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1.
Article in English | WPRIM | ID: wpr-915497

ABSTRACT

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 reported peripheral neuropathy symptoms of numbness/ tingling at the baseline, and at 4weeks after completion of chemotherapy. Candidate psychiatric factors associated with CIPN were assessed at the baseline, using the Composite Scale of Morningness, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale. To examine the association between chronotype and CIPN, we built logistic regression models, adjusting for demographic, clinical, and other psychiatric variables. @*Results@#Among 48 participants, 29 participants developed CIPN. The morning chronotype was inversely associated with CIPN (odds ratio, 0.06; confidence interval, 0.01–0.74; P = 0.028) after adjusting for age, BMI, education, type of operation, alcohol use, smoking, sleep quality, depression, and anxiety. @*Conclusion@#Our results suggest that the morning chronotype is a protective factor against the development of CIPN in patients with breast cancer who were treated with docetaxel.

2.
Article in English | WPRIM | ID: wpr-925669

ABSTRACT

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. @*Results@#A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction. @*Conclusion@#This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

3.
Article in English | WPRIM | ID: wpr-925668

ABSTRACT

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 institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response. @*Results@#Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83. @*Conclusion@#Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

4.
Journal of Breast Cancer ; : 97-105, 2021.
Article in English | WPRIM | ID: wpr-891290

ABSTRACT

In the PALOMA-3 trial, the median progression-free survival (PFS) was longer among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) treated with palbociclib plus fulvestrant than those treated with placebo plus fulvestrant. This subgroup analysis examined the efficacy and safety of palbociclib among Korean patients enrolled in PALOMA-3 (n = 43 [palbociclib group, n = 24; placebo group, n = 19]). In both groups, > 40% of patients were pre/perimenopausal at enrollment. The median PFS was significantly prolonged with palbociclib vs. placebo (12.3 [95% confidence interval (CI), 9.1–not estimable] vs. 5.4 months [95% CI, 1.9–9.2]; hazard ratio, 0.40 [95% CI, 0.19–0.83]; one-sided p = 0.005), and the confirmed objective response was 21.1% and 11.8%, respectively (odds ratio, 2.0 [95% CI, 0.24–24.8]). Neutropenia was the most common adverse event associated with palbociclib. Overall, palbociclib plus fulvestrant was effective and generally safe among Korean patients with HR+/HER2− ABC, regardless of menopausal status.

5.
Journal of Breast Cancer ; : 97-105, 2021.
Article in English | WPRIM | ID: wpr-898994

ABSTRACT

In the PALOMA-3 trial, the median progression-free survival (PFS) was longer among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) treated with palbociclib plus fulvestrant than those treated with placebo plus fulvestrant. This subgroup analysis examined the efficacy and safety of palbociclib among Korean patients enrolled in PALOMA-3 (n = 43 [palbociclib group, n = 24; placebo group, n = 19]). In both groups, > 40% of patients were pre/perimenopausal at enrollment. The median PFS was significantly prolonged with palbociclib vs. placebo (12.3 [95% confidence interval (CI), 9.1–not estimable] vs. 5.4 months [95% CI, 1.9–9.2]; hazard ratio, 0.40 [95% CI, 0.19–0.83]; one-sided p = 0.005), and the confirmed objective response was 21.1% and 11.8%, respectively (odds ratio, 2.0 [95% CI, 0.24–24.8]). Neutropenia was the most common adverse event associated with palbociclib. Overall, palbociclib plus fulvestrant was effective and generally safe among Korean patients with HR+/HER2− ABC, regardless of menopausal status.

