Yun-Gyoung Kim

In Vivo Tumor Growth Rate Measured by US in Preoperative Period and Long Term Disease Outcome in Breast Cancer Patients

Objective The aim of our study was to evaluate the effect of tumor growth rate, calculated from tumor size measurements by US, on breast cancer patients’ outcome. Patients and Methods Breast cancer patients who received at least two serial breast ultrasonographies (US) in our institution during preoperative period and were surgically treated between 2002 and 2010 were reviewed. Tumor growth rate was determined by specific growth rate (SGR) using the two time point tumor sizes by US. Results A total of 957 patients were analyzed. The median duration between initial and second US was 28 days (range, 8–140). The median initial tumor size was 1.7cm (range, 0.4–7.0) and median second size was 1.9cm (range, 0.3–7.2). 523(54.6%) cases had increase in size. The median SGR(x10-2) was 0.59 (range, -11.90~31.49) and mean tumor doubling time was 14.51 days. Tumor growth rate was higher when initial tumor size was smaller. Lymphovascular invasion, axillary lymph node metastasis, and higher histologic grade were significantly associated with higher SGR. SGR was significantly associated with disease-free survival (DFS) in a univariate analysis (p = 0.04), but not in a multivariate Cox analysis (p>0.05). High SGR was significantly associated with worse DFS in a subgroup of initial tumor size >2cm (p = 0.018), but not in those with tumor size <2cm (p>0.05). Conclusion Our results showed that tumor growth rate measured by US in a relatively short time interval was associated with other worse prognostic factors and DFS, but it was not an independent prognostic factor in breast cancer patients.

Abstract P2-03-18: Discovery of novel amplified genes in primary breast cancer with copy number and gene expression analysis of whole exome and transcriptome sequencing data

Introduction: Copy number alteration of genome is common in breast cancer and tend to have more driver role than single point mutations. Traditionally, genome-wide analysis of DNA copy number changes were done by array CGH or SNP array method. Here, we did DNA whole exome sequencing (WES) and RNA-seq using Next Generation Sequencing (NGS) technology to find common genes or chromosomal regions of which DNA copy was highly amplified and at the same time RNA expression was also upregulated. Materials and Method: RNA and DNA were extracted fromfresh frozen tissues of 93 breast cancer patients. WES and RNA-seq were done using NGS technology (Illumina HiSeq 2000). As a control, normal DNA from all matched patients were also sequenced. GATK was used to gain mean depth and coverage data for targeted regions.CNVs were calculated with ExomeCNV, a statistical method to detect somatic CNVs using depth-of-coverage information from mapped short sequence reads.To estimate expression levels, the relative transcript abundances were measured in FPKM using Cufflinks. Results and Discussion: DNA of 1,737 genes were highly amplified (log R>1.0) in two or more samples. The two most commonly amplified chromosomes were chromosome 8 and 17. We applied a cut-off for higher gene expression as relative FPKM >1.5. ERBB2 amplifications and high expression were most common (21.5%) of all genes and it was in agreement withHER-2 IHC and FISH result. Among previously reported amplified genes, FGFR1 (5.4%) and PVT1 (8.6%) in chromosome 8, CCND1 , PAK1 (3.2%) and EMSY (4.3%) in chromosome 11, CCNE1 (4.3%) in chromosome 19 were also identified in this study. IGF1R high amplification and expression was found in two samples, and ESR1 , MDM2 , KIT was found in only one sample each. We found uncommon but novel and recurrent highly amplified and expressed genes: CLK4 in 5q (3.2%), AHI / MYB in 6q (3.2%), MMP7 (2.2%) and MALAT1 in 11q (1.1%), and NEK8 in 17q (4.3%) We designed FISH probe for this 5 new genes and confirmed the high amplifications in each sample with FISH. Functional study of these genes will be followed for the driver role of these genes in carcinogenesis and progression of breast cancer cells. Citation Format: Eunshin Lee, Woosung Lim, Kyung-Min Lee, Tae-kyung Yoo, Jongjin Kim, Han-Byoel Lee, Yun-Gyoung Kim, YoungJoon Kang, Min Kyoon Kim, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han Han. Discovery of novel amplified genes in primary breast cancer with copy number and gene expression analysis of whole exome and transcriptome sequencing data [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-03-18.

Abstract P2-05-07: Feasibility and sensitivity of fine-needle aspiration biopsies for the detection of somatic mutations using next-generation sequencing in breast cancer

Background/Purpose: Next-generation sequencing (NGS) is being incorporated rapidly into clinical practice. Fine-needle aspiration biopsy (FNAB) specimens have been used feasibly in molecular analysis including direct sequencing and microarrays. They are readily available and enriched in malignant cells, thus providing opportunities for genomic analysis for more clinical samples. In this study, we assessed the feasibility and sensitivity of FNAB for the detection of somatic mutations by NGS compared to bulk tissue. Methods: Bulk tissue and FNAB was sampled via skin superficial to the palpable tumor from surgically resected breast cancer specimen. DNA was extracted from the bulk tissues and FNAB samples obtained from twelve patients. Somatic mutations detected from whole exome sequencing (WES) by next-generation sequencing (NGS) (HiSeq 2500, Illumina) were analyzed for corresponding pairs of bulk tissue and FNAB. Verification of somatic mutations detected exclusively from FNAB and known to be clinically relevant to breast cancer was carried out by Sanger sequencing. Invasive tumor percentages of bulk tissues were evaluated using hematoxylin and eosin (HE San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-07.

