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Purpose@#Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. @*Materials and Methods@#Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. @*Results@#During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. @*Conclusion@#Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.
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Purpose@#According to the American Joint Committee on Cancer’s 8th Edition Manual, lobular carcinoma in situ (LCIS) is no longer considered a malignant disease, although it may be a precursor to the development of breast cancer. The present study aimed to evaluate the clinicopathological features and prognosis of LCIS. @*Methods@#This study retrospectively analyzed clinicopathological features and prognosis data of LCIS among patients who underwent breast surgery at Severance Hospital, Seoul, South Korea from 1991 to 2016. @*Results@#Of the 47 patients, 49 cases of LCIS were confirmed by postoperative pathology. The mean patient age was 48.15±8.34 years. Most patients (81.6%) did not have palpable tumors at diagnosis, and 51.0% showed no microcalcification on mammography. Breast-conserving surgery was performed more frequently than total mastectomy (77.6% vs. 22.4%). The mean tumor size was 1.63±2.11 cm. There were only 3 cases of pleomorphic LCIS. Hormone receptor-positive tumors were noted in 47 cases, however, the hormone receptor status was unknown in the other 2 cases. There were no LCIS recurrences or deaths during the follow-up period (mean 56 months). @*Conclusion@#LCIS is often incidentally diagnosed without clinical symptoms, especially in women aged <50 years. The prognosis of LCIS is excellent in cases that are surgically treated.
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Purpose@#According to the American Joint Committee on Cancer’s 8th Edition Manual, lobular carcinoma in situ (LCIS) is no longer considered a malignant disease, although it may be a precursor to the development of breast cancer. The present study aimed to evaluate the clinicopathological features and prognosis of LCIS. @*Methods@#This study retrospectively analyzed clinicopathological features and prognosis data of LCIS among patients who underwent breast surgery at Severance Hospital, Seoul, South Korea from 1991 to 2016. @*Results@#Of the 47 patients, 49 cases of LCIS were confirmed by postoperative pathology. The mean patient age was 48.15±8.34 years. Most patients (81.6%) did not have palpable tumors at diagnosis, and 51.0% showed no microcalcification on mammography. Breast-conserving surgery was performed more frequently than total mastectomy (77.6% vs. 22.4%). The mean tumor size was 1.63±2.11 cm. There were only 3 cases of pleomorphic LCIS. Hormone receptor-positive tumors were noted in 47 cases, however, the hormone receptor status was unknown in the other 2 cases. There were no LCIS recurrences or deaths during the follow-up period (mean 56 months). @*Conclusion@#LCIS is often incidentally diagnosed without clinical symptoms, especially in women aged <50 years. The prognosis of LCIS is excellent in cases that are surgically treated.
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Objective@#The aim of this study was to compare the survival rates of Korean females aged 40 to 49 years with breast cancer detected by supplemental screening ultrasound (US) or screening mammography alone. @*Materials and Methods@#This single-institution retrospective study included 240 patients with breast cancer (mean age, 45.1 ± 2.8 years) detected by US or mammography who had undergone breast surgery between 2003 and 2008. Medical records were reviewed for clinicopathologic characteristics and detection methods. Disease-free survival (DFS) and overall survival (OS) were compared between patients with breast cancer in the US and mammography groups using the log-rank test. Multivariable cox regression analysis was used to identify independent variables associated with DFS and OS. @*Results@#Among the 240 cases of breast cancer, 43 were detected by supplemental screening US and 197 by screening mammography (mean follow-up: 7.4 years, 93.3% with dense breasts). There were 19 recurrences and 16 deaths, all occurring in the mammography group. While the US group did not differ from the mammography group in tumor stage, the patients in this group were more likely to undergo breast-conserving surgery and radiation therapy than the mammography group.The US group also showed better DFS (p = 0.016); however, OS did not differ between the two groups (p = 0.058). In the multivariable analysis, the US group showed a lower risk of recurrence (hazard ratio, 0.097; 95% confidence interval, 0.001–0.705) compared to the mammography group. @*Conclusion@#Our study found that Korean females aged 40–49 years with US-detected breast cancer showed better DFS than those with mammography-detected breast cancer. However, there were no statistically significant differences in OS.
