Seock-Ah Im

Seock-Ah Im
Seoul National University | SNU · Department of Internal Medicine

MD, PhD

About

800
Publications
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Introduction

Publications

Publications (800)
Article
Background: AZD5305 is a potent, highly selective PARP1 inhibitor and trapper with superior preclinical tolerability, target engagement and efficacy vs 1st generation dual PARP1/2 inhibitors (PARPi). This is the first report of the ongoing Phase 1/2a PETRA (NCT04644068) trial. Methods: Pts with advanced breast, ovarian, prostate or pancreatic cance...
Article
Background: MEDI5752 is a monovalent bispecific antibody targeting PD-1 and CTLA-4. The bispecific format is engineered to preferentially inhibit these two checkpoints on activated T cells in tumors, where co-expression is particularly abundant. This may maximize tumor-specific response and reduce the peripheral toxicity that is common when targeti...
Article
Background: The majority of BRCA-mutant or HRR-deficient ovarian cancers are initially sensitive to PARP inhibitors (PARPis) but eventually develop resistance. The most commonly reported PARPi resistance mechanisms are (1) reversal of HRR deficiency through (a) reversion mutations in BRCA or other HRR genes (eg, RAD51C/D) or (b) DNA end resection r...
Article
Full-text available
Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these “HER2-low” cancers. METHODS We conducted a phase 3 trial involving patien...
Article
506 Background: Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy (ASTRRA) trial, at 63 months median follow-up, showed that the addition of 2 years of ovarian function suppression (OFS) to Tamoxifen (TAM) significantly improved dis...
Article
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 cance...
Article
3025 Background: Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate composed of a humanized anti-HER2 monoclonal antibody and a topoisomerase I inhibitor payload, is approved for pts with unresectable or metastatic HER2+ BC with ≥2 prior anti-HER2–based therapies. T-DXd showed improved progression-free survival vs trastuzumab emtansine (T-D...
Article
1000 Background: In the DESTINY-Breast03 (NCT03529110) primary analysis (data cutoff [DCO], May 21, 2021), T-DXd showed superiority over T-DM1 in pts with HER2+ mBC, with a significant improvement of progression-free survival by blinded independent central review (HR, 0.284; 95% CI, 0.217-0.373; P < 0.001), and a safety profile consistent with prio...
Article
531 Background: While the relationship between mammographic breast density (MD) decline and anti-hormone therapy efficacy has been reported in estrogen-receptor (ER)-positive breast cancer, it is still unclear in premenopausal women and in the case of adding ovarian function suppression (OFS) to anti-hormone therapy. We aimed to investigate the MD...
Article
107 Background: MEDI5752 is a monovalent bispecific antibody targeting PD-1 and CTLA-4. A phase I, open-label study (NCT03530397) of MEDI5752 monotherapy 2.25–2500 mg IV Q3W showed encouraging antitumor activity in advanced solid tumors. Maximum tolerated dose was not reached; doses <1500 mg were better tolerated than doses ≥1500 mg. Here we presen...
Article
Purpose: To conduct an updated exploratory analysis of overall survival (OS) with a longer median follow-up of 73.3 months and evaluate the prognostic value of molecular analysis by circulating tumor DNA (ctDNA). Patients and methods: Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced b...
Article
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Background: Trastuzumab emtansine is the current standard treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer whose disease progresses after treatment with a combination of anti-HER2 antibodies and a taxane. Methods: We conducted a phase 3, multicenter, open-label, randomized trial to com...
Article
Full-text available
Background HER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact of low expression of HER2 on survival outcomes in HER2-negative non-metastatic breast cancer (BC). Methods Patients with HER2-negative non-metastatic BC from 6 centres within the Asian Breast Cancer Cooperative Group (ABCCG) (n = 28,280)...
Article
Objective: Using a parallel-process latent growth model (LGM), this study examined whether posttraumatic stress symptoms (PTSS) are associated with the trajectory of sleep disturbance (SD) and fatigue and whether the SD trajectory mediates the PTSS-fatigue relationship. Methods: Data were from 215 patients with breast cancer recruited from a ter...
Article
Objective The object of this longitudinal cohort study was to investigate whether chronotype affects the incidence of chemotherapy-induced nausea and vomiting (CINV) among patients with breast cancer. Methods The study included a total of 203 breast cancer patients who received neoadjuvant chemotherapy using a regimen of doxorubicin and cyclophosp...
