Search

Background The hormone receptor (HR)-positive metastatic breast cancer (MBC) patients show a diverse range of tumor mutational burden (TMB), but its biological and clinical implication has been largely unrevealed. Here we report genomic landscape of 117 HR+ MBC patients who were included in the pre-screening tissue genomic analysis of MUTATION-1 study (SABCS 2021; Abs P1-19-03) according to TMB of tumors. Patients and method The MUTATION-1 study (NCT03608865) enrolled HR-positive MBC patients who received prior ≥ 1 line of systemic therapy, and performed prescreening with whole exome sequencing (WES) and RNA-seq of fresh-frozen tissue of metastatic or recurred tumors. Patients who met upper 30% of TMB were eligible for treatment phase and received durvalumab plus tremelimumab. This study analyzed 117 prescreening tissues of MUTATION-1 study patients for mutation and transcriptomic landscape analysis. (WES, n=117; RNA-seq, n=107) Results The 117 patients showed diverse TMB (range 0~21.7 mut/Mb, median 2.0 mut/Mb) and genomic alterations. The most frequently mutated gene included PIK3CA (29.1%), TP53 (27.4%), ESR1 (23.9%), GATA3 (19.7%), and MAP3K1 (12.0%). There was no association between patient survival and TMB. We estimated single base substitution (SBS) mutational signature of patients with SigMA algorithm. The patients were classified according to their dominant mutational signatures: APOBEC (25.6%), HRD (41.0%), clockwise (28.2%), SBS8, and SBS17. The APOBEC patients showed higher TMB (median 3.47 mut/Mb) and higher mutation prevalence in PIK3CA (63.3% vs. 29.1%), ARID1A (16.7% vs. 6.0%), and NF1 (16.7% vs. 6.8%) compared with other patients. The high TMB positively correlated with time from MBC diagnosis to biopsy. Tumors with TMB ≥ 5 mut/Mb were exclusively found in patients diagnosed as MBC ≥ 36 months before the timing of biopsy. In the matched RNA-seq analysis, TMB was higher in luminal B and HER2-enriched intrinsic subtype patients than basal or luminal A subtype. The high TMB (≥ 3.16 mut/Mb, cutoff used for treatment phase patient selection) patients showed upregulation of G2/M checkpoint, MYC, E2F1, and MTORC1 signature compared to low TMB patients. In the tumor microenvironment analysis by CIBESORT, PIK3CA mutant patients showed lower score of cytotoxic T cell than others. Conclusions The high TMB in HR+ breast cancer was associated with longer time duration from MBC diagnosis to biopsy, high APOBEC signature, and cell cycle/MYC signature gene upregulation. Further therapeutic targeting of high TMB patients is warranted based on their genomic and immunologic characteristics. Citation Format: Min Hwan Kim, Yohan Yang, Eunyoung Kim, Yong Wha Moon, Gun Min Kim, Seul-Gi Kim, Yee Soo Chae, Jieun Lee, Jae Ho Jeong, Kyung-Hun Lee, Han Jo Kim, Joo Young Jung, Su-Jin Koh, Kyoung Eun Lee, Hee-Jun Kim, Kyong Hwa Park, Seungtaek Lim, Yeon Hee Park, Sangwoo Kim, Joo Hyuk Sohn. Genomic characterization of hormone receptor-positive advanced breast cancer with high tumor mutational burden: fresh-frozen tissue genomic analysis from MUTATION-1 study (KCSG BR17-04) [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 P5-14-04.

