Goyang, South Korea
Goyang, South Korea

Time filter

Source Type

Park I.H.,Center for Breast Cancer | Lee H.,Center for Clinical Trial | Lee K.S.,Center for Breast Cancer | Kang H.S.,Center for Breast Cancer | And 4 more authors.
Annals of Oncology | Year: 2012

Background: We investigated the relationship between resumption or persistence of menstruation after cytotoxic chemotherapy (RM) and disease-free survival (DFS) in premenopausal patients with early breast cancer. Methods: Medical records from 872 patients who received cytotoxic chemotherapy for stage I to III breast cancer were retrospectively reviewed. Results: The median patient age was 41 years (range, 21-54) and the median follow-up duration was 6.2 years (range, 0.7-10.4). Six hundred ninety-two patients (79.4%) were hormone receptor (HR) positive and the majority of these received tamoxifen therapy after completing chemotherapy. The chemotherapy-induced amenorrhea (CIA) rate was 76.7% (n = 669), and 51.8% (n = 452) experienced RM during the follow-up period. One hundred twenty-one (13.9%) patients had persistent menstruation without CIA. DFS was significantly affected by younger age at diagnosis (≤35 years) (P = 0.013), tumor size > 2 cm (P < 0.001), node positivity (P < 0.001), HR negativity (P < 0.001), HER2 positivity (P = 0.010), and RM (P < 0.001). HR negativity [hazard ratio 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.006], tumor size > 2 cm (hazard ratio 2.1, 95% CI 1.4-3.0, P < 0.001), node positivity (hazard ratio 3.0, 95% CI 2.0-4.7, P < 0.001), and RM (hazard ratio 1.8, 95% CI 1.2-2.7, P = 0.004) remained significant factors for DFS on multivariate analysis. Conclusions: A considerable proportion of premenopausal patients treated with chemotherapy experienced RM after CIA. RM was a poor prognostic factor for DFS in premenopausal patients with early breast cancer. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Swain S.M.,MedStar Washington Hospital Center | Baselga J.,Sloan Kettering Cancer Center | Kim S.-B.,University of Ulsan | Ro J.,Center for Breast Cancer | And 10 more authors.
New England Journal of Medicine | Year: 2015

Background: In patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months. Methods: We randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis. Results: The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained. Conclusions: In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. Copyright © 2015 Massachusetts Medical Society.


Swain S.M.,MedStar Washington Hospital Center | Kim S.-B.,University of Ulsan | Cortes J.,University of Barcelona | Ro J.,Center for Breast Cancer | And 10 more authors.
The Lancet Oncology | Year: 2013

Background: CLEOPATRA is a phase 3 study to compare the efficacy and safety of pertuzumab, trastuzumab, and docetaxel with placebo, trastuzumab, and docetaxel in patients with HER2-positive first-line metastatic breast cancer. The results of the primary analysis showed significantly longer median progression-free survival in the pertuzumab group than in the placebo group. Interim analysis of overall survival favoured the pertuzumab group but was not significant. Here, we report results for overall survival after an additional year of follow-up. Methods: The study was a double-blind randomised trial undertaken at 204 centres in 25 countries. Patients with HER2-positive metastatic breast cancer who had not received previous chemotherapy or biological treatment for their metastatic disease were randomly assigned to receive either pertuzumab, trastuzumab, and docetaxel (n=402) or the same regimen with a matching placebo replacing pertuzumab (n=406). Randomisation was in a 1:1 ratio, stratified by geographical region and previous treatment status. The primary endpoint was progression-free survival (assessed independently), which has been reported previously; no follow-up data were gathered for the primary endpoint. Secondary endpoints included overall survival, progression-free survival (assessed by investigator), objective response rate, and safety. Median follow-up was 30 months in both groups. Efficacy endpoints were analysed in the intention-to-treat population and safety was analysed by treatment received. The study is completed but safety and survival data continue to be followed up. This trial is registered with ClinicalTrials.gov, number NCT00567190. Findings: In the intention-to-treat population, 267 patients died by data cutoff (May 14, 2012), 154 (38%) of 406 in the placebo group and 113 (28%) of 402 in the pertuzumab group. Median overall survival was 37·6 months (95% CI 34·3-NE [not estimable]) in the placebo group but had not been reached (95% CI 42·4-NE) in the pertuzumab group (hazard ratio 0·66, 95% CI 0·52-0·84; p=0·0008). Investigator-assessed median progression-free survival was 12·4 months (95% CI 10·4-13·5) in the placebo group and 18·7 months (16·6-21·6) in the pertuzumab group (hazard ratio 0·69, 95% CI 0·58-0·81). Serious adverse events were reported in 115 (29%) of 396 patients who received placebo, trastuzumab, and docetaxel and 148 (36%) of 408 who received pertuzumab, trastuzumab, and docetaxel, and included febrile neutropenia, neutropenia, diarrhoea, pneumonia, and cellulitis. Overall, adverse events were similar to those reported at the primary analysis with respect to frequency, severity, and specificity. Interpretation: Our analysis shows a significant improvement in overall survival with pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer, compared with placebo, trastuzumab, and docetaxel. Since this effect was not achieved at the expense of adverse events, this regimen represents a substantial improvement on the standard of care for this population of patients. Funding: F Hoffmann-La Roche, Genentech. © 2013 Elsevier Ltd.


