Sy Bae

Abstract P2-09-19: Zerumbone suppresses IL-1b-induced cell migration and invasion through inhibition of IL-8 expression and MMP3 expression in human triple negative breast cancer cells

Background: Inflammation is a key regulatory process in breast cancer progression and severity. Several studies have demonstrated that prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transitions (EMT), which is the principle mechanism involved in metastasis and tumor invasion. Disruption of the signaling pathways involved in EMT may therefore provide an effective treatment strategy for currently difficult to treat or untreatable cancers such as TNBC. The interleukin (IL)-1 plays a pivotal role on breast cancer proliferation, invasion and/or inflammation. Here, we investigated the correlation of MMP-3 and IL-8 on IL-1b-induced cell migration and invasion as well as the inhibitory effect of zerumbone on IL-1β-induced MMP-3 and IL-8. Methods: Triple negative breast cancer cells (Hs578T and MDA-MB231) were cultured DMEM with 10% FBS and 1% antibiotics. The levels of IL-8 and MMP-3 mRNA were analyzed by real-time PCR. The levels of secreted IL-8 and MMP-3 protein expression were analyzed by ELISA and western blot analysis, respectively. Cell viabilities by drug were analyzed by MTT assay. Cell invasion and migration was detected by Boyden chamber assay. Results: The level of IL-8 and MMP-3 mRNA and protein expression significantly increased by IL-1β treatment in both Hs578T cells and MDA-MB231 cells. In addition, IL-1β-induced cell migration and invasion also increased in Hs578T and MDA-MB231 cells. On the other hand, the levels of basal and IL-1β-induced IL-8 and MMP-3 expression were decreased by zerumbone. Conclusion: IL-1β induces the migration and invasion of breast cancer cells through IL-8 and MMP-3 expression. These effects are significantly suppressed by zerumbone. Therefore, we suggest that zerumbone may act as a useful therapeutic agent for treatment of triple negative breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-19.

P5-14-02: Clinicopathologic and Prognostic Difference of Screen Detected Breast Cancer Compared with Symptomatic Breast Cancer.

Background: Breast cancer screening program makes it possible to detect early cancer, thus to reduce breast cancer mortality. The authors studied clinicopathologic characteristics and prognosis of screen detected invasive breast cancer compared with symptomatic breast cancer. Furthermore, we compared the result according to molecular subtypes (luminal A, luminal B, Her2, triple negative), so intended to identify the role of screening in each subtypes. Material and Methods: From January 2002 to June 2008, 3141 patients who underwent operation for the treatment of invasive ductal carcinoma(NOS) at Samsung medical center were included. Among them, 1025 patient were screen detected, 2116 patient were symptomatic, out of screening over 2 years. We reviewed the medical records retrospectively. Result: Screen detected breast cancer was associated with older patients, smaller tumor size, more hormone receptor- positive, less lymph node involvement, lower stage and reduced mortality compared with symptomatic breast cancer (P Conclusion: Compared to symptomatic breast cancer patients, screen detected breast cancer patients have favorable pathological and molecular characteristics, so better outcomes. According to the molecular subtype, only in luminal A subtype, screen detected breast cancer shows both overall and disease free survival benefit, and also acts as an independent prognostic factor itself. So, screening program seems to have a different efficacy depending on the molecular subtype of breast cancer Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-02.

Abstract P6-09-36: Tamoxifen resistance: EGFR expression in hormone receptor-positive and HER2 negative breast cancer

Purpose: Crosstalk between growth factor receptor tyrosine kinases (RTKs) and the estrogen receptor (ER) represents one of the most important mechanisms of endocrine resistance. EGFR and HER2 have been recognized as prominent factors associated with endocrine resistance. Most previous studies did not identify subgroups by HER2 overexpression and/or included breast cancer with HER2 overexpression. Accordingly, we analyzed HR positive (HR+) tumors without HER2 overexpression (HER2-). Methods: We analyzed the clinical data of 2,166 patients with HR+HER2- breast tumors, between January 2007 and July 2013.We included only patients who had endocrine therapy with tamoxifen. Immunostaining for EGFR was interpreted as positive when at least 10% of the tumor cells showed moderate to strong membrane staining. Results: EGFR expression (EGFR+) was present in 109 patients (5%). EGFR expression was significantly associated with more advanced stage and higher grades. In the univariate analyses, EGFR+ tumors were associated with poorer prognosis than EGFR- tumors (5-year DFS, EGFR+ vs. EGFR-, 91.2% vs. 96.6%, P Conclusion: EGFR expression could be prognostic factor in hormone receptor-positive and HER2 negative breast cancer, for tamoxifen resistance. Citation Format: Bae SY, Nam SJ, Lee SK, Kim SW, Lee JE, Yu JH. Tamoxifen resistance: EGFR expression in hormone receptor-positive and HER2 negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-36.

