Sanghwa Kim

Prognostic Nomogram for Prediction of Axillary Pathologic Complete Response After Neoadjuvant Chemotherapy in Cytologically Proven Node-Positive Breast Cancer.

AbstractTo develop a nomogram predicting probability of axillary pathologic complete response (pCR) in patients with cytologically proven axillary node-positive breast cancer who received neoadjuvant chemotherapy (NAC).The current management of axillary intervention in node-positive breast cancer patients who received NAC is axillary lymph node dissection (ALND) regardless of axillary pCR.We reviewed the records of 415 patients with cytologically proven node-positive breast cancer that were treated with NAC followed by surgery between 2008 and 2012 at Severance Hospital, Yonsei University Health System. Baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were analyzed. A nomogram was developed using a binary logistic regression model with a training cohort and validated in an independent cohort of 110 patients.Axillary pCR was achieved in 38.8% of the patients who underwent ALND after NAC. Axillary pCR was associated with initial clinical nodal status, negative estrogen receptor status, positive human epidermal growth factor receptor 2 (HER2) status with trastuzumab, and clinical nodal and tumor responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (AUC 0.82, 95% CI, 0.78–0.86) and calibration fit. The nomogram was independently validated, indicating the good predictive power of the model (AUC 0.80, 95% CI, 0.72–0.88).Our nomogram might help predict axillary pCR after NAC in patients with initially node-positive breast cancer. Patients with a high probability of achieving axillary pCR could be spared ALND, avoiding postoperative morbidity.

No effect of tumor-infiltrating lymphocytes (TILs) on prognosis in patients with early triple-negative breast cancer: Validation of recommendations by the International TILs Working Group 2014.

The aim of this study was to examine the International TILs Working Group 2014 (IWG) recommendations for evaluating the clinical utility of tumor‐infiltrating lymphocytes (TILs) in patients with early triple‐negative breast cancer (TNBC).

Characteristics and Survival of Breast Cancer Patients with Multiple Synchronous or Metachronous Primary Cancers

Purpose Newly developed extra-mammary multiple primary cancers (MPCs) are an issue of concern when considering the management of breast cancer survivors. This study aimed to investigate the prevalence of MPCs and to evaluate the implications of MPCs on the survival of breast cancer patients. Materials and Methods A total of 8204 patients who underwent surgery at Severance Hospital between 1990 and 2012 were retrospectively selected. Clinicopathologic features and survival over follow-up periods of ≤5 and >5 years were investigated using univariate and multivariate analyses. Results During a mean follow-up of 67.3 months, 962 MPCs in 858 patients (10.5%) were detected. Synchronous and metachronous MPCs were identified in 23.8% and 79.0% of patients, respectively. Thyroid cancer was the most prevalent, and the second most common was gynecologic cancer. At ≤5 years, patients with MPCs were older and demonstrated significantly worse survival despite a higher proportion of patients with lower-stage MPCs. Nevertheless, an increased risk of death in patients with MPCs did not reach statistical significance at >5 years. The causes of death in many of the patients with MPCs were not related to breast cancer. Stage-matched analysis revealed that the implications of MPCs on survival were more evident in the early stages of breast disease. Conclusion Breast cancer patients with MPCs showed worse survival, especially when early-stage disease was identified. Therefore, it is necessary to follow screening programs in breast cancer survivors and to establish guidelines for improving prognosis and quality of life.

Comparisons of Oncologic Outcomes between Triple-Negative Breast Cancer (TNBC) and Non-TNBC among Patients Treated with Breast-Conserving Therapy.