Objective This study aimed to explore perceptions of the meaning of life among Korean patients living with advanced cancer. Method The study employed a mixed-methods design, and 16 participants were included in the analysis. Qualitative data gathered from in-depth interviews were analyzed using Colaizzi's phenomenological method. Quantitative survey data were analyzed using descriptive statistics, the Mann–Whitney U test, the Kruskal–Wallis test, and Spearman's ρ correlation. Results Participants experienced both the existence of meaning and the will to find meaning in terms of four categories: “interpersonal relationships based on attachment and cohesion” (three themes — family as the core meaning of one's life, supportive and dependent interconnectedness with significant others, and existential responsibility embedded in familism), “therapeutic relationships based on trust” (one theme — communication and trust between the patient and medical staff), “optimism” (two themes — positivity embodied through past experiences and a positive attitude toward the current situation), and “a sense of purpose with advanced cancer” (two themes — the will to survive and expectations for the near future). The meaning in life questionnaire (MLQ) and the purpose in life scale (PIL) showed a significant positive correlation tendency with the functional assessment of chronic illness therapy-spiritual well-being scale (FACIT-Sp). The patient health questionnaire (PHQ-9) showed significant negative correlation tendency with both the MLQ-presence of meaning (MLQ-PM) and PIL-Initiative (PIL-I) questionnaires. Significance of results Finding meaning in life helps advanced cancer patients realize their will to live. It also acts as a coping mechanism that palliates negative experiences in the fight against the disease. In particular, among advanced cancer patients in the Korean culture, the dynamics of relationships with family and medical staff was a key axis that instilled optimism and will to live. These results suggest that considering the meaning of life in advanced cancer patients by reflecting Korean culture in the treatment process improves the quality of care.

Purpose Literature is scarce regarding cancer care utilization during the massive outbreak of coronavirus disease 2019 (COVID-19) in the Republic of Korea. We investigated functional impairments in mental health and their relationships with depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization among cancer patients in the COVID-19 pandemic era.Materials and Methods We used an online survey with questions related to the disturbances faced by patients with cancer in utilizing healthcare services in the pandemic era. Current mental health status was assessed using the Work and Social Adjustment Scale (WSAS), Stress and Anxiety to Viral Epidemics-6 (SAVE-6) scale, Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI), Brief Resilience Scale (BRS), Cancer-Related Dysfunctional Beliefs about Sleep Scale (C-DBS), and Fear of COVID-19 over Cancer (FCC).Results Among the 221 responders, 95 (43.0%) reported disruptions in healthcare service utilization during the COVID-19 pandemic. Logistic regression analysis revealed that functional impairment in the mental health of these patients was expected due to disruptions in healthcare service utilization, high levels of depression, anxiety regarding the viral epidemic, fear of COVID over cancer, and low resilience. Mediation analysis showed that patient resilience and cancer-related dysfunctional beliefs about sleep partially mediated the effects of viral anxiety on functional impairment.Conclusion In this pandemic era, patients with cancer experience depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization, which may influence their functional impairments in mental health.

ObjectivesIt has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries.MethodsThis international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors.ResultsA total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5–19.5) in Japan, 23.0 days (95% CI 19.9–26.1) in Korea, and 15.0 days (95% CI 13.0–17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01–1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00–1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77–1.35; p = 0.89).Significance of resultsSWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer.

A multicenter prospective study to evaluate the feasibility of Physician Orders for Life-Sustaining Treatment (POLST) in oncology practice was conducted between June and December 2017. Factors associated with POLST completion and follow-up outcomes were analyzed.Patients with terminal cancer, aged ≥ 20 years and capable of communicating, were enrolled from seven hospitals. Demographic data were collected and updated in February 2021. Descriptive statistics and logistic regression analyses were conducted.Among 336 patients, 105 (31.3%) completed POLST, which was more common in male (p = 0.029), patients with better performance (p 0.001), longer duration of follow-up (p = 0.037), and those living with children (p = 0.023). Male (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.17-3.51; p = 0.012), having good performance status (OR, 2.38; 95% CI, (1.35-4.19); p = 0.003), transferred from other departments (OR, 0.50; 95% CI, (0.26-0.98); p = 0.045), and living with children (OR, 1.94; 95% CI, (1.11-3.47); p = 0.020) were significant predictors of POLST completion. Patients who completed POLST were more likely to enroll in hospice care (p = 0.012) or experience out-of-hospital death (p = 0.016) at end-of-life (EOL). POLST completion showed a strong association with hospice enrollment at EOL (OR, 2.61; 95% CI, (1.08-6.32); p = 0.033).Gender, patient performance, timing of POLST discussion, and type of household were associated with POLST completion. Earlier discussions on POLST could reinforce hospice enrollment or non-aggressive EOL care.

