Survival analysis of breast cancer patients after diagnosis of second primary malignancies, focusing on the second primary hematologic malignancy

Purpose@#Although the overall survival (OS) of breast cancer patients is increasing with improved detection and therapies, so is the risk of breast cancer patients developing subsequent malignancies. We investigated the OS of breast cancer survivors according to sites of second primary malignancies (SPM). The OS of the second primary hematologic malignancy (SPHM) was then compared with that of metastatic breast cancer (MBC). @*Methods@#We retrospectively analyzed patients diagnosed with primary breast cancer between 1998 and 2019. Only those with SPM were eligible for analysis. First, the OS of patients with SPM diagnosed as the first event after the diagnosis of breast cancer was analyzed. Next, the OS of patients with SPHM, with or without breast cancer relapse, was compared with that of patients with MBC, matched using the propensity score. @*Results@#Patients diagnosed with SPM without breast cancer relapse as the first event had a significantly better OS than did patients with MBC, but the OS of those with SPHM as the first event did not differ significantly from that of patients with MBC (hazard ratio [HR], 1.558; 95% confidence interval [CI], 0.856–2.839; P = 0.147). The OS of patients with SPHM with or without breast cancer relapse was worse than that of the MBC group after propensity score matching (HR, 1.954; 95% CI, 1.045–3.654; P = 0.036). @*Conclusion@#Prognosis of SPM diagnosed as the first event was statistically better than that of MBC, except in case of SPHM. Patients with SPHM, with or without MBC, showed poor OS before and after propensity score matching.

Can chemotherapy be omitted for patients with N0 or N1 endocrine-sensitive breast cancer treated with gonadotropin-releasing hormone agonist and tamoxifen?

Purpose@#Whether administering chemotherapy followed by tamoxifen plus a gonadotropin-releasing hormone (GnRH) agonist to treat patients with lower-risk hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer provides a greater benefit than administering tamoxifen plus GnRH agonist alone remains unclear. This study aimed to compare the outcomes of propensity score-matched (PSM) patients who underwent these 2 types of treatment plans. @*Methods@#This retrospective study included patients treated at our institution between 2009 and 2019. Eligible patients had HR-positive, HER2-negative, invasive breast cancer who had undergone surgery. There were 579 patients with HR-positive, HER2-negative breast cancer who were treated with a GnRH agonist and tamoxifen; patients with pathologic N2 and those who received neoadjuvant chemotherapy were excluded. After 1:1 PSM of patients who underwent GnRH agonist treatment and tamoxifen with versus without chemotherapy, 122 patients from these 2 groups were analyzed. Survival rates were calculated using the Kaplan-Meier method and compared via the log-rank test. @*Results@#After PSM, there were no significant differences in several baseline characteristics between the 2 groups. After a median follow-up of 62.8 months, the patients in both groups demonstrated similar outcomes with no significant difference in disease-free survival (P = 0.596). @*Conclusion@#Patients derived no significant survival benefit from undergoing a chemotherapy regimen before receiving tamoxifen and GnRH agonist therapy compared to forgoing such chemotherapy.

The Prediction of HER2-Targeted Treatment Response Using 64CuTetra- Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report / 한국유방암학회지

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent 64 Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status.64 Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with 64 Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate 64 Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that 64 CuDOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.

Comparison of the Efficacy between First-Line Treatment Regimens for Patients with Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer

Purpose@#Endocrine therapy is the first-line treatment recommended for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer without visceral crisis. However, this recommendation has not been followed clinically because of efficacy issues. In this study, the survival of patients with HR-positive/HER2-negative metastatic breast cancer was evaluated based on the following first-line treatment regimens: the combination of palbociclib plus letrozole, conventional endocrine therapy, or chemotherapy. @*Methods@#Medical records were reviewed for this retrospective analysis. Patients with HR-positive/HER2-negative metastatic breast cancer were included. Progression-free survival (PFS) and overall survival (OS) were compared based on first-line treatment regimens. @*Results@#A total of 184 patients were included in the analysis. The first-line treatments were palbociclib plus letrozole in 46 patients (25.0%), endocrine therapy in 40 patients (21.7%), and chemotherapy in 98 patients (53.3%). The PFS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=3.43, p<0.001) and chemotherapy (hazard ratio=2.88, p=0.001) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.430). The OS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=5.34, p=0.009) and chemotherapy (hazard ratio 4.23, p=0.043) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.451). @*Conclusion@#The combination regimen of palbociclib and letrozole could be recommended as the first-line treatment of choice in patients with HR-positive/HER2-negative metastatic breast cancer.

Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status / 한국유방암학회지

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer.METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis.RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188).CONCLUSION: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

A cavernous hemangioma located in the axillary area: Challenges in preoperative diagnosis and operation

Cavernous hemangiomas are benign neoplasms of endothelial cells. Although this neoplasm has the potential to develop in all parts of the body, it rarely develops in the axilla; in fact, there are only two case reports of axillary cavernous hemangiomas in the literature. Here, we describe a third case, which occurred in a 30-year-old Korean woman. The patient presented with a palpable mass in the left axilla that was initially thought to be either a phyllodes tumor or a lymphoma based on imaging studies. However, the results of an excisional biopsy led to a diagnosis of cavernous hemangioma. Although uncommon, a cavernous hemangioma can be encountered unexpectedly, presenting as a mass in axilla. Although usually curative, surgery may be challenging not only because of the rarity of the condition, but also because of inconsistent preoperative findings and the involvement of large vessels.

Predictive Value of the Standardized Uptake Value of 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Assessing Axillary Lymph Node Metastasis in Different Subtypes of Breast Cancer

PURPOSE@#This study aimed to examine the association between the maximum standardized uptake value (SUVmax) of different molecular subtypes of primary breast cancer with axillary lymph node (ALN) metastasis.@*METHODS@#The medical records of 633 patients, who underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for preoperative staging, were retrospectively reviewed. The cohort was stratified by the following molecular subtypes with immunohistochemical examination: luminal A, luminal B, human epidermal growth factor receptor 2 positive (HER2+), and triple negative. We evaluated the optimal cutoff SUVmax to predict ALN metastasis in each subtype using the receiver operating characteristic (ROC) analysis. Moreover, the risk factors for ALN metastasis were evaluated.@*RESULTS@#Overall, the SUVmax was positively correlated with the number of metastatic ALN (p=0.001). The mean SUVmax was higher in aggressive subtypes (4.5±0.2, 6.1±0.4, 6.5±0.5, and 7.5±0.5 in luminal A, luminal B, HER2+, and triple negative, respectively, p<0.001). Upon ROC analysis, the SUVmax of the HER2+ subtype predicted ALN metastasis most accurately, with a cutoff value of 5.5, area under the curve (AUC) of 0.708, sensitivity of 74.2%, and specificity of 64.6% (p=0.002). The triple negative subtype did not show a significant difference in SUVmax between patients with and without metastasis (p=0.13). Subtype-adjusted SUVmax, HER2 positivity, lymphovascular invasion, and T stage were significant predictors for ALN metastasis.@*CONCLUSION@#The SUVmax of primary breast cancer may be an independent predictor of ALN metastasis, being the most accurate in the HER2+ subtype. As PET/CT could facilitate tailored axillary management, this approach could be considered for the initial staging and treatment planning in patients with breast cancer.

Efficacy of Combined Aromatase Inhibitor and Luteinizing Hormone-Releasing Hormone Agonist in Premenopausal Metastatic Breast Cancer

PURPOSE: Endocrine therapy is the preferred treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated the efficacy of combined aromatase inhibitor (AI) and luteinizing hormone-releasing hormone (LHRH) agonist in premenopausal patients with HR-positive MBC. METHODS: We retrospectively analyzed the medical records of 21 HR-positive premenopausal MBC patients treated with combined AI and LHRH agonist therapy. RESULTS: The median follow-up period was 32.9 months. The overall response rate was 47.6%, with three complete responses (14.3%) and seven partial responses (33.3%). Nine patients (42.9%) achieved stable disease lasting more than 6 months; thus, the clinical benefit rate was 90.4%. The median time to progression was 45.4 months. No patients experienced grade 3 or 4 toxicity. CONCLUSION: Combined AI and LHRH agonist treatment safely and effectively induced remission or prolonged disease stabilization, suggesting that this could be a promising treatment option for HR-positive premenopausal patients with MBC.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment / 한국유방암학회지

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

Factors Associated with Metastatic Breast Cancer in Patients Who Show Long-Term Stable Disease Status

