Language：English   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publisher：The Showa University Society  

Genomic medicine, along with the inclusion of cancer gene panel testing in insurance claims was started in Japan in June 2019. Showa University Hospital in Tokyo, Japan started cancer gene panel testing in July 2020 and accumulated 160 cases by December 2022. Of the 159 cases that reached the expert panel （EP）, 84 （52.8％） were recommended gene mutation-based treatment, whereas 15 （18％） were managed with medical therapy. Unfortunately, of the 84 patients were offered the recommended treatment, 15 （9.4％） died within 3 months after reaching the EP. Of the 19 patients （68％） who received genetic counseling, 11 （39％） underwent genetic testing, and 6 （21％） were positive for genetic mutations. These results suggested that a comprehensive treatment strategy and appropriate timing of testing are essential for early initiation of treatment. Moreover, identification of possible genetic disorders is crucial for patients and their families, for timely access to care. To achieve these goals and improve the medical care system, recruitment and training of specialists on drugs, clinical trials, and genetics are necessary.

DOI： 10.14930/jshowaunivsoc.84.82

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Language：Japanese   Publisher：横浜 : 日本がん・生殖医療学会  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I031998158

Language：Japanese   Publisher：The Japanese Society for Hereditary Tumors  

Hereditary breast and ovarian cancer (HBOC) is associated with a significantly increased risk of breast and ovarian cancer. Risk-reducing salpingo-oophorectomy (RRSO) has proven to reduce the incidence of ovarian/fallopian tube cancer as well as the cancer-specific and overall mortality. According to the National Comprehensive Cancer Network (NCCN) guidelines, RRSO is generally recommended for women aged 35–40 years with BRCA1 pathogenic mutations, who have already given birth. In patients with BRCA2 pathogenic mutations, RRSO can be delayed until 40–45 years of age.

Of the 78 women who underwent RRSO, occult cancer was observed in three women (3.8%), two were BRCA1 (44 and 73 years old) and one was a BRCA2 (47 years old) pathogenic mutation carrier. Although MRI was performed for these three women one month before RRSO, there was no evidence of malignancy, and serum level of CA-125 was not elevated. These three women were diagnosed with stage I.

The age of all three women diagnosed with ovarian cancer was higher than that recommended in the NCCN guidelines. RRSO at a recommended age in the NCCN guidelines is considered to be appropriate for Japanese women.

DOI： 10.18976/jsht.20.3_136

CiNii Article

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Language：English   Publishing type：Research paper (scientific journal)  

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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