Purpose Few large-scale studies have focused on the prevalence of symptoms and signs during the last days of patients diagnosed with advanced cancer. Identifying the patterns of specific symptoms according to cancer type is helpful to provide end-of-life care for patients with advanced cancer. We investigated the prevalence and severity of symptoms and signs associated with impending death in patients with advanced cancer. Methods In this secondary analysis of an international multicenter cohort study conducted in three East Asian countries, we compared the severity of symptoms and signs among dying patients 3 days before death according to the type of primary cancer using one-way analysis of variance (ANOVA). Post hoc analysis was conducted for multiple comparisons of each symptom according to the type of primary cancer. Results We analyzed 2131 patients from Japan, Korea and Taiwan. Fatigue, dry mouth, drowsiness and dyspnea were present in nearly half of the patients, and edema of lower extremities was the most common sign in all dying patients. According to cancer type, edema of lower extremities was the most common symptom and fatigue/ ascites were the most severe symptoms in digestive tract cancer. For lung cancer, respiratory secretion was the most prevalent and dyspnea/ respiratory secretion were the most severe symptoms. Conclusion We demonstrated the prevalence and severity of symptoms and signs associated with impending death of patients with advanced cancer in East Asia. Our study can enable clinicians to recognize the specific symptoms and signs at the very end of life.

Background: Hormone-receptor (HR) positive breast cancer is the main subtype of breast cancer. Although overall survival of HR-positive metastatic breast cancer (MBC) patients has improved by various therapies including endocrine therapies, CDK4/6 inhibitors, and cytotoxic chemotherapy, it is still considered incurable. Immune checkpoint inhibitors have rarely been clinically tested in HR-positive breast cancer, despite proving anti-cancer activity in early and metastatic triple-negative breast cancer in various trials. We evaluated efficacy and safety of combined durvalumab and tremelimumab in the HR-positive MBC, which was enriched with high tumor mutational burden (TMB). Methods: HR-positive MBC patients who received prior 1 or more lines of therapy in metastatic setting were prescreened with whole exome sequencing (WES) using metastatic or recurred tumor biopsies. Criterion of high TMB was defined as upper 30%. In the beginning, the criterion of high TMB was 2.1 mutations per Mb, based on the retrospective WES database in Yonsei Cancer Center and this criterion was recalculated every 30 cases. Patients who met upper 30% of TMB were treated with combined durvalumab (1500mg every 4 weeks upto 13 doses) and tremelimumab (75mg every 4 weeks upto 4 doses). Response was evaluated every 2 cycles using RECIST 1.1 and toxicity was evaluated using NCI-CTCAE 4.03. Tumor-infiltrating lymphocyte (TIL) and PD-L1 expression were also analyzed to investigate a correlation with TMB. Results: Biopsies of recurrent or metastatic tumors were taken from a total of 119 patients for WES assay. A median turn-around-time of TMB data was 30.0 days (range, 16~67). Of these 119 patients, a median number of nonsynonymous mutations was 2.0 per Mb (range, 0~21.7) with upper 30% criterion of 3.1. High TMB showed a trend toward old age (P=0.074) and single positivity of estrogen receptor (ER) or progesterone receptor (PR) compared to positivity of both ER and PR (P=0.055). TMB was positively correlated with TILs (r=0.289, P=0.005). Thirty patients with high TMB received study treatment with a median 2 cycles (range, 1~13). A median prior lines of therapies in metastatic setting was 4 (range, 1~9). The objective response and clinical benefit rates were 6.3% (2 PRs of 30) and 20% (2 PRs plus 4 SDs of 30). There was one treatment-related mortality due to pneumonitis. Immune-related adverse events included endocrinopathy (n=3; hypothyroidism in 2, hyperthyroidism in 1), enteritis (n=2), skin rash (n=2), pneumonitis (n=1), and so on. Biomarker analyses are underway. Conclusions: WES-based TMB using metastatic tumor biopsy was a feasible platform to prescreen HR-positive MBC patients. Combined durvalumab and tremelimumab showed a modest activity and good tolerability in heavily treated, HR-positive MBC with high TMB. Citation Format: Yong Wha Moon, Eunyoung Kim, Min Hwan Kim, Gun Min Kim, Seul-Gi Kim, YeeSoo Chae, Jieun Lee, Jae Ho Jeong, Kyung-Hun Lee, Han Jo Kim, Joo Young Jung, Su-Jin Koh, Kyoung Eun Lee, Hee-Jun Kim, Kyong Hwa Park, Seungtaek Lim, Yeon Hee Park, Tae Hoen Kim, Sewha Kim, Yohan Yang, Sangwoo Kim, Joohyuk Sohn. Phase II trial of durvalumab and tremelimumab in the hormone receptor-positive metastatic breast cancer with high tumor mutational burden selected by whole exome sequencing: Korean cancer study group trial (KCSG BR17-04) [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 P1-19-03.