Purpose The optimum local surgical strategy regarding breast-conserving therapy (BCT) for triple-negative breast cancer (TNBC) is controversial. To investigate whether BCT is appropriate for patients with TNBC, we evaluated the clinical outcomes of BCT in women with TNBC compared to those of women without TNBC, using a large, single-center cohort. Materials and Methods We performed a retrospective analysis of 1533 women (TNBC n=321; non-TNBC n=1212) who underwent BCT for primary breast cancer between 2000 and 2010. Clinicopathological characteristics, locoregional recurrence-free survival (LRFS), and overall survival (OS) were analyzed. Results Tumors from the TNBC group had a higher T stage (T2 37.4% vs. 21.0%, p<0.001), a lower N stage (N0 86.9% vs. 75.5%, p<0.001), and a higher histologic grade (Grade III 66.8% vs. 15.4%, p<0.001) than the non-TNBC group. There were no differences in 5-year LRFS rates between the TNBC and non-TNBC groups (98.7% vs. 97.8%, p=0.63). The non-TNBC group showed a slightly better 5-year OS than the TNBC group; however, the difference was not significant (96.2% vs. 97.3%, p=0.72). In multivariate analyses, TNBC was not associated with poor clinical outcomes in terms of LRFS and OS [hazard ratio (HR) for LRFS=0.37, 95% confidence interval (CI): 0.10–1.31; HR for OS=1.03, 95% CI: 0.31–3.39]. Conclusion TNBC patients who underwent BCT showed non-inferior locoregional recurrence compared to non-TNBC patients with BCT. Thus, BCT is an acceptable surgical approach in patients with TNBC.

Association Between Insulin Resistance and Luminal B Subtype Breast Cancer in Postmenopausal Women

AbstractCurrently, there is limited information on the clinical characteristics of breast cancer patients with insulin resistance. Hence, the purpose of this study was to investigate the association between insulin resistance and clinicopathological factors in newly diagnosed breast cancer patients without diabetes.We assessed 760 patients with breast cancer treated between 2012 and 2014. We compared the clinicopathological characteristics between patients with and without insulin resistance using univariate and multivariate analyses, including after stratification by menopausal status. Insulin resistance was defined according to the homeostatic model assessment of insulin resistance.Of 760 patients, 26.4% had insulin resistance. Age, menopausal status, body mass index, tumor size, histologic grade, Ki-67 expression, and breast cancer subtype significantly differed according to the presence of insulin resistance. Multivariate analysis revealed that postmenopausal status and obesity were significantly associated with insulin resistance. In postmenopausal women, older age, obesity, larger tumor size, advanced stage, and high proliferative luminal B subtype were significantly associated with insulin resistance. In contrast, in premenopausal patients, only obesity was related to insulin resistance. Multivariate analysis indicated that insulin resistance was independently correlated with obesity, larger tumor size, and the luminal B/human epidermal growth factor receptor-2-negative subtype in postmenopausal but not premenopausal patients.Insulin resistance was significantly associated with larger tumors and proliferative luminal B subtype breast cancer in postmenopausal women only. These findings suggest that insulin resistance could mechanistically induce tumor progression and might be a good prognostic factor, and that it could represent a therapeutic target in postmenopausal patients with breast cancer.

Preoperative Magnetic Resonance Imaging and Survival Outcomes in T1–2 Breast Cancer Patients Who Receive Breast-Conserving Therapy

Purpose The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. Methods A total of 954 patients who had T1–2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. Results Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. Conclusion Preoperative MRI did not influence survival outcomes in T1–2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1–2 breast cancer may not translate into longer RFS and OS.

Next-generation sequencing of BRCA1/2 in breast cancer patients: potential effects on clinical decision-making using rapid, high-accuracy genetic results

Purpose We evaluated the clinical role of rapid next-generation sequencing (NGS) for identifying BRCA1/2 mutations compared to traditional Sanger sequencing. Methods Twenty-four paired samples from 12 patients were analyzed in this prospective study to compare the performance of NGS to the Sanger method. Both NGS and Sanger sequencing were performed in 2 different laboratories using blood samples from patients with breast cancer. We then analyzed the accuracy of NGS in terms of variant calling and determining concordance rates of BRCA1/2 mutation detection. Results The overall concordance rate of BRCA1/2 mutation identification was 100%. Variants of unknown significance (VUS) were reported in two cases of BRCA1 and 3 cases of BRCA2 after Sanger sequencing, whereas NGS reported only 1 case of BRCA1 VUS, likely due to differences in reference databases used for mutation identification. The median turnaround time of Sanger sequencing was 22 days (range, 14–26 days), while the median time of NGS was only 6 days (range, 3–21 days). Conclusion NGS yielded comparably accurate results to Sanger sequencing and in a much shorter time with respect to BRCA1/2 mutation identification. The shorter turnaround time and higher accuracy of NGS may help clinicians make more timely and informed decisions regarding surgery or neoadjuvant chemotherapy in patients with breast cancer.