Park S.,Yonsei University | Park B.-W.,Yonsei University | Kim T.H.,Inje University | Jeon C.W.,Korea Institute of Radiological and Medical Sciences | And 4 more authors.
Annals of Surgical Oncology | Year: 2013

Background: This study was designed to evaluate the impact of lack of either estrogen receptor (ER) or progesterone receptor (PR) on characteristics and outcomes among luminal A breast cancer subtype treated with endocrine with or without chemotherapeutic agents. Methods: The luminal A subtype was categorized into three subgroups: ER+/PR+, ER+/PR-, and ER-/PR+. All tumors were human epidermal growth factor receptor 2 (HER2) negative. Clinicopathological features and survival were analyzed using the Severance Hospital dataset (n = 1,180) and were validated by the nationwide Korean Breast Cancer Society (KBCS) registry (n = 9,916). Results: Despite the different distribution of ER/PR status, tumor stage, grade, and local therapies between the two datasets, similarly ER+/PR+ showed smaller size and good differentiation, ER+/PR- patients had the oldest age at diagnosis, and ER-/PR+ was associated with the youngest age at onset and grade III tumor. Single hormone receptor-positive subgroups demonstrated worse disease-related outcomes than the ER+/PR+ subgroup. These associations were confirmed by the KBCS dataset. This trend was also demonstrated in the subpopulation of 1,944 patients with Ki-67 < 14 %. Inferior survival of single receptor-positive tumors was more definite among node-positive patients even when receiving both chemo-endocrine therapies. Conclusions: Current results suggest that the luminal A subtype is also heterogeneous and each subgroup has unique clinicopathologic characteristics. Lack of either ER or PR expression is associated with worse survival, especially among node-positive luminal A subtype. © 2012 Society of Surgical Oncology.


Park I.H.,Center for Breast Cancer | Ro J.,Center for Breast Cancer | Park S.,National Cancer Center | Lim H.-S.,University of Ulsan | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2012

Active metabolites of tamoxifen are formed mainly by the action of cytochrome P450 2D6 (CYP2D6). Since there are controversies regarding associations between CYP2D6 polymorphisms and outcomes among women with early breast cancer (EBC) treated with tamoxifen, the present evaluation of links with clinical outcomes was conducted. We analyzed a total of 716 patients treated with tamoxifen for hormone receptor positive EBC between 2001 and 2005 at the National Cancer Center, Korea. All patients received tamoxifen 20 mg/day for more than 6 months. DNA obtained from whole blood samples was genotyped for CYP2D6 variants associated with reduced (*10,*41) and absent (*5) activity. Of the total of 716 patients, 558 (77.9%) received adjuvant or neoadjuvant chemotherapy prior to the tamoxifen therapy. From the genotyping of CYP2D6, 152 (21.2%) patients were classified as having the wild type (W/W), 376 (52.7%) one variant allele (W/V), and 188 (26.1%) two variant alleles (V/V). Seventy (9.8%) patients experienced disease recurrence with a median follow-up of 5.6 (range, 0.6-10.3) years. Although known prognostic factors, including tumor size, nodal status, Ki67, PgR negativity, and HER2 positivity showed strong associations with the recurrence free survival (RFS) in this population, no significant association with any of the CYP2D6 genetic variants was evident (P = 0.61; hazard ratio [HR] = 1.14; 95% CI 0.68-1.92). This remained the case after subgroup analysis according to different adjuvant treatments. Polymorphisms of CYP2D6 were not associated with clinical outcomes in EBC patients receiving adjuvant tamoxifen treatment. © 2011 Springer Science+Business Media, LLC.


