Basic Facts of Breast Cancer in Korea in 2014: The 10-Year Overall Survival Progress

We, the Korean Breast Cancer Society (KBCS), present the facts and the trends of breast cancer in Korea in 2014. Data on the total number of newly diagnosed patients was obtained from the Korea Central Cancer Registry database, other data were collected from the KBCS online registry database, and the overall survival data of patients were updated from Statistics Korea. A total of 21,484 female patients were newly diagnosed with breast cancer in 2014. The crude incidence rate and the age-standardized incidence rate (ASR) of breast cancer in female patients, including carcinoma in situ, were 83.4 cases and 63.9 cases per 100,000 women, respectively. The ASR showed an annual increase of 6.1% from 1999 to 2014; however, although the increase of the ASR had slowed since 2008, the incidence rate itself continuously increased. The proportion of early breast cancer increased consistently, and the pathological features changed accordingly. While breast-conserving surgery was mainly performed, the proportion of total mastectomy was slightly increased. The total number of breast reconstruction surgeries increased rapidly. The 5-year and 10-year overall survival rates for all stages of breast cancer patients were 91.2% and 84.8%, respectively. The overall survival rate of Korean patients with breast cancer was extremely high, compared with other developed countries. Thus, we consider that the clinical characteristics of breast cancer have changed over the past decade. A nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea.ope

Health-related quality of life in disease-free survivors of breast cancer with the general population

BACKGROUND: Although most of the literature about health-related quality of life (HRQoL) focuses on breast cancer patients, few studies compared the HRQoL in disease-free breast cancer survivors with that of the general population. MATERIALS AND METHODS: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Breast Cancer Module, McGill Quality of Life Questionnaire, Beck Depression Inventory, and Brief Fatigue Inventory to 1933 disease-free survivors for over 1 year after being diagnosed with stage 0 to III breast cancer. We performed multivariate-adjusted analyses in all HRQoL comparisons. RESULTS: The scores for some health-related quality of life [corrected] HRQoL scales were comparable for both disease-free breast cancer survivors and the general female population, but [corrected] there was a [corrected] clinically significant difference between the two groups [corrected] in cognitive and social functioning, fatigue, insomnia, financial difficulties, body image, future perspective, breast symptoms, and arm symptoms. [corrected] CONCLUSIONS: Disease-free survivors of breast cancer had good HRQoL, which was less affected by the type of treatment than it was by demographic characteristics, time since surgery, comorbidity, fatigue, and depression.ope

CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.ope

Depression and Coping in Breast Cancer Patients

PURPOSE: The objective of this study was to investigate the predictors of depression and coping and the correlation between depression and use of coping among breast cancer patients in Korea. METHODS: Of 1,250 eligible breast cancer patients attending Yonsei University Severance Hospital, 1,160 completed our surveys. Depression and coping were assessed using the Beck Depression Inventory and Korean Cancer Coping Questionnaire. Socio-demographic characteristics were included in the survey and medical factors were compiled by reviewing each patient's medical chart. RESULTS: Education, economic status, the level of daily activities, menopause and the type of surgery significantly predicted depression. Age, education, economic status, time since surgery, the level of daily activities, and menopause were significant predictors for personal coping; marriage, education, economic status, time since surgery, the surgical method and radiotherapy significantly predicted interpersonal coping. Personal coping and interpersonal coping had significant negative correlations with depression. CONCLUSION: Many factors are significant predictors but education and economic status are the most significant and consistent predictors for both depression and coping in breast cancer patients. Psychosocial intervention should be planned according to different characteristics of breast cancer patients, in order to reduce depression and enhance effective coping.ope

Mitogen-activated Protein Kinases Activities and c-erbB-2 Expression in Breast Cancer Carcinogenesis and Progression

