記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recently, homologous recombination deficiency (HRD) has become a new target for hereditary cancers. Molecular-based approaches for hereditary cancers in the clinical setting have been reviewed. In particular, the efficacy of the PARP inhibitor has been considered by several clinical trials for various kinds of hereditary cancers. This indicates that the PARP inhibitor can be effective for any kind of BRCA mutated cancers, regardless of the organ-specific cancer. Homologous recombination deficiency (HRD) has become a new target for hereditary cancers, indicating the necessity to confirm the status of HRD-related genes. ARID1A, ATM, ATRX, PALB2, BARD1, RAD51C and CHEK2 are known as HRD-related genes for which simultaneous examination as part of panel testing is more suitable. Both surgical and medical oncologists should learn the basis of genetics including HRD. An understanding of the basic mechanism of homologous repair recombination (HRR) in BRCA-related breast cancer is mandatory for all surgical or medical oncologists because PARP inhibitors may be effective for these cancers and a specific strategy of screening for non-cancers exists. The clinical behavior of each gene should be clarified based on a large-scale database in the future, or, in other words, on real-world data. Firstly, HRD-related genes should be examined when the hereditary nature of a cancer is placed in doubt after an examination of the relevant family history. Alternatively, HRD score examination is a solution by which to identify HRD-related genes at the first step. If lifetime risk is estimated at over 20%, an annual breast MRI is necessary for high-risk screening. However, there are limited data to show its benefit compared with BRCA. Therefore, a large-scale database, including clinical information and a long-term follow-up should be established, after which a periodical assessment is mandatory. The clinical behavior of each gene should be clarified based on a large-scale database, or, in other words, real-world data.

DOI： 10.3390/curroncol32020090

PubMed

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記述言語：日本語   出版者・発行元：昭和大学学士会  

我が国では，2019年6月にがん遺伝子パネル検査が保険収載され，昭和大学病院では，2020年7月よりがん遺伝子パネル検査が開始された．2022年12月までに160例を実施，エキスパートパネル（以下，EP）到達例は159件で，そのうち84例（52.8％）に遺伝子変異に基づく治療が推奨され，15例（18％）が薬剤投与に至った．しかし，EP到達例のうち15例（9.4％）が推奨治療を提示されたものの提示から3か月未満で死亡されていた．また，生殖細胞系列由来が疑われる病的バリアント（以下，PGPV）として遺伝外来受診を推奨されたのは28例（18％）で，そのうち19例（68％）が遺伝カウンセリングを受け，11例（39％）が遺伝学的検査を受検，6例（21％）が遺伝子変異陽性であった．この結果から，幅広く該当する治療を探索するがん遺伝子パネル検査は，適切な時期に行うことが治療到達性に重要であると考えられた．また，遺伝性疾患は，患者や家族にとって重要な情報でありケアを受けられることが望まれ，今後はPGPVを示唆された患者全員が遺伝カウンセリングをはじめ必要なサポートが受けられるように改善していく必要がある．そのためには，薬剤や治験，遺伝の専門家の確保や育成，診療システムの改善が重要である．

DOI： 10.14930/jshowaunivsoc.84.82

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記述言語：日本語   出版者・発行元：横浜 : 日本がん・生殖医療学会  

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その他リンク： https://ndlsearch.ndl.go.jp/books/R000000004-I031998158

記述言語：日本語   出版者・発行元：一般社団法人 日本遺伝性腫瘍学会  

遺伝性乳癌卵巣癌（hereditary breast and ovarian cancer : HBOC）は，癌の易罹患性症候群である．HBOC関連卵巣癌に関して，最も確実に予後を改善する方法としてリスク低減卵管卵巣摘出術（risk reducing salpingooophorectomy : RRSO）が推奨されている．NCCNガイドラインVersion 1．2020では家族計画が終了していればBRCA1の病的バリアント保持者では35歳から40歳を目安に，BRCA2の病的バリアント保持者では40歳から45歳を目途にRRSOを行うことを推奨している．

がん研有明病院（以下，当院）ではこれまでに78例のHBOC症例にRRSOを施行してきたが，3例（3.8％）のオカルト癌を経験した．3例の内訳は，2例がBRCA1病的バリアント保持者（73歳と44歳）で，1例がBRCA2 病的バリアント保持者（47歳）であった．いずれもNCCNガイドラインのRRSO施行推奨年齢を超えていた．3例とも手術の1か月前に骨盤MRI，腫瘍マーカーの測定を行っていたが，いずれも悪性所見を認めなかった．当院の経験においてもサーベイランスでの早期発見は困難であるということ，そしてNCCNガイドラインのRRSO施行推奨年齢は日本人においても妥当である可能性が示唆された．

DOI： 10.18976/jsht.20.3_136

CiNii Article

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Individuals carrying pathogenic BRCA1 or BRCA2 mutations have an increased lifetime risk of breast and/or ovarian cancer. The incidence of breast cancer amongst disease-free BRCA mutation carriers under surveillance and the clinical and pathological characteristics of those who subsequently develop the disease remain unclear in Japan. We reviewed the records of 155 individuals with BRCA1 or BRCA2 mutations identified by genetic testing between January 2000 and December 2016. At the time of genetic testing, 26 individuals with one of these mutations had no history of breast cancer and were therefore enrolled in a surveillance program that included biannual ultrasonography, clinical breast examination, annual mammography, and conditional magnetic resonance imaging for the early detection of primary breast cancer. During the surveillance period, 5 individuals with BRCA1 or BRCA2 mutations were diagnosed with primary breast cancer. The mean surveillance duration until breast cancer diagnosis was 48 months. The incidence of primary breast cancer during surveillance in initially disease-free BRCA mutation carriers was 4.23%/year. In two cases, the tumors were only detectable on MRI. The case 5 patient who presented with a tumor that was detected by self-examination, which then grew rapidly, had stage IIB triple-negative breast cancer. In conclusion, our results show that some challenges exist in the early detection of breast cancers in BRCA1 or BRCA2 mutation carriers. There are also some difficulties in approaching those individuals in Japanese society.

DOI： 10.1007/s12282-019-00971-6

PubMed

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