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PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual introduced a new prognostic staging system for breast cancer. This study aimed to evaluate the changes in staging distribution and predictive power of the new staging system.METHODS: Of the 12,275 patients with breast cancer identified from the Severance Breast Cancer Registry who underwent surgery between 1978 and 2016, 12,125 patients met the inclusion criteria.RESULTS: In both the 7th and 8th staging systems, stage I patients constituted the largest proportion (38.2% and 48.4%). Migration from the 7th to 8th edition of the AJCC manual resulted in a decrease in stage II population and an increase in stage I and III populations. A total of 1,293 (15.4%) patients were upstaged, and 1,201 (14.3%) were downstaged. Downstaged patients had better recurrence-free and overall survival (p < 0.001). Pathologic complete response after neoadjuvant therapy showed good prognosis as p stage 0, and yp stages I and III showed poorer outcomes than the same p stage (p < 0.001).CONCLUSIONS: Staging migrations are common in early breast cancer under the prognostic staging system. The prognostic staging system of the 8th edition of the AJCC manual discriminates survival outcomes better than the anatomical staging system of the 7th edition of the AJCC manual.
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Humans , Breast Neoplasms , Breast , Joints , Neoadjuvant Therapy , PrognosisABSTRACT
Purpose@#Sentinel lymph node biopsy (SLNB) is the standard axillary procedure in early breast cancer patients. In a randomized trial, the survival rates were not different when axillary lymph node dissection (ALND) was omitted in patients with 1 or 2 lymph node metastases who underwent breast conserving surgery. This study aimed to compare the outcomes in patients who underwent total mastectomy (TM) with 1 or 2 metastatic nodes according to the types of axillary surgery. @*Methods@#In total, 79,058 patients registered in the Korean Breast Cancer Society database who underwent TM were included in the analysis. The inclusion criteria were history of TM and SLNB, pathologic T stage 1 or 2, clinically negative axillary lymph nodes, 1 or 2 metastatic axillary lymph nodes, no radiation therapy, and no neoadjuvant therapy. We divided the patients into the SLNB only and SLNB + ALND groups. The groups were matched by propensity scores. We retrospectively analyzed the differences in the overall survival (OS) between the 2 groups. @*Results@#A total of 883 patients were matched in a 1:4 ratio for the SLNB only and SLNB + ALND groups in the cohort from 1999 to 2014. There were no significant differences in OS between the 2 groups (P = 0.413). Subgroup analysis revealed a significant survival benefit in the SLNB + ALND group in the T2 subgroup (P = 0.013). @*Conclusion@#OS did not differ between the 2 groups in early breast cancer patients with 1 or 2 metastatic axillary lymph nodes who underwent TM. Omission of ALND may be considered in selected patients.
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Purpose@#Sentinel lymph node biopsy (SLNB) is the standard axillary procedure in early breast cancer patients. In a randomized trial, the survival rates were not different when axillary lymph node dissection (ALND) was omitted in patients with 1 or 2 lymph node metastases who underwent breast conserving surgery. This study aimed to compare the outcomes in patients who underwent total mastectomy (TM) with 1 or 2 metastatic nodes according to the types of axillary surgery. @*Methods@#In total, 79,058 patients registered in the Korean Breast Cancer Society database who underwent TM were included in the analysis. The inclusion criteria were history of TM and SLNB, pathologic T stage 1 or 2, clinically negative axillary lymph nodes, 1 or 2 metastatic axillary lymph nodes, no radiation therapy, and no neoadjuvant therapy. We divided the patients into the SLNB only and SLNB + ALND groups. The groups were matched by propensity scores. We retrospectively analyzed the differences in the overall survival (OS) between the 2 groups. @*Results@#A total of 883 patients were matched in a 1:4 ratio for the SLNB only and SLNB + ALND groups in the cohort from 1999 to 2014. There were no significant differences in OS between the 2 groups (P = 0.413). Subgroup analysis revealed a significant survival benefit in the SLNB + ALND group in the T2 subgroup (P = 0.013). @*Conclusion@#OS did not differ between the 2 groups in early breast cancer patients with 1 or 2 metastatic axillary lymph nodes who underwent TM. Omission of ALND may be considered in selected patients.
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PURPOSE: To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. MATERIALS AND METHODS: Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer—Lemeshow goodness of fit test. RESULTS: The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. CONCLUSION: The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.
