TEST:

BRACAnalysis CDx™

Despite treatment with PARPi for postoperative recurrence, a sustained response was not achieved owing to BRCA reversion mutations. It is essential to acknowledge the rarity of BRCA reversion mutations, which limit the effectiveness of PARPi.

P1; Active, not recruiting --> Completed

"The gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer."

She was diagnosed with recurrent breast cancer (other: pectoralis major muscle, mediastinal and right parasternal connective tissue), and treatment was started with endocrine therapy (anastrozole)...Abemaciclib was added to fulvestrant, but 5 months later, the patient developed a cough and CT scans showed interstitial pneumonia...Treatment was continued with Avastin + paclitaxel, and the patient maintained stable disease...Since gynecological malignant tumors generally have a poorer prognosis than breast cancer, it was considered necessary to cooperate with the gynecology department regarding the treatment plan. Conclusion We report a rare case of uterine metastasis from breast cancer, adding some literature review

Weekly Paclitaxel therapy was scheduled as preoperative chemotherapy, followed by AC therapy...Postoperative adjuvant therapy will be AC therapy, followed by radiation therapy, followed by hormone therapy, with the addition of Olaparib...Since male breast cancer frequently has BRCA2 pathogenic variants, is often discovered at an advanced stage, and is recommended to be treated in the same way as female breast cancer, it was thought that there would be great benefits to performing BRCA genetic testing. In the future, it will be necessary to proceed with screening for prostate cancer and genetic counseling for blood relatives, and to utilize the results of this genetic test in the health management of the patient and his/her blood relatives

Seven cases were administered TAM after surgery. In one case of encapsulated papillary carcinoma, the father and aunt had breast cancer, and the family history suggested the possibility of a positive BRACAnalysis, but the result was negative, which was an extremely interesting result

After that, because it was difficult to obtain intravenous drip infusion, a CV port was placed in the right subclavian vein, and docetaxel therapy was initiated...In the fourth course, perhaps because G-Lasta was administered, no FN was observed, but anemia with Hb of 5.0 was observed and a blood transfusion was required...In this case, the patient had triple-negative breast cancer with cold agglutinin disease, but during postoperative chemotherapy, she developed FN and severe anemia, making treatment difficult. It seems important to educate patients about infection control and to visit a hospital when they experience symptoms of anemia

The patient had PD-L1 CPS of 10 or higher, and pembrolizumab + gemcitabine + carboplatin was started in March. Two weeks after admission, the patient's respiratory condition worsened, he developed DIC, and passed away. [Discussion] Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition, but in cases of rapidly progressing respiratory failure in cancer patients, PTTM must be kept in mind when carrying out differential diagnosis and treatment

Since BRACAnalysis became covered by insurance, BRCA genetic testing has been actively conducted, but because this case occurred at a young age, it is thought that genetic testing is necessary again for past cases. In addition, it was thought that there is a need to improve team medical care for the unique nature of diagnosis and treatment during pregnancy and childbirth, fertility, breast reconstruction, etc

As for adverse events, Grade 3 neutropenia was observed in six cases (60%) during ICI + Paclitaxel + Carboplatin treatment...One case (10%) showed allergic symptoms due to epirubicin during the first K of EC treatment, and the treatment was discontinued and surgery was performed, but the patient achieved pCR...ICI was continued in cases with postoperative pCR, and ICI + Capecitabine was administered in non-pCR cases, and there has been no recurrence...As for adverse events, irAEs were detected early and appropriate responses were made, allowing chemotherapy to be continued. There were more adverse events such as neutropenia than in previous reports, and appropriate drug suspension and reduction are considered necessary

The median follow-up period from the date of diagnosis of metastasis or recurrence was 51.6 months. 129 patients were included, of which 50 (38.8%) underwent BRACAnalysis, and 6 (4.7%) were gBRCA PV patients. All gBRCA PV patients were gBRCA2 PV.

As mentioned above, we provide treatment to patients with early-stage breast cancer and advanced recurrent breast cancer in cooperation with various facilities in the area, but many challenges remain. By further improving the hospital-community collaboration system through the creation of a community collaboration pass, regular study sessions and information exchange meetings with doctors from nearby hospitals and clinics, sharing of medical record information, collaboration with facility-based doctors, etc., it is expected that the medical environment for breast cancer patients in rural areas where there are few breast specialists will improve

Gemcitabine+Carboplatin therapy was administered while waiting for the test results to come out, and it was highly effective. In such a situation, for patients with NTRK fusion genes, which are companion diagnostics for Entrectinib, and PALB2 gene mutations, which are suggested to be sensitive to Olaparib, early use of CGP testing contributes to improving prognosis, so the significance of early implementation of CGP testing is also being questioned. In one case experienced in our department, it is possible that better Carboplatin response and Olaparib sensitivity could have been maintained if CGP had been performed early