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 the nation-wide real-world setting. Method: This complete enumeration study included the patients with HER2-positive mBC who received T-DM1 as palliative therapy from August 2017 to December 2018 under the registry of Health Insurance Review & Assessment Service in Korea. Safety and outcomes of T-DM1 including overall response rate (ORR), progression-free survival (PFS), and overall survival were evaluated. Factors significant in univariate analysis were analyzed in multivariate model. Result: From the sixty institutions, a total of 824 patients were enrolled. Mean age was 58 years-old, 818 patients (99.3%) were female and 516 patients (62.6%) had relapsed after curative treatment. About 40% patients received T-DM1 as first or second line treatment, 21.5% received it as third line and 37.3% as fourth or over line. During a median follow-up of 16.8 months, the ORR was 32.8%, median PFS was 7.2 months and median OS was not reached. In multivariate analysis, clinical factors associated with the lower PFS were age (< 65 year-old, hazard ratio[HR] 1.53, 95% confidence interval[CI]: 1.214-1.919, p < 0.001), poor ECOG performance status (PS ≥ 2, HR 1.98, 95% CI: 1.493-2.626, p < 0.001), previous pertuzumab use (HR 1.40, 95% CI: 1.118-1.742, p = 0.003) and previous lapatinib use (HR 1.29, 95% CI: 1.047-1.586, p =0.017). The common grade 3-4 adverse events were thrombocytopenia (13.0%), neutropenia (2.9%), and elevation of liver enzyme (2.5%). Hypokalemia (≤ 3.0 mmol/L) and any-grade bleeding event such as epistaxis and gum-bleeding occurred in 25 (3.1%) and 94 patients (11.4%), respectively. Conclusion: This is the first, nationwide, real-world data about T-DM1 use of the HER2-positive metastatic breast cancer patients in Korea. The efficacy and toxicity profile of T-DM1 in the real-world practice were comparable with those of randomized trials. Patients’ factors and previous anti-HER2 therapy could predict the outcomes of T-DM1. Further studies to reveal the subtypes of good responders to T-DM1 and the sequence of anti-HER2 therapy are warranted. Citation Format: Sun Kyung Baek, Jae-Ho Jeong, Yeon-Hee Park, Hee Kyung Ahn, Min Hwan Kim, In Hae Park, Young Ju Suh, Dae-Won Lee, Sung Hoon Sim, Jee Hyun Kim, Hyun-Jeong Shim, Yeesoo Chae, Su-Jin Koh, Hyorak Lee, Jieun Lee, Jae-Ho Byun, Youngmi Seol, Eun Mi Lee, Jin Seok Ahn, Kyung-Hae Jung, Seock-Ah Im, Keun Seok Lee, Joohyuk Sohn, Kyoung Eun Lee. A nationwide real-world study for evaluation of efficacy and safety of T-DM1 in patients with HER2-positive locally-advanced unresectable or metastatic breast cancer in Korea (KCSG BR19-15) [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 P1-18-32.

Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of monoclonal antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the key resistance mechanisms. BR18-13(KM-10A) study is a phase 2 clinical trial evaluating efficacy and safety of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than 2 HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was June 8, 2021. Results: 17 patients were enrolled and followed for a median of 6.2 months. At data cutoff, 17 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: 9 kinase mutations (H1047X), 5 helical mutations (E545X), 2 other point mutations, and 1 amplification. Overall, response rate was 64.7% and disease control rate was 82.4%. Eleven patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). Two patients who have reached PR remain on investigational treatment until the data cutoff point, and the longest one is on treatment for 12.0 months. The median progression-free survival assessed in data cutoff time was 5.9 months. One patient ended treatment due to CNS disease progression, but her visceral metastatic lesions were decreased with experimental treatment. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 study, Trastuzumab biosimilar plus Gedatolisib presented 64.7% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA mutation. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong-Won Lee, Keon Uk Park, Eunmi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Miso Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo Young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, Inhae Park, Kyong Hwa Park. Phase II study of trastuzumab biosimilar (Herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy (BR 18-13, KM-10A): Interim analysis [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 P5-16-03.

BackgroundSevere graft versus host disease (GVHD) is the main reason for non-relapse mortality following allogeneic hematopoietic cell transplantation (HCT). We investigated the serum protein profiles of patients who had undergone HCT to identify predictive biomarkers of severe acute GVHD (aGVHD).MethodsSerum samples were collected for 30 patients from day − 7 to day + 14 of HCT. The serum levels of plasma beta2-microglobulin (β2-MG), soluble vascular cell adhesion molecule-1 (sVCAM-1), platelet factor 4, and TNFSF-14 were measured by ELISA as potential biomarkers following 310 cytokine profiling array.ResultsThe median age of the study patients was 53.5 years (range, 19–69). All grade and grade 2–4 aGVHD developed in 21 (70.0%) and 17 (56.7%) patients, respectively. Compared with their baseline levels on day − 7, β2-MG and sVCAM-1 were significantly increased on day + 14 of the HCT procedure (P = 0.028 andP P = 0.028 andP = 0.035, respectively).ConclusionHigher sVCAM- levels at baseline and on day + 14 in HCT patients could be a significant predictive biomarker of severe aGVHD.

Objective Accurate prognostication is important for patients and their families to prepare for the end of life. Objective Prognostic Score (OPS) is an easy-to-use tool that does not require the clinicians’ prediction of survival (CPS), whereas Palliative Prognostic Score (PaP) needs CPS. Thus, inexperienced clinicians may hesitate to use PaP. We aimed to evaluate the accuracy of OPS compared with PaP in inpatients in palliative care units (PCUs) in three East Asian countries. Method This study was a secondary analysis of a cross-cultural, multicenter cohort study. We enrolled inpatients with far-advanced cancer in PCUs in Japan, Korea, and Taiwan from 2017 to 2018. We calculated the area under the receiver operating characteristics (AUROC) curve to compare the accuracy of OPS and PaP. Results A total of 1,628 inpatients in 33 PCUs in Japan and Korea were analyzed. OPS and PaP were calculated in 71.7% of the Japanese patients and 80.0% of the Korean patients. In Taiwan, PaP was calculated for 81.6% of the patients. The AUROC for 3-week survival was 0.74 for OPS in Japan, 0.68 for OPS in Korea, 0.80 for PaP in Japan, and 0.73 for PaP in Korea. The AUROC for 30-day survival was 0.70 for OPS in Japan, 0.71 for OPS in Korea, 0.79 for PaP in Japan, and 0.74 for PaP in Korea. Significance of results Both OPS and PaP showed good performance in Japan and Korea. Compared with PaP, OPS could be more useful for inexperienced physicians who hesitate to estimate CPS.

Background The multinational BREAKOUT study (NCT03078036) sought to determine the prevalence of germline BRCA1/2 (gBRCA1/2) and somatic BRCA1/2 (sBRCA1/2) mutations and mutations in other homologous recombination repair (HRR) genes in women with HER2-negative metastatic breast cancer (MBC) starting first-line chemotherapy. Methods Genetic testing for gBRCA, sBRCA, and HRR gene mutations was performed in patients who started first-line chemotherapy for MBC in the last 90 days (341 patients across 14 countries) who were not selected based on risk factors for gBRCA mutations. We report data from the Asian cohort, which included patients in Japan (7 sites), South Korea (10 sites), and Taiwan (8 sites). Results Of 116 patients screened, 104 patients were enrolled in the Asian cohort. The median age was 53.0 (range 25–87) years. gBRCA1/2, gBRCA1, and gBRCA2 mutations were detected in 10.6% (11/104), 5.8% (6/104), and 4.8% (5/104) of patients, respectively; none had mutations in both gBRCA1 and gBRCA2. gBRCA1/2 mutations were detected in 10.0% (6/60) and 11.6% (5/43) of patients with hormone receptor-positive and triple-negative MBC, respectively. HRR gene mutations were tested in 48 patients without gBRCA mutations, and 5 (10.4%) had at least one HRR mutation in sBRCA, ATM, PALB2, and CHEK2. Conclusion We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC. Study registration NCT03078036.

