Active Surveillance of Papillary Thyroid Cancer: Past, Present, and Future / 이화의대지

Active surveillance (AS) of papillary thyroid microcarcinoma was first suggested by Dr. Akira Miyauchi at Kuma Hospital in 1993. Based on several subsequent evidences, AS was approved by the American Thyroid Association in 2015. AS is no longer an experimental treatment but has become an acceptable standard of care for patients with low-risk thyroid cancers. No molecular markers, such as BRAF mutations, have been identified to predict the prognosis of papillary thyroid cancer. However, future molecular studies may reveal the relationship between genetic mutations and thyroid cancer prognosis. AS involves closely monitoring thyroid cancer over time, instead of immediately treating it with surgery. Patients and medical doctors should consider these two options: observation or surgery.

Accuracy of Digital Breast Tomosynthesis for Detecting Breast Cancer in the Diagnostic Setting: A Systematic Review and Meta-Analysis

Objective@#To compare the accuracy for detecting breast cancer in the diagnostic setting between the use of digital breast tomosynthesis (DBT), defined as DBT alone or combined DBT and digital mammography (DM), and the use of DM alone through a systematic review and meta-analysis. @*Materials and Methods@#Ovid-MEDLINE, Ovid-Embase, Cochrane Library and five Korean local databases were searched for articles published until March 25, 2020. We selected studies that reported diagnostic accuracy in women who were recalled after screening or symptomatic. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random effects model was used to estimate pooled sensitivity and specificity. We compared the diagnostic accuracy between DBT and DM alone using meta-regression and subgroup analyses by modality of intervention, country, existence of calcifications, breast density, Breast Imaging Reporting and Data System category threshold, study design, protocol for participant sampling, sample size, reason for diagnostic examination, and number of readers who interpreted the studies. @*Results@#Twenty studies (n = 44513) that compared DBT and DM alone were included. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI] 0.86–0.93) and 0.90 (95% CI 0.84–0.94), respectively, for DBT, which were higher than 0.76 (95% CI 0.68–0.83) and 0.83 (95% CI 0.73–0.89), respectively, for DM alone (p < 0.001). The area under the summary receiver operating characteristics curve was 0.95 (95% CI 0.93–0.97) for DBT and 0.86 (95% CI 0.82–0.88) for DM alone. The higher sensitivity and specificity of DBT than DM alone were consistently noted in most subgroup and meta-regression analyses. @*Conclusion@#Use of DBT was more accurate than DM alone for the diagnosis of breast cancer. Women with clinical symptoms or abnormal screening findings could be more effectively evaluated for breast cancer using DBT, which has a superior diagnostic performance compared to DM alone.

Efficacy of erector spinae plane block with opioid-sparing analgesic technique in breast-conserving surgery

Purpose@#Breast-conserving surgery (BCS) is a surgical method designed to minimize intraoperative tissue injury. Although this technique is minimally invasive, it can cause significant postoperative pain and may be a risk factor for persistent pain.Erector spinae plane block (ESPB) is an easy interfascial plane block for analgesia in patients undergoing breast surgery. The primary outcome was the numeric rating scale scores measured separately on the breast and axilla. Secondary outcomes included correlation between pain score and skin sensitivity test. @*Methods@#Forty patients were divided into 2 groups (ESPB group and control group). Patients in the ESPB group received an ESPB 30 minutes before the induction of general anesthesia, whereas patients in the control group did not receive any regional analgesia during the perioperative period. @*Results@#Median pain scores of the breast were significantly lower in the ESPB group than that in the control group at 12, 24, and 48 hours after surgery. However, the median pain scores of the axilla were not significantly different between the groups, and the pain score was unrelated to skin sensitivity. @*Conclusion@#ESPB can effectively alleviate acute postoperative pain with an opioid-sparing analgesic technique in patients undergoing BCS, and a strong correlation is lacking between pain scores and skin sensitivity test.