Abstract P3-14-12: Oncologic outcomes of immediate breast reconstruction after neoadjuvant chemotherapy in breast cancer patients: A matched case control study

Introduction: Although the indication for total mastectomy (TM) with immediate breast reconstruction (IBR) has been expanded, IBR after neoadjuvant chemotherapy (NACT) is still controversy. We assumed that TM with IBR after NACT is feasible surgical treatment in breast cancer patients. Methods: A retrospective review of breast cancer patients who underwent TM with IBR after NACT between 2008 and 2015 at a single center was conducted. These cases were matched by 1:5 to patients who underwent mastectomy alone after NACT. Matching variables included age, clinical T and N staging before NACT, response to NACT, and pathologic staging after NACT. Pathological stage was followed by seventh American Joint Committee on Cancer (AJCC) classification. Results: Overall, 31 patients were identified in the TM with IBR group (Study group) and 85 patients (Control group) were matched. In the study group, 13 (41.9%) patients underwent nipple-sparing mastectomy (NSM) and 18 (58.1%) underwent skin-sparing mastectomy (SSM). Median follow-up duration was 29.2 (7-31) and 38.8 (11-85) months for the study and control group, respectively. Median age was 37.0 (26-57) and 40.0 (24-56) years for the study and control group, respectively. The clinicopathologic characteristics of both groups are summarized in Table1. Disease-free survival (p=0.520), local recurrence-free survival (p=0.610), distant metastasis-free survival (p=0.795), and over survival (p=0.971) did not differ significantly between two groups. Conclusion: TM with IBR after NACT is feasible surgical treatment option in breast cancer patients. Citation Format: Ryu JM, Lee JE, Kim SW, Yu J, Rayzah M, Lee SK, Mansoor A, Bae SY, Park S, Paik H-J, Kim I, Bang SI, Jeon BJ, Mun G-H, Pyon J-K. Oncologic outcomes of immediate breast reconstruction after neoadjuvant chemotherapy in breast cancer patients: A matched case control study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-14-12.

Abstract P1-11-01: Depression and anxiety after adjuvant ovarian function suppression in premenopausal breast cancer patients

Purpose The results of the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT) showed that ovarian function suppression (OFS) in premenopausal early breast cancer patients improves disease control. However, mood swings after OFS is one of the chief complaints to make patients stop undergoing endocrine therapy. Studies about complications of OFS in breast cancer patients are not established well. We designed this randomized controlled trial to evaluate psychological functioning of patients after undergoing adjuvant OFS by goserelin. Patients and Methods We randomly assigned 64 premenopausal women with hormone receptor positive early breast cancer to the tamoxifen or tamoxifen plus goserelin group for a period of 1 year. Participants were screened for depression and generalized anxiety disorder using Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAM-A), Anxiety Sensitivity Index (ASI) and Albany panic and phobia questionnaire (APPQ) at baseline, 6 months and 12 months. Brain-derived Neurotrophic Factor (BDNF) levels were measured, as well. The results were analyzed by using a linear mixed model and a generalized linear mixed model. Results Thirty two patients were distributed in each group, equally. Linear mixed-mixed model analyses revealed that, compared with HAM-A scores of each group at baseline, HAM-A scores at 12 months showed increments (p=0.0078). Among HAM-A questions, Questions for intellectual, sensory and autonomic status were scored significantly high at 12 months (p=0.0018, p=0.0132, p=0.0006). Platelet BDNF levels reported a statistically significant rise at 12 months (p=0.0006). There was no significant time-by-study group effect in all scales. Conclusion Compared with the patients without OFS, patients with Goserelin showed no difference in anxiety or depression scales. Thought the levels of anxiety of each group at 12 months were increased, they do not indicate medical interventions. Patients with increased levels of BDNF at 12 months are expected to have good recovery from anxious and depressive symptoms. Citation Format: Yi HW, Nam SJ, Kim SW, Lee JE, Lee SK, Bae SY, Park S, Paik H-J, Ryu JM. Depression and anxiety after adjuvant ovarian function suppression in premenopausal breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-11-01.

