The Clinical Impact of Body Mass Index on Breast Cancer in Korea: A Nationwide Population-Based Cohort Study

Purpose@#Although increasing body mass index (BMI) is regarded as a potential risk factor for breast cancer (BC) in postmenopausal women, research on premenopausal women has produced conflicting results. We investigated the association between BMI and BC according to menopausal status in Korean. @*Methods@#We analyzed clinical data from 186,835 women aged 20 years or older between 2003 and 2008 using a sample cohort from the national database in Korea. We identified women newly diagnosed with BC and estimated the risk of BC according to BMI (kg/m2). Subjects were categorized into five groups according to World Health Organization recommendations for Asians: underweight, <18.5 kg/m2; normal weight, 18.5–22.9 kg/m2; overweight, 23.0–24.9 kg/m2; obese class I, 25.0–29.9 kg/m2; and obese class II, ≥30.0 kg/m2. @*Results@#1,372 women in the cohort were newly diagnosed with BC. A positive relationship between BMI and BC was detected and the hazard ratio in each group compared with the normal weight group was 0.57 (95% CI, 0.42–0.78), 1.27 (1.11–1.45), 1.25 (1.09–1.44), and 1.28 (0.95–1.73), respectively. BMI was determined to be an important risk factor for BC in postmenopausal women (p for trend was 0.015). We failed to find a significant correlation between BMI and BC in premenopausal women. @*Conclusion@#BMI is positively associated with BC in postmenopausal Korean women.

Current Practices toward Fertility Issues for Young Breast Cancer Patients: A Survey of the Korean Breast Cancer Society; The SMARTSHIP Study

Purpose@#This study aimed to investigate and analyze the current fertility-related practices for breast cancer patients; the results are intended to help improve the quality of life of young patients and survivors. @*Methods@#This study collected voluntary responses to a questionnaire that was used to survey Korean breast cancer specialists. The questionnaire consisted of five categories: knowledge, practice behaviors regarding fertility preservation, barriers to discussing fertility preservation, attitude toward fertility issues, and demographics and medical background. @*Results@#A total of 120 copies of the questionnaire were distributed; the response rate was 89%. The section of the questionnaire regarding knowledge indicated that most respondents had adequate fertility preservation knowledge for cancer patients. However, 13.1% of the respondents indicated that they thought pregnancy increased the cancer recurrence risk. Respondents’ knowledge and attitudes about fertility preservation were not correlated with actual practice. The absence of patient’s expressions (24.30%), high recurrence risk (27.10%), insufficient time in the clinic (21.50%), and hospital conditions such as no reproductive specialists or infertility clinic (16.82%), were considered major barriers to discussing fertility issues. @*Conclusion@#Although more than 50% of the respondents thought that cancer treatment is more important than fertility preservation and it is complex and difficult, the Korean breast surgical oncologists were generally encouraging when discussing fertility issues with young breast cancer patients. Hence, breast clinicians should share with young patients the updated evidence regarding the feasibility and safety of pregnancy after cancer treatment and the available options so that the best decisions can be made.

Current Practices toward Fertility Issues for Young Breast Cancer Patients: A Survey of the Korean Breast Cancer Society; The SMARTSHIP Study

Purpose@#This study aimed to investigate and analyze the current fertility-related practices for breast cancer patients; the results are intended to help improve the quality of life of young patients and survivors. @*Methods@#This study collected voluntary responses to a questionnaire that was used to survey Korean breast cancer specialists. The questionnaire consisted of five categories: knowledge, practice behaviors regarding fertility preservation, barriers to discussing fertility preservation, attitude toward fertility issues, and demographics and medical background. @*Results@#A total of 120 copies of the questionnaire were distributed; the response rate was 89%. The section of the questionnaire regarding knowledge indicated that most respondents had adequate fertility preservation knowledge for cancer patients. However, 13.1% of the respondents indicated that they thought pregnancy increased the cancer recurrence risk. Respondents’ knowledge and attitudes about fertility preservation were not correlated with actual practice. The absence of patient’s expressions (24.30%), high recurrence risk (27.10%), insufficient time in the clinic (21.50%), and hospital conditions such as no reproductive specialists or infertility clinic (16.82%), were considered major barriers to discussing fertility issues. @*Conclusion@#Although more than 50% of the respondents thought that cancer treatment is more important than fertility preservation and it is complex and difficult, the Korean breast surgical oncologists were generally encouraging when discussing fertility issues with young breast cancer patients. Hence, breast clinicians should share with young patients the updated evidence regarding the feasibility and safety of pregnancy after cancer treatment and the available options so that the best decisions can be made.