In January 2018, the OlympiAD trial approved the PARP inhibitor (olaparib) for metastatic and recurrent breast cancer, and the companion diagnostic BRACAnalysis CDx was also covered by insurance...It is important to screen appropriate cases in order to select the appropriate surgical procedure, perioperative treatment, and recurrence treatment, and it is also important not to overlook the application of PARP inhibitors not only for metastatic recurrence treatment but also as postoperative adjuvant therapy. At present, RRM cannot be performed as part of insurance treatment at our hospital, but we hope that facility requirements will be expanded in the future

The BRACAnalysis® diagnostic system (Myriad Genetics) was approved for insurance coverage in Japan as a companion diagnostic for olaparib in July 2018 and as a genetic test for hereditary breast and ovarian cancer (HBOC) in April 2020, and has been introduced in our department...In our hospital, we believe that the number of BRCA genetic tests will increase in the future, and the number of people who are positive for BRCA1/2 pathogenic variants will also increase. We would like to further strengthen and improve our testing system, fully return the test results to the test subjects, and further strengthen and improve our medical care system for those who are positive for BRCA1/2 pathogenic variants and our response to at-risk individuals

Since this BRCA-positive patient had bilateral breast cancer, there was no need to consider preventive resection of the breasts, but as for the ovaries, simultaneous RRSO with breast cancer could not be performed at our hospital, and the patient is currently taking Abemaciclib, and the ovaries are under surveillance. Even if the test is performed for the purpose of companionship to Olaparib, it will be diagnosed as HBOC. Therefore, it is necessary to provide information at an appropriate time in parallel with treatment

Introduction BRCA genetic testing (BRACAnalysisNa® diagnostic system: hereafter referred to as BRCA testing) was covered by insurance in July 2018 as a companion diagnostic for olaparib, and in April 2020 as HBOC treatment...We are working on creating a DVD based on the patient information form by the end of this year so that the necessary information can be conveyed regardless of who is handling the case. We hope to further improve the skills of nurses and improve the support system

Since Olaparib was approved for insurance coverage in 2018, our hospital has also started offering BRACAnalysis testing...The method of providing information to patients has been unified within the hospital, and the method used at our hospital is well known to staff, so we have a system in place to propose testing to all patients eligible for BRACAnalysis, which is also thought to be a factor in the increase in the number of tests. Currently, the system is set up so that BRACAnalysis tests are performed after patients are examined by the Department of Genetics, but the increasing burden on the Department of Genetics due to the increasing number of tests is becoming an issue, and a review of the system is being considered

In addition, the indications for olaparib as a recurrence metastasis and postoperative drug therapy have been expanded... The number of BRACAnalysis diagnostics sent out from April to November 2022 was 11 (0 perioperative cases), and the number of sent out from the same period in 2023 was 62 (20 perioperative cases), and the number of sent out increased 5.6 times due to the change of the attending physician. In addition, the number of sent out from April to November 2023 was 52 for Doctor A and 10 for Doctor B, and the sending out rate from October to November was 51% (17/33 cases) for Doctor A and 20% (7/34 cases) for Doctor B. Although genetic testing is not mandatory in breast cancer treatment, it is mandatory to provide information on the clear benefits brought by the test results, such as drug selection and future cancer risk. Shared decision making is important regarding the desire for genetic testing, and the results of this verification suggest that the number of sent out tests may differ depending on the attending physician's awareness of genetic testing and explanation skills.

Conclusion Of the eight cases of breast cancer positive for BRCA gene mutation, five cases of metastatic recurrence and three cases of postoperative adjuvant treatment were administered olaparib. Appropriate collection of genomic information is important for identifying suitable cases and developing optimal treatment strategies

In April 2018, insurance coverage for BRACAnalysis was started for patients with HER2-negative advanced recurrent breast cancer, and the scope of testing and the scope of Olaparib have been gradually expanded to date... The mean age at the time of breast cancer diagnosis in the 14 mutation-positive cases was 51.6 years (range, 36-78 years). There were three cases of progression or systemic recurrence, and two cases of metachronous bilateral breast cancer. Cases that met the requirements for HBOC diagnosis included five cases aged 45 years or younger, four cases of triple negative cases aged 60 years or younger (one of which was 45 years or younger), two cases of unilateral multiple onset, two cases of a history of ovarian cancer, nine cases of a family history, and one case of male breast cancer.

In the future, CRRM should be carefully recommended in accordance with the patient's values and wishes, taking into account the uncertainty of the evidence. Our hospital has a system in place that crosses medical departments, including surveillance and follow-up, and we believe that the environment in which necessary information can be obtained is a great benefit to both patients and medical professionals

In addition, two patients with recurrence would have been eligible for perioperative treatment with Orapalib or Pembrolizumab... There were 17 HBOC cases (19 lesions) during the study period, including 6 with BRCA1 and 11 with BRCA2. The median age was 43 years (range 31-57 years). 12/17 patients had a family history of breast or ovarian cancer, and some had a family history of pancreatic, prostate, gastric, or colorectal cancer.

