BRCA2 Loss-of-function

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Malignant Breast Neoplasm2
BRCA2 Loss-of-function	Pidnarulex + QuarfloxinSubstitutes	Predictive	D	Supports Sensitivity Response	4	accepted	EID1925 The authors show that in the CX-5461 and CX-3543, G-quadruplex stabilizing agents, demonstrate specific toxicity against BRCA deficient breast cancer derived cells and polyclonal patient-derived xenog… (full text at CIViC) PMID 28211448 · Xu et al., 2017 · Open in CIViC	civic
BRCA2 Loss-of-function	Talazoparib	Predictive	B	Supports Sensitivity Response	4	accepted	EID4839 In part 2 of a two-part dose-escalation phase I trial (NCT01286987), 71 patients with Ewings sarcoma, breast, ovarian, small cell lung, or pancreatic cancers received 1.0 mg/day talazoparib treatment.… (full text at CIViC) PMID 28242752 · de Bono et al., 2017 ·

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Malignant Breast Neoplasm2

BRCA2 Loss-of-function

Pidnarulex + QuarfloxinSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID1925

The authors show that in the CX-5461 and CX-3543, G-quadruplex stabilizing agents, demonstrate specific toxicity against BRCA deficient breast cancer derived cells and polyclonal patient-derived xenog… (full text at CIViC)

PMID 28211448 · Xu et al., 2017 · Open in CIViC

civic

BRCA2 Loss-of-function

Talazoparib

Predictive

Supports Sensitivity Response

accepted

EID4839

In part 2 of a two-part dose-escalation phase I trial (NCT01286987), 71 patients with Ewings sarcoma, breast, ovarian, small cell lung, or pancreatic cancers received 1.0 mg/day talazoparib treatment.… (full text at CIViC)

PMID 28242752 · de Bono et al., 2017 ·

Malignant Ovarian Neoplasm2
BRCA2 Loss-of-function	Olaparib	Predictive	B	Supports Sensitivity Response	4	accepted	EID212 The combination of PARP inhibition (Olaparib) with BRCA mutation results in irreparable and lethal DNA damage. Response rates are higher in BRCA2 mutation positive women with high grade serous or undi… (full text at CIViC) PMID 23346317 · Goff, 2013 · Open in CIViC	civic
BRCA2 Loss-of-function	Talazoparib	Predictive	B	Supports Sensitivity Response	3	accepted	EID4875 In part 2 of a two-part dose-escalation phase I trial (NCT01286987), 71 patients with Ewings sarcoma, breast, ovarian, small cell lung, or pancreatic cancers received 1.0 mg/day talazoparib treatment.… (full text at CIViC) PMID 28242752 · de Bono et al., 2017 · Open in CIViC	civic

Malignant Ovarian Neoplasm2

BRCA2 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID212

The combination of PARP inhibition (Olaparib) with BRCA mutation results in irreparable and lethal DNA damage. Response rates are higher in BRCA2 mutation positive women with high grade serous or undi… (full text at CIViC)

PMID 23346317 · Goff, 2013 · Open in CIViC

civic

BRCA2 Loss-of-function

Talazoparib

Predictive

Supports Sensitivity Response

accepted

EID4875

PMID 28242752 · de Bono et al., 2017 · Open in CIViC

civic

Malignant Pancreatic Neoplasm2
BRCA2 Loss-of-function	Mitomycin	Predictive	D	Supports Sensitivity Response	2	accepted	EID1308 In pancreatic cell lines PL11 (FANCC-deficient) and CAPAN1 (BRCA2-mutated), sensitivity to DNA cross-linking agents was observed compared to FANCC/BRCA2 wildtype cell lines (Su86.86, CFPAC, AsPc1, and… (full text at CIViC) PMID 16243825 · van der Heijden et al., 2005 · Open in CIViC	civic
BRCA2 Loss-of-function	Olaparib	Predictive	B	Supports Sensitivity Response	3	rejected	EID6076 A multicenter phase II study included pancreatic cancer patients with a germline BRCA1/2 mutation after gemcitabine treatment. Olaparib was administered at 400 mg twice per day. Tumor response rate wa… (full text at CIViC) PMID 25366685 · Kaufman et al., 2015 · Open in CIViC	civic