Subject(s)
Humans , Biopsy , Breast Neoplasms , Breast , Calibration , Carcinoma, Ductal , Carcinoma, Intraductal, Noninfiltrating , Cohort Studies , Discrimination, Psychological , Logistic Models , Medical Records , Methods , Multivariate Analysis , Necrosis , Nomograms , Pathology , ErbB Receptors , Risk Factors , ROC Curve , UltrasonographyABSTRACT
PURPOSE: Sentinel lymph node (SLN) biopsy (SLNB) is widely performed for axillary staging in patients with breast cancer. Based on the results of frozen section examination (FSE), surgeons can decide to continue further axillary dissections. This study aimed to verify the accuracy of FSE for SLNs. METHODS: We reviewed the records of 4,219 patients who underwent SLNB for primary invasive breast cancer between 2007 and 2016 at the Severance Hospital. We evaluated factors associated with the false-negative results of FSE for SLNs using the Generalized Estimating Equations model. RESULTS: A total of 1,397 SLNs from 908 patients were confirmed to be metastatic. Seventy-one patients (1.7%) had confirmed pathologic N2 or N3 stage. Among metastatic SLNs, micrometastasis was found in 234 (16.8%). The overall accuracy of SLNB was 98.5%. The sensitivity and false-negative rate of FSE were 86.4% and 13.6%, respectively. Several clinicopathological factors, including the size of SLN metastases, suspicious preoperative axillary lymph nodes, and luminal B subtype, were associated with a higher rate of false-negative results. CONCLUSION: Most patients were not indicated for axillary lymph node dissection. Some patients may show transition in their permanent pathology due to the size of the metastatic node. However, the false-negative results of FSE for SLNs based on the size of the metastatic node did not change our practice. Therefore, intraoperative FSE for SLN should not be routinely performed for all breast cancer patients.
Subject(s)
Humans , Biopsy , Breast Neoplasms , Breast , False Negative Reactions , Frozen Sections , Lymph Node Excision , Lymph Nodes , Neoplasm Metastasis , Neoplasm Micrometastasis , Pathology , Phenobarbital , Sentinel Lymph Node Biopsy , SurgeonsABSTRACT
BACKGROUND/AIMS@#The aromatase inhibitors (AIs) are well known anti-hormonal therapy in endocrine-responsive breast cancer patients. It can lead to dyslipidemia and be the risk factor of cardiovascular disease due to low estrogen level. However, some recent studies comparing AIs with placebo have shown controversial results. The aim of this study was to investigate lipid profiles, measurement of carotid intima-media thickness (IMT) and the presence of plaque among endocrine-responsive breast cancer treated with AIs compared to ones that were not treated with AIs.@*METHODS@#A total of 85 postmenopausal women, who underwent breast cancer surgery during the age of 50 to 64 without history of statin use were included. There were 42 patients who were treated with AIs over 1 year (group 1) and 43 patients without AIs use (group 2). Serum total cholesterol, high density lipoprotein cholesterol, triglycerides, fasting blood glucose, carotid IMT, and presence of plaque were assessed.@*RESULTS@#The baseline characteristics were similar between two groups and there was no significant difference in carotid IMT irrespective of AIs administration. However, ultrasonographic evaluation of carotid artery revealed that the presence of plaque in AI users was significantly higher than in non-AI users (66.7% vs. 41.9%, p = 0.02; odds ratio, 4.21 in adjusted model; p = 0.01). History of diabetes was also the significant risk factor for the plaque formation.@*CONCLUSIONS@#There was no significant difference in lipid profile itself between two groups, but more importantly the presence of the plaque was much higher indicating possible detrimental effect of AI on cardiovascular system.