Risk Factors Associated with Discordant Ki-67 Levels between Preoperative Biopsy and Postoperative Surgical Specimens in Breast Cancers

Purpose The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values. Patients and Methods Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67–1.5 × interquartile range (IQR)] or (upper quartile + 1.5 × IQR) and were evaluated according to clinicopathological parameters by logistic regression analysis. Results The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15) and 10 (IQR, 25), respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676). Of 310 patients, 44 (14.2%) showed outliers of ΔKi-67 (range, ≤-20 or ≥28). A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR) expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9%) patients and a significant proportion of patients with discordant cases had ≥1 risk factor. Conclusion Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67 values should be cautious considering types of specimens and clinicopathological risk factors.

Abstract OT2-4-02: Testing BRCA 1/2 mutation using next generation sequencing (BRCANGS)

Testing BRCA 1/2 mutation is important for patients with breast cancer, and Sanger sequencing is a standard method to identify BRCA 1/2 mutation. Next generation sequencing (NGS) is a high-throughput parallel sequencing that can provide genetic information with high accuracy. NGS is a faster and cost-effective method to detect gene mutations compared to Sanger sequencing. This study is a prospective non-randomized obsevational study which evaluates the clinical role of NGS testing for BRCA 1/2 compared to Sanger sequencing. Eligibility criteria are wome aged 19 to 80 years, patients with breast or ovarian cancer history in 2nd degree family members, male breast cancer, bilateral breast cancer, patient with breast cancer under 40 year of age, simultaneous breast and ovarian cancer, patients with epithelial ovarian cancer, and breast cancer with other simultaneous extramammary malignancy. Primary endopont of the study is the overall accuracy of NGS compared to Sanger sequencing. Seconary endponts are sensitivity, specifcity, false negative, and false positive rates of NGS compared to Sanger method. Target accrual of the pilot study is 12 patients, and futher extension of patients accrual is scheduled after the anlaysis of the pilot study. This study is approved by institutial review board of Severance Hospital. The study is conducted and planned by Prof. HS Park, Yonsei University College of Medicine, Seoul, Korea and supported by Korea Breast Cancer Foundation. ClinicalTrials.gov identifier is NCT02151747. Citation Format: Hyung Seok Park, Seo Jin Park, Sanghwa Kim, Jegyu Ryu, Jee Ye Kim, Seho Park, Seung Il Kim, Joo Hyuk Sohn, Jong Rak Choi. Testing BRCA 1/2 mutation using next generation sequencing (BRCANGS) [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 OT2-4-02.

Abstract P1-01-12: Preoperative breast MRI does not affect survival outcomes in T1-2 breast cancer patients who underwent breast-conserving therapy

Purpose: The aim of the study is to evaluate the efficacy of preoperative breast MRI in T1-2 women with breast cancer. Methods: Total 1179 patients, who had T1-2 breast cancer and underwent definitive surgery between 2007 and 2010, were reviewed in this study. Preoperative breast MRI was performed in 981 women with breast cancer. We divided patients into two groups: Patients underwent preoperative MRI and breast-conserving therapy (BCT), those who did not undergo preoperative MRI but BCT. Patients underwent preoperative MRI and total mastectomy were excluded. Clinicopathological features were analyzed using Chi-square or Fisher’s exact test if indicated. Survival analyses were examined using Kaplan-Meier method and log-rank test. Cox-proportional hazard model was accessed as multivariate analysis. Results: In 873 patients who underwent BCT, 675 patients (77.3%) received preoperative MRI, and 198 (22.7%) patients did not. Clinicopathological features including T-stage, Nodal status, histologic type, progesterone receptor, histologic grade, age group (≤ 35 vs. > 35 yr), adjuvant chemotherapy, radiation, and hormone therapy were not significantly different between two groups. Patients aged 50 or younger received more preoperative MRI than those over aged 50 years (42.8 % vs. 51.5%, p=0.02). Estrogen receptor positive-tumors were more common in patients with preoperative MRI (74.9% vs. 67.2%, p=0.03). HER2 over-expression was frequently found in women without preoperative MRI (7.9% vs. 14.6%, p 0.05). ER was an independent prognostic factor for RFS and OS (all p Conclusions: Routine use of preoperative MRI in women with T1-2 breast cancer may not translate into better RFS and OS. Citation Format: Jegyu Ryu, Sanghwa Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Seung il Kim. Preoperative breast MRI does not affect survival outcomes in T1-2 breast cancer patients who underwent breast-conserving therapy [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 P1-01-12.