PURPOSE: This study aimed to analyze the basic clinical characteristics and survival of patients with breast cancer whose disease had been stably maintained for more than 24 months after systemic therapy. METHODS: We retrospectively reviewed the medical records of patients with primary breast cancer who underwent surgery. Among these patients, patients with stage IV disease at diagnosis or those who developed distant metastasis during the follow-up period after surgery were included in this analysis. Patients whose disease remained stable for more than 24 months were classified as the long-term stable disease group. The remaining patients were classified as the control group. RESULTS: A total of 245 patients were eligible for this analysis. Patients in the long-term stable disease group showed a lower rate of histologic type III, a higher rate of hormone receptor positivity, and received less adjuvant chemotherapy. In the long-term stable disease group, the most frequent site of metastasis was the lungs, whereas in the control group, it was the bones. Overall survival was significantly better in the long-term stable disease group than in the control group (p<0.001). In univariate analysis, factors affecting the overall survival rate were the duration from diagnosis to metastasis, the absence of lymphatic infiltration, and the presence of hormone receptors. In multivariate analysis, the duration from diagnosis to metastasis and the absence of lymphatic infiltration were significant factors affecting the overall survival rate. CONCLUSION: Disease progression was observed in many patients even after the disease had been stable for more than 24 months after systemic therapy. Although these patients had better outcomes compared with the others, continuous observation and possible additional treatment might be helpful for some patients.

Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients

PURPOSE: The 40S ribosomal protein S6 kinase-1 (S6K1) is a crucial downstream effector of the PI3K/AKT/mTOR pathway. S6K1 overexpression is found in 10% to 30% of breast cancers and is associated with aggressive disease and poor prognosis. Herein, we investigated the relationship between the expression of phosphorylated S6K1 (p-S6K1) and efficacy of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. METHODS: We retrospectively analyzed the data of 36 patients with HER2-positive metastatic breast cancer treated with lapatinib between January 2010 and September 2014. The p-S6K1 expression status of the primary tumor was assessed via immunohistochemistry using a mouse monoclonal antibody. RESULTS: Fourteen of the 36 patients (38.9%) had p-S6K1-positive tumors. The median progression-free survival (PFS) of patients with p-S6K1-positive tumors was significantly longer than that of patients with p-S6K1-negative tumors (13.4 months vs. 7.1 months, p=0.025). In multivariate analysis, p-S6K1 positivity remained an independent, favorable predictive factor for PFS (hazard ratio, 0.32; 95% confidence interval, 0.11–0.97; p=0.044). CONCLUSION: The high expression of p-S6K1 was significantly associated with prolonged PFS, suggesting that p-S6K1 can be a potential biomarker for predicting the efficacy of lapatinib in patients with HER2-positive metastatic breast cancer.

The Effect of Reproductive Factors on Breast Cancer Presentation in Women Who Are BRCA Mutation Carrier / 한국유방암학회지

PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased risks for breast cancers. However, the clinical presentation of breast cancer among women who are carriers of the BRCA1 or BRCA2 (BRCA1/2 carriers) mutations is heterogenous. We aimed to identify the effects of the reproductive histories of women with the BRCA1/2 mutations on the clinical presentation of breast cancer. METHODS: We retrospectively analyzed clinical data on women with proven BRCA1 and BRCA2 mutations who were recruited to the Korean Hereditary Breast Cancer study, from 2007 to 2014. RESULTS: Among the 736 women who were BRCA1/2 mutation carriers, a total of 483 women had breast cancers. Breast cancer diagnosis occurred at significantly younger ages in women who experienced menarche at ≤14 years of age, compared to those who experienced menarche at >14 years of age (37.38±7.60 and 43.30±10.11, respectively, p<0.001). Additionally, the number of full-term pregnancies was significantly associated with the age of diagnosis, especially in women with the BRCA2 mutation. The prevalence of advanced stages (stage II or III vs. stage I) of disease in parous women was higher than in nulliparous women (68.5% vs. 55.2%, p=0.043). This association was more pronounced in women with the BRCA2 mutation (hazard ratio, 2.67; p=0.014). CONCLUSION: Our results suggest that reproductive factors, such as the age of onset of menarche and the presence of parity, are associated with the clinical presentation patterns of breast cancer in BRCA1/2 mutation carriers.