Article
Background: KEYNOTE-522 (NCT03036488) is a phase 3 study of neoadjuvant pembro + chemo vs placebo + chemo, followed by adjuvant pembro vs placebo in patients with early-stage TNBC. The primary analysis showed a statistically significant and clinically meaningful improvement in event-free survival (EFS) with pembro + chemo followed by pembro. To ass...
Article
Background: T-DXd is a HER2-targeting antibody-drug conjugate approved for the treatment of pts with advanced HER2+ mBC based on the DESTINY-Breast01 study (NCT03248492). DESTINY-Breast03 (NCT03529110) isa randomized, multicenter, open-label, phase 3 study assessing the efficacy and safety of T-DXd vs. T-DM1 in pts with HER2+ mBC previously treated...
Article
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...
Article
Purpose: T-DM1, an antibody-drug conjugate, has significant antitumor activity in patients with HER2-positive metastatic breast cancer (mBC) patients who had progressed after trastuzumab-based chemotherapy. This study was conducted to investigate the clinical practice and factors related with outcomes of T-DM1 use for HER2-positive mBC patients in...
Article
Background: More than two thirds of patients with advanced breast cancer (ABC) have estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) tumors. In most countries, current standard-of-care first-line treatments include an aromatase inhibitor or fulvestrant, a selective ER degrader, combined with cyclin-depende...
Article
Background: Anthracyclines and taxanes are the preferred regimens for patients with advanced breast cancer and are usually introduced in earlier lines. Tumors refractory to anthracycline and taxanes are aggressive and often show rapid progression. Although single sequential chemotherapy is standard of care, combination chemotherapy is required for...
Article
Background: In the phase 3 KEYNOTE-355 trial (NCT02819518), pembrolizumab (pembro) combined with chemotherapy (chemo) showed statistically significant improvements in OS and PFS compared to placebo + chemo in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 with a combined positive scor...
Article
Background: Despite the availability of multiple HER2-targeted therapies, most patients (pts) with advanced HER2-positive BC experience disease progression, and an unmet medical need remains. Zanidatamab (zani) binds to HER2 across a range of expression levels and induces formation of receptor clusters, resulting in receptor internalization and dow...
Article
Background: Molecular plasticity of breast cancer is crucial for the development of therapy-resistant disease. In this investigation, we studied changes in molecular signatures between pretherapeutic (pre-Tx) and post-therapeutic (post-NACT) tumor samples from patients included in the PENELOPE-B (NCT01864746) trial. The phase III PENELOPE-B study d...
Article
Full-text available
Breast cancer is the most commonly diagnosed cancer worldwide and is one of the leading causes of cancer death. The incidence, pathological features, and clinical outcomes in breast cancer differ by geographical distribution and across racial and ethnic populations. Importantly, racial and ethnic diversity in breast cancer clinical trials is lackin...
Article
Background: The addition of pembrolizumab to neoadjuvant chemotherapy led to a significantly higher percentage of patients with early triple-negative breast cancer having a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery in an earlier analysis of this phase 3 trial of neoadjuvan...
Article
Background: The purpose of this longitudinal prospective cohort study was to investigate the role of chronotype in the incidence of chemotherapy-induced peripheral neuropathy (CIPN) among women with breast cancer. Methods: We recruited women with breast cancer awaiting adjuvant chemotherapy, including four cycles of docetaxel. Participants repor...
Article
Full-text available
Background Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase ll trial comparing palbociclib + ET versus capecitabine in premenopausal women with hormone receptor positive, HER2 negative metastatic breast cancer (MBC). This exploratory analysis investigated pot...
Article
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 wa...
Article
Full-text available
Purpose: Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase 3 MONALEESA-7 trial of pre-/perimenopausal patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). The median...
Article
PURPOSE We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1). METHODS The phase III KAITLIN study ( NCT01966471 ) included adults with excised HER2-positive EBC (node-positive...
Article
Full-text available
Nearly all estrogen receptor (ER)‐positive (POS) metastatic breast cancers become refractory to endocrine (ET) and other therapies, leading to lethal disease presumably due to evolving genomic alterations. Timely monitoring of the molecular events associated with response/progression by serial tissue biopsies is logistically difficult. Use of liqui...
Article
Molibresib is an orally bioavailable, selective, small molecule BET protein inhibitor. Results from a first time in human study in solid tumors resulted in the selection of a 75 mg once daily dose of the besylate formulation of molibresib as the recommended Phase 2 dose (RP2D). Here we present the results of Part 2 of this study, investigating safe...