Risk Factors for a False-Negative Result of Sentinel Node Biopsy in Patients with Clinically Node-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although sentinel lymph node biopsy (SLNB) can accurately represent the axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the main concern in the patients who receive SLNB alone instead of ALN dissection (ALND). MATERIALS AND METHODS: We analyzed 1,886 patientswho underwent ALND after negative results of SLNB, retrospectively. A logistic regression analysis was used to identify risk factors associated with a false-negative (FN) result. Cox regression model was used to estimate the hazard ratio of factors affecting disease-free survival (DFS). RESULTS: Tumor located in the upper outer portion of the breast, lymphovascular invasion, suspicious node in imaging assessment and less than three sentinel lymph nodes (SLNs) were significant independent risk factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to 4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI, 1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative group (FN and true-negative), but in ALN-positive group (FN and true-positive), FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS. CONCLUSION: In patients with risk factors for a FN such as suspicious node in imaging assessment, upper outer breast cancer, less than three harvested nodes, we need attention to find another metastatic focus in non-SLNs during the operation. It may contribute to provide an exact prognosis and optimizing adjuvant treatments.

Ex Vivo Shear-Wave Elastography of Axillary Lymph Nodes to Predict Nodal Metastasis in Patients with Primary Breast Cancer / 한국유방암학회지

PURPOSE: There is still a clinical need to easily evaluate the metastatic status of lymph nodes during breast cancer surgery. We hypothesized that ex vivo shear-wave elastography (SWE) would predict precisely the presence of metastasis in the excised lymph nodes. METHODS: A total of 63 patients who underwent breast cancer surgery were prospectively enrolled in this study from May 2014 to April 2015. The excised axillary lymph nodes were examined using ex vivo SWE. Metastatic status was confirmed based on the final histopathological diagnosis of the permanent section. Lymph node characteristics and elasticity values measured by ex vivo SWE were assessed for possible association with nodal metastasis. RESULTS: A total of 274 lymph nodes, harvested from 63 patients, were examined using ex vivo SWE. The data obtained from 228 of these nodes from 55 patients were included in the analysis. Results showed that 187 lymph nodes (82.0%) were nonmetastatic and 41 lymph nodes (18.0%) were metastatic. There was significant difference between metastatic and nonmetastatic nodes with respect to the mean (45.4 kPa and 17.7 kPa, p<0.001) and maximum (55.3 kPa and 23.2 kPa, p<0.001) stiffness. The elasticity ratio was higher in the metastatic nodes (4.36 and 1.57, p<0.001). Metastatic nodes were significantly larger than nonmetastatic nodes (mean size, 10.5 mm and 7.5 mm, p<0.001). The size of metastatic nodes and nodal stiffness were correlated (correlation coefficient of mean stiffness, r=0.553). The area under curve of mean stiffness, maximum stiffness, and elasticity ratio were 0.794, 0.802, and 0.831, respectively. CONCLUSION: Ex vivo SWE may be a feasible method to predict axillary lymph node metastasis intraoperatively in patients undergoing breast cancer surgery.

Local Control of Brain Metastasis: Treatment Outcome of Focal Brain Treatments in Relation to Subtypes / 한국유방암학회지

PURPOSE: To investigate treatment options for local control of metastasis in the brain, we compared focal brain treatment (FBT) with or without whole brain radiotherapy (WBRT) vs. WBRT alone, for breast cancer patients with tumor relapse in the brain. We also evaluated treatment outcomes according to the subtypes. METHODS: We conducted a retrospective review of breast cancer patients with brain metastasis after primary surgery. All patients received at least one local treatment for brain metastasis. Surgery or stereotactic radiosurgery was categorized as FBT. Patients were divided into two groups: the FBT group received FBT+/-WBRT, whereas the non-FBT group received WBRT alone. Subtypes were defined as follows: hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative (TN). We examined the overall survival after brain metastasis (OSBM), brain metastasis-specific survival (BMSS), and brain metastasis-specific progression-free survival (BMPFS). RESULTS: A total of 116 patients were identified. After a median follow-up of 50.9 months, the median OSBM was 11.5 months (95% confidence interval, 9.0-14.1 months). The FBT group showed significantly superior OSBM and BMSS. However, FBT was not an independent prognostic factor for OSBM and BMSS on multivariate analyses. In contrast, multivariate analyses showed that patients who underwent surgery had improved BMPFS, indicating local control of metastasis in the brain. FBT resulted in better BMPFS in patients with HR-negative/HER2-positive cancer or the TN subtype. CONCLUSION: We found that patients who underwent surgery experienced improved local control of brain metastasis, regardless of its extent. Furthermore, FBT showed positive results and could be considered for better local control of brain metastasis in patients with aggressive subtypes such as HER2-positive and TN.