The Examination of Ovarian Reserve in Premenopausal Patients with Hormone Receptor Positive Breast Cancer / 이화의대지

The evaluation of menopausal status is an important subject in the field of treatment of hormone receptor positive breast cancer. According to the menopausal status, endocrine therapy should be categorized by individual patient. However, the gonadal injury caused by various therapeutic drugs and its recovery would confuse the interpretation of clinical and biological markers for ovarian reserve. There are some methods to examine the functional ovarian reserve indirectly. Ultrasonography for counting follicles is a relatively reliable procedure, although it is not feasible because of time-labor consumption and high cost. Biological marker from blood samples such as serum follicle stimulating hormone (FSH), serum estradiol (E2), serum inhibin, or anti-Müllerian hormone (AMH) would be a better choice. The examination of serum FSH and E2 is already recommended as biomarkers for measuring functional ovarian reserve in many guidelines. However, there are limitation of serum FSH and E2 in patients with chemotherapy-induced amenorrhea and treated by tamoxifen. AMH is promising biomarker in the field of infertility treatment even in the patients treated by chemotherapy. It might be a possible biomarker to determine the menopausal status for decision-making whether aromatase inhibitor could be applicable or not in hormone positive breast cancer patients with chemotherapy induced amenorrhea or treated by tamoxifen.

The Molecular Subtype Dependent Effect of Concurrent Radiotherapy and Systemic Therapy on Breast Cancer: Analysis of a Human In Vivo Model of Metastatic Brain Lesions

PURPOSE: The molecular subtype of breast cancer is an important predictive factor. Therefore, we investigated the effects of concurrent or serial radiotherapy and systemic therapy on metastatic brain lesions according to the molecular subtype of breast cancer. METHODS: The present retrospective study examined data from 66 patients with breast cancer and metastatic brain lesions, who were treated using radiotherapy between January 1990 and July 2014. Patients were classified into the following three subtypes based on their hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status: HR+/HER2− (luminal A, 13 patients), HR+/HER2+ (luminal B, 21 patients), HR−/HER2+ (HER2, 22 patients), or HR−/HER2− (triple negative, 10 patients). The brain lesions and their responses to treatment were evaluated using brain computed tomography or magnetic resonance imaging. Progression of brain disease was defined by a ≥20% increase in the sum of the lesion's diameters or the development of a new brain lesion. Progression-free survival was calculated from the initiation of radiotherapy to the first instance of brain disease progression or last follow-up. RESULTS: Patients in the HER2 group who had received concur-rent radiotherapy and systemic therapy (mainly HER2-targeted therapy) exhibited significantly better progression-free survival than did patients who had received radiotherapy followed by systemic therapy (p=0.037). However, concurrent radiotherapy and systemic therapy did not significantly improve progression-free survival in the luminal A (p=0.527), luminal B (p=0.462), or triple negative (p=0.558) groups. CONCLUSION: Concurrent radiotherapy and mainly HER2-targeted systemic therapy significantly prolonged progression-free survival in the HER2 group.

Evaluation of the Survival Benefit of Different Chemotherapy Regimens in Patients with T1-2N0 Triple-Negative Breast Cancer / 한국유방암학회지

PURPOSE: This study aimed to evaluate the survival benefit of different adjuvant chemotherapy regimens in patients with T1-2N0 triple-negative breast cancer. METHODS: Of 67,321 patients who were registered in the Korean Breast Cancer Society nationwide database between January 1999 and December 2008, 4,033 patients with T1-2N0 triple-negative breast cancer were included. The overall survival of patients who did not receive adjuvant chemotherapy was compared with those treated with adjuvant anthracycline and cyclophosphamide (AC), 5-fluorouracil, anthracycline, and cyclophosphamide (FAC), or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). RESULTS: The median follow-up was 52.5 months. Chemotherapy was used in 87.4% of patients; it was used more commonly in patients with T2 tumors, those who were younger, had a higher histologic grade, and who showed lymphovascular invasion. The 5-year cumulative overall survival rate was 95.4%. Younger age, breast-conserving surgery, and adjuvant chemotherapy were significantly associated with improved overall survival. The 5-year cumulative overall survival rate of patients who did not receive adjuvant chemotherapy and those treated with AC, FAC, and CMF were 92.5%, 95.9%, 95.3%, and 95.9%, respectively. On multivariate analysis, the administration of any adjuvant chemotherapy regimen was significantly associated with improved overall survival (p=0.038). No significant difference in survival benefit was observed among the three different treatment groups. CONCLUSION: A standard adjuvant chemotherapy regimen with the least drug-related toxicity might be a reasonable treatment for patients with T1-2N0 triple-negative breast cancer.