Active Surveillance of Papillary Thyroid Cancer: Past, Present, and Future / 이화의대지

Active surveillance (AS) of papillary thyroid microcarcinoma was first suggested by Dr. Akira Miyauchi at Kuma Hospital in 1993. Based on several subsequent evidences, AS was approved by the American Thyroid Association in 2015. AS is no longer an experimental treatment but has become an acceptable standard of care for patients with low-risk thyroid cancers. No molecular markers, such as BRAF mutations, have been identified to predict the prognosis of papillary thyroid cancer. However, future molecular studies may reveal the relationship between genetic mutations and thyroid cancer prognosis. AS involves closely monitoring thyroid cancer over time, instead of immediately treating it with surgery. Patients and medical doctors should consider these two options: observation or surgery.

Accuracy of Digital Breast Tomosynthesis for Detecting Breast Cancer in the Diagnostic Setting: A Systematic Review and Meta-Analysis

Objective@#To compare the accuracy for detecting breast cancer in the diagnostic setting between the use of digital breast tomosynthesis (DBT), defined as DBT alone or combined DBT and digital mammography (DM), and the use of DM alone through a systematic review and meta-analysis. @*Materials and Methods@#Ovid-MEDLINE, Ovid-Embase, Cochrane Library and five Korean local databases were searched for articles published until March 25, 2020. We selected studies that reported diagnostic accuracy in women who were recalled after screening or symptomatic. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random effects model was used to estimate pooled sensitivity and specificity. We compared the diagnostic accuracy between DBT and DM alone using meta-regression and subgroup analyses by modality of intervention, country, existence of calcifications, breast density, Breast Imaging Reporting and Data System category threshold, study design, protocol for participant sampling, sample size, reason for diagnostic examination, and number of readers who interpreted the studies. @*Results@#Twenty studies (n = 44513) that compared DBT and DM alone were included. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI] 0.86–0.93) and 0.90 (95% CI 0.84–0.94), respectively, for DBT, which were higher than 0.76 (95% CI 0.68–0.83) and 0.83 (95% CI 0.73–0.89), respectively, for DM alone (p < 0.001). The area under the summary receiver operating characteristics curve was 0.95 (95% CI 0.93–0.97) for DBT and 0.86 (95% CI 0.82–0.88) for DM alone. The higher sensitivity and specificity of DBT than DM alone were consistently noted in most subgroup and meta-regression analyses. @*Conclusion@#Use of DBT was more accurate than DM alone for the diagnosis of breast cancer. Women with clinical symptoms or abnormal screening findings could be more effectively evaluated for breast cancer using DBT, which has a superior diagnostic performance compared to DM alone.

Efficacy of erector spinae plane block with opioid-sparing analgesic technique in breast-conserving surgery

Purpose@#Breast-conserving surgery (BCS) is a surgical method designed to minimize intraoperative tissue injury. Although this technique is minimally invasive, it can cause significant postoperative pain and may be a risk factor for persistent pain.Erector spinae plane block (ESPB) is an easy interfascial plane block for analgesia in patients undergoing breast surgery. The primary outcome was the numeric rating scale scores measured separately on the breast and axilla. Secondary outcomes included correlation between pain score and skin sensitivity test. @*Methods@#Forty patients were divided into 2 groups (ESPB group and control group). Patients in the ESPB group received an ESPB 30 minutes before the induction of general anesthesia, whereas patients in the control group did not receive any regional analgesia during the perioperative period. @*Results@#Median pain scores of the breast were significantly lower in the ESPB group than that in the control group at 12, 24, and 48 hours after surgery. However, the median pain scores of the axilla were not significantly different between the groups, and the pain score was unrelated to skin sensitivity. @*Conclusion@#ESPB can effectively alleviate acute postoperative pain with an opioid-sparing analgesic technique in patients undergoing BCS, and a strong correlation is lacking between pain scores and skin sensitivity test.