Purpose: Increased level mitogen-activated protein kinase (MAPK) and activation of MAPK have been reported in human breast cancers, especially in breast cancers with HER2/neu overexpression. To understand the relationship between the MAPK protein expressions and other clinico- pathological parameters, we examined the status of MAPKs in 20 breast cancers compared to those of paired normals. Methods: A total of 20 breast cancers and paired normal breast tissues were included in this study. Tissues were obtained at the operation room and stored at -80℃. Tissue proteins were extracted and the concentration was determined by Bio-Rad protein assay method. Western blot analysis were performed to determine the level of MAPKs expressions using 100 ㎍ of tissue protein in 8%, 10%, or 12% sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). MAPK assays were carried out by a non-radioactive method developed by Cell Signaling Tech. as recommened by the manufacturer. Clinico-pathological information was provided from the Breast Cancer Registry of Department of Surgery, Yonsei University College of Medicine. Results: The levels of MAPKs were higher in 95% of breast cancers compared to those of paired normals. The levels of ERK1/2 were significantly higher in cancer tissues compared to paired normals but the activated forms were not. The levels of JNK, p38, and MKP1 proteins were significantly increased in the cancer tissue compared to the paired normals. The levels of ERK1/2 and activated ERK1/2 proteins were not different between tumor stages. There were no significant differences of the levels of ERK1/2 and activated ERK1/2 proteins between HER2-negative and HER2-positive cancers. There were significantly higher levels of activated ERK1/2 proteins in ER-positive cancers than those in ER-negative cancers (P＜0.05). Conclusion: The levels of MAPKs, but not the activated forms, seem to be increased in breast cancer tissues compared to those of paired normals. The levels of activated MAPKs seem to be associated with estrogen receptor expression in cancer tissues.ope

Association of shared decision-making with type of breast cancer surgery: a cross-sectional study

BACKGROUND: Although some studies examined the association between shared decision-making (SDM) and type of breast cancer surgery received, it is little known how treatment decisions might be shaped by the information provided by physicians. The purpose of this study was to identify the associations between shared decision making (SDM) and surgical treatment received. METHODS: Questionnaires on SDM were administered to 1,893 women undergoing primary curative surgery for newly diagnosed stage 0-II localized breast cancer at five hospitals in Korea. Questions included being informed on treatment options and the patient's own opinion in decision-making. RESULTS: Patients more likely to undergo mastectomy were those whose opinions were respected in treatment decisions (adjusted odds ratio, aOR), 1.40; 95% confidence interval (CI), 1.14-1.72) and who were informed on chemotherapy (aOR, 2.57; CI, 2.20-3.01) or hormone therapy (aOR, 2.03; CI, 1.77-2.32). In contrast, patients less likely to undergo mastectomy were those who were more informed on breast surgery options (aOR, 0.34; CI, 0.27-0.42). In patients diagnosed with stage 0-IIa cancer, clinical factors and the provision of information on treatment by the doctor were associated with treatment decisions. In patients diagnosed with stage IIb cancer, the patient's opinion was more respected in treatment decisions. CONCLUSION: Our population-based study suggested that women's treatment decisions might be shaped by the information provided by physicians, and that women might request different information from their physicians based on their preferred treatment options. These results might need to be confirmed in other studies of treatment decisions.ope

Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2

BACKGROUND: The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported. METHODS: Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety. RESULTS: Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients. CONCLUSION: Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00863655.ope

Ductal Carcinoma in Situ (DCIS) and Ductal Carcinoma in Situ with Microinvasion (DCIS-MI) of the Breast

Purpose: The use of mammographic screening has led to the early detection of breast cancers as well as the increasing incidence of ductal carcinoma in situ (DCIS) and DCIS with microinvasion (MI). The biologic behaviors and management of DCIS and DCIS with MI remain uncertain and controversial. We designed this study to investigate the differences in clinical behavior and association with pathological parameter of both DCIS and DCIS with MI. Methods: DCIS with MI was defined as DCIS with and invasive area of 1 ㎜ or less in greatest dimension. We analyzed and compared the clinico-pathological features and treatment outcomes of 155 DCIS patients and 73 DCIS with MI patients. Chi-square test, student t-test and Kaplan-Meier method using SPSS 9.0 for MS-windows were used to verify the statistical significance. Results: Both DCIS with MI and DCIS were most prevalent in women in the fifth decade, and the mean ages of the two groups were 45.0 and 46.8 years old, respectively. The primary tumors of DCIS with MI were more palpable (72.6% vs. 56.8%, P=0.032) upon physical examination and larger (3.1±0.21 ㎝ vs. 2.6±0.12 ㎝, P=0.037) than those of the DCIS group. The rate of axillary lymph node metastasis was higher in the DCIS with MI group (8.3% vs. 0.7%, P=0.003). The DCIS with MI group was more commonly associated with high nuclear grade (50% vs. 28%, P=0.028). The DCIS with MI group was also linked with comedo type, although not to a statistically significant degree (67.6% vs. 52.6%, P=0.095). In terms of hormone receptor, there was no significant difference between the groups. There were three systemic metastases in DCIS patients and two DCIS with MI patients (P＞0.05). There were no local-regional recurrences in either groups. The 8-year disease-free survival rates of the DCIS and DCIS with MI groups were 98.1% and 95.8% respectively (P＞0.05). Conclusion: DCIS with MI has several clinical-pathological characterisitcs: more palpable on physical examination, larger in size, higher incidence of lesions with comedo necrosis and high nuclear grade. Examination of the axillary lymph node with less invasive techniques may be necessary in cases with suspicious invasion. Since DCIS with MI is thought to be a transitional disease entity between DCIS and invasive ductal carcinoma and has a metastatic potential, a careful histologic evaluation is necessary for the diagnosis of DCIS.ope

