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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. P5-03-14-P5-03-14
    Abstract: Backgrounds Since OlympiAD study, National Comprehensive Cancer Network guideline recommends assessment of germline BRCA1/2 mutation in all patients with recurrent or metastatic breast cancer to identify candidates for PARP inhibitor therapy, which is not always possible in clinical practice due to limited resources for testing. Data on the prevalence of gBRCA mutation is still lacking, especially in patients with non-high risk for hereditary breast and ovarian cancer syndrome. In this study, we investigated prevalence of gBRCA mutation in unselected Korean patients with HER2-negative advanced BC in a prospective cohort and analyzed oncologic outcome. Methods Eligible patients were diagnosed with HER2-negative advanced BC and had initiated palliative systemic treatment. Peripheral blood was prospectively drawn from each patient and gBRCA mutation status was assessed by next generation sequencing using NGeneBio BRCAaccuTest®. In 100 patients, somatic mutations including BRCA1/2 from tumor tissue were investigated using targeted panel sequencing. To estimate the prevalence of gBRCA mutation with margin of error to be no more than ±4% at the 95% confidence interval in a population size of 20,000, 583 patients were to be enrolled. Results A total of 583 patients were enrolled between Oct 2019 and Mar 2022, and the prevalence of gBRCA mutation was analyzed in 570 patients, excluding ineligible patients. Median age was 54 years old (range 26-87) and 567 patients were female. 475 patients had HR+/HER2- BC and 94 patients had triple negative breast cancer (TNBC). The overall prevalence of gBRCA1/2 pathogenic mutation was 7.3% (42/570) in unselected patients. The prevalence of gBRCA1 mutation was 1.6%(9/570) overall, 0.8%(4/475) in HR+/HER2- BC, and 5.3%(5/94) in TNBC. The prevalence of gBRCA2 mutation was 5.8%(33/570) overall, 6.3%(30/475) in HR+/HER2- BC, 3.2%(3/94) in TNBC. Prevalence in low risk TNBC ( & gt;60 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 10.5% (2/19, all 2 patients had gBRCA2 mutation). Prevalence in low risk HR+/HER2- ( & gt;40 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 5.9% (18/307, 17 patients had gBRCA2 mutation). The overall prevalence of gBRCA1/2 pathogenic mutation in Korean patients with low risk HER2-negative advanced BC was 6.1%. The result of somatic mutation, treatment patterns and clinical outcome according to gBRCA1/2 mutation will be further analyzed. Conclusions The prevalence of gBRCA mutation among Korean patients with HER2-negative advanced BC classified as low risk (6.1%) in this study supports routine testing of gBRCA mutation in this population. Citation Format: Hee Kyung Ahn, Jee Hung Kim, Mirae Kim, Seri Park, Su-Jin Koh, Joo Hyuk Sohn, Myoung Joo Kang, Kyung Hae Jung, Kyoung Eun Lee, Jieun Lee, Sung Ae Koh, Yee Soo Chae, Jae Ho Byun, In Hae Park, Hee-Jun Kim, Jee Hyun Kim, Han Jo Kim, Joo Young Jung, Jung Lim Lee, Yoon Young Cho, Kyong Hwa Park, Ji-Yeon Kim, Seock-Ah Im, Yeon Hee Park. Prevalence of germline BRCA mutations in unselected Korean patients with HER2-negative breast cancer: A Prospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-14.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 1098-1098
    Abstract: 1098 Background: Combining immune checkpoint inhibitors with chemotherapy has become a promising therapeutic strategy in metastatic breast cancer. Eribulin is a potent microtubule inhibitor and modulates the immune microenvironment of tumor cells. Therefore, combining eribulin to nivolumab may synergize antitumor efficacy in metastatic breast cancer. Methods: Adult patients with histologically confirmed recurrent/metastatic HER2- breast cancer were enrolled prospectively from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). Key eligibility criteria included prior treatment with taxanes and/or anthracyclines, ≥1 measurable disease, and ≤2 prior cytotoxic chemotherapies in the metastatic setting. Patients received nivolumab 200 mg intravenously (IV) on day 1 plus eribulin 1.4 mg/m 2 IV on day 1 and 8 of every 3 weeks until disease progression or intolerable toxicity. The dose level was determined from safety profile of three patients in run-in phase. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included investigator-assessed objective response rate (ORR) per RECIST v1.1, disease control rate (DCR), overall survival (OS), and toxicity profile of the combination treatment. The association between PD-L1 expression by SP142 Ab and efficacy was analyzed. Results: From August 2019 to June 2021, 90 patients (HR+HER2- 45 pts/TNBC 45 pts), with a median age of 51 (range 31–71), were enrolled in the study. With a median study follow-up time of 16.3 months, 68 (75.6%) patients experienced progressive disease. PFS rate at 6-months was 49.6% and 24.1% in patients with HR+HER2- and TNBC group, respectively. Median PFS was 5.6 months (95% CI: 4.3-6.8) and 3.0 months (95% CI: 1.3-4.7) for HR+HER2- and TNBC group, respectively. ORRs were 53.3% (CR:0, PR: 24) for HR+HER2- and 21.8% (CR1, PR: 12) for TNBC. Patients with PD-L1+ tumors (PD-L1 expression ≥ 1% on TC or IC) had similar ORR compared to PD-L1- tumors (ORR 50% vs. 53.8% in HR+HER2-, 30.8% vs. 29.0% in TNBC). The most common grade 3/4 adverse event was neutropenia (15/90, 16.7%), and the most common immune-related adverse events were grade 1/2 hypothyroidism (19/90, 21.1%) and grade 1/2 pruritus (16/90, 17.8%). Five patients had discontinued study treatment due to immune-related adverse events (3 pneumonitis, 1 hepatitis, 1 skin rash). Conclusions: In this parallel phase II clinical trial, the addition of nivolumab to eribulin showed promising efficacy and tolerable safety profile in previously treated HER2- MBC. Further survival and exploratory analyses to find predictive markers will be followed. Clinical trial information: NCT04061863. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 3
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 186, No. 2 ( 2021-04), p. 453-462
    Type of Medium: Online Resource
    ISSN: 0167-6806 , 1573-7217
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 4
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 54, No. 4 ( 2022-10-15), p. 1121-1129
    Abstract: Purpose We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.Materials and Methods We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008] , 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014] , 302 patients).Results Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.