Nipple-sparing mastectomy through periareolar incision with immediate reconstruction

PURPOSE: Nipple-sparing mastectomy (NSM) has become increasingly popular due to improved cosmesis without compromising oncologic safety. Radial and inframammary incisions are usually used to achieve NSM, with periareolar incisions usually being avoided because of the risk to nipple-areola complex viability. In an attempt to maximize esthetic effects, we performed NSM through periareolar incision with immediate reconstruction. We report our initial experience.METHODS: This case series consisted of all consecutive patients (n = 34) who underwent NSM through a periareolar incision in our institution between August 2017 and December 2018. All patients underwent NSM through periareolar incision followed by immediate reconstruction with an implant or deep inferior epigastric perforator flap. Patient demographics, tumor and treatment characteristics, and short-term postoperative outcomes were reviewed.RESULTS: The mean patient age was 46.74 ± 6.69 years (range, 38–62 years), and the mean operation time was 96.68 ± 28.00 minutes. Indications included in situ cancer in 12 cases and invasive cancer in 22 cases. There was 1 major complication (postoperative hematoma) requiring operative reintervention. No other complications including fistula, implant exposure, or reconstruction failure was observed. At the time of writing, no case of local recurrence has been observed.CONCLUSION: Our initial report shows that NSM with immediate reconstruction may successfully be performed through periareolar incision. This method maximizes esthetic effects and may be an appropriate surgical option for NSM.

Routine low-dose calcium supplementation after thyroidectomy does not reduce the rate of symptomatic hypocalcemia: a prospective randomized trial

PURPOSE: Routine supplementation of high-dose calcium significantly decreased the risk of postoperative symptomatic hypocalcemia after thyroidectomy. However, there is an ongoing debate about whether the same results can be achieved with low-dose calcium supplementation. METHODS: Patients (n = 138) who underwent total thyroidectomy for thyroid cancer were 1:1 randomly assigned to receive oral supplements of 1,500 mg/day elemental calcium and 1,000 IU/day cholecalciferol for 2 weeks or no supplementation. Primary objective was to compare the incidence of symptomatic hypocalcemia for 3 days after total thyroidectomy. Secondary objective was to find the predictors for postoperative hypocalcemia in patients with thyroid cancer. RESULTS: Sixty-five patients in the calcium group and 69 patients in the control group were finally analyzed. The incidence of symptomatic hypocalcemia showed no difference between the calcium and control group (32.3% vs. 21.7%, P = 0.168). The total dosage of intravenous calcium (593.4 ± 267.1 mg vs. 731.6 ± 622.7 mg, P = 0.430) administered to patients with symptomatic hypocalcemia was also comparable between groups. In a multivariate analysis, parathyroid hormone level of 13 pg/mL at postoperative day 1 was only predictive for symptomatic hypocalcemia, and its incidence was 20.9 times (95% confidence interval, 6.8–64.5) higher in patients with parathyroid hormone <13 pg/mL. Other factors did not predict the development of hypocalcemia, including clinicopathological features and routine supplementation of low-dose calcium. CONCLUSION: Routine low-dose calcium supplementation did not reduce the risk of postoperative hypocalcemia. Patients who may benefit from calcium supplementation should be carefully selected.

Human Epidermal Growth Factor Receptor 2-Subtype Invasive Ductal Carcinoma Recurring as Basal-Human Epidermal Growth Factor Receptor 2-Subtype Squamous Cell Carcinoma / 한국유방암학회지

Squamous cell carcinoma of the breast and its subtype, basal-human epidermal growth factor receptor 2 (HER2) phenotype, are very rare. Herein, we report a patient who developed recurrence of squamous cell carcinoma of the breast with basal-HER2 subtype 6 years after the initial diagnosis of invasive ductal carcinoma of the HER2 subtype. To the best of our knowledge, recurrence of invasive ductal carcinoma in the form of metaplastic squamous cell carcinoma of basal-HER2 subtype has not been reported previously. We present a pathological perspective of our experience.

Anticancer Effect of Selenium / 이화의대지

Selenium is an essential microelement in animals including human. Selenium plays an important role in cellular functions such as deoxygenation and detoxification. Also, it can be used in treatment of cardiac disease, hepatic disease, AIDS and various cancers. Recent meta-analysis showed that high selenium exposure was associated with decreased risk of several cancers. Selenium has an effect on anticarcinogesis through several mechanisms, which are regulation of cell cycles, apoptosis, DNA damage and repair, inhibition of cellular adhesion and migration, anti-angiogenesis and immune modulation. Even though many laboratory studies have provided convincing evidence of these mechanisms, results from epidemiologic and clinical studies of selenium does not coincide with each other. Well-designed trials considering dosage and chemical form of selenium supplement as well as confounding factors and long-term follow-up of them would be needed to use selenium in chemoprevention and therapy of cancers.

