BACKGROUND: The effects of subclinical hyperthyroidism on fracture risk induced by thyroid-stimulating hormone (TSH) suppression therapy in patients with thyroid cancer still remains controversial. We performed a meta-analysis and systematic review to evaluate the effects of TSH suppression therapy on osteoporotic fracture in patients with thyroid cancer. METHODS: We performed a systematic search to identify studies which included osteoporotic fractures (hip fracture and vertebral fracture) in patients on TSH suppression therapy for thyroid cancer. Main outcome measures were occurrence and risk of osteoporotic fractures including hip and vertebral fractures between patients and controls. RESULTS: A systematic search yielded a total of 8 studies appropriate for review which included osteoporotic fracture outcome in patients on TSH suppression therapy for thyroid cancer. Studies with larger number of subjects showed the higher risk of osteoporotic fracture in group with TSH suppression therapy, although studies with smaller sample size presented a similar risk of fracture with control group. CONCLUSIONS: Although studies were limited by small numbers, results suggested possible association between chronic TSH suppression therapy and the increased risk of osteoporotic fractures in patients with thyroid cancer.
Hip ; Humans ; Hyperthyroidism ; Osteoporotic Fractures ; Outcome Assessment (Health Care) ; Sample Size ; Thyroid Gland ; Thyroid Neoplasms ; Thyrotropin

Background: Aromatase inhibitors (AIs) play an important role in the endocrine therapy of postmenopausal breast cancer patients, with a recent tendency to extend the duration of their use. However, AIs may increase the risk of osteoporotic bone fractures. This meta-analysis evaluated the risk of osteoporotic fractures of the hip, spine, and other locations in breast cancer patients using AIs. Methods: We performed a systematic search to identify randomized controlled clinical trials that investigated osteoporotic fractures in breast cancer patients on AI therapy. The main outcomes were the incidence and risk of osteoporotic fractures in general and of hip, vertebral, and non-vertebral fractures in AI users and controls. Results: The systematic review found a total of 30 randomized controlled trials including 117,974 participants. The meta-analysis showed a higher incidence of osteoporotic fracture in AI users: The crude risk ratio for all osteoporotic fractures was 1.35 (95% confidence interval [CI], 1.29–1.42;P < 0.001), for hip fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), for vertebral fractures 1.84 (95% CI, 1.36–2.49; P < 0.001), and for non-vertebral fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), respectively, compared to the controls. Conclusion Our meta-analysis suggested an increased risk of osteoporotic fractures for AI therapy in patients with breast cancer that was most expressed for vertebral fractures. Breast cancer patients on AIs need to be monitored for osteoporosis and osteoporotic fractures, and active prevention measures should be implemented.

PURPOSE: The risk for lymphedema (LE) after neoadjuvant chemotherapy (NCT) in breast cancer patients has not been fully understood thus far. This study is conducted to investigate the incidence and time course of LE after NCT. MATERIALS AND METHODS: A total of 313 patients with clinically node-positive breast cancer who underwent NCT followed by surgery with axillary lymph node (ALN) dissection from 2004 to 2009 were retrospectively analyzed. All patients received breast and supraclavicular radiation therapy (SCRT). The determination of LE was based on both objective and subjective methods, as part of a prospective database. RESULTS: At a median follow-up of 5.6 years, 132 patients had developed LE: 88 (28%) were grade 1; 42 (13%) were grade 2; and two (1%) were grade 3. The overall 5-year cumulative incidence of LE was 42%. LE first occurred within 6 months after surgery in 62%; 1 year in 77%; 2 years in 91%; and 3 years in 96%. In a multivariate analysis, age (hazard ratio [HR], 1.66; p < 0.01) and the number of dissected ALNs (HR, 1.68; p < 0.01) were independent risk factors for LE. Patients with both of these risk factors showed a significantly higher 5-year cumulative incidence of LE compared with patients with no or one risk factor (61% and 37%, respectively; p < 0.001). The addition of adjuvant chemotherapy did not significantly correlate with LE. CONCLUSION: LE after NCT, surgery, and SCRT developed early after treatment, and with a high incidence rate. More frequent surveillance of arm swelling may be necessary in patients after NCT, especially during the first few years of follow-up.
Arm ; Breast Neoplasms ; Breast* ; Chemotherapy, Adjuvant ; Drug Therapy* ; Follow-Up Studies ; Humans ; Incidence ; Lymph Nodes ; Lymphedema* ; Multivariate Analysis ; Prospective Studies ; Retrospective Studies ; Risk Factors