Abstract P1-12-13: Factors associated with adherence to adjuvant endocrine therapy in patients with hormone receptor positive breast cancer

Background/Purpose Adjuvant endocrine therapy in patients with hormone receptor positive breast cancer reduces recurrence and mortality, but many patients are non-adherent to anti-hormonal medication. In order to increase the adherence, it is important to know about factors associated with adherence. So we investigated factors associated with adherence to anti-hormonal medication using variable questionnaires. Methods We carried out a cross-sectional survey of a sample of women who underwent surgery due to breast cancer in the Seoul National University Hospital Breast Care Center from 2007 to 2011 and treated with anti-hormonal medication. Questionnaires were sent to 1,000 patients. The questionnaire booklet included the Medication Adherence Report Scale-5(MARS-5), Women’s Health Questionnaire(WHQ), Beliefs about Medicine Questionnaire(BMQ), Satisfaction with Information about Medicines Scale(SIMS). And to identify patient’s clinical characteristics, we reviewed electronic medical records, retrospectively. Result The response rate of questionnaire was 40.8%(408/1000). Of the answered patients, 263 patients were treated with tamoxifen and 145 patients were treated with aromatase inhibitors(AIs). 197 of 408 answered patients(48.3%) were classified as non-adherence. The rate of non-adherence was 132/263(50.1%) and 65/145(44.8%) in patients treated with tamoxifen and AIs. Of the all answered patients, non-adherent patients had more depressed mood (p Conclusion This study showed associations between depressive mood of breast cancer patients treated with anti-hormonal therapy and adherence. And beliefs and satisfaction with information about medication also associated with adherence. To improve adherence, we should evaluate and correct patient’s mood. And we should provide proper information about medications. Citation Format: Jongjin Kim, Wonshik Han, Hyeong-Gon Moon, Min Kyoon Kim, Eunshin Lee, Tae-Kyung Yoo, Han-Byoel Lee, Young Joon Kang, Yun-Gyoung Kim, Tae Ryung Kim, Dong Young Noh. Factors associated with adherence to adjuvant endocrine therapy in patients with hormone receptor positive breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-13.

Abstract P1-12-07: Characteristics of recurrence after completing adjuvant tamoxifen therapy for 5 years

Background Treatment with tamoxifen (TMX) reduces the recurrence rate and increase overall survival in patients with hormone receptor positive breast cancer. Up to now, 5-year TMX therapy is generally accepted, but it is demonstrated that the rate of late recurrence after 5 years is considerably higher in hormone receptor positive type than in other subtype. Several clinical trials such as ATLAS and aTTom showed the benefit of continuing tamoxifen up to 10 years instead of stopping at 5 years without increasing mortality due to the effect of extended tamoxifen medication. Method We collected data of 1633 hormone receptor positive breast cancer patients who received surgery at Seoul National University Hospital from 1997 to 2007, and had completed 5-year TMX therapy with no recurrence within 5 years after diagnosis. Mean age of the patients was 43.3, and the patients have estrogen receptor or progesterone receptor. We included from the stage I to stage IV patients underwent curative surgery and received adequate adjuvant therapy such as chemotherapy or radiation therapy after surgery. We excluded the cases treated aromatase inhibitor (AI) or switched to AI. Result Among these patients, recurrences after 5 years of TMX therapy were found in 93 patients (late recurrence group). Local recurrences and distant metastases were found in 43 and 50 patients, respectively. Electronic medical records were retrospectively reviewed for clinicopathological factors. When comparing between patients with no recurrence and patients with late recurrence, p53 and HER-2 expression were significantly related to late recurrence (p=0.01, p Conclusion our data shows that p53 and HER-2 expression is associated to late recurrence and especially HER-2 expression is related to distant metastasis after completing TMX for 5 years. On the basis of the result of large clinical trials, extending TMX therapy significantly reduces recurrence rate and increase survival. Our result support continuing TMX in patients with HER-2 expression and high nuclear grade is considerable after 5 years of TMX medication. Citation Format: Eunshin Lee, Han-Byoel Lee, Young Joon Kang, Yun-Gyoung Kim, Tae-kyung Yoo, Jongjin Kim, Min Kyoon Kim, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han. Characteristics of recurrence after completing adjuvant tamoxifen therapy for 5 years [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-07.