A clinicogenetic model to predict lymph node invasion by use of genome-based biomarkers from exome arrays in prostate cancer patients

PURPOSE: Genetic variations among prostate cancer (PCa) patients who underwent radical prostatectomy (RP) and pelvic lymph node dissection were evaluated to predict lymph node invasion (LNI). Exome arrays were used to develop a clinicogenetic model that combined clinical data related to PCa and individual genetic variations. MATERIALS AND METHODS: We genotyped 242,186 single-nucleotide polymorphisms (SNPs) by using a custom HumanExome BeadChip v1.0 (Illumina Inc.) from the blood DNA of 341 patients with PCa. The genetic data were analyzed to calculate an odds ratio as an estimate of the relative risk of LNI. We compared the accuracies of the multivariate logistic model incorporating clinical factors between the included and excluded selected SNPs. The Cox proportional hazard models with or without genetic factors for predicting biochemical recurrence (BCR) were analyzed. RESULTS: The genetic analysis indicated that five SNPs (rs75444444, rs8055236, rs2301277, rs9300039, and rs6908581) were significant for predicting LNI in patients with PCa. When a multivariate model incorporating clinical factors was devised to predict LNI, the predictive accuracy of the multivariate model was 80.7%. By adding genetic factors in the aforementioned multivariate model, the predictive accuracy increased to 93.2% (p=0.006). These genetic variations were significant factors for predicting BCR after adjustment for other variables and after adding the predictive gain to BCR. CONCLUSIONS: Based on the results of the exome array, the selected SNPs were predictors for LNI. The addition of individualized genetic information effectively enhanced the predictive accuracy of LNI and BCR among patients with PCa who underwent RP.

Metastasis-Free Interval Is Closely Related to Tumor Characteristics and Has Prognostic Value in Breast Cancer Patients with Distant Relapse / 한국유방암학회지

PURPOSE: We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. METHODS: We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short ( or =2 years and or =5 years). Overall survival after metastasis (OSM) was estimated. RESULTS: Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer. CONCLUSION: MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy.

Prospective Evaluation of the Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Negative Axillary Conversion after Neoadjuvant Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. 18Fluorodeoxyglucose-positron emission tomography (18F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both 18F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both 18F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.

Survival Benefit of Zoledronic Acid in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitors / 한국유방암학회지

PURPOSE: A growing body of evidence indicates that zoledronic acid (ZA) can improve the clinical outcome in patients with breast cancer and low estrogen levels. In the present study, we aimed to investigate the survival benefit of ZA administration in postmenopausal Korean women with breast cancer who were also receiving aromatase inhibitors. METHODS: Between January 2004 and December 2010, 235 postmenopausal breast cancer patients undergoing aromatase inhibitor therapy were investigated. All patients were postmenopausal, as confirmed by laboratory tests. Of these patients, 77 received adjuvant upfront ZA for at least 1 year in addition to conventional adjuvant treatment. The remaining 158 patients never received ZA and were treated according to the St. Gallen guidelines. RESULTS: The baseline characteristics for ZA treatment were not different between the two groups. The median follow-up time was 62 months, and the patients who received ZA in addition to aromatase inhibitors showed a better recurrence-free survival compared to those who received aromatase inhibitors alone (p=0.035). On multivariate analysis, the patients who received ZA showed a better recurrence-free survival independent of the tumor size, nodal status, progesterone receptor, and histological grade. For this model, Harrell c index was 0.743. The hazard ratio of ZA use for recurrence-free survival was 0.12 (95% confidence interval, 0.01-0.99). CONCLUSION: Our findings suggest that upfront use of ZA as part of adjuvant treatment can offer a survival benefit to postmenopausal breast cancer patients receiving aromatase inhibitor treatment.