Malignant Pancreatic Neoplasm2

BRCA2 Loss-of-function

Mitomycin

Predictive

Supports Sensitivity Response

accepted

EID1308

In pancreatic cell lines PL11 (FANCC-deficient) and CAPAN1 (BRCA2-mutated), sensitivity to DNA cross-linking agents was observed compared to FANCC/BRCA2 wildtype cell lines (Su86.86, CFPAC, AsPc1, and… (full text at CIViC)

PMID 16243825 · van der Heijden et al., 2005 · Open in CIViC

civic

BRCA2 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

rejected

EID6076

A multicenter phase II study included pancreatic cancer patients with a germline BRCA1/2 mutation after gemcitabine treatment. Olaparib was administered at 400 mg twice per day. Tumor response rate wa… (full text at CIViC)

PMID 25366685 · Kaufman et al., 2015 · Open in CIViC

civic

Malignant Prostate Neoplasm6
BRCA2 Loss-of-function	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID1524 In a study of 2,019 patients with prostate cancer, 18 had germ-line BRCA1 mutations, 61 had germ-line BRCA2 mutations and 1,940 were non-carriers. Patients with BRCA1/2 mutations had a 2-fold higher … (full text at CIViC) PMID 23569316 · Castro et al., 2013 · Open in CIViC	civic
BRCA2 Loss-of-function	Cisplatin + DasatinibCombination	Predictive	D	Supports Sensitivity Response	3	submitted	EID8981 Transcriptomic analysis of BRCA2-null metastatic castration-resistant prostate cancers revealed activation of the SRC signaling pathway. Platinum-based chemotherapies have shown efficacy in BRCA2-alte… (full text at CIViC) PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC	civic
BRCA2 Loss-of-function	Dasatinib + TalazoparibCombination	Predictive	D	Supports Sensitivity Response	4	submitted	EID8980 Transcriptomic analysis of BRCA2-null metastatic castration-resistant prostate cancers revealed activation of the SRC signaling pathway, which may be related to PARP inhibitor resistance. Preclinical … (full text at CIViC) PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC	civic
BRCA2 Loss-of-function	Olaparib	Predictive	B	Supports Sensitivity Response	4	accepted	EID650 In a phase 2 trial of patients with metastatic, castration-resistant prostate cancer, treated with olaparib tablets at a dose of 400 mg twice a day, all 7 patients harbouring BRCA2 loss of function al… (full text at CIViC) PMID 26510020 · Mateo et al., 2015 · Open in CIViC	civic
BRCA2 Loss-of-function	Dasatinib + OlaparibCombination	Predictive	D	Supports Sensitivity Response	4	submitted	EID8979 Transcriptomic analysis of BRCA2-null metastatic castration-resistant prostate cancers revealed activation of the SRC signaling pathway, which may be related to PARP inhibitor resistance. Preclinical … (full text at CIViC) PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC	civic
BRCA2 Loss-of-function	Bosutinib + TalazoparibCombination	Predictive	D	Supports Sensitivity Response	3	submitted	EID8982 Transcriptomic analysis of BRCA2-null metastatic castration-resistant prostate cancers revealed activation of the SRC signaling pathway, which may be related to PARP inhibitor resistance. Preclinical … (full text at CIViC) PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC	civic

Malignant Prostate Neoplasm6

BRCA2 Loss-of-function

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID1524

In a study of 2,019 patients with prostate cancer, 18 had germ-line BRCA1 mutations, 61 had germ-line BRCA2 mutations and 1,940 were non-carriers. Patients with BRCA1/2 mutations had a 2-fold higher … (full text at CIViC)