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PURPOSE: Pregnancy-associated breast cancer (PABC) is rare, and its cause and prognosis are not well known. Additionally, treatment is limited with respect to the risk to the fetus. The purpose of this study was to investigate the characteristics and treatment trends of PABC and the survival rate according to the treatment. METHODS: In the Korean Breast Cancer Society Registry database, women younger than 50 years and who were diagnosed with breast cancer from 1996 to 2015 were included. PABC was defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. RESULTS: We examined 411 patients with PABC and 83,381 patients with non-PABC. Over time, the proportions of patients undergoing breast-conserving surgery and sentinel lymph node biopsy increased, and neoadjuvant chemotherapy and radiation therapy administration rates also increased. In the past, the overall survival of patients with PABC was poorer than that of patients with non-PABC, but there was no difference in overall survival rates in more recent years. There was no difference in overall survival rates between patients who received neoadjuvant chemotherapy (hazard ratio [HR], 1.28; 95% confidence interval [CI], 0.66–2.49; p=0.459), but PABC conferred poorer prognosis than non-PABC in patients receiving adjuvant chemotherapy (HR, 1.63; 95% CI, 1.27–2.08; p < 0.001). CONCLUSION: There was no difference in the prognosis between patients with PABC and those with non-PABC receiving neoadjuvant chemotherapy. The increase in neoadjuvant chemotherapy according to current treatment guidelines is expected to improve the survival rate of patients with PABC.
Subject(s)
Female , Humans , Pregnancy , Breast Neoplasms , Breast , Chemotherapy, Adjuvant , Drug Therapy , Fetus , Mastectomy, Segmental , Prognosis , Sentinel Lymph Node Biopsy , Survival RateABSTRACT
PURPOSE: Sentinel lymph node biopsy (SLNB) can be performed when node-positive disease is converted to node-negative status after neoadjuvant chemotherapy (NCT). Tattooing nodes might improve accuracy but supportive data are limited. This study aimed to investigate the feasibility of charcoal tattooing metastatic axillary lymph node (ALN) at presentation followed by SLNB after NCT in breast cancers. MATERIALS AND METHODS: Twenty patientswith cytology-proven node metastases prospectively underwent charcoal tattooing at diagnosis. SLNB using dual tracers and axillary surgery after NCT were then performed. The detection rate of tattooed node and diagnostic performance of SLNB were analyzed. RESULTS: All patients underwent charcoal tattooingwithout significant morbidity. Sentinel and tattooed nodes could be detected during surgery after NCT. Nodal pathologic complete response was achieved in 10 patients. Overall sensitivity, false-negative rate (FNR), negative predictive value, and accuracy of hot/blue SLNB were 80.0%, 20.0%, 83.3%, and 90.0%, respectively. Retrieving more nodes and favorable nodal response were associated with improved performance. The best accuracy was observed when excised tattooed node was calculated together (FNR, 0.0%). Cold/non-blue tattooed nodes of five patients were removed during non-sentinel axillary surgery but clinicopathological parameters did not differ compared to patients with hot/blue tattooed node detected during SLNB, suggesting the importance of the tattooing procedure itself to improve performance. CONCLUSION: Charcoal tattooing of cytology-confirmed metastatic ALN at presentation is technically feasible and does not limit SLNB after NCT. The tattooing procedure without additional preoperative localization is advantageous for improving the diagnostic performance of SLNB in this setting.
Subject(s)
Humans , Breast Neoplasms , Breast , Charcoal , Diagnosis , Drug Therapy , Lymph Nodes , Neoadjuvant Therapy , Neoplasm Metastasis , Prospective Studies , Sentinel Lymph Node Biopsy , TattooingABSTRACT
PURPOSE: We investigated the changes in serum 25-hydroxyvitamin D (25[OH]D) levels before and after neoadjuvant chemotherapy (NCT) and the associations with pathologic complete response (pCR) and survival in patients with breast cancer. METHODS: Serum 25(OH)D concentrations were measured pre- and post-NCT in 374 patients between 2010 and 2013. Based on a cutoff of 20 ng/mL, patients were categorized into “either sufficient” or “both deficient” groups. The associations with clinicopathological data, including pCR and survival, were analyzed using multivariable analyses. RESULTS: Patients with either pre- or post-NCT sufficient 25(OH)D levels accounted for 23.8%, and the overall pCR rate was 25.9%. Most patients showed 25(OH)D deficiency at diagnosis and 65.8% showed decreased serum levels after NCT. Changes in 25(OH)D status were associated with postmenopause status, rural residence, baseline summer examination, and molecular phenotype, but not pCR. No association between survival and 25(OH)D status was found, including in the subgroup analyses based on molecular phenotypes. CONCLUSION: Most Korean patients with breast cancer showed vitamin D deficiency at diagnosis and a significant decrease in the serum concentration after NCT. No association with oncologic outcomes was found. Therefore, although optimal management for vitamin D deficiency is urgent for skeletal health, further research is warranted to clearly determine the prognostic role of vitamin D in patients with breast cancer who are candidates for NCT.