Risk Factors of Local Recurrence in Phyllodes Tumor

Purpose: A phyllodes tumor is a rare disease of the breast, which shows various clinicopathological aspects. However, there is some controversy over its clinical behavior, pathologic characteristics, and local recurrence rates. Therefore, the clinicopathological characteristics of phyllodes tumor and the risk factor that influence a local recurrence after surgery were analyzed. Methods: The medical records of 56 patients with a phyllodes tumor who had undergone surgery at the Department of Surgery, Yonsei University, from 1986 to 1998, were analyzed retrospectively. The median follow up period was 57.2 months (12∼245 months). The microscopic slides were re-examined and the pathologic criteria analyzed were cellular atypia, stromal cellularity, pleomorphism, necrosis, differentiation, tumor margin, and number of mitoses. The malignancy was reclassified using the histological criteria reported by Pietruszka et al. (benign was 0∼4 mitoses/10 high- power fields, borderline 5∼9 mitoses, and malignant more than 10 mitoses). The clinical features evaluated included age, preoperative diagnosis, tumor size, surgical methods, and local recurrence. Results: The mean age was 41 years 14∼69 years) and the mean tumor size was 4.5 ㎝ (1∼12 ㎝). Only 9 cases (16.1%) were preoperatively diagnosed as having a phyllodes tumor. The most commonly performed surgical procedures were local or wide excision (46 cases, 82.1%), and a mastectomy in 10 cases (17.9%). Out of 56 cases reviewed, 43 (76.8%) were confirmed as being a benign, 7 (12.5%) as being a borderline, and 5 (1.8%) as being a malignant phyllodes tumor. Cellular atypia was minimal in 40 cases (71.4%) and prominent in 14 cases (25.0%). The stromal cellularity was minimal in 32 cases (57.1%) and prominent in 23 cases (41.1%). Pleomorphism and necrosis were represented in only 1 case (1.8%). The tumor margin was infiltrating in 11 cases (19.6%) and pushing in 43 cases (76.8%). A local recurrence developed in 9 cases (16.1%). There were no dependable histopathological features to predict a local recurrence except for cellular atypia, stromal cellularity, and an infiltrating tumor margin. Conclusion: From the above results, the strong prognostic factors that can be used to predict a local recurrence appear to be cellular atypia, stromal cellularity, and an infiltrating tumor margin.ope

Does Chemotherapy Really Affect the Quality of Life of Women with Breast Cancer?

PURPOSE: The aims of this cross-sectional study were to explore and evaluate the impact of adjuvant chemotherapy on quality of life in breast cancer patients according to the survival time from surgery. METHODS: Completed questionnaires were collected from 534 women with breast cancer. Clinical and sociodemographic characteristics were reviewed and Functional Assessment of Cancer Therapy-Breast cancer instrument, global quality of life, Beck Depression Inventory, and unmet sexuality needs were administered. Descriptive statistics, t-tests, chi-square tests and multiple analysis of covariance were performed while controlling for confounding variables. RESULTS: Statistically significant differences were found between chemotherapy and no chemotherapy group on depression (p=0.026), unmet sexuality needs (p=0.010), breast cancer specific concerns (p=0.010), physical well-being (p=0.001), and emotional well-being (p=0.028). Chemotherapy effects also varied according to survival time since surgery such as for group 1 (3 years since surgery) on depression (p=0.019) and physical well-being (p=0.028) respectively; however, there were no significant differences between chemotherapy and no chemotherapy group for group 2 (1-3 years since surgery). CONCLUSION: As expected, breast cancer patients who underwent adjuvant chemotherapy experienced significantly worse quality of life than those who did not receive chemotherapy. Furthermore, the adverse chemotherapy effects on the quality of life appear to vary according to the time since surgery. These results suggest that health care professionals may need to address long-term as well as short-term chemotherapy side-effects and intervene accordingly to enhance quality of life of breast cancer patients.ope