Article
Background In the phase 3 KEYNOTE-522 trial, neoadjuvant pembrolizumab+chemotherapy followed by adjuvant pembrolizumab monotherapy resulted in a statistically significant improvement in pathologic complete response (pCR) and event-free survival, compared with neoadjuvant chemotherapy alone, in patients with early-stage TNBC. In the phase 1b KEYNOTE...
Article
Full-text available
Background To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients. Materials and methods We identified 54 patients who had received salvage WBRT...
Article
Purpose: This phase II study determined the efficacy of lacnotuzumab added to gemcitabine plus carboplatin (gem-carbo) in patients with advanced triple-negative breast cancer (TNBC). Experimental design: Female patients with advanced TNBC, with high levels of tumor-associated macrophages, and not amenable to curative treatment by surgery or radi...
Article
Objective: Patients with breast cancer receiving neoadjuvant chemotherapy are at increased risk of poor health-related quality of life (HRQOL). This study examined clinical caseness on depression and anxiety mediate the relationship between resilience and HRQOL in patients with breast cancer. Methods: A total of 193 patients with breast cancer u...
Article
Full-text available
Purpose In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free survival (PFS; primary endpoint), with an enhanced effect in patients with PIK3CA/AKT1/PTEN-altered tumors (FoundationOne next-generation sequencing [NGS]...
Article
Purpose: The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings. Materials and methods: Patients who had the tumor sequenced using institutio...
Article
Full-text available
Purpose: We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients. Materials and methods: This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled. Re...
Article
Full-text available
Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PD...
Article
Full-text available
PURPOSE This analysis evaluated the genomic landscape of premenopausal patients with hormone receptor–positive and human epidermal growth factor receptor 2–negative advanced breast cancer and the association of genetic alterations with response to ribociclib in the phase III MONALEESA-7 trial. METHODS Premenopausal patients were randomly assigned...
Preprint
Full-text available
Background/Aims: Palbociclib is a cyclin dependent kinase 4 and 6 inhibitor which shows promising effect in hormone receptor positive breast cancer. The purpose of this study is to evaluate the real-world efficacy and toxicity of palbociclib plus endocrine therapy. Methods: This is a retrospective study performed in two tertiary referral hospitals...
Article
Full-text available
Background This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC). Methods The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+,...
Article
Background In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness o...
Conference Paper
p>Purpose: The vast majority of advanced ER POS breast cancers eventually cease responding to endocrine (ET) and other therapies leading to evolution of lethal disease. However, timely monitoring of the molecular events associated with response/progression in tissue biopsies is logistically difficult. The use of liquid biopsies, such as CTC and ctD...
Article
This pooled analysis of MONALEESA trials evaluated the safety of ribociclib plus endocrine therapy (RIB + ET) with a focus on dose reductions in first-line patients. In the dose reduction analysis, data were pooled from MONALEESA-2 (all patients), MONALEESA-3 (patients receiving treatment as first-line ET) and MONALEESA-7 (patients receiving combin...
Article
1017 Background: Targeting ER activity and/or E synthesis is a mainstay of ER+ BC treatment, but many pts relapse during/after adjuvant endocrine therapy (ET) or develop resistance via ESR1 mutations that drive E-independent transcription and proliferation. Most tumors remain ER signaling-dependent and pts may respond to second-/third-line ET after...
Article
3564 Background: Pembrolizumab (pembro), an anti-PD-1 antibody, is approved for the treatment of patients (pts) with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair (MMR) deficient colorectal cancer, both as first-line treatment and after progression following treatment with fluoropyrimidine, oxaliplatin, and i...
Article
519 Background: About one third of patients with hormone-receptor-positive (HR+), HER2‐ primary breast cancer with residual invasive disease after neoadjuvant chemotherapy will relapse despite adjuvant endocrine therapy. Therapeutic inhibition of cyclin-dependent kinase 4 and 6 (CDK 4/6) by palbociclib combined with endocrine therapy demonstrated h...
Article
1026 Background: The Federation of Asian Clinical Oncology (FACO) conducted an international retrospective cohort study of oligometastatic breast cancer (BC) (OLIGO-BC1) (UMIN No.000030047). At ASCO2020, we demonstrated that locoregional and systemic therapy prolonged overall survival (OS) for patients with oligometastatic BC, especially for cases...