Endoscopic Thyroidectomy Via the Cervico-axillary Approach for Thyroid Cancer: Initial Experience in a Single Institute / 대한내분비외과학회지

PURPOSE: Endoscopic thyroidectomy using a cervico-axillary approach (CAA) provides optimal visualization with a smaller dissection plane. Despite the excellent cosmetic results and high patient satisfaction, the surgical and oncologic safety of CAA endoscopic surgery has not been fully established. The present study evaluated the feasibility, safety, and surgical outcomes of CAA endoscopic thyroidectomy. METHODS: From October 2009 to April 2012, 100 patients with papillary thyroid cancer underwent CAA endoscopic thyroidectomy. Patient demographics, pathologic features, and surgical outcomes including complications and recurrence were collected. RESULTS: CAA endoscopic thyroidectomy was successful in all patients, and none required conversion to open thyroidectomy. All patients underwent ipsilateral thyroid lobectomy with or without central compartment neck dissection. The mean tumor size was 1.0±0.6 cm (range, 0.5~1.6), and 35.0% of tumors showed extrathyroidal extension. The mean number of harvested lymph nodes was 4.1±4.4, and metastasis was found in 12.0% of patients. The mean surgical time was 175.2±50.4 min, mean intraoperative blood loss was 42.5±69.2 ml, and the mean hospital stay was 3.3±0.6 days. There were five cases of postoperative transient hypocalcemia and eight cases of vocal cord palsy. No permanent complication or postoperative bleeding was observed. Patients continued to be seen for a median period of 63.7 months, and no recurrence of thyroid cancer was seen. CONCLUSION: CAA endoscopic thyroidectomy is a feasible and safe procedure for low-risk thyroid cancer, with excellent cosmesis. It can be recommended as an alternative option for selected patients with low-risk thyroid cancer.

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

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.

Survival Improvement in Korean Breast Cancer Patients Due to Increases in Early-Stage Cancers and Hormone Receptor Positive/HER2 Negative Subtypes: A Nationwide Registry-Based Study / 한국유방암학회지

PURPOSE: The aim of this study was to investigate whether the observed changes over time in the survival rates vary according to the intrinsic subtypes of breast cancer diagnosed. METHODS: Data from 46,320 breast cancer patients in the Korean Breast Cancer Registry who underwent surgery between 1999 and 2006 were reviewed. Among them, results from 25,887 patients with available data about the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were analyzed. Patients were classified into two cohorts according to the year in which they underwent surgery: 1999-2002 and 2003-2006. RESULTS: The patients treated in the latter time period showed significantly better overall survival (OS) compared with those in the former period when adjusted for follow-up duration. The proportion of hormone receptor+/HER2-subtype and stage I breast cancer were significantly higher in the latter period (47.4% vs. 54.6%, p<0.001; 31.0% vs. 39.6%, p<0.001, respectively). Improvement in OS between the former and latter periods was seen in all subtypes of breast cancer, including triple-negative cancers (all p-values <0.001 in univariate and multivariate analyses). CONCLUSION: Improvement in survival in Korean breast cancer patients over the study years is being observed in all subtypes of breast cancer, implying that increases in both early-stage detection and the proportion of less aggressive cancers contribute to this improvement.

Endocrine Therapy for Breast Cancer / 이화의대지

Breast cancer is the second most common cancer in Korean women and its mortality rate has increased steadily. Although breast cancer is heterogeneous tumor, hormone receptor-positive tumors comprise about 75 percent of all breast cancers. Therefore endocrine therapy that works by targeting estrogen receptor is a pivotal treatment for breast cancers. There are selective estrogen receptor modulators, such as tamoxifen and raloxifene, aromatase inhibitors, such as anastrozole, letrozole and exemestane, fulvestrant and luteinizing hormone-releasing hormone agonists used in endocrine therapy. Endocrine therapy is effective in treating early breast cancer as an adjuvant therapy and metastatic breast cancer as a palliative therapy. Also in women who are at high risk for breast cancer, tamoxifen or raloxifene can prevent breast cancer. Studies for neoadjuvant endocrine therapy are emerging. Considering side effects of each drug and overcoming drug resistance are needed to maximize effectiveness of treatment and advance endocrine therapy.

Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer / 한국유방암학회지

PURPOSE: Forkhead box P3 (Foxp3) is known as the most specific marker for regulatory T lymphocytes, which play an important role in immune tolerance to disturb antitumor immunity. The present study aimed to investigate the prognostic significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast cancer. METHODS: Immunohistochemical studies with Foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, not otherwise specified. Foxp3 Treg infiltration and the ratios between Foxp3 Treg and CD4 or CD8 T cells were separately analyzed for the tumor bed and tumor periphery to evaluate their association with different clinicopathological parameters and patients' outcome. RESULTS: The tumor periphery was considerably more densely infiltrated by Foxp3 Treg, CD4, and CD8 T cells than the tumor bed. Unfavorable clinicopathological parameters (a Ki-67 labeling index of > or =14%, a worse histologic grade, a worse nuclear grade, hormone receptor negativity, human epidermal growth factor receptor 2 positivity, and tumor recurrence) were associated with increased Foxp3 Treg infiltration and a high ratio between Foxp3 Treg and CD4/CD8 T cells. In the tumor periphery, as Foxp3 Treg infiltration and the Foxp3 Treg/CD8 ratio increased, patients' 5-year disease-free survival rate decreased. CONCLUSION: The infiltration densities of Foxp3 Treg, CD4, and CD8 T cells were markedly different between the tumor bed and periphery. Besides the absolute count of Foxp3 Treg, the ratio between Foxp3 Treg and effector T cells was a significant prognostic factor in breast cancer.

Correlation between the molecular subtype of breast cancer and the in vitro adenosine triphosphate-based chemosensitivity assay / 대한외과학회지

PURPOSE: The empirical use of a chemotherapy regimen shows different results in individual breast cancer patient treatment. Recent studies showed the effectiveness of the adenosine triphosphate-based chemotherapy response assay (ATP-CRA). However, little is known about the correlation between chemosensitivity and breast cancer molecular subtypes. Therefore, we investigated whether the result of ATP-CRA is associated with a molecular subtype of breast cancer. METHODS: Two hundred eighty-seven patients diagnosed with breast cancer and receiving ATP-CRA at Mokdong Hospital, Ewha Womans University between September 2007 and December 2010 were enrolled in this study. Hormone receptor status, HER2/neu expression, and results of chemosensitivity tests of the patients was analyzed. RESULTS: In all of four subtypes, the combination of two agents showed significant higher mean cell death rate than a single agent. Within the breast cancer cell lines in this study, the range of chemosensitivity response was very wide and varied for each patient. For this reason, the molecular subtype of breast cancer is inconclusive in choosing an effective chemotherapeutic agent and in vitro chemosensitivity test, prior to therapy, could be a useful method for planning chemotherapy for each patient. CONCLUSION: Chemosensitivity response to anticancer agents was found to vary depending on the individual breast cancer patients. The molecular subtype of breast cancer is inconclusive to choose the effective chemotherapeutic agent and the in vitro chemosensitivity test, prior to therapy, could be more useful for planning chemotherapy for each patient.

Chemotherapy Response Assay Test and Prognosis for Breast Cancer Patients Who Have Undergone Anthracycline- and Taxane-Based Chemotherapy / 한국유방암학회지

PURPOSE: A chemotherapy response assay test is performed to evaluate the degree of tumor growth inhibition by a chemotherapeutic agent. Several studies have been done on its usefulness; however, to the best of our knowledge, only a few studies concerning the relationship between chemotherapy response assay test results and breast cancer patients' prognoses have been conducted. Thus, we performed this study to analyze this relationship. METHODS: Among breast cancer patients who underwent curative surgery and neoadjuvant or adjuvant chemotherapy between August 2004 and December 2009, 102 were enrolled in this study. Chemotherapeutic regimens for patients were doxorubicin plus taxane or doxorubicin plus cyclophosphamide followed by taxane. We divided these patients into two groups (sensitive group [n=19] and resistant group [n=83]) and analyzed the relationship between chemosensitivity results and patient prognosis. RESULTS: The sensitive group was associated with poor disease-free survival (DFS) (p=0.003) and overall survival (OS) (p<0.001). No significant differences were observed in tumor histology (p=0.548), tumor size (p=0.479), number of metastatic lymph nodes (p=0.326), histologic grade (p=0.077), or nuclear grade (p=0.216) between the two groups. However, in respect to molecular subtype, the HER2-positive type and triple negative breast cancer were more frequently observed in the sensitive group (p=0.001). In a univariate and multivariate analysis for DFS, doxorubicin sensitivity was significantly associated with a poor prognosis (p<0.05). CONCLUSION: Better chemosensitivity results are associated with a poor prognosis in breast cancer patients who have undergone anthracycline- and taxane-based chemotherapy, however, examination of additional cases and the use of a longer study period are needed.

