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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-03-21)
    Abstract: Comprehensive cancer genomic profile (CGP) tests are being implemented under Japanese universal health insurance system. However, the clinical usefulness of CGP test for breast cancer patients has not been evaluated. Of the 310 patients who underwent CGP testing at our institution between November 2019 and April 2021, 35 patients with metastatic breast cancer whose treatment strategy was discussed by our molecular tumor board within the study period were investigated after exclusion of 2 cases that could not be analyzed. The turn-around time, drug accessibility, and germline identification detection were evaluated. The subtype was luminal in 20 patients (57.1%), triple-negative in 12 patients (34.3%), and luminal-HER2 in 3 patients (8.6%). Actionable gene mutations were detected in 30 patients (85.7%), and 7 patients (20.0%) were recommended for clinical trial participation, with the drug administered to 2 patients (5.7%). Three patients (8.6%) died due to disease progression before the test results were disclosed. We report the results of an initial assessment of the utility of CGP testing for patients with metastatic breast cancer under Japanese universal health insurance system. Conducting CGP tests at a more appropriate time could provide patients with greater benefit from treatments based on their specific gene mutations.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 2
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: Trastuzumab and fulvestrant combination therapy is one of the treatment options for patients with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer; however, there are limited studies evaluating the efficacy of this combination therapy. Methods We retrospectively reviewed the data of women with hormone receptor- and HER2-positive metastatic breast cancer who received trastuzumab and fulvestrant combination therapy between August 1997 and August 2020 at the Cancer Institute Hospital. The primary endpoint of this study was progression-free survival, and the secondary endpoints were response rate, overall survival and safety. Results We reviewed the data of 1612 patients with recurrent or metastatic breast cancer, of which 118 patients were diagnosed with hormone receptor- and HER2-positive breast cancer. Of these, 28 patients who received trastuzumab and fulvestrant combination therapy were eligible for this study. The median treatment line for advanced breast cancer was 6 (range, 1–14), the median progression-free survival was 6.4 months (95% confidence interval [CI], 3.46–8.17), and the median overall survival was 35.3 months (95% CI, 20.0–46.7). Of the 28 patients, partial response was observed in 1 (4%), stable disease in 17 (61%), and progressive disease in 10 (36%) patients. The disease control rate was 64%. Adverse events of grade ≥ 3 were not observed. Conclusions Trastuzumab and fulvestrant combination therapy showed moderate clinical efficacy and no severe toxicity after standard anti-HER2 treatment, which is a reasonable treatment option for patients with hormone receptor- and HER2-positive metastatic breast cancer. These data contribute to understanding the efficacy of trastuzumab and fulvestrant combination therapy as control data for further development of anti-HER2 agents plus hormone therapy.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 3
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 180, No. 2 ( 2020-04), p. 331-341
    Type of Medium: Online Resource
    ISSN: 0167-6806 , 1573-7217
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 4
    In: Cancer Science, Wiley, Vol. 113, No. 5 ( 2022-05), p. 1808-1820
    Abstract: Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6i) significantly improve progression‐free survival and have become the standard therapy for estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer patients. Treatment surveillance by radiological imaging has some limitations in detection and repeated biopsy genomic profiling is not clinically feasible. Serial circulating tumor DNA (ctDNA) analysis may provide insights into treatment response. Here we performed serial ctDNA analysis ( n  = 178) on 33 patients. Serial ctDNA analysis identified disease progression with sensitivity of 75% and specificity of 92%. In eight of 12 patients (61%) responding to CDK4/6i who eventually developed progressive disease, serial sampling every 3 or 6 months captured the initial rise of ctDNA with an average lead time of 3 months. In three of eight patients that did not respond to CDK4/6i (progressive disease at first radiological assessment, 3 months), biweekly sequencing within the first cycle of CDK4/6i treatment (1 month) detected sustained ctDNA levels (≥0.2% variant allele frequency), with lead time of 2 months. Serial ctDNA analysis tracked RECIST response, including clinically challenging scenarios (bone metastases or small‐sized target lesions), as well as detecting acquired genetic alterations linked to CDK4/6i resistance in the G 1 to S transition phase. Circulating tumor DNA analysis was more sensitive than carcinoembryonic antigen or cancer antigen 15‐3 serum tumor markers at monitoring tumor response to CDK4/6i treatment. Our findings indicated the possible clinical utility of serial ctDNA analysis for earlier progressive disease detection and real‐time monitoring of CDK4/6i response.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 5
    In: Annals of Oncology, Elsevier BV, Vol. 32 ( 2021-07), p. S320-
    Type of Medium: Online Resource
    ISSN: 0923-7534
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2003498-2
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P5-01-15-P5-01-15