PURPOSE: Preoperative chemotherapy has been used to increase the rate of breast conserving surgery (BCS) in Caucasian women. However, whether it would also increase the rate of BCS in Korean women has not been verified. The aim of this study was to determine the effectiveness of preoperative chemotherapy to make BCS possible in Korean women who have locally advanced cancer without any increase of locoregional recurrence according to operation methods (BCS vs. mastectomy). METHODS: From August 2002 to April 2005, 205 patients with stage II or III breast cancer were enrolled in a phase III randomized trial of preoperative chemotherapy. Surgeons decided on the type of surgery (mastectomy or BCS) at initial diagnosis. By randomization, patients received four cycles of either docetaxel/capecitabine or doxorubicin/cyclophosphamide followed by surgery and crossover to the other treatment as postoperative chemotherapy. RESULTS: The mean tumor size was 3.29 cm and the mean breast volume was 489 cc at diagnosis. After preoperative chemotherapy, clinical response was shown in 76.0% of the patients. Of the 71 patients planned for a mastectomy at initial diagnosis, 27 patients underwent BCS (38.0%). Clinical T stage after preoperative chemotherapy, pathologic T size and lymphatic invasion were correlated with conversion to BCS. In multivariate analysis, only lymphatic invasion showed statistical significance. Locoregional disease-free survival did not statistically differ between the two operation methods for the patients who were planned for a mastectomy at the initial exam. CONCLUSION: This study showed that preoperative chemotherapy also increased the rate of BCS, while avoiding any increase of locoregional recurrence in Korean women with locally advanced breast cancer.
Breast ; Breast Neoplasms ; Disease-Free Survival ; Female ; Humans ; Mastectomy ; Mastectomy, Segmental ; Multivariate Analysis ; Neoadjuvant Therapy ; Random Allocation ; Recurrence

BACKGROUND: This study was conducted to explore the effect of known risk factors, focusing on risk factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, in consideration of interaction among East-Asian women. METHODS: Case-control study with 2,123 cases and 2,121 controls with mammographic density was conducted. Using the mammographic film, breast density was measured using Breast Imaging-Reporting and Data System. To identify the association of selected reproductive factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, stratified analysis was conducted according to breast density groups and interaction effects was assessed. The results were presented with adjusted OR and 95% CIs. RESULTS: Significant interaction effect between age at first birth and breast density on breast cancer (P = 0.048) was observed. Women with age at first birth ≥ 28 years old showed increased breast cancer risk in extremely dense breast group (≥ 75%) (OR = 1.627, 95% CI = 1.190–2.226). However, women with fatty breast (< 50%) and heterogeneously dense breast (50%–75%) did not show an increased association. Age at menarche, age at menopause, number of children, and family history of breast cancer did not show significant interaction with breast cancer and similar risk patterns were observed. CONCLUSIONS: Age at first birth showed significant interaction with breast density on breast cancer risk. Further studies considering biologically plausable model between exposure, intermediate outcomes and breast cancer risk with prospective design need to be undertaken in East Asian women.
Asian Continental Ancestry Group ; Birth Order ; Breast Neoplasms ; Breast ; Case-Control Studies ; Child ; Female ; Humans ; Information Systems ; Menarche ; Menopause ; Prospective Studies ; Reproductive History ; Risk Factors

Purpose: The ACOSOG Z0011 trial has proven the oncological safety of sentinel lymph node biopsy (SLBx) for node negative breast cancer. Accordingly, treatment paradigm including axilla surgery was changed. We retrospectively reviewed breast cancer patients to evaluate the clinical effect of paradigm shift in breast cancer surgery after applying the Z0011 criteria. Methods: All women who underwent breast-conserving surgery at the National Cancer Center between January 1, 2000, and December 31, 2015, were enrolled and classified according to the Z0011 criteria. The primary endpoint of the study was the disease-free survival rates, and the secondary was the adverse events, especially arm lymphedema. Results: Total 361 patients were enrolled the study (271 axillary lymph node dissection [ALND] group, 90 SLBx group). After the Z0011 guideline was adopted in our institute, the use of ALND decreased, and lymph node sampling (removing only a few axillary lymph nodes) replaced ALND. The total mean number of retrieved nodes were more in ALND group (13.02) than SLBx group (3.43). However, there was no difference in the mean number of positive nodes between two groups (2.34 in ALND group vs. 1.12 in SLBx group, P=0.001). During follow-up, 25 patients experienced disease recurrence: 22 from the ALND group and three from the SLBx group. All of died seven patients were from the ALND group. The ALND group had more complications than the SLBx group (P=0.02). Arm edema occurred more frequently in the ALND group (29.5%) than in the SLBx group (5.6%), although without statistical significance (P=0.07). Conclusion In our study, we concluded that SLBx can be used safely in Z0011-eligible cohort without increased risk of locoregional recurrence. Moreover, we found that omission of ALND is favored to reduce some serious complications such as arm lymphedema.

