (T-DM1, n=495) in comparison to lapatinib plus capecitabine (n=496), in treatment of advanced HER2 p… (full text at CIViC) PMID 23020162 · Verma et al., 2012 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1764In the single arm Phase II study (TDM4258g) breast cancer patients who had progressed on previous anti-HER2 therapy were given transtuzumab emtansine (T-DM1), a HER2 monoclonal antibody and antimicrot… (full text at CIViC) PMID 21172893 · Burris et al., 2011 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1432In a randomized phase II study, first line treatment of HER2-positive metastatic breast cancer with trastuzumab emtansine (T-DM1) resulted in improved progression free survival and fewer serious adver… (full text at CIViC) PMID 23382472 · Hurvitz et al., 2013 · Open in CIViC | civic |
| Lapatinib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID1008This Phase III trial compared the activity of lapatinib vs. trastuzumab vs. sequential trastuzumab followed by lapatinib vs. lapatinib plus trastuzumab in an adjuvant treatment setting. 8381 women we… (full text at CIViC) PMID 26255196 · Zardavas et al., 2015 · Open in CIViC | civic |
| Neratinib + TrastuzumabSequential | HER2-Positive Breast CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID8047Primarily based on the results from the phase III ExteNET clinical trial (Study 3004, NCT00878709), on July 17, 2017, the FDA approved neratinib (NERLYNX, HKI-272) for extended adjuvant therapy of adu… (full text at CIViC) PMID 29523624 · Singh et al., 2018 · Open in CIViC | civic |
| 〃 | HER2-Positive Breast CarcinomaALIAS | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID8049The initial 2 year follow-up of the Phase III clinical trial (exteNET, NCT00878709) where early stage HER2 positive breast cancer patients underwent adjuvant trastuzumab therapy and then either receiv… (full text at CIViC) PMID 29146401 · Martin et al., 2017 · Open in CIViC | civic |
| Palbociclib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1561In a panel of 47 breast cancer cell lines, HER2 overexpressing cells were among those more sensitive to CDK4/6 inhibitor Palbociclib (PD0332991). In the trastuzumab sensitive cell line Bt474, palbocic… (full text at CIViC) PMID 19874578 · Finn et al., 2009 · Open in CIViC | civic |
| Pilaralisib + TrastuzumabCombination | HER2-Positive Breast CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID1448In 5 trastuzumab resistant HER2 overexpressing breast cancer cell lines, combination of the pan-PI3K inhibitor XL147 (pilaralisib) and trastuzumab treatment induced cell death to similar or greater le… (full text at CIViC) PMID 23204226 · Chakrabarty et al., 2013 · Open in CIViC | civic |