Subject(s)
Humans , Breast Neoplasms , Breast , Diagnosis , Drug Therapy , Neoadjuvant Therapy , Phenotype , Polymerase Chain Reaction , Postmenopause , Treatment Outcome , Vitamin D , Vitamin D DeficiencyABSTRACT
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.
Subject(s)
Female , Humans , Aromatase , Asian People , Bone Density , Breast Neoplasms , Breast , Chemotherapy, Adjuvant , Cholesterol , Consent Forms , Observational Study , Quality of LifeABSTRACT
PURPOSE: Clinicopathologic characteristics of patients with both thyroid and breast cancer during their lifetime were analyzed to investigate the association between the two malignancies according to the order of incidence.METHODS: A total of 405 patients who underwent surgery for breast and thyroid cancer at Severance Hospital between 1995 and 2014 were retrospectively selected and classified into 3 groups according to the order of incidence of the two cancers: simultaneous cancer (S), thyroid cancer followed by breast cancer (TB), and breast cancer followed by thyroid cancer (BT). Univariate analysis was conducted to compare parameters.RESULTS: S, TB, and BT groups were 166 (41.0%), 96 (23.7%), and 143 (35.3%) patients, respectively. In TB and BT groups, tumor size and surgical site for secondary cancer were smaller; therefore, adjuvant treatments were less frequently required for secondary cancer. ER positive rate was 77.1% in S, 75% in TB, and 63.7% in BT groups (P=0.027). The ratio of ER negative was higher in the group with BRAF mutation. Survival rate for index tumor was higher in order from TB, and BT, followed by S groups without statistical difference.CONCLUSION: It is difficult to find a significant difference according to the order of occurrence except by screening test, and more studies are needed in the future. Establishing an appropriate screening program is important in order to detect secondary breast or thyroid cancer after surgery for thyroid or breast cancer.
Subject(s)
Humans , Breast Neoplasms , Breast , Incidence , Mass Screening , Neoplasms, Second Primary , Retrospective Studies , Survival Rate , Thyroid Gland , Thyroid NeoplasmsABSTRACT
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.
Subject(s)
Female , Humans , Breast Neoplasms , Breast , Carcinoma in Situ , Developed Countries , Incidence , Korea , Mammaplasty , Mastectomy, Segmental , Mastectomy, Simple , Online Systems , Registries , Survival RateABSTRACT
PURPOSE: The present study aimed to examine the clinical implications of CD4, CD8, and FOXP3 expression on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer using a web-based database, and to compare the immunohistochemical expression of T-lymphocyte markers using primary and metastatic HER2-positive tumor tissues before and after HER2-targeted therapy. METHODS: Using the cBioPortal for Cancer Genomics and Kaplan-Meier plotter, the mRNA expression, association between T-lymphocyte markers, and survival in HER2-positive cancers were investigated according to various cutoff levels. Immunohistochemistry analysis was performed using paired primary and metastatic tissues of 29 HER2-positive tumors treated with systemic chemotherapy and HER2-directed therapy. RESULTS: HER2 mRNA was mutually exclusive of T-lymphocyte markers, and a significant correlation between T-cell markers was observed in the cBioPortal for Cancer Genomics. According to analysis of the Kaplan-Meier plotter, the impact of T-lymphocyte marker expression on survival was statistically insignificant in clinical HER2-positive tumors, irrespective of the cutoff levels. However, in the intrinsic HER2-positive subtype, the individual analyses of T-cell markers except for FOXP3 and combined analysis showed significantly favorable survival irrespective of cutoff points. Although the small clinical sample size made it difficult to show the statistical relevance of immunohistochemistry findings, good responses to neoadjuvant treatments might be associated with positive expression of combined T-lymphocyte markers, and approximately half of the samples showed discordance of combined markers between baseline and resistant tumors. CONCLUSION: T-lymphocyte markers could be favorable prognostic factors in HER2-positive breast cancers; however, a consensus on patient section criteria, detection methods, and cutoff value could not be reached. The resistance to HER2-directed therapy might involve different and personalized mechanisms, and further research is required to understand the association between immune function and HER2 expression and to overcome the resistance mechanisms to HER2-targeted therapies.