Patterns and Biologic Features of p53 Mutation Types in Korean Breast Cancer Patients / 한국유방암학회지

PURPOSE: The p53 gene is one of the most frequently mutated genes in breast cancer. We investigated the patterns and biologic features of p53 gene mutation and evaluated their clinical significance in Korean breast cancer patients. METHODS: Patients who underwent p53 gene sequencing were included. Mutational analysis of exon 5 to exon 9 of the p53 gene was carried out using polymerase chain reaction-denaturing high performance liquid chromatography and direct sequencing. RESULTS: A total of 497 patients were eligible for the present study and p53 gene mutations were detected in 71 cases (14.3%). Mutation of p53 was significantly associated with histologic grading (p<0.001), estrogen receptor and progesterone receptor status (p<0.001), HER2 status (p<0.001), Ki-67 (p=0.028), and tumor size (p=0.004). The most frequent location of p53 mutations was exon 7 and missense mutation was the most common type of mutation. Compared with patients without mutation, there was a statistically significant difference in relapse-free survival of patients with p53 gene mutation and missense mutation (p=0.020, p=0.006, respectively). Only p53 missense mutation was an independent prognostic factor for relapse-free survival in multivariate analysis, with an adjusted hazard ratio of 2.29 (95% confidence interval, 1.08-4.89, p=0.031). CONCLUSION: Mutation of the p53 gene was associated with more aggressive clinicopathologic characteristics and p53 missense mutation was an independent negative prognostic factor in Korean breast cancer patients.

Long-Term Survival Analysis of Korean Breast Cancer Patients at a Single Center: Improving Outcome Over Time

PURPOSE: The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. MATERIALS AND METHODS: A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.

Prognostic Factors for Patients with Bone-Only Metastasis in Breast Cancer

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.

Clinical Outcomes of Ductal Carcinoma In Situ of the Breast Treated with Partial Mastectomy without Adjuvant Radiotherapy

PURPOSE: Some recent trials suggest that postoperative adjuvant radiotherapy (RT) may be safely omitted after breast-conserving surgery (BCS) for some patients with ductal carcinoma in situ (DCIS). In this study, we reviewed clinical outcomes of patients with DCIS treated with partial mastectomy (PM) without adjuvant RT. MATERIALS AND METHODS: Medical records of 28 patients (29 breasts) with DCIS who were treated with PM, but without RT, between April 1991 and December 2010 were retrospectively analyzed. Based on established criteria (2.0 cm or less in size and no comedonecrosis), 18 patients were treated without RT after PM. Seven patients (8 breasts) who did not receive RT due to refusal were also included in this study. Three other patients were excluded because data concerning comedonecrosis were not available. RESULTS: For the 25 patients included in this study, the mean age of the 18 patients who met the criteria was 47.9+/-6.2 years, and 47.6+/-12.7 years for the 7 patients who did not. The mean sizes of the primary tumors were 0.6+/-0.4 cm and 0.9+/-0.3 cm, respectively, in these two groups. Among these 25 patients (26 breasts) treated without RT, we observed no ipsilateral breast tumor recurrence or mortality within a mean follow-up of 84 months. CONCLUSION: Based on this small number of cases, patients with DCIS, who were selected for tumor size less than 2 cm and absence of comedonecrosis, may be treated successfully with BCS; adjuvant RT may be omitted.

Coexistence of Medullary and Papillary Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: The simultaneous occurrence of two distinct neoplasms derived from different cells of origin is a recognized entity. It presents uncommonly in all organs,and very rarely in the thyroid gland. METHODS: Six patients with concurrent medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) were seen between January 2000 and June 2007. Clinicopathological features were evaluated, and follow-up for the patients was obtained. RESULTS: All patients were female, with ages ranging from 39 to 63 years (mean age, 55.4 years). Five of six patients were incidentally detected during a medical check-up. The medullary carcinomas measured from 0.5 to 4.0 cm in diameter (mean diameter, 1.72 cm), while the papillary carcinomas ranged from 0.2 to 1.4 cm in diameter (mean diameter, 0.72 cm). Treatment consisted of a total thyroidectomy (n=5) and hemithyroidectomy (n=1) with central compartment node dissection. In twopatients, prophylactic bilateral neck dissection was also added. Supplemental radioactive iodine treatment was administered in five patients. During a mean follow-up period of 41.8 months, two patients showed recurrence in the lateral neck nodes, one recurrence from a papillary carcinoma and the other recurrence from a medullary carcinoma. After re-operation for the recurrent lesions, allof the patients were alive andfree of disease. CONCLUSION: Attention should be given to the possibility of the simultaneous occurrence of MTC and PTC. Treatment for concurrent MTC and PTC should be based on the treatment for MTC, considering the more aggressive behavior of the tumor than PTC.