Characteristics of BRCA1/2 Mutation-Positive Breast Cancers in Korea: A Comparison Study Based on Multicenter Data and the Korean Breast Cancer Registry / 한국유방암학회지

PURPOSE: Mutations in BRCA genes are the main cause of hereditary breast cancer in Korea. The aim of this study was to investigate the characteristics of breast cancers involving BRCA1 (BRCA1 group) and BRCA2 (BRCA2 group) mutations. METHODS: We retrospectively reviewed the medical records of patients with BRCA1 (BRCA1 group) or BRCA2 (BRCA2 group) mutation positive breast cancer from multiple centers and compared the data to that of the Korean Breast Cancer Society registry (registry group). RESULTS: The patients of the BRCA1 group were diagnosed at a younger age (median age, 37 years) and had tumors of higher histological (61.3% with histological grade 3) and nuclear (37.5% with nuclear grade 3) grade than those of the registry group. In addition, the frequency of ductal carcinoma in situ in the BRCA1 group was lower (3.7%) than in the registry group, and the BRCA1 group were more likely to be triple-negative breast cancer (61.3%). Patients in the BRCA2 group were also younger at diagnosis (mean age, 41 years) and were more likely to have involvement of the axillary node than the registry group (45.5% vs. 33.5%, p=0.002). The BRCA1 and BRCA2 groups did not show a correlation between tumor size and axillary node involvement. CONCLUSION: We report the characteristics of BRCA mutation positive breast cancer patients in the Korean population through multicenter data and nation-wide breast cancer registry study. However, BRCA-mutated breast cancers appear highly complex, and further research on their molecular basis is needed in Korea.

Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in HER2-Positive Patients / 한국유방암학회지

PURPOSE: The measurement of serum human epidermal growth factor receptor 2 (HER2) extracellular domain levels is a well-established method for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targeted treatment. However, little is known about the value of serum HER2 for detecting disease relapse following curative surgical treatment in breast cancer patients. The purpose of this study was to evaluate the sensitivity of serum HER2, carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detection of disease recurrence in postoperative breast cancer patients with a primary HER2-positive tumor. METHODS: Serial measurements were taken of serum HER2, CEA, and CA 15-3 levels in patients with primary invasive HER2-positive breast cancer who underwent curative surgical treatment between January 2008 and December 2010. Following treatment, serum HER2 levels were monitored every 6 months using a chemiluminescence immunoassay. RESULTS: Overall, 264 patients were analyzed in this retrospective study. The median follow-up period was 27.7 months, and 24 patients relapsed during follow-up. The sensitivity of serum HER2, CEA, and CA 15-3 for the detection of disease recurrence was 37.5%, 25.1%, and 12.5%, respectively. Sensitivity increased to 45.8% when all three tumor markers were combined in the analysis. In a subgroup of patients without liver disease, the sensitivity of serum HER2, CEA, and CA 15-3 was 57.1%, 21.4%, and 14.3%, respectively. Of the 264 patients in this study, 80 patients had chronic hepatitis, liver cirrhosis, or abnormal aspartate aminotransferase or alanine aminotransferase levels during the follow-up period. Following the exclusion of these patients, the sensitivity of serum HER2 for the detection of disease recurrence increased to 57.1%. CONCLUSION: Serial serum HER2 measurement may be useful for the detection of disease relapse in patients with HER2-positive breast cancer. Abnormal liver function can result in elevated serum HER2 in the absence of disease recurrence.