Purpose: Sentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph nodepositive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC. Methods: This single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND. Results: This study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6–155) in the SLNB group and 99 (range 2–159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001). Conclusion As an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.

Purpose: This study aimed to determine the incidence of male breast cancer (MBC) and its survival outcomes in Korea, and to compare these results to those for female breast cancer (FBC). Materials and Methods: We searched the Korea Central Cancer Registry and identified 227,122 breast cancer cases that were diagnosed between 1999 and 2016. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to sex, age, histological type, and cancer stage. Results: The 227,122 patients included 1,094 MBC cases and 226,028 FBC cases. Based on the age-standardized rate, the male: female ratio was 0.0055:1. The most common ages at diagnosis were 60-69 years for MBC and 40-49 years for FBC (p < 0.001). Male patients were less likely than female patients to receive adjuvant radiotherapy (7.5% vs. 21.8%, p < 0.001) or adjuvant chemotherapy (40.1% vs. 55.4%, p < 0.001). The 5-year OS rates after diagnosis were 88.8% for all patients, although it was significantly lower for MBC than for FBC (76.2% vs. 88.9%, p < 0.001). In both groups, older age (≥ 60 years) was associated with shorter survival. The 5-year OS rates for the invasive histological types were 75.8% for men and 89.0% for women. The 5-year OS rates in both groups decreased with increasing cancer stage. Conclusion MBC was diagnosed at older ages than FBC, and male patients were less likely to receive radiotherapy and chemotherapy. The survival outcomes were worse for MBC than for FBC, with even poorer outcomes related to older age, the inflammatory histological types, and advanced stage. It is important that clinicians recognize the differences between FBC and MBC when treating these patients.

PURPOSE: The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. MATERIALS AND METHODS: A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next follow-up; arm swelling that persisted over two consecutive examinations was considered PLE. RESULTS: At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). CONCLUSION: One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication.
Arm ; Breast Neoplasms* ; Breast* ; Combined Modality Therapy* ; Drug Therapy ; Follow-Up Studies ; Humans ; Incidence ; Lymph Nodes ; Lymphedema* ; Multivariate Analysis ; Risk Factors*

PURPOSE: The aim of this study is to evaluate stage IV breast cancer at the initial presentation by the review of a single institute' data. We also tried to figure out the factors to predict stage IV breast cancer. METHODS: We reviewed the prospectively collected database of 1,424 consecutive patients with primary breast cancer at the National Cancer Center in Korea from October 2000 to January 2005. RESULTS: The proportion of stage IV breast cancer was 2.7% (38/1,424). The median tumor size of the stage IV patients was 4.1 cm. The most common metastatic site was bone (47.4%) followed by lung (44.7%) and liver (36.8%). Metastases were found in 0.9% (6/672) of the T1 tumors, 2.4% (13/535) of the T2 tumors, 8.3% (4/48) of the T3 tumors, and 27.1% (13/48) of the T4 tumors (p<0.001). On multivariate analysis, the statistically significant predictors of distant metastasis were tumor size (> or =2 cm) (p=0.026), positive lymph node status (p<0.001), alkaline phosphatase (>104 IU/L) (p=0.013), aspartate transferase (>40 IU/L) (p=0.003) and CA15-3 (>32 U/mL) (p=0.025). CONCLUSION: Our study showed that the factors to predict distant metastasis of breast cancer were large size of tumor, positive lymph node status, elevated alkaline phosphatase, aspartate transferase and CA15-3. Therefore breast cancer patients with those clinical characteristics should be carefully evaluated to detect distant metastasis.
Alkaline Phosphatase ; Aspartic Acid ; Breast Neoplasms* ; Breast* ; Humans ; Korea ; Liver ; Lung ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prospective Studies ; Transferases