Evidence map›Paper›PMID 41961224›Full record

Observational studyBreast cancer (Tokyo, Japan)2026

BRCA1/2 Reversion Mutations in Japanese Patients with Metastatic Breast Cancer Progressing on Olaparib: OLIVE (WJOG15321B).

Hitomi Sakai, Rika Kusumoto-Matsuo, Mari Hosonaga, Kazuki Nozawa, Manabu Futamura, Yuko Tanabe, Toru Mukohara, Kazuhiro Shiraishi, Tatsuya Toyama, Hiroyuki Yasojima and 9 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Breast cancer (Tokyo, Japan), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Hitomi SakaiAdvanced Cancer Translational Research Institute, Showa Medical University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. sakai-h@med.showa-u.ac.jp.ORCID http://orcid.org/0000-0001-8396-9121
Rika Kusumoto-MatsuoAdvanced Cancer Translational Research Institute, Showa Medical University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Mari HosonagaBreast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Kazuki NozawaDepartment of Breast Oncology, Aichi Cancer Center, Nagoya, Japan.
Manabu FutamuraDepartment of Breast Surgery, Gifu University Hospital, Gifu, Japan.
Yuko TanabeDepartment of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
Toru MukoharaDepartment of Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Kazuhiro ShiraishiDepartment of Medical Oncology, NHO Nagoya Medical Center, Nagoya, Japan.
Tatsuya ToyamaDepartment of Breast Surgery, Nagoya City University, Nagoya, Japan.
Hiroyuki YasojimaDepartment of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, Japan.
Noriyuki WatanabeDepartment of Breast and Endocrine Surgery, Osaka International Cancer Institute, Osaka, Japan.
Hideki SakaiDepartment of Medical Oncology, Hyogo Cancer Center, Akashi, Japan.
Tsutomu IwasaDepartment of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Nobumichi TakeuchiDepartment of Oncology, Ina Central Hospital, Ina, Japan.
Hiroshi TadaDepartment of Surgery, Division of Breast and Endocrine Surgery, Tohoku University Hospital, Sendai, Japan.
Kazuko SakaiDepartment of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
Natsuko ChibaDepartment of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan.
Toshimi TakanoBreast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Junji TsurutaniAdvanced Cancer Translational Research Institute, Showa Medical University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA key resistance mechanism to PARP inhibitors is the development of BRCA1/2 reversion mutations that restore the protein function.

methodsPatients with metastatic breast cancer and germline BRCA1/2 mutations were recruited from 14 institutions and treated with olaparib. Targeted next-generation sequencing was performed on circulating tumor DNA (ctDNA) extracted from blood collected at base line and progression on olaparib (Guardant360). The primary objective was to evaluate the frequency of BRCA1/2 reversion mutations in this group.

resultsFrom November 2021 to October 2023, 60 patients were enrolled. The median age was 50.5 years (32–85). Of these, 12 (20.0%) had germline BRCA1 mutation and 48 (80.0%) had germline BRCA2 mutation. The median number of prior chemotherapies was 2 (0–7). Two patients had received platinum. Among patients with tumor progression on olaparib who had available ctDNA results, BRCA1/2 reversion mutations were identified in 25.0% (2/8; 95% CI 3.2–65.1%) with germline BRCA1 mutation and 23.5% (8/34, 95% CI 10.7–41.2%) with germline BRCA2 mutation. In one patient, BRCA2 reversion mutations were found in ctDNA seven months before radiological confirmation of progression on olaparib and again after progression. Among the ten cases with BRCA1/2 reversion mutations, all but one case involved secondary indels on primary indel sites. Reversion mutations were not observed in the C-terminal regions of BRCA1/2.

conclusionBRCA1/2 reversion mutations were detected in ctDNA as a mechanism of resistance to olaparib. Certain genomic regions and mutation types appeared to be particularly prone to reversion mutations. CLINICAL

trial registrationUMIN000046007.

Indexed as

BRCA1 ProteinBRCA2 ProteinBreast NeoplasmsDrug Resistance, NeoplasmPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsAdultAgedAged, 80 and overCirculating Tumor DNADisease ProgressionEast Asian PeopleFemaleGerm-Line MutationHumansBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanCirculating Tumor DNAolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsBRCA1/2olaparibPARP inhibitorresistancereversion mutation

Identifiers

PMID41961224
PMCPMC13124753

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.