Abstract P3-01-03: Optimal concentration of indocyanine green in near-infrared fluorescence guided sentinel lymph node biopsy in breast cancer

Background: Near-infrared (NIR) fluorescence-guided sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) has been successfully applied in various kinds of cancers, especially in breast cancer. Optimizing the concentration of ICG without using human serum albumin in natural lymphatic system is still required. Methods: 25mg of ICG was diluted with distilled water (DW) or normal saline (NS). Dilution concentrations used for measurement were 0.25μg/mL, 0.5μg/mL, 2.5μg/mL, 5.0μg/mL, 25μg/mL, and 250μg/mL. The brightness of fluorescence was measured by an image system called Visual Navigator (SH System, Korea). We used graphic software (GIMP, version 2.8.14, The GIMP Team) to measure the brightness. We assumed that drained serous lymphatics from a breast cancer patient can reflect a natural lymphatic condition injected with ICG in the operation field. Drained lymphatics were mixed to reduce the concentration of ICG by half that was diluted with DW or NS. We also measured the brightness of fluorescence diluted with DW or NS that was mixed with drained lymphatics. After this screening test, we subdivided the range which brightness was measured as 100 and adjusted the intensity of illumination for more specific results. Results: Highest brightness values were measured as 100 between 2.5μg/mL and 25μg/mL concentration of ICG with DW dilution in screening settings, and the values of brightness were measured as 100 between 2.5μg/mL and 5.0μg/mL concentration of ICG with NS dilution. When drained lymphatics were mixed together, the values of brightness were measured as 100 between 2.5μg/mL and 25μg/mL concentration of ICG with DW or NS dilution. After subdividing the ICG concentration to 2.5μg/mL, 3.13μg/mL, 5.0μg/mL, 6.25μg/mL, 12.5μg/mL and 25μg/mL with adjusting the intensity of illumination, the highest brightness value was measured as 76 in 5.0μg/mL concentration of ICG with DW dilution. When diluting with NS, the highest brightness value was measured as 61 in 5.0μg/mL ICG concentration. After mixing with drained lymphatics, the highest brightness value was both 79 in 5.0μg/mL concentration of ICG with DW and NS dilution. Conclusions: This study showed a practically optimal ICG concentration range in fluorescence guided SLNB. The optimal range of ICG concentration is from 3.13μg/mL to 6.25μg/mL with DW or NS dilution. Although 5.0μg/mL met the best result, adjustment for individual settings may be considered. Citation Format: Paik H-J, Yi HW, Park S, Ryu JM, Nam SJ, Lee JE, Kil WH, Lee SK, Bae SY, Kim SW. Optimal concentration of indocyanine green in near-infrared fluorescence guided sentinel lymph node biopsy in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-03.

Abstract P3-01-08: Sentinel lymph node biopsy alone after neoadjuvant chemotherapy in patients with cytologically proven node-positive breast cancer

Background The purpose of this study was to identify the feasibility and accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in patients with axillary lymph node (ALN) metastasis at diagnosis. Methods This is a retrospective study of 332 patients who were diagnosed with invasive breast cancer and ALN metastasis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2013. Patients were classified into five groups according to surgical procedure for the ALNs and pathologic results; group 1, patients with negative SLN status and no further dissection was performed; group 2, patients with negative SLN status undergoing further axillary lymph node dissection (ALND); group 3, patients with positive or undetected SLNs undergoing further ALND; group 4, patients without residual axillary metastasis undergoing complete ALND; and group 5, patients with pathologic nodal positive disease undergoing ALND. Results Sentinel lymph nodes identification rate after NAC was 99.1% and false negative rate was 24.1%. The median number of retrieved SLNs was 4 (range, 1–10). There was no difference in the overall survival among the groups (p=0.06). There was no significant difference in the disease-free survival rate between the SLNB only and complete ALN dissection groups who revealed a pathologic complete node response (79.6% versus 80.5%) and the rate of axillary recurrence demonstrated no significant differences among the groups. (p=0.225) There was a statistical difference of recurrence between group 1 versus 2, and group 1 versus 4 in hormone receptor-negative patients. (p=0.027) Conclusion SLNB after NAC in breast cancer patients with initial ALN metastasis may help identify downstaging to negative nodal status and thereby reduce the surgical morbidity by avoiding standard ALN dissection. Citation Format: Park S, Ryu JM, Paik H-J, Yi HW, Bae SY, Lee SK, Kil WH, Kim SW, Lee JE, Nam SJ. Sentinel lymph node biopsy alone after neoadjuvant chemotherapy in patients with cytologically proven node-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-08.

Abstract P5-09-17: Prognostic significance of progesterone receptor in hormonal receptor-positive breast cancer: Association with endocrine resistance

Background: Endocrine therapy has dramatic improvements of prognosis in patients with hormonal receptor positive breast cancer. However, long-term follow up shows that endocrine resistance is still major clinical concern. Although the value of estrogen receptor (ER) level can predict response to endocrine treatment in hormonal receptor positive breast cancers, few markers are available that can predict response to endocrine treatment. We attempted to identify molecular markers, especially progesterone receptor (PR), associated with endocrine failure in breast cancer. Methods: We reviewed the medical records of 2513 breast cancer patients who underwent breast surgery and endocrine therapy at Samsung Medical Center between March 2007 and July 2011. Patients were compared according to ER and PR expression and to assess the clinical and biological features of ER+positive/PR-negative breast cancers to understand how PR might be a useful marker of these activities. ER and PR expression accessed using Allred score, the ‘positive” was defined that total score is larger than 2. Results PR negative tumors were found more frequently in postmenopausal women (post- 11.2% vs. pre- 2.5%, P Conclusion: In HR positive breast cancers, PR negative tumors were found more frequently in elderly, postmenopausal women. However, PR negative tumors are shown more aggressive and poorer survival than PR positive tumors despite of endocrine therapy, especially in premenopausal women. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-09-17.