Article
1001 Background: The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2− ABC (median, not reached...
Article
1013 Background: The development of CDK4/6 inhibitors represents a significant advance in the treatment of metastatic breast cancer (MBC). To better understand the impact of treatment and drug resistance at the molecular level, we performed multi-omics profiling of matched pre-treatment, on-treatment, and post-progression tumor biopsies from patien...
Article
1000 Background: In PALOMA-3, a randomized, double-blind, placebo-controlled, phase 3 study, PAL+FUL significantly prolonged progression-free survival (PFS) compared with placebo (PBO) + FUL (1-sided P<0.0001). The final protocol-specified OS analysis, which was conducted with a median follow-up of 44.8 months (mo), showed improved OS with PAL+FUL...
Article
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 fo...
Article
3584 Background: Patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that progressed on ≥2 prior therapies have limited treatment options, with median OS ranging from 6-9 months (mo). In the dose-escalation phase of this first-in-human multicohort study (NCT02720068), the anti-lymphocyte activation gene (LAG)-3 antib...
Article
TPS1103 Background: Modulating estrogen synthesis and/or ER activity is the mainstay of treatment for pts with ER+ BC. Despite substantial progress, many pts experience relapse during/after adjuvant endocrine therapy. However, even though resistant to aromatase inhibitors (AIs) or tamoxifen, growth and survival of the majority of tumors are thought...
Article
TPS1101 Background: More than two thirds of patients with advanced breast cancer (ABC) have estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) tumors. Current standard-of-care first-line treatments include an aromatase inhibitor (AI) or fulvestrant, a selective ER degrader (SERD), combined with cyclin-depend...
Article
3113 Background: JPI-547 is an oral inhibitor of PARP 1/2 and Tankyrase 1/2. JPI-547 demonstrated anti-tumor activity in BRCA-deficient xenograft models as a single-agent and in combination with chemotherapy and immune checkpoint inhibitors. Methods: This is the first in human (FIH) phase I study of JPI-547 in patients (pts) with advanced solid tum...
Poster
Background: Chemotherapy with immune checkpoint inhibitors can improve outcomes vs chemotherapy alone in patients (pts) with metastatic TNBC; however, many still have poor clinical outcomes. BEGONIA is an ongoing 2 part, multicenter, multiarm, open-label platform study evaluating safety and efficacy of D (anti–PD-L1)+P and D±P combined with novel t...
Chapter
Cancer has been defined as a genetic disorder caused by the accumulation of genetic alterations, which result from various internal and external DNA damage that is left unrepaired. One of the main characteristics of cancer is a partial loss of DNA damage repair (DDR) pathway, resulting in increased DNA damage levels and replication stress. DDR inhi...
Article
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An amendment to this paper has been published and can be accessed via the original article.
Article
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PurposeTo identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC).Methods In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified...
Article
Purpose: We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy. Materials and methods: Patients with HER2-negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician's choi...
Article
Full-text available
This post‐hoc analysis of MONARCH 2 and MONARCH 3 assesses the efficacy, safety, and pharmacokinetics (PK) of abemaciclib in combination with endocrine therapy (ET) in East Asian patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2‐negative (HER2‐) advanced breast cancer. MONARCH 2 and MONARCH 3 are global, random...
Article
Background Pembrolizumab showed durable antitumour activity and manageable safety in metastatic triple-negative breast cancer in the single-arm KEYNOTE-012 and KEYNOTE-086 trials. In this study, we compared pembrolizumab with chemotherapy for second-line or third-line treatment of patients with metastatic triple-negative breast cancer. Methods KEY...
Conference Paper
p> Background: Triple-negative breast cancer (TNBC) is associated with poor survival outcomes and treatment options are limited. These tumors lack therapeutic targets and become rapidly resistant to chemotherapy. The anti–PD-1 antibody pembrolizumab showed durable antitumor activity and manageable safety in patients with TNBC in the KEYNOTE-012, KE...
Conference Paper
Background: KEYNOTE-119 (NCT02555657) is a randomized, open-label phase 3 study of pembrolizumab (pembro) monotherapy vs single-agent chemotherapy (chemo) in patients with previously treated metastatic triple-negative breast cancer (mTNBC). The results showed directionally favorable improvement in overall survival (OS) with pembro compared to chemo...
Conference Paper
Background Margetuximab (M) is an investigational Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab (T). Compared with T, M has higher affinity for both the 158V (high-binding) and 158F (low-binding) allotypes of the activating Fc receptor CD16A. M enhances innate immunity more effectively than T in vitro, inc...