    Abstract: Background: Hormone receptor positive breast cancers accounts for approximately 70% of metastatic breast cancers (MBCs), and it is often treated with an anti-hormonal agent as long as possible unless with visceral and aggressive metastasis.CDK4/6 inhibitorsare effective as first- or second-line treatments for metastatic hormone receptor positive HER2 negative breast cancer (HR+ HER2-). When disease progression due to resistance to CDK4/6 treatment occurs, treatment modification is required. Currently, monitoring of treatment response relies solely on imaging.Therefore, through thisstudy, we aim to evaluate ctDNA as a potential biomarker to monitor response to CDK4/6 treatment. Materials & Methods: Patients were recruited from the Cancer Institute Hospital of Japan Foundation for Cancer Research (JFCR).Hormone positive HER2 negative (HR+ HER2-) MBC patients treated with CDK4/6 inhibitors were collected at different timepoints up till 24 months or if patient develops disease progression. These samples were sequenced using a targeted pan-cancer panel that utilizes ultradeep NGS with molecular barcodes.This panel is able to detect all classes of mutations such as single nucleotide variants (SNV), copy number variants (CNV) and fusions. Results:A total of 78 samples from 20patients was sequenced. CDK4/6 was administered as early line treatments. The average total coverage was 56,933X and average molecular coverage was 4,442X.The majority of mutations detected prior to CDK4/6 treatment were TP53, PIK3CAand ESR1. The ctDNA profile is consistent with the clinical status in most patients. ctDNA showed greater dynamics of tumor response to CDK4/6 inhibitor compared to tumor markers CEA and CA15-3.ctDNA was also more sensitive at detecting onset of progression disease compared to imaging. We observed an increase in ctDNA mutation frequency 2-3 months earlier than imaging in 2 patients. From the 20 patients, 7 patients developed progression disease(PD) during our evaluation and required a different treatment. 5 of the 7 patients (71.4%) have ESR1 mutations prior to start of treatment and these patients developed PD within 6 months of treatment. In contrast, no ESR1 mutations were detected in patients who did not develop disease progression. Discussion: In this study, we observed that ctDNA was more sensitive at detecting onset of progression disease compared to imaging. This is essential as early detection of poor response enables timely change of treatment for patients. Patients carrying ESR1mutations respond poorly to CDK4/6 treatment. This might be due to resistance of ESR1mutants to fulvestrant or aromatase inhibitor component of the CDK4/6 treatment regimen. Conclusion: Monitoring of ctDNA is useful to assess treatment response of CDK4/6 inhibitors in metastatic breast cancer patients. Citation Format: Tomoko Shibayama, Yoon Ming Chin, Makiko Ono, Takayuki Kobayashi, Hiu Ting Chan, Fumitaka Hara, Mari Hosonaga, Kokoro Kobayashi, Rina Inagaki, Yoshinori Ito, Takayuki Ueno, Shunji Takahashi, Shinji Oono, Yusuke Nakamura, Siew Kee Low. Monitoring of CDK4/6 inhibitor treatment response through blood liquid biopsy in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-15.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-15-02-P1-15-02
    Abstract: Background: Recently, chemotherapy-induced reactivation of hepatitis B virus (HBV) has been reported not only in patients with HBV surface antigen positive (HBsAg+) but also in patients with resolved HBV (HBsAg-, anti-HBV-core antibody positive (anti-HBc+). The incidnce of HBV reactivation after adjuvant/neo-adjuvant chemotherapy for breast cancer in patients with resolved HBV infection remains unclear. In this study, we surveyed the incidence of HBV reactivation in Japanese breast cancer patients who received adjuvant/neo-adjuvant chemotherapy. Methods: A total of 3042 breast cancer patients who received neoadjuvant and/or adjuvant chemotherapy from June 2008 to December 2016 were included in this study. HBsAg, anti-HBc and anti-HBV-surface antibody (anti-HBs) were tested before chemotherapy. Serum HBV-DNA levels were subsequently measured and monitored for one year after the completion of adjuvant/neo-adjuvant chemotherapy if the patient exhibited a resolved HBV infection. Results: Of the 3042 patients (pts), 32 (1.05%)cases were positive for HBsAg and 2992 pts were negative for HBsAg. 301 pts (9.9 %) were revealed resolved HBV infection; 221 pts were with anti-HBc+ and anti-HBs+, 40 pts were with anti-HBc+ and anti-HBs-, and 130 pts were with anti-HBc- and anti-HBs+. Of the 130 pts with anti-HBc- and anti-HBs+, 77 pts were previously vaccinated for hepatitis B. The antibody-positive rate by age group was 2.7% (1/37) for patients in their 20s, 4.1% (14/344) for those in their 30s, 6.5% (67/1037) for those in their 40s, 9.4% (77/817) for those in their 50s, 16.6% (109/655) for those in their 60s, 20% (30/150) for those in their 70s, and 0% (0/2) for those in their 80s. Among the 301 pts with resolved HBV infection, 71 pts were monitored for one year after the completion of their chemotherapy. The median monitoring period was 579 days (386-3458). In our monitoring period, only one patient (1.4%) was diagnosed with HBV reactivation based on a slightly elevated HBV-DNA level at 1-year-test. No death or hepatitis due to HBV reactivation occurred during the monitoring period. Conclusions: The prevalence of resolved HBV infection in Japan showed an increasing trend with age. Adjuvant/neoadjuvant chemotherapy for breast cancer patients with resolved HBV infection has a risk of HBV reactivation. Our study suggested the risk of reactivation was low and the risk of a flare of HBV disease could be controlled with screening and carefully monitoring. Citation Format: Takayo Fukuda, Masaya Hattori, Yukinori Ozaki, Lina Inagaki, Mari Hosonaga, Ippei Fukada, Kokoro Kobayashi, Fumikata Hara, Takayuki Kobayashi, Sachiyo Yoshio, Takayuki Ueno, Toshimi Takano, Shinji Ohno. Low incidence of hepatitis B reactivation after chemotherapy in Japanese breast cancer patients with resolved HBV [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-15-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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