    Type of Medium: Online Resource
    ISSN: 1598-2998 , 2005-9256
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2022
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  • 5
    In: The Lancet Oncology, Elsevier BV, Vol. 20, No. 12 ( 2019-12), p. 1750-1759
    Type of Medium: Online Resource
    ISSN: 1470-2045
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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  • 6
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 200, No. 1 ( 2023-07), p. 37-45
    Type of Medium: Online Resource
    ISSN: 0167-6806 , 1573-7217
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-21-01-P1-21-01
    Abstract: Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM & gt;4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p=0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p & lt;0.001; HER2+, 18.5%, p=0.004; TNBC, 16.9%, p=0.071). Multivariate analysis of cohort B showed that shorter time interval to BM, TNBC subtype, extracranial systemic disease, number of BM & gt;4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p=0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 & gt;37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS. Citation Format: Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki Chung, Kyung Su Kim, Won Sup Yoon, Jin Hee Kim, Jihye Cha, Yoon Kyeong Oh, In Ah Kim. Multicenter study for brain metastasis from breast cancer in Korea: The significance of molecular subtype (KROG 1612) [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 P1-21-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e14008-e14008
    Abstract: e14008 Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM 〉 4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p = 0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p 〈 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis showed that shorter time interval to BM, TNBC subtype, extracranial systemic disease, number of BM 〉 4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p = 0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 〉 37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: European Journal of Cancer, Elsevier BV, Vol. 103 ( 2018-11), p. 127-136
    Type of Medium: Online Resource
    ISSN: 0959-8049
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 1007-1007
    Abstract: 1007 Background: Endocrine treatment is preferred recommendation by clinical guidelines in premenopausal as well as postmenopausal women with hormone receptor(HR)-positive, HER2-negative metastatic breast cancer(MBC). In real-world clinical practice, however, substantial numbers of patients are treated with chemotherapy in earlier lines based on endocrine resistance and/or on physician’s concern of worse prognosis associated with aggressive tumor behavior and younger age. In terms of the chemotherapy regimens, capecitabine seems one of the most popular options. The purpose of this phase II study is to assess the safety and the clinical anti-tumor activity of exemestane plus GNRH agonist in combination with palbociclib versus capecitabine in premenopausal HR-positive MBC patients. Methods: This is a prospective, two-arm, randomized, multi-center open-label phase II study of the Korean Cancer Study Group. Patients were allowed with previous 1 line of chemotherapy for MBC. De Novo metastatic patients should have been treated with tamoxifen before enrollment. Patients were randomized to chemotherapy (capecitabine 1250 ㎎/㎡twice a day from day 1 to 14 every 3 weeks) or endocrine therapy combination (exemestane 25 mg for 28 days and palbociclib 125 mg for 21 days every 4 weeks with GNRH agoinst). Primary endpoint was Progression-Free Survival (PFS). Results: Among 189 patients enrolled between 2016 and 2018 from 14 centers, 184 patients were randomly assigned to chemotherapy (n = 92) or endocrine therapy with palbociclib (n = 92). Median age was 44 (range 28-58). De Novo MBC was found equally in both arm (30%). During median 14 months of follow-up, median PFS was superior in endocrine with palbociclib than in capecitabine arm [19.0 vs. 11.3 months, p = 0.0493 by log-rank test; Hazard Ratio (HR) 0.643 (0.415-0.999), p = 0.0493]. Approximately half of the patients (51%) were treatment naïve in the advanced setting (49% for palbociclib vs. 51% for capecitabine). Grade III or more hematologic toxicities were more common in palbociclib than in capecitabine with statistical significance (60.9% vs. 19.2%, p 〈 0.0001). Diarrhea (11% vs. 38%) and Hand-Foot syndromes (1% vs. 76%) were more common in capecitabine arm. Conclusions: Exemestane plus palbociclib with ovarian suppression showed clinical benefit in terms of PFS compared with capecitabine in patients with premenopausal ER-positive MBC. Clinical trial information: NCT02592746.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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