Ko K.L.,Center for Breast Cancer | Shin I.S.,Center for Breast Cancer | You J.Y.,Center for Breast Cancer | Jung S.-Y.,Center for Breast Cancer | And 2 more authors.
Breast Cancer Research and Treatment | Year: 2013

Tamoxifen is known to reduce the risk of breast cancer in women at high risk and also reduces mammographic breast density (MD) in a preventive setting. We investigated the efficacy of MD reduction (MDR) for predicting recurrence in estrogen receptor (ER)-positive patients in an adjuvant setting. A total of 1,066 ER-positive breast cancer patients who were enrolled in this study underwent curative surgery and received adjuvant tamoxifen for at least 2 years at our institution between January 2003 and December 2008. Using a computerized system, a single radiologist reviewed all mammograms and classified MD patterns on the basis of the Breast Imaging Reporting and Data System. MDR was assessed using the baseline mammogram taken before surgery (preMD) and the follow-up mammogram taken after the start of adjuvant tamoxifen (postMD). MDR positivity was defined as downgrading of the postMD grade, with the preMD grade as a reference. Patients were divided into 2 groups, MDR-positive and MDR-negative, for statistical analysis. Patients who showed MDR after an average of 19 months of adjuvant tamoxifen treatment had a 65 % lower risk of recurrence than patients who did not show MDR. Furthermore, significant risk reduction according to MDR had a predictive power for any type of recurrence pattern including loco-regional recurrence (87 % reduction) and systemic recurrence (52 % reduction) in ER-positive breast cancer patients, especially in women ≤50 years. In our study, only 4 patients (0.4 %) showed contralateral breast recurrence during the mean 61-month follow-up period and none of them experienced MDR. In conclusion, MDR during adjuvant tamoxifen therapy was independently associated with a lower risk of systemic and loco-regional recurrence in ER-positive breast cancer patients, especially in young women. For patients who do not experience MDR after approximately 1.5 years of tamoxifen therapy, more caution should be taken and other treatment strategies are warranted. © 2013 Springer Science+Business Media New York.


Woo H.D.,National Cancer Center | Park K.-S.,National Cancer Center | Shin A.,National Cancer Center | Ro J.,Center for Breast Cancer | Kim J.,National Cancer Center
Asian Pacific Journal of Cancer Prevention | Year: 2013

The glycemic index (GI) and glycemic load (GL) have been considered risk factors for breast cancer, but association studies of breast cancer risk using simple GI and GL might be affected by confounding effects of the overall diet. A total of 357 cases and 357 age-matched controls were enrolled, and dietary intake was assessed using a validated food frequency questionnaire (FFQ) with 103 food items. GI and GL dietary patterns were derived by reduced rank regression (RRR) method. The GI and GL pattern scores were positively associated with breast cancer risk among postmenopausal women [OR (95%CI): 3.31 (1.06-10.39), p for trend=0.031; 9.24 (2.93-29.14), p for trend <0.001, respectively], while the GI pattern showed no statistically significant effects on breast cancer risk, and the GL pattern was only marginally significant, among premenopausal women (p for trend=0.043). The GI and GL pattern scores were positively associated with the risk of breast cancer in subgroups defined by hormone receptor status in postmenopausal women. The GI and GL patterns based on all food items consumed were positively associated with breast cancer.


Park I.H.,Center for Breast Cancer | Lee K.S.,Center for Breast Cancer | Ro J.,Center for Breast Cancer
Clinical Breast Cancer | Year: 2015

Background We assessed the effect of chemotherapy regimens beyond first-line agents on the clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC).Patients and Methods We included 240 patients who were prospectively enrolled into various clinical trials and were receiving cytotoxic chemotherapy for HER2-negative MBC at the National Cancer Center, Korea, from October 2002 to September 2012. Clinicopathologic data were collected for the analysis.Results A total of 240, 209, and 166 patients received first-, second-, and third-line chemotherapy, respectively. The median age was 49 years (range, 28-77 years), and most had hormone receptor-positive cancer (n = 177; 73.8%). The median progression-free survival (PFS) was 7.6 months for first-line (PFS1) versus 5.1 months for second-line (PFS2) versus 3.6 months for third-line (PFS3) chemotherapy. The PFS from previous chemotherapy significantly affected subsequent PFS: PFS1 for PFS2, PFS1 ≥ 7.6 months, hazard ratio (HR) 0.647; 95% confidence interval (CI), 0.0.484-0.864 (P =.003); PFS2 for PFS3, PFS2 ≥ 5.1 months, HR 0.676; 95% CI, 0.0.484-0.944; P =.022). The median overall survival was 31.2 months (95% CI, 26.4-36.0 months). Hormone receptor positivity (HR 0.548; 95% CI, 0.261-0.499; P <.001) and PFS1 ≥ 7.6 months (HR 0.361; 95% CI, 0.393-0.765; P <.001) were significant factors for survival on multivariate analysis.Conclusion The efficacy of previous treatment significantly affected the outcomes of subsequent treatment. We have confirmed that the succession of chemotherapy is justified in patients with MBC who benefited from previous chemotherapy. © 2015 The Authors. Published by Elsevier Inc. All rights reserved.


