Jisun Kim

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer

The aim of this study was to determine the relationship between the body mass index (BMI) at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS) and breast-cancer-specific survival (BCSS) outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029), and BCSS (P = 0.013) in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48) and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99). In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19) and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44). Being underweight (BMI < 18.50 kg/m2) with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00–3.95) and BCSS (HR = 2.24, 95% CI = 1.12–4.47). There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.

Patient reporting pain intensity immediately after surgery can be associated with underlying depression in women with breast cancer.

The aims of this study were to determine the prevalence of severe, definite depression symptoms, as measured using the Center for Epidemiological Studies Depression Scale (CES‐D), and the association between high CES‐D scores (i.e., ≥25) and sociodemographic and perioperative factors during perioperative period.

Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy

Purpose The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers. Materials and Methods We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort. Results BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities. Conclusion We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.

Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer

Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) has been successful in treating a considerable proportion of patients with metastatic melanoma. In addition, some patients with several other solid tumors were recently reported to have benefited clinically from such ACT. However, it remains unclear whether ACT using TILs is broadly applicable in breast cancer, the most common cancer in women. In this study, the utility of TILs as an ACT source in breast cancers was explored by deriving TILs from a large number of breast cancer samples and assessing their biological potentials. We successfully expanded TILs ex vivo under a standard TIL culture condition from over 100 breast cancer samples, including all breast cancer subtypes. We also found that the information about the percentage of TIL and presence of tertiary lymphoid structure in the tumor tissues could be useful for estimating the number of obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a considerable level of central memory phenotype T cells (about 20%), and a large proportion of TIL samples were reactive to autologous tumor cells in vitro. Furthermore, the in vitro tumor-reactive autologous TILs could also function in vivo in a xenograft mouse model implanted with the primary tumor tissue. Collectively, these results strongly indicate that ACT using ex vivo expanded autologous TILs is a feasible option in treating patients with breast cancer.

BRCA1/ 2-negative, high-risk breast cancers ( BRCAX ) for Asian women: genetic susceptibility loci and their potential impacts

Abstract“BRCAX” refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci and their potential impacts on preventive strategy. We performed a genome-wide association study involving 1,469 BRCAX cases from the Korean Hereditary Breast Cancer study, and high-risk breast cancer cases (1,482 Asians and 9,902 Europeans) from the Breast Cancer Association Consortium. We also evaluated the previously reported susceptibility loci for their roles in the high-risk breast cancers. We have identified three novel loci (PDE7B, UBL3, and a new independent marker in CDKN2B-AS1) associated with BRCAX, and replicated previously reported SNPs (24 of 92) and moderate/high-penetrance (seven of 23) genes for Korean BRCAX. For the novel candidate loci, evidence supported their roles in regulatory function. We estimated that the common low-penetrance loci might explain a substantial part of high-risk breast cancer (39.4% for Koreans and 24.0% for Europeans). Our study findings suggest that common genetic markers with lower penetrance constitute a part of susceptibility to high-risk breast cancers, with potential implications for a more comprehensive genetic screening test.

Chronological Improvement in Survival of Patients with Breast Cancer: A Large-Scale, Single-Center Study

Purpose This study aimed to chronologically evaluate survival of patients with breast cancer in Korea and investigate the observed changes during the last 20 years. We also sought to determine factors that may influence outcomes and changes in the duration of survival over time. Methods We retrospectively analyzed a total of 10,988 patients with breast cancer who were treated at our institution between January 1993 and December 2008. We divided the study period into three periods (P1, 1993–1997; P2, 1998–2002; and P3, 2003–2008). We retrospectively reviewed the collected data from the Asan database, including age at diagnosis, clinical manifestations, pathology report, surgical methods, types of adjuvant treatment modalities, type of recurrence, and follow-up period. Results At a median follow-up of 8.2 years, we observed that survival outcomes have improved recently. The 5-year breast cancer-specific survival (BCSS) rate also increased from 82.8% in P1 to 92.6% in P3 (p<0.001). The survival rate in patients with tumors at each stage increased in similar patterns in all patients, and, remarkably, there was a significant survival improvement in patients with stage III breast cancer (P1 vs. P3: 5-year BCSS, 57.4% vs. 80.0%, p<0.001). The time period was a significant prognostic factor in multivariate analysis (P1 vs. P2: hazard ratio [HR], 0.83, p=0.035; P1 vs. P3: HR, 0.75, p=0.015). Conclusion The study results suggest an improvement in breast cancer survival in Korea, which is consistent with the development of treatments and early detection.

Comparing Accuracy of Mammography and Magnetic Resonance Imaging for Residual Calcified Lesions in Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy

Background Neoadjuvant systemic therapy (NST) is performed to increase the rate of breast‐conserving surgery in advanced breast cancer patients. Although magnetic resonance imaging (MRI) is accurate in predicting residual cancer, if calcification remains, the issue of whether to perform the surgery on the basis of the residual tumor prediction range in mammography (MMG) or MRI has not yet been elucidated. This study aimed to estimate the accuracy of predicting residual tumor after NST for residual microcalcification on mammographic and enhancing lesion on MRI. Patients and Methods This was a single‐center, retrospective study. We included breast cancer patients who underwent NST, had microcalcifications in the post‐NST MMG, and underwent surgery from January 2, 2013 to December 30, 2014 at Asan Medical Center. Patients with post‐NST MMG as well as MRI were included. Final pathologic tumor size with histopathology and biomarker status were obtained postoperatively. Results In total, 151 patients were included in this study. Overall, MRI correlated better than MMG in predicting the tumor size (intraclass correlation coefficient [ICC], 0.769 vs. 0.651). For hormone receptor (HR)‐positive (HR+)/HER2− subtype, MMG had higher correlation than MRI (ICC = 0.747 vs. 0.575). In HR− subtype, MRI had a strong correlation with pathology (HR−/HER2+ or triple negative (TN), ICC = 0.939 vs. 0.750), whereas MMG tended to overestimate the tumor size (HR−/HER2+ or TN, ICC = 0.543 vs. 0.479). Conclusion Post‐NST residual microcalcifications on MMG have a lower correlation with residual tumor size than MRI. Other than HR+/HER2− subtype, the extent of calcifications on preoperative evaluation might not be accurate in evaluating the residual extent of the tumor after NST. Micro‐Abstract In breast cancer, the extent of the malignant‐looking calcification usually does not decrease after neoadjuvant systemic treatment, making it difficult to know the extent of the tumor in surgical planning. Comparing different imaging tools for such cases, magnetic resonance imaging was shown to be more precise in predicting residual cancer, especially in the hormone receptor‐negative subtype.

