BRCA1 Loss-of-function

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Malignant Breast Neoplasm2
BRCA1 Loss-of-function	Pidnarulex + QuarfloxinSubstitutes	Predictive	D	Supports Sensitivity Response	4	accepted	EID1924 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
BRCA1 Loss-of-function	Talazoparib	Predictive	B	Supports Sensitivity Response	4	accepted	EID4838 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

BRCA1 Loss-of-function

Pidnarulex + QuarfloxinSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID1924

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

BRCA1 Loss-of-function

Talazoparib

Predictive

Supports Sensitivity Response

accepted

EID4838

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 Mesothelioma1
BRCA1 Loss-of-function OR BAP1 Loss-of-function	Rucaparib	Predictive	B	Supports Sensitivity Response	3	accepted	EID11739 In this phase 2a clinical trial, 26 patients with either BRCA1-deficient or BAP1-deficient mesotheliomas were treated with Rucaparib. 38% of the patients were BAP1 and BRCA1 negative, 89% were BAP1 ne… (full text at CIViC) PMID 33515503 · Fennell et al., 2021 · Open in CIViC	civic

Malignant Mesothelioma1

BRCA1 Loss-of-function OR BAP1 Loss-of-function

Rucaparib

Predictive

Supports Sensitivity Response

accepted

EID11739

In this phase 2a clinical trial, 26 patients with either BRCA1-deficient or BAP1-deficient mesotheliomas were treated with Rucaparib. 38% of the patients were BAP1 and BRCA1 negative, 89% were BAP1 ne… (full text at CIViC)

PMID 33515503 · Fennell et al., 2021 · Open in CIViC

civic

Malignant Ovarian Neoplasm2
BRCA1 Loss-of-function	Olaparib	Predictive	B	Supports Sensitivity Response	4	accepted	EID211 The combination of PARP inhibition (Olaparib) with BRCA mutation results in irreparable and lethal DNA damage. Response rates are higher in BRCA1 mutation positive women with high grade serous or undi… (full text at CIViC) PMID 23346317 · Goff, 2013 · Open in CIViC	civic
BRCA1 Loss-of-function	Talazoparib	Predictive	B	Supports Sensitivity Response	3	accepted	EID4876 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

BRCA1 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID211

The combination of PARP inhibition (Olaparib) with BRCA mutation results in irreparable and lethal DNA damage. Response rates are higher in BRCA1 mutation positive women with high grade serous or undi… (full text at CIViC)

PMID 23346317 · Goff, 2013 · Open in CIViC

civic

BRCA1 Loss-of-function

Talazoparib

Predictive

Supports Sensitivity Response

accepted

EID4876

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

civic

Malignant Pancreatic Neoplasm1
BRCA1 Loss-of-function	Olaparib	Predictive	B	Supports Sensitivity Response	3	rejected	EID6075 In multicenter phase II study included individuals with a germline BRCA1/2 mutation and pancreatic cancer after gemcitabine treatment. Olaparib was administered at 400 mg twice per day. Tumor respons… (full text at CIViC) PMID 25366685 · Kaufman et al., 2015 · Open in CIViC	civic

Malignant Pancreatic Neoplasm1

BRCA1 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

rejected

EID6075

In multicenter phase II study included individuals with a germline BRCA1/2 mutation and pancreatic cancer after gemcitabine treatment. Olaparib was administered at 400 mg twice per day. Tumor respons… (full text at CIViC)

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

civic

Malignant Prostate Neoplasm2
BRCA1 Loss-of-function	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID1523 In a study of 2,019 patients with prostate cancer, 18 had germline BRCA1 mutations, 61 had germline BRCA2 mutations and 1,940 were non-carriers. Patients with BRCA1/2 mutations had a 2-fold higher in… (full text at CIViC) PMID 23569316 · Castro et al., 2013 · Open in CIViC	civic
BRCA1 Loss-of-function	Olaparib	Predictive	C	Supports Sensitivity Response	2	accepted	EID845 1/1 patients with BRCA1 homozygous deletion had a response to olaparib in this phase 2 study. PMID 26510020 · Mateo et al., 2015 · Open in CIViC	civic

Malignant Prostate Neoplasm2

BRCA1 Loss-of-function

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID1523

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

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

civic

BRCA1 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID845

1/1 patients with BRCA1 homozygous deletion had a response to olaparib in this phase 2 study.

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

civic

Pancreatic Adenocarcinoma1
BRCA1 Loss-of-function	Olaparib	Predictive	A	Supports Sensitivity Response	5	accepted	EID7384 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

BRCA1 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID7384

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
BRCA1 Loss-of-function	Olaparib	Predictive	A	Supports Sensitivity Response	5	accepted	EID11216 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

BRCA1 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID11216

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
BRCA1 Loss-of-function	Olaparib	Predictive	A	Supports Sensitivity Response	5	accepted	EID11201 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
BRCA1 Loss-of-function	Olaparib	Predictive	B	Supports Sensitivity Response	5	accepted	EID5815 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

BRCA1 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID11201

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

civic

BRCA1 Loss-of-function

Olaparib

Predictive

Supports Sensitivity Response

accepted

EID5815

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 (12 items)

Clinical significance (0)