Background: Some factors associated with spiritual well-being in dying patients have previously been reported. However, there has been no cross-cultural study comparing factors related to spiritual well-being. The current investigation may shed light on this under-investigated area through a comparison of diverse factors. Aim: We aimed to (1) examine factors associated with spiritual well-being in the last days and (2) compare those factors across three East Asian countries. Design: This is an international multicenter prospective cohort study. Setting/participants: Newly admitted inpatients with far advanced cancer in palliative care units in Japan, Korea and Taiwan were enrolled. Each patient was classified into one of two groups based on spiritual well-being score in the last days of life. Univariate and multivariate analyses were performed to identify the factors related to better spiritual well-being score in each country. Results: A total of 1761 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. Seven variables were significant in Japan, three in Korea, and five in Taiwan. “Good death scale [acceptance],” “fatigue” and “expressed wish for hastened death” were unique in Japan. “Visit from a pastoral care worker within 48 h of death” was unique in Korea. “Patient’s preferences for place of death,” “dyspnea” and “continuous deep sedation” were unique in Taiwan. Conclusions: This study found novel factors related to spiritual well-being in the last days of life, several of which differed according to country. Recognition of factors associated with spiritual well-being can improve the quality of palliative care.

IntroductionThere is an increased demand for services for hospitalised older patients with acute medical conditions due to rapidly ageing population. The COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS) study will test the effectiveness of comprehensive geriatric assessment (CGA) and multidisciplinary intervention by comparing it with conventional care among acute hospitalised older adults in Korea.Methods and analysisA multicentre trial within a cohort comprising three substudies (randomised controlled trials) will be conducted. The intervention includes CGA and CGA-based multidisciplinary interventions by physicians (geriatricians, oncologists), nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is living at home 3 months after discharge. In addition to assessing the economic effects of the intervention, a cost-utility analysis will be conducted.Ethics and disseminationThe study protocol was reviewed and approved by the ethics committees of Seoul National University Bundang Hospital and each study site. The study findings will be published in peer-reviewed journals. Subgroup and further in-depth analyses will subsequently be published.Trial registration numberKCT0006270.

Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of dual antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the resistance mechanisms. This randomized phase 2 pilot study evaluated safety and efficacy of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than two HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was Aug 4, 2020. Results: As a pilot study, 15 patients were enrolled and followed for a median of 2.3 months. At data cutoff, 11 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: H1047R, H1047L, E542Q, E542K, E453K, N345K, and PIK3CA amplification. Five patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). All patients who have reached PR remain on investigational treatment at the data cutoff point, and the longest one is on treatment for 7.8 months. One of the SD patients ended treatment due to disease progression, and the other two have been undergoing treatment. Overall, response rate was 45.5% and disease control rate was 72.7%. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 pilot study, Trastuzumab biosimilar plus Gedatolisib presented 45.5% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA aberration. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong Won Lee, Keon Uk Park, Eun Mi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Mi So Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, In Hae Park, Kyong Hwa Park. Phase II pilot study of trastuzumab biosimilar (herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis] [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-39.