No Association of Positive Superficial and/or Deep Margins with Local Recurrence in Invasive Breast Cancer Treated with Breast-Conserving Surgery

Purpose We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy. Materials and Methods In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed. Results Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57). Conclusion Superficial and/or deep margin involvement following BCS is not an important predictor for LR.

Simple Age Specific Cutoff Value for Sarcopenia Evaluated by Computed Tomography

Objective: Until now, cutoff values of low skeletal muscle mass using computed tomography (CT) were driven by optimal stratification to predict mortality in cancer patients. The aim of the present study was to investigate the simple, age-specific, cutoff value of low skeletal muscle mass by CT in healthy adults. Design: This is a retrospective, observational, single-center study. Setting: This study was performed in the health screening department of a university-affiliated hospital during a 10-year period. Patients: Medical records of 1,422 patients presenting to the health screening department were reviewed. Cross-sectional area of psoas muscle at the level of the third lumbar vertebra on abdominal CT was measured and adjusted by height (mm²/m²). This value (psoas muscle index [PMI]) was assumed to represent whole skeletal muscle mass. We divided the patients according to age, sex, and defined cutoff value of low skeletal muscle mass as 2 SDs below the mean. Intervention: None. Measurements and Main Results: Among 1,422 patients, 550 patients (38.6%) were male. The mean PMI was 896.60 (mm²/m²) for men and 570.54 (mm²/m²) for women. Cutoff values of PMI for men were 592.3 mm²/m² for 20-39 years, 474.0 mm²/m² for 40-49 years, 422.2 mm²/m² for 50-59 years, 374.4 mm²/m² for 60-69 years, and 331.5 mm²/m² for 70-89 years. The values for women were 399.9 mm²/m² for 20-39 years, 287.7 mm²/m² for 40-49 years, 242.5 mm²/m² for 50-59 years, 220.4 mm²/m² for 60-69 years, and 147.6 mm²/m² for 70-89 years. Conclusions: Cutoff values of low skeletal muscle mass using CT differed in healthy adults as age increased. Further studies on the effect of sarcopenia intervention using this cutoff value are needed.

Abstract P5-10-10: Effect of prolonged cold ischemic time on immunohistochemical testing of estrogen receptor, progesterone receptor and HER2 expression in breast cancer

Background: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the most important predictive and prognostic biomarkers in breast cancer. The American Society of Clinical Oncology/College of American Pathologists recommends that the time from tumor removal to fixation (cold ischemic time) should be kept within 1 hour. Through this study we mean to review the actual cold ischemic time in real practice and analyze whether delayed formalin fixation effects immunohistochemical (IHC) testing results. Methods: Patients, who received surgery for invasive or in situ breast cancer in Seoul National University Hospital, Seoul, Korea between February and December 2013, were retrospectively reviewed. Cold ischemic time was calculated by extracting the time of formalin fixation from the time when surgery ended. All patients were equally divided into two groups (short ischemic group, long ischemic group) according to median cold ischemic time. Chi-square test was done for ER and PR positive/negative (0% negative, ≥1% positive) and student t-test was done for ER and PR percentage. Also χ 2 test was done for HER2 positive/negative and scoring system ranging from 0 to 3+. Results: A total of 615 patients were included in this study. The median cold ischemic time was 2h 43min 4sec (range 6min 36sec – 84h 26min 20sec). Only 48 patients had a cold ischemic time shorter than 1 hour. No association between ER, PR expression and cold ischemic time was found in the χ 2 test (p=0.581, p=0.954) and student t-test (p=0.648, p=0.978). As for HER2 expression, in the long ischemic group, there were significantly more patients with positive immunohistochemical testing results (χ 2 test, p=0.016), and significantly higher grades in HER2 scoring system (χ 2 test, p=0.022). Compared to IHC results, FISH testing for HER2 amplification showed no significant difference (χ 2 test, n=145, p=0.500). This tendency was persisted when patients were divided into four groups by 25 quartile of cold ischemic time. Conclusions: Our findings show that the actual cold ischemic time in practice is longer than recommended guidelines. Despite that, ER, PR expression was not associated with cold ischemic time. As for HER2 expression, longer cold ischemic time was associated with more HER2 positive and higher HER2 score. But this tendency was not showed in FISH testing for HER2 amplification. Citation Format: Tae-Kyung Yoo, Hyeong-Gon Moon, Jisun Kim, Jun Woo Lee, Min Kyoon Kim, Eunshin Lee, Jongjin Kim, Wonshik Han, In-Ae Park, Dong-Young Noh. Effect of prolonged cold ischemic time on immunohistochemical testing of estrogen receptor, progesterone receptor and HER2 expression in 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 P5-10-10.