6.
Article in English | WPRIM | ID: wpr-897462

ABSTRACT

Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

7.
Cancer Research and Treatment ; : 1096-1103, 2021.
Article in English | WPRIM | ID: wpr-913815

ABSTRACT

Purpose@#Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed. @*Materials and Methods@#Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety. @*Results@#Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia. @*Conclusion@#Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

8.
Cancer Research and Treatment ; : 1084-1095, 2021.
Article in English | WPRIM | ID: wpr-913792

ABSTRACT

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 human epidermal growth factor receptor 2–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 choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions. @*Results@#Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population. @*Conclusion@#In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

9.
Article in English | WPRIM | ID: wpr-889758

ABSTRACT

Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

10.
Article in English | WPRIM | ID: wpr-874347

ABSTRACT

Purpose@#This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. @*Materials and Methods@#We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. @*Results@#Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). @*Conclusion@#Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

11.
Journal of Breast Cancer ; : 182-193, 2020.
Article | WPRIM | ID: wpr-835603

ABSTRACT

Purpose@#Endocrine therapy is a standard treatment for hormone receptor-positive breast cancer, which accounts for 60%–75% of all breast cancer. Hormone receptor positivity is a prognostic and predictive biomarker in breast cancer. Approximately 50%–80% of breast cancer is also positive for androgen receptor (AR), but the prognostic and predictive value of AR expression in breast cancer is controversial. Here, we investigated AR expression and its prognostic value in patients with surgically resected breast cancer in Korea. @*Methods@#We retrospectively reviewed the medical records of patients who had surgically resected breast cancer to collect AR expression data and other clinicopathological data. The optimal cut-off for AR positivity was determined using a receiver operating characteristic curve analysis. @*Results@#We reviewed 957 patients with surgically resected breast cancer from June 2012 to April 2013. The median follow-up was 62 months, and relapse events occurred in 101 (10.6%) patients. Unlike the cut-off value of 1% or 10% in previous reports, 35% was determined to be best for predicting relapse-free survival (RFS) in this study. At the cut-off value of 35%, 654 (68.4%) patients were AR-positive. AR expression was more prevalent in luminal A (87.6%) and luminal B (73.1%) types than in human epidermal growth factor receptor 2-positive (56.2%) or triple-negative (20.6%) types. AR expression of ≥ 35% was significantly related to longer RFS in a multivariate analysis (hazard ratio, 0.430; 95% confidence interval, 0.260–0.709; p = 0.001). @*Conclusion@#We propose a cut-off value of 35% to best predict RFS in patients with surgically resected breast cancer. AR expression was positive in 68.4% of patients, and AR positivity was found to be an independent prognostic factor for longer RFS.

12.
Article in English | WPRIM | ID: wpr-835509

ABSTRACT

Metastatic disease involving the thyroid gland is uncommon. Thyroid metastases has been previously described from several primary cancers of lung, breast, and kidney. Because of the lower incidence and ambiguous clinical significance, it is not easy to consider thyroid metastasis and decide the optimal time for performing diagnostic examination. Here, we reported two cases of metastatic diseases of thyroid in patients who had underlying Hashimoto’s thyroiditis: a 39-year-old woman who had thyroid metastasis of breast cancer with underlying Hashimoto’s thyroiditis, and a 44-year-old woman with metastatic lung cancer.

13.
Cancer Research and Treatment ; : 1178-1187, 2020.
Article | WPRIM | ID: wpr-831138

ABSTRACT

Purpose@#Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated. Material and MethodsThis study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers. @*Results@#Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040). @*Conclusion@#MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

14.
Article | WPRIM | ID: wpr-831120

ABSTRACT

Purpose@#Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data. @*Materials and Methods@#The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study. @*Results@#The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations. @*Conclusion@#L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