Purpose In the randomised phase II LEO trial, we investigated the effect of adding everolimus (EVE) to letrozole (LET) in ovarian-suppressed premenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent/metastatic breast cancer. Methods Patients with progression or prior exposure to tamoxifen with or without gonadotropin-releasing hormone agonists, either sequentially or concurrently, in adjuvant or metastatic setting were randomly assigned (2:1) to the EVE arm (leuprorelin + LET + EVE) or the LET arm (leuprorelin + LET) until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS). Secondary end-points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Results Between January 2014 and October 2018, 137 patients were enrolled (median age, 44 years [range, 24–56]). Of them, 75% had endocrine-sensitive disease, and 61% had visceral metastasis. With the median follow-up of 32.4 months, the median PFS was 18.1 months in the EVE arm and 13.8 months in the LET arm (HR 0.73, P = 0.137). Among patients with visceral metastases, the median PFS was significantly longer in the EVE arm (16.4 versus 9.5 months, P = 0.048). The median OS was not reached in both arms. The CBR was significantly higher in the EVE arm (83% versus 62%, P = 0.010). The ORR was similar between the two arms. The most common grade 3/4 adverse events in the EVE arm were neutropenia, alanine aminotransferase elevation and anaemia. Conclusions EVE plus LET with ovarian-suppression resulted in longer PFS in tamoxifen-exposed HR+, HER2– metastatic breast cancer patients with visceral metastasis.

Due to prolonged survival and the relatively young median age of patients, the quality of life (QOL) of breast cancer survivors is an important issue in Korea. We conducted an educational program for breast cancer survivors, and evaluated its impact on knowledge, QOL, and lifestyle changes. This study utilized a single-arm pretest-posttest design. Participants were tested before and after an educational program to measure changes in knowledge. To measure QOL change, we conducted a QOL survey at the time of enrollment and again 6 months later. Regarding the knowledge test, mean scores increased from 9.62 to 14.74 points following education (p

A caregiver’s prognostic awareness can affect clinical decisions for the patient. The purpose of this study was to examine the impact of family caregivers’ prognostic awareness on the quality of life (QOL) and emotional state of both patients with advanced cancer and their caregivers. This prospective cohort study was conducted from December of 2016 to January of 2018. A total of 159 patients with advanced cancer and an equal number of caregivers participated. The investigation tools used include the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-Palliative, the McGill Quality of Life Questionnaire, and the Patient Health Questionnaire-9, and evaluation was performed at baseline, 3 months, and 6 months. Covariance analysis with a general linear modeling was used to compare changes in quality of life scores according to the caregivers’ awareness of the prognosis. Mean patient overall QOL score increased in the group of caregivers who were aware of prognosis and decreased in the caregivers who were not aware of the prognosis (p = 0.018). The changes over time in the patients’ QOL scores associated with symptoms improved with caregiver awareness (pain, p = 0.017; dyspnea, p = 0.048; appetite loss, p = 0.045). The percentage of depressed patients was smaller after 3 months in the group with caregivers aware of the prognosis (baseline to 3 months p = 0.028). Caregivers who did not understand their patients’ prognosis exhibited better existential well-being (p = 0.036), and the incidence of depression was lower in this group at 3 months (p = 0.024). Caregivers’ prognostic awareness may improve the quality of life and mood in patients with advanced cancer; however, this awareness may harm the quality of life and mood of the caregivers. These results may aid in developing in-depth interventions regarding prognosis for both patients and their caregivers.

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 (>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- (>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.

The risk of opioid-related aberrant behavior (OAB) in Korean cancer patients has not been previously evaluated. The purpose of this study is to investigate the Opioid Risk Tool (ORT) in Korean cancer patients receiving opioid treatment.Data were obtained from a multicenter, cross-sectional, nationwide observational study regarding breakthrough cancer pain. The study was conducted in 33 South Korean institutions from March 2016 to December 2017. Patients were eligible if they had cancer-related pain within the past 7 days, which was treated with strong opioids in the previous 7 days.We analyzed ORT results of 946 patients. Only one patient in each sex (0.2%) was classified as high risk for OAB. Moderate risk was observed in 18 males (3.3%) and in three females (0.7%). Scores above 0 were primarily derived from positive responses for personal or familial history of alcohol abuse (in men), or depression (in women). In patients with an ORT score of 1 or higher (n = 132, 14%), the score primarily represented positive responses for personal history of depression (in females), personal or family history of alcohol abuse (in males), or 16-45 years age range. These patients had more severe worst and average pain intensity (proportion of numeric rating scale ≥ 4: 20.5% vs. 11.4%,The score of ORT was very low in cancer patients receiving strong opioids for analgesia. Higher pain intensity may associate with positive response to one or more ORT item.

Purpose The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.Materials and Methods We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.Results The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).Conclusion Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.