Young Joon Kang

Risk Factors Associated with Distant Metastasis and Survival Outcomes in Breast Cancer Patients with Locoregional Recurrence

Purpose To decide the optimal treatment for breast cancer patients with locoregional recurrence (LRR), it is important to determine which group has the highest risk of subsequent distant metastasis (DM). We aimed to investigate the factors associated with DM in patients with LRR. Methods We reviewed the data of 208 patients with LRR as the first event after primary surgery for breast cancer at our institution between 1997 and 2010, to identify significant factors associated with DM. Subsequently, Kaplan-Meier curves and the Cox regression method were used to analyze the correlation between clinical factors and survival. Results DM occurred in 33.2% (68/208) of LRR patients. The median DM-free interval was 23 months. Some clinical factors were associated with DM in univariate analysis, including the type of primary surgery (p=0.026), tumor size (p=0.005), nodal status (p=0.011), and administration of initial adjuvant chemotherapy (p=0.001). In addition, regional rather than local recurrence and a disease-free interval (DFI; duration between primary surgery and LRR) ≤30 months were also significant (p<0.001 for both). However, only a shorter DFI reached significance in multiple logistic regression analysis. Cox regression analysis of DM-free survival showed that both a shorter DFI and regional recurrence were significant factors with hazard ratios of 2.1 (95% confidence interval [CI], 1.21-3.65) and 1.85 (95% CI, 1.04-3.28), respectively. Conclusion DFI was the most important factor associated with subsequent DM in patients with LRR as a first event of failure.

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.

Can We Skip Intraoperative Evaluation of Sentinel Lymph Nodes? Nomogram Predicting Involvement of Three or More Axillary Lymph Nodes before Breast Cancer Surgery

Purpose The American College of Surgeons Oncology Group Z0011 trial reported that complete dissection of axillary lymph nodes (ALNs) may not be warranted in women with clinical T1-T2 tumors and one or two involved ALNs who were undergoing lumpectomy plus radiation followed by systemic therapy. The present study was conducted to identify preoperative imaging predictors of ≥ 3 ALNs. Materials and Methods The training set consisted of 1,917 patients with clinical T1-T2 and node negative invasive breast cancer. Factors associated with ≥ 3 involved ALNs were evaluated by logistic regression analysis. The validation set consisted of 378 independent patients. The nomogram was applied prospectively to 512 patients who met the Z0011 criteria. Results Of the 1,917 patients, 204 (10.6%) had ≥ 3 positive nodes. Multivariate analysis showed that involvement of ≥ 3 nodes was significantly associated with ultrasonographic and chest computed tomography findings of suspicious ALNs (p < 0.001 each). These two imaging criteria, plus patient age, were used to develop a nomogram calculating the probability of involvement of ≥ 3 ALNs. The areas under the receiver operating characteristic curve of the nomogram were 0.852 (95% confidence interval [CI], 0.820 to 0.883) for the training set and 0.896 (95% CI, 0.836 to 0.957) for the validation set. Prospective application of the nomogram showed that 60 of 512 patients (11.7%) had scores above the cut-off. Application of the nomogram reduced operation time and cost, with a very low re-operation rate (1.6%). Conclusion Patients likely to have ≥ 3 positive ALNs could be identified by preoperative imaging. The nomogram was helpful in selective intraoperative examination of sentinel lymph nodes.

The treatment outcomes and the use of adjuvant therapies in breast cancer patients with severe co-morbidities

Purpose Studies have suggested a potential role of patient’s co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies. Methods The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. Results There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA I, II, and III, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA I, II and III group, respectively, p<0.001). The ASA 3 patients also showed significantly higher rate of breast cancer recurrence when compared to other groups (180 (10.0%), 80 (12.0%) and 9 (20.5%) in ASA I, II, and III, respectively, p = 0.041). Significantly fewer patients in the high co-morbidity group received adjuvant therapies (77 (4.3%), 44 (6.6%) and 8 (18.2%) in ASA I, II, and III, respectively, p<0.001). The increased recurrence of breast cancer in the high morbidity group was mostly seen in patients who did not receive adjuvant therapies. The incidence of serious adverse effect during the adjuvant therapy did not differ according to the co-morbidity conditions. Conclusions In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high co-morbidity group was mostly seen in patients who did not receive adjuvant therapies. Considering the relatively low rates of serious adverse effects in high co-morbidity patients who received adjuvant therapies, active use of adjuvant therapies in selected patients may improve survival outcomes in breast cancer patients with severe co-morbidities.

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.