After that, she was treated with ①ANA (combined with Demosmab), ②fulvestrant, ③TS-1, ④Capecitabine, and transferred to our hospital at her own request. At the time of transfer, multiple liver metastases were found, and treatment was continued with ⑤abemaciclib+FUL, ⑥PTX+BEV, and ⑦eribulin...⑩Treatment with CPT-11 resulted in PD, and the patient passed away after developing BSC. [Discussion] In the former gBRCA2 mutation, a mutant protein is produced in which the latter 45% of the BRCA2 molecule, including the DNA binding domain, is shortened, while in the latter sBRCA2 mutation, a deletion that slightly shortens the RAD51 binding site, producing a mutant protein that is only shortened by 3.6% of the total. Although there have been no reports of molecular function analysis specific to this mutation, it is possible that the former mutation may have partially restored function, which may have contributed to the mechanism of primary resistance to olapalib

Hereditary breast and ovarian cancer syndrome (HBOC) genetic testing and risk reduction surgery for those with a history of breast and ovarian cancer are now covered by insurance, and with the introduction of olaparib, HBOC treatment has become increasingly important...As there are cases without a family history, it is necessary to provide appropriate information for cases where it is applicable. Subsequent treatment, such as risk-reducing surgery for HBOC cases, requires shared decision-making on a case-by-case basis

Introduction In the Phase III OlympiA study, Olaparib demonstrated a statistically significant and clinically meaningful extension of overall survival compared to placebo in postoperative chemotherapy in patients with high-risk early breast cancer who were BRCA gene mutation-positive and Her2-negative after completing local treatment and standard preoperative or postoperative chemotherapy...Conclusion In HER 2 negative hormone receptor positive early breast cancer patients with BRCA1/2 pathogenic variants, the RS value of Oncotype-DX tends to be high. Since insurance coverage for BRACAnalysis® is still conditional, we would like to improve the prognosis of BRCA gene mutation-positive early breast cancer by utilizing Oncotype-DX as well

Background Breast cancer treatment based on BRCA pathogenic variants (PSVs) is entering a new era with the expansion of the indications for perioperative chemotherapy with olaparib... In this study, a correlation was observed between BRCA-PSV and NLR, an immune indicator. Regarding prognosis, cases with high TILs had a poor prognosis, suggesting the complexity of BRCA-PSV and tumor immune responses

BRACAnalysis testing was performed in 11 patients with low HER2 expression as a companion diagnostic for olaparib, and 2 patients had pathological variants of the BRCA2 gene, making olaparib an appropriate treatment. (Summary) Trastuzumab deruxtecan showed favorable response rates and treatment durations in HER2-positive and HER2-low expressing metastatic recurrent breast cancer. The efficacy and safety of trastuzumab deruxtecan were confirmed

Conclusion In a survey of breast cancer patients who underwent genetic testing, more than half of the cases felt it was a financial burden, similar to previous reports of patients with solid cancers who underwent chemotherapy. Further economic and toxicity evaluations that take into account different background factors are needed

Almost all cases were referred within the hospital, but cooperation with local family doctors is believed to lead to early detection of diseases caused by gene mutations. In particular, BRCA1/2 mutations are associated with a high risk of developing malignant tumors other than breast cancer, and as such require follow-up of over a year, this is considered to be effective

There were 261 new surgical cases during the above period, all of which were female. Fifteen cases (5.7%) were eligible for BRACAnalysis® to confirm the applicability of olaparib adjuvant therapy based on clinical staging, and all were single-case cases. Of these, 11 cases (4.2%) had no family history of breast cancer, ovarian cancer, or pancreatic cancer.

First-line chemotherapy with gemcitabine + nab-paclitaxel failed due to tumor growth and worsening abdominal distention...BRCA-mutated pancreatic cancer is more likely to respond to mFFX, including platinum, and BRCA mutations have been reported to be highly prevalent in PACC. It is important to evaluate the presence of BRCA mutations in patients with PACC prior to treatment.

HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.

Olaparib has shown good results in patients with germline BRCA1/2 mutation-positive HER2-negative advanced/recurrent breast cancer who have a history of receiving anthracycline and taxane-based therapies. It was considered that even in recurrent breast cancer, the presence or absence of BRCA1/2 mutations should be actively sought even in advanced cases, and the administration of olaparib should be considered.

In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer.

"Myriad Genetics, Inc...and Personalis, Inc...announced a non-exclusive collaboration through which Myriad will market the Personalis®ImmunoID NeXT ultra-comprehensive biomarker discovery platform to its pharmaceutical partners who use the MyRisk® Hereditary Cancer Test, BRACAnalysis CDx® and/or MyChoice® CDx cancer tests."

The diagnosis of gBRCA PV-positive PC has increased revealed in recent years. These tumors appear to be sensitive to platinum-based chemotherapy, with long term survival observed in gATM PV + LPV-positive patients.

The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.

Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued...To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.

P1; Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

No abstracts available

P1; Trial completion date: May 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Dec 2024