Comparison of Endoscopic Thyroidectomy versus Conventional Thyroidectomy in Patient Satisfaction with Cosmetic Result / 대한내분비외과학회지

PURPOSE: Endoscopic thyroidectomy has brought lots of advantages to the patients since its first introduction. The aim of this study is to evaluate the functional and cosmetic satisfaction of patients receiving endoscopic thyroidectomy with patients receiving conventional thyroidectomy. METHODS: From October 2009 to January 2010, 98 patients underwent with conventional (n=69) or endoscopic (n=22) thyroidectomy. Of these patients 91 who had responded to a questionnaire distributed during the visit outpatient clinic visit. The questionnaire responses were analyzed to compare the satisfaction and postoperative results of these patients. RESULTS: The patient mean age was 45.5±10.1 years and the male to female ratio was 1:8.1. Perceived cosmetic satisfaction was significantly greater in patients who received conventional thyroidectomy than in those who received endoscopic thyroidectomy (P=0.03). Otherwise, there were no significant differences concerning functional problems. The conventional surgery was significantly longer than the endoscopic surgery (P=0.001). However, there were no significant differences in estimated blood loss, postoperative hospital stayand complication rates (P>0.05). CONCLUSION: Endoscopic thyroidectomy might bring satisfactory cosmetic result compared to conventional thyroidectomy. However, further studies are necessary.

Changes in the Hormone Receptors and the HER2 Expression in Primary and Recurrent Breast Cancer / 한국유방암학회지

PURPOSE: This study aimed at evaluating the pattern of changes in estrogen receptor (ER), progesterone receptor (PR) and the HER2 expression in primary and recurrent breast cancer. METHODS: In the study, we analyzed the changes of the ER and PR and the HER2 immunohistochemical expression to identify the patterns of changes and the predictive factors for the changes in 153 patients with primary and recurrent breast cancer between 1991 and 2005. RESULTS: There was a significant decrease in the positive rate of ER (50.3% to 38.6%, p<0.001), PR (43.8% to 26.8%, p=0.0095) and the HER2 (40.3% to 36.3%, p<0.001) expression in the primary breast cancers and recurrent breast cancers. The rate of triple negativity (ER/PR/HER2: all negative) was increased from 25.8% to 43.5% (p<0.001). Among 44 (28.6%) patients with changes in ER and ER status changed from positive to negative in 31 patients (20.3%) and negative to positive in 13 patients (8.3%) (p=0.007). For 58 patients (37.9%) who showed a change of the PR, the PR status changed from positive to negative in 42 patients (27.5%) and vice versa in 16 patients (10.4%) (p=0.0006). Twenty one patients (16.9%) changed from HER2 positive to HER2 negative and vice versa in 9 patients (7.3%) (p=0.029) among the 30 patients (24.2%) with changes in the HER2 expression. A multivariate analysis indicated that hormonal therapy was a significant factor that had an influence on the ER (odds ratio, 4.4) and PR (odds ratio, 2.6) changes. There were no significant differences in the survival rates according to the changes of the ER and PR, and the HER2 expression. CONCLUSION: The more common changes from positive to negative among the ER, PR, and HER2 indicated poor tumor biology of recurrent tumor. Therefore, the assessment of the ER, PR, and HER2 statuses is important for effectively treating recurrent breast cancer and especially those who have a previous history of hormonal therapy although survival benefit was not observed in this study.