Abstract P2-18-04: No further axillary dissection in sentinel lymph node-negative breast cancer after neoadjuvant chemotherapy in patients with initial cytologically-proven axillary node metastasis

Background In patients with fine needle aspiration (FNA)-proven axillary lymph node metastasis at diagnosis (cN+), the current standard surgical procedure is axillary lymph node dissection (ALND) at definitive surgery after neoadjuvant chemotherapy (NAC). However, growing evidences suggest that SLNB after NAC is feasible and may demonstrate acceptable performance in selected patients. We performed sentinel lymph node biopsy in patients treated with cytologically-confirmed axillary lymph nodes metastases at presentation, who converted to a clinically negative axillary status after NAC (ycN0). Patients and methods We retrospectively evaluated 240 patients with invasive breast cancer with ultrasound-guided FNA-proven axillary nodal metastases at the time of diagnosis. All patients received NAC and underwent surgery at Samsung medical center between October 2007 and May 2013. Among these patients, 75 patients underwent SLNB. These patients converted to clinically node-negative disease (ycN0) after NAC on breast MRI or PET/CT scan. A combined detection technique was used with radioisotope and blue dye for the detection of SLN. Patients with negative SLN on frozen pathology and low clinical suspicion of metastasis during operation were not performed further ALND. Results The detection rate of SLNB was 93.3% (70/75), and median number of retrieved sentinel lymph nodes was 3.0 (range 1-8). False negative rate was 6.7% (1/15). Of these 75 patients, 35 (46.6%) patients had positive sentinel lymph nodes (ypN+) and underwent ALND. Thirty-five (46.6%) patients had tumor-free sentinel lymph nodes (ypN0sn) and 20 patients of them were followed without subsequent ALND. In these SLN-negative patients without further ALND, 9 patients were HER2-enriched subtypes and 9 patients, TNBC subtypes. Only two of them were Luminal B subtypes. The median follow-up period was 12.0 months (range 0-26 months) with 2 events; 1 regional recurrence in ipsilateral supraclavicular node and 1 systemic recurrence in brain on postoperative 7 months and 5 months, respectively. There has not occurred an ipsilateral axillary recurrence so far. Conclusions Although the follow-up was not long enough to conclude, this study tried to demonstrate that SLNB after NAC was feasible and further ALND may not be necessary in patients with SLN-negative disease (ypN0sn). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-04.

Abstract P3-11-01: Matched-pair analysis of patients with male and female breast cancer

Purpose: Male breast cancer (MBC) is extremely rare, accounting for less than 1% of all malignancies in men and only 1% of all breast carcinomas. The treatment and surveillance guidelines on male breast cancers are less recognized. The aim of this study is to evaluate our single institution9s experience with MBC over the past 15 years and to contrast differences between female and MBC. Methods: MBC diagnosed from 1994 to 2010 at the Department of Surgery, Samsung Medical Center (Seoul, Korea) was retrospectively analyzed. Clinical data and tumor characteristics were examined. Each MBC was matched with female counterparts by 1:N varied matching ratio that showed accordance in seven variables (year of diagnosis, age, tumor stage, nodal stage, tumor grade, estrogen receptor(ER), progesterone receptor(PR)). Results: 39 male/184 female matched-pairs were available for analysis. The median duration of follow-up was 3.8 years. The median age of MBC patients was 50 years and the median size of tumor was 2.0cm. The proportion of positivity of ER and PR status was 97.4% and 84.6%, respectively. Despite of higher positive rate of hormone receptor, the rate of hormone therapy in MBC patients was significant lower than female conterpart (p = 0.002). Men and women with breast cancer had similar disease-free survival (DFS) and disease-specific overall survival (DSS). Five MBC patients had a recurrence during follow up period and 4 of them were expired. The 10-years DFS was 73.1% in men and 80.5% in women (p = 0.348). The 10-years DSS was 74.1% in men and 87.1% in women, respectively (p = 0.207). Conclusion: This study showed no disease free and overall survival differences between male and female breast cancer patients and revealed that gender is no predictor for survival in breast cancer. Male patients receive obviously less adjuvant treatment compared their female matched patients. It would be better to do more aggressive treatment in MBC to improve the survival outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-11-01.