Park I.H.,Center for Breast Cancer | Kwon Y.,Center for Breast Cancer | Ro J.Y.,Cornell College | Lee K.S.,Center for Breast Cancer | Ro J.,Center for Breast Cancer
Breast Cancer Research and Treatment | Year: 2010

It is not known whether the HER2 status of malignant CSF cells coincides with that of the original breast carcinoma cells. We investigated whether CSF cytology specimens were suitable to evaluate HER2 status by fluorescence in situ hybridization (FISH) in patient with leptomeningeal metastasis (LM). Both formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and liquid based CSF cytology specimens were evaluated for HER2 status in 16 patients with LM. We evaluated HER2 gene amplification using FISH on destained CSF cytology slides containing a minimum of 20 malignant cells per slide, and compared these with the HER2 status by immunohistochemistry (IHC) or FISH in FFPE tissues. HER2 was considered positive when the HER2:CEP17 ratio was ≥2.0 or IHC 3+. Of 16 cases, four were HER2 positive and 12 were HER2 negative by FISH analysis in CSF cytology. All CSF-positive cases were HER2 positive by IHC in FFPE tissue. Of 12 HER2 FISH-negative cases in CSF cytology, 10 were HER2 negative (IHC 0 or 1+) and two were IHC 2+ in FFPE tissue. Two IHC 2+ cases had HER2:CEP17 ratios of 1.27 and 2.1, respectively, by FISH in FFPE tissue. As a result, the HER2 status concordance rate between metastatic breast cancer cells in CSF and FFPE primary tissue by IHC and FISH was very high. When CSF cytology specimens were appropriately prepared and had adequate cellularity without dry artifacts, the CSF cytology was suitable to evaluate HER2 status by FISH analysis in patients with LM. © 2010 Springer Science+Business Media, LLC.


Park I.H.,Center for Breast Cancer | Ro J.,Center for Breast Cancer | Lee K.S.,Center for Breast Cancer | Kim E.-A.,Center for Breast Cancer | And 6 more authors.
Journal of Clinical Oncology | Year: 2010

Purpose: Goserelin and letrozole in premenopausal patients can result in clinical outcomes comparable to those obtained by letrozole alone in postmenopausal patients with metastatic breast cancer (MBC). Patients and Methods: A total of 73 patients with hormone-responsive MBC were included. Of those, 35 premenopausal patients received goserelin (3.6 mg subcutaneously every 28 days) plus letrozole (2.5 mg orally daily), and 38 postmenopausal patients received letrozole alone as their first-line endocrine therapy in a metastatic setting. Results: Baseline characteristics were similar in the two groups, except for a younger age (median, 41 v 53.5 years; P < .001) and a shorter disease-free interval (median, 1.8 v 3.3 years; P = .03) in the premenopausal group. Clinical benefit rates were comparable between the two groups (77% v 74%; P = .77). With the median follow-up of 27.4 months, there was no statistical difference in the median time to progression between the two groups (9.5 months [95% CI, 6.4 to 12.1 months] v 8.9 months [95% CI, 6.4 to 13.3 months]). In patients who did not receive bisphosphonate, letrozole ± goserelin caused a greater loss of bone mineral density at 6 months compared with that of patients receiving bisphosphonate treatment (premenopausal group, -16.7% v 53.9%; P = .002 and postmenopausal group, -13.3% v 17.4%; P = .04 at the lumbar spine). Conclusion: Clinical efficacies in premenopausal MBC patients with combined letrozole and goserelin therapy were comparable to those in postmenopausal patients treated with letrozole alone. Although letrozole ± goserelin resulted in a modest increase in bone resorption, concurrent treatment with bisphosphonate could prevent bone loss at 6 months. © 2010 by American Society of Clinical Oncology.

Loading Center for Breast Cancer collaborators
Loading Center for Breast Cancer collaborators