Subject(s)
Humans , Biomarkers , Breast , Breast Neoplasms , Consensus , Drug Resistance , Drug Therapy , Epidermal Growth Factor , Genomics , Immunohistochemistry , Neoadjuvant Therapy , Prognosis , ErbB Receptors , RNA, Messenger , Sample Size , T-LymphocytesABSTRACT
BACKGROUND: Sclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs), which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI. METHODS: We included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years) treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years). The subjects were randomly assigned to take either 5 mg alendronate with 0.5 microg calcitriol (n=46), or placebo (n=44) for 6 months. RESULTS: Postmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8+/-13.6 pmol/L vs. 23.1+/-4.8 pmol/L, P0.05). CONCLUSION: Serum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.
Subject(s)
Female , Humans , Alendronate , Aromatase Inhibitors , Bone Density , Breast Neoplasms , Calcitriol , Estrogens , Hip , Osteocytes , Osteogenesis , Osteoporosis , Spine , SteroidsABSTRACT
PURPOSE: Newly developed extra-mammary multiple primary cancers (MPCs) are an issue of concern when considering the management of breast cancer survivors. This study aimed to investigate the prevalence of MPCs and to evaluate the implications of MPCs on the survival of breast cancer patients. MATERIALS AND METHODS: A total of 8204 patients who underwent surgery at Severance Hospital between 1990 and 2012 were retrospectively selected. Clinicopathologic features and survival over follow-up periods of 5 years were investigated using univariate and multivariate analyses. RESULTS: During a mean follow-up of 67.3 months, 962 MPCs in 858 patients (10.5%) were detected. Synchronous and metachronous MPCs were identified in 23.8% and 79.0% of patients, respectively. Thyroid cancer was the most prevalent, and the second most common was gynecologic cancer. At 5 years. The causes of death in many of the patients with MPCs were not related to breast cancer. Stage-matched analysis revealed that the implications of MPCs on survival were more evident in the early stages of breast disease. CONCLUSION: Breast cancer patients with MPCs showed worse survival, especially when early-stage disease was identified. Therefore, it is necessary to follow screening programs in breast cancer survivors and to establish guidelines for improving prognosis and quality of life.
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Breast/pathology , Breast Neoplasms/diagnosis , Multivariate Analysis , Neoplasm Metastasis , Neoplasm Staging , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Second Primary/diagnosis , Prognosis , Quality of Life , Republic of Korea/epidemiology , Retrospective Studies , Survival AnalysisABSTRACT
PURPOSE: To evaluate the positive predictive value (PPV) of bilateral whole-breast ultrasonography (BWBU) for detection of synchronous breast lesions on initial diagnosis of breast cancer and evaluate factors affecting the PPV of BWBU according to varying clinicoimaging factors. METHODS: A total of 75 patients who had synchronous lesions with pathologic confirmation at the initial diagnosis of breast cancer during January 2007 and December 2007 were included. The clinical factors of the patients were evaluated. One observer retrospectively reviewed the imaging studies of the index breast cancer lesion and the synchronous lesion. The PPV for additional biopsy was calculated for BWBU and various clinical and imaging factors affecting the PPV for BWBU were evaluated. RESULTS: The overall PPV for additional biopsy was 25.7% (18 of 70). The PPV for synchronous lesions detected both on mammography and BWBU, and detected only on BWBU, was 76.9% (10 of 13) and 14.3% (7 of 49), respectively. There was no clinical factor affecting the PPV for BWBU. Among the imaging factors, ipsilateral location of the synchronous lesion to the index lesion (P=0.06) showed a marginal statistically significant correlation with malignancy in the synchronous breast lesion. A mass with calcification on mammography presentation (P<0.01), presence of calcification among the ultrasonography findings (P<0.01), and high Breast Imaging Reporting and Data System final assessment (P<0.01) were imaging factors that were associated with malignancy in the additional synchronous lesion. CONCLUSION: BWBU can detect additional synchronous malignancy at the diagnosis of breast cancer with a relatively high PPV, especially when mammography findings are correlated with ultrasonographic findings.