Association of Human Epidermal Growth Factor Receptor 2 with Radiotherapy Resistance in Patients with T1N0M0 Breast Cancer / 한국유방암학회지

PURPOSE: Preclinical studies have shown that human epidermal growth factor receptor 2 (HER2) status is associated with resistance to radiotherapy (RT). In this study, we evaluated the overall survival of a T1N0M0 breast cancer cohort in Korea according to the use of RT and the HER2 status. METHODS: We analyzed data collected from 11,552 patients with invasive breast cancer who were enrolled in the Korean Breast Cancer Society Registration Program between 1999 and 2007. Data on the TNM stage, estrogen receptor status, progesterone receptor status, HER2 status, operation method, and the use of RT were analyzed. RESULTS: The median follow-up period was 51 months. A significant improvement in overall survival after RT was observed only in the HER2(-) group. In this group, the 10-year overall survival rate was 95.5% for patients who did not receive RT and 96.3% for patients who received RT (p=0.037). In contrast, in the HER2(+) group, RT was not associated with a survival benefit (p=0.887). Multivariate analysis showed that RT was significantly associated with a reduction in mortality in the HER2(-) group (hazard ratio, 0.738; 95% confidence interval, 0.549-0.993; p=0.045). CONCLUSION: We found that postoperative RT was not associated with a survival benefit in HER2(+) breast cancer patients, suggesting that HER2(+) breast cancers could be RT resistant.

Changing Patterns in the Clinical Characteristics of Korean Breast Cancer from 1996-2010 Using an Online Nationwide Breast Cancer Database / 한국유방암학회지

PURPOSE: Breast cancer is one of the most frequent malignancies in Korean women, and its incidence is increasing at a rapid rate. Since 1996, the Korean Breast Cancer Society has collected nationwide breast cancer data using an online registration program and analyzed the data biennial. The purpose of this study was to evaluate the characteristics of Korean breast cancer and to analyze changes in these characteristics over the period of time. METHODS: Data were collected from 41 medical schools (74 hospitals), 24 general hospitals, and 6 private clinics. Data on the total number, gender, and age of newly-diagnosed breast cancer patients were collected through a questionnaire. Additional data were collected and analyzed from the online database. RESULTS: In 2010, 16,398 patients in Korea were newly diagnosed with breast cancer. The crude incidence rate of female breast cancer was 67.2 cases per 100,000, and the median age at diagnosis was 49 years. The incidence of breast cancer was highest in patients aged between 40 and 49 years. Since 1996, there has been a significant increase in the proportion of early-stage cancers (detected in stage 1 or 2), the percentage of estrogen receptor-positive cancers, and in the proportion of patients receiving breast-conserving surgery. CONCLUSION: The incidence and clinical characteristics of Korean breast cancer are slowly changing to the patterns of Western countries. To understand changing patterns in the characteristics of Korean breast cancer, the nationwide data should be continuously analyzed.

Different Prognostic Significance of Bcl-2 Based on Cancer Molecular Subtype / 한국유방암학회지

PURPOSE: B-cell lymphoma (bcl)-2 is an anti-apoptotic gene, and it is a poor prognostic factor in various malignant tumors. However, the prognostic significance of bcl-2 expression in breast cancer remains controversial. We investigated the prognostic significance of bcl-2 according to cancer molecular subtype. METHODS: We analyzed 411 patients with primary invasive breast cancer who underwent surgery at our institution between 1999 and 2001. The subtypes were classified as luminal (estrogen receptor [ER]+ and/or progesterone receptor [PR]+, irrespective of human epidermal factor receptor 2 [HER2]), triple-negative (ER-, PR-, and HER2-), or HER2 (ER- ,PR-, and HER2+). RESULTS: A total of 236 (57.4%) cases were positive for bcl-2, and bcl-2 expression was significantly associated with earlier stage, lower grade, expression of hormone receptor positivity, and HER2 negativity. No difference in disease-free survival (DFS) was observed based on bcl-2 expression. However, the prognostic significance of bcl-2 varied with subtype; bcl-2 was not a prognosticator in patients with the luminal and HER2 subtypes. However, patients with bcl-2(+) tumors of the triple-negative subtype showed significantly worse DFS than those with bcl-2(-) tumors (p=0.048). In a multivariate analysis, bcl-2 expression remained a significant predictor of recurrence in patients with the triple-negative subtype (hazard ratio, 3.26; 95% confidence interval, 1.40-7.59; p=0.006). CONCLUSION: The prognostic significance of bcl-2 varied with molecular subtype; bcl-2 expression was a poor prognosticator in patients with the triple-negative subtype, but not in those with the luminal and HER2 subtypes.