PMID 23569316 · Castro et al., 2013 · Open in CIViC

civic

BRCA2 Loss-of-function

Cisplatin + DasatinibCombination

Predictive

Supports Sensitivity Response

submitted

EID8981

Transcriptomic analysis of BRCA2-null metastatic castration-resistant prostate cancers revealed activation of the SRC signaling pathway. Platinum-based chemotherapies have shown efficacy in BRCA2-alte… (full text at CIViC)

PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC

civic

BRCA2 Loss-of-function

Dasatinib + TalazoparibCombination

Predictive

Supports Sensitivity Response

submitted

EID8980

Transcriptomic analysis of BRCA2-null metastatic castration-resistant prostate cancers revealed activation of the SRC signaling pathway, which may be related to PARP inhibitor resistance. Preclinical … (full text at CIViC)

PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC

civic

BRCA2 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID650

In a phase 2 trial of patients with metastatic, castration-resistant prostate cancer, treated with olaparib tablets at a dose of 400 mg twice a day, all 7 patients harbouring BRCA2 loss of function al… (full text at CIViC)

PMID 26510020 · Mateo et al., 2015 · Open in CIViC

civic

BRCA2 Loss-of-function

Dasatinib + OlaparibCombination

Predictive

Supports Sensitivity Response

submitted

EID8979

PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC

civic

BRCA2 Loss-of-function

Bosutinib + TalazoparibCombination

Predictive

Supports Sensitivity Response

submitted

EID8982

PMID 33334906 · Chakraborty et al., 2021 · Open in CIViC

civic

Pancreatic Adenocarcinoma1
BRCA2 Loss-of-function	Olaparib	Predictive	A	Supports Sensitivity Response	5	accepted	EID7385 In the phase 3 POLO trial patients who had germline BRCA1/2 mutation and metastatic pancreatic adenocarcinoma that had not progressed during first-line platinum-based chemotherapy were allocated to ma… (full text at CIViC) PMID 31157963 · Golan et al., 2019 · Open in CIViC	civic

Pancreatic Adenocarcinoma1

BRCA2 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID7385

In the phase 3 POLO trial patients who had germline BRCA1/2 mutation and metastatic pancreatic adenocarcinoma that had not progressed during first-line platinum-based chemotherapy were allocated to ma… (full text at CIViC)

PMID 31157963 · Golan et al., 2019 · Open in CIViC

civic

Triple-Negative Breast Carcinoma1
BRCA2 Loss-of-function	Olaparib	Predictive	A	Supports Sensitivity Response	5	accepted	EID11217 Report 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

Triple-Negative Breast Carcinoma1

BRCA2 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID11217

Report 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

HER2 Negative Breast Cancer2unmapped disease
BRCA2 Loss-of-function	Olaparib	Predictive	A	Supports Sensitivity Response	5	accepted	EID11202 Report 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 Loss-of-function	Olaparib	Predictive	B	Supports Sensitivity Response	3	accepted	EID5816 302 patients (234 with progression events) with HER2-negative metastatic breast cancer and with a confirmed deleterious or suspected deleterious germline BRCA mutation (164 BRCA1, 129 BRCA2) had signi… (full text at CIViC) PMID 28578601 · Robson et al., 2017 · Open in CIViC	civic

HER2 Negative Breast Cancer2unmapped disease

BRCA2 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID11202

PMID 34081848 · Tutt et al., 2021 · Open in CIViC

civic

BRCA2 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID5816

302 patients (234 with progression events) with HER2-negative metastatic breast cancer and with a confirmed deleterious or suspected deleterious germline BRCA mutation (164 BRCA1, 129 BRCA2) had signi… (full text at CIViC)

PMID 28578601 · Robson et al., 2017 · Open in CIViC

civic

Evidence by cancer (16 items)

Clinical significance (0)