15.
Journal of Breast Cancer ; : 268-278, 2020.
Article in English | WPRIM | ID: wpr-914815

ABSTRACT

Purpose@#This study was performed to investigate the effect of the interval between the start of gonadotropin-releasing hormone agonist (GnRHa) and the start of chemotherapy on ovarian protection in patients with breast cancer. @*Methods@#This was a prospective observational cohort study that included 136 patients with breast cancer below 40 years who received GnRHa during chemotherapy for fertility preservation. Plasma anti-Müllerian hormone (AMH) levels were measured before chemotherapy (baseline) and after chemotherapy. Subjects were divided into 3 groups according to the interval between the start of GnRHa and the start of chemotherapy for analysis: 1–6 days, 7–13 days, and ≥ 14 days. The ratio of the post-chemotherapy AMH value to the baseline AMH (pcAMH) at each time point were compared among the 3 groups.Ranked analysis of covariance was used for statistical analysis, adjusted for age, body mass index (BMI), and the existence of polycystic ovaries (PCOs). In addition, recovery of ovarian function (AMH ≥ 1 ng/mL) at 12 months was evaluated. @*Results@#The median age of the patients was 32 years. There was no difference in the baseline AMH levels among the 3 groups (mean ± standard error: 5.0 ± 0.4 ng/mL [1–6 days], 5.3 ± 0.7 ng/mL [7–13 days], and 8.1 ± 1.3 ng/mL [≥ 14 days]; p = 0.250). The pcAMH at 3, 6, 12, 24, and 36 months were not significantly different among the 3 groups (p-values were 0.332, 0.732, 0.830, 0.148, and 0.393, respectively). In multivariate analysis, young age (p = 0.024), low BMI (p = 0.013), and the existence of PCO (p = 0.015) were predictors for AMH ≥ 1 ng/mL at 12 months. @*Conclusion@#There was no difference in the ovarian protective effect according to the difference in the timing of administration of GnRHa.

16.
Article in English | WPRIM | ID: wpr-719720

ABSTRACT

PURPOSE: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS. RESULTS: There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs. 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea. CONCLUSION: Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.


Subject(s)
Arm , Breast Neoplasms , Breast , Capecitabine , Diarrhea , Disease-Free Survival , Epidermal Growth Factor , Global Health , Hand-Foot Syndrome , Humans , Neutropenia , Quality of Life , Triple Negative Breast Neoplasms , Weights and Measures
17.
Article in English | WPRIM | ID: wpr-719428

ABSTRACT

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.


Subject(s)
Academies and Institutes , Asians , DNA , Humans , Korea , Methods , Paraffin , Point Mutation , Precision Medicine , Prevalence
19.
Article in English | WPRIM | ID: wpr-763149

ABSTRACT

PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.


Subject(s)
Apoptosis , Autophagy , Blotting, Western , Cell Cycle , Cell Death , Cell Line , Cell Proliferation , Cell Survival , DNA Damage , Fluorescent Antibody Technique , Humans , Phosphotransferases , Protein Isoforms , Stomach Neoplasms
20.
Article in Korean | WPRIM | ID: wpr-759626

ABSTRACT

BACKGROUND: Hypercalcemia is an important metabolic emergency condition in cancer patients. Bisphosphonate is the treatment of choice for hypercalcemia, whereas calcitonin and hydration with furosemide are recommended for acute supportive therapy. However, data regarding real-world treatment patterns and outcomes of pharmacological treatments are limited. Therefore, we aimed to investigate the treatment patterns and clinical outcomes of hypercalcemia treatment in solid tumor patients. METHODS: Electronic medical records of 123 adults with solid cancers and albumin-corrected calcium levels >10.5 mg/dL or ionized calcium levels >1.35 mmol/L were reviewed. We retrospectively analyzed the pharmacological treatment and recovery rate according to the severity of hypercalcemia. RESULTS: A total of 177 cases were identified, of which 49 were not treated and 30 were treated with hydration only. In moderate-to-severe cases, 86.5% received pharmacological treatment. Thirty-four cases (19.2%) were treated with bisphosphonate alone and 58 cases (32.8%) were treated with bisphosphonate and calcitonin. In mild hypercalcemia cases, the recovery rate was higher for those receiving hydration only or pharmacological treatment (79.7%) than for those receiving no treatment (61.4%, p = 0.041). Most moderate-to-severe cases were treated with medication and of those treated, 56.3% recovered. The recovery rate was lower in those treated with bisphosphonate alone (38.2%) than in those who underwent calcitonin combination treatment (73.7%, p = 0.001). CONCLUSIONS: Bisphosphonate combined with calcitonin was found to be more effective than bisphosphonate alone for the treatment of moderate-to-severe hypercalcemia. Considering the current shortage of calcitonin, further efforts are required to ensure its stable supply.


Subject(s)
Adult , Calcitonin , Calcium , Electronic Health Records , Emergencies , Furosemide , Humans , Hypercalcemia , Retrospective Studies
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