ABSTRACT
Fertility preservation is a major concern in young patients diagnosed with breast cancer and planning to receive multimodality treatment, including gonadotoxic chemotherapy with or without age-related decline through long-term endocrine therapy. Most breast cancer patients undergo multimodality treatments; many short-term and long-term side effects arise during these therapies. One of the most detrimental side effects is reduced fertility due to gonadotoxic treatments with resultant psychosocial stress. Cryopreservation of oocytes, embryos, and ovarian tissue are currently available fertility preservation methods for these patients. As an adjunct to these methods, in vitro maturation or gonadotropinreleasing hormone agonist could also be considered. It is also essential to communicate well with patients in the decision-making process on fertility preservation. It is essential to refer patients diagnosed with breast cancer on time to fertility specialists for individualized treatment, which may lead to desirable outcomes. To do so, a multimodal team-based approach and in-depth discussion on the treatment of breast cancer and fertility preservation is crucial. This review aims to summarize infertility risk related to currently available breast cancer treatment, options for fertility preservation and its details, barriers to oncofertility counseling, and psychosocial issues.
ABSTRACT
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.
ABSTRACT
Purpose@#We evaluated the relationship between breast pathologic complete response (BpCR) and axillary pathologic complete response (ApCR) after neoadjuvant chemotherapy (NACT) according to nodal burden at presentation. As the indications for NACT have expanded, clinicians have started clinical trials for the omission of surgery from the treatment plan in patients with excellent responses to NACT. However, the appropriate indications for axillary surgery omission after excellent NACT response remain unclear. @*Methods@#Data were collected from patients in the Korean Breast Cancer Society Registry who underwent NACT followed by surgery between 2010 and 2020. We analyzed pathologic axillary nodal positivity after NACT according to BpCR stratified by tumor subtype in patients with cT1-3/N0-2 disease at diagnosis. @*Results@#A total of 6,597 patients were identified. Regarding cT stage, 528 (9.5%), 3,778 (67.8%), and 1,268 (22.7%) patients had cT1, cT2, and cT3 disease, respectively. Regarding cN stage, 1,539 (27.7%), 2,976 (53.6%), and 1,036 (18.7%) patients had cN0, cN1, and cN2 disease, respectively. BpCR occurred in 21.6% (n = 1,427) of patients, while ApCR and pathologic complete response (ypCR) occurred in 59.7% (n = 3,929) and ypCR 19.4% (n = 1,285) of patients, respectively. The distribution of biologic subtypes included 2,329 (39.3%) patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease, 1,122 (18.9%) with HR-positive/HER2-positive disease, 405 (6.8%) with HR-negative/HER2-positive disease, and 2,072 (35.0%) with triple-negative breast cancer . Among the patients with BpCR, 89.6% (1,122/1,252) had ApCR. Of those with cN0 disease, most (99.0%, 301/304) showed ApCR. Among patients with cN1-2 disease, 86.6% (821/948) had ApCR. @*Conclusion@#BpCR was highly correlated with ApCR after NACT. In patients with cN0 and BpCR, the risk of missing axillary nodal metastasis was low after NACT. Further research on axillary surgery omission in patients with cN0 disease is needed.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
PURPOSE: Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent meta-analysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. MATERIALS AND METHODS: Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. RESULTS: Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). CONCLUSION: Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.
Subject(s)
Humans , Abdominal Pain , Alopecia , Anorexia , Appointments and Schedules , Breast Neoplasms , Breast , Cyclophosphamide , Diarrhea , Disease-Free Survival , Doxorubicin , Drug Therapy , Drug-Related Side Effects and Adverse Reactions , Dyspepsia , Febrile Neutropenia , Headache , Incidence , Mucositis , Muscle Weakness , Myalgia , NauseaABSTRACT
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
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: IBTR! 2.0 nomogram is web-based nomogram that predicts ipsilateral breast tumor recurrence (IBTR). We aimed to validate the IBTR! 2.0 using an external data set. MATERIALS AND METHODS: The cohort consisted of 2,206 patients, who received breast conserving surgery and radiation therapy from 1992 to 2012 at our institution, where wide surgical excision is been routinely performed. Discrimination and calibration were used for assessing model performance. Patients with predicted 10-year IBTR risk based on an IBTR! 2.0 nomogram score of 10% were assigned to groups 1, 2, 3, and 4, respectively. We also plotted calibration values to observe the actual IBTR rate against the nomogram-derived 10-year IBTR probabilities. RESULTS: The median follow-up period was 73 months (range, 6 to 277 months). The area under the receiver operating characteristic curve was 0.607, showing poor accordance between the estimated and observed recurrence rate. Calibration plot confirmed that the IBTR! 2.0 nomogram predicted the 10-year IBTR risk higher than the observed IBTR rates in all groups. High discrepancies between nomogram IBTR predictions and observed IBTR rates were observed in overall risk groups. Compared with the original development dataset, our patients had fewer high grade tumors, less margin positivity, and less lymphovascular invasion, and more use of modern systemic therapies. CONCLUSIONS: IBTR! 2.0 nomogram seems to have the moderate discriminative ability with a tendency to over-estimating risk rate. Continued efforts are needed to ensure external applicability of published nomograms by validating the program using an external patient population.
Subject(s)
Humans , Breast Neoplasms , Breast , Calibration , Cohort Studies , Dataset , Discrimination, Psychological , Follow-Up Studies , Mastectomy, Segmental , Nomograms , Radiotherapy , Recurrence , ROC CurveABSTRACT
Robotic surgical systems enhance surgical accuracy and efficiency by applying advanced technologies such as artificial arm joints to provide higher degrees of freedom of movement and high-quality three-dimensional images. However, the application of robotic surgical systems to breast surgery has not been widely attempted. The robotic system would improve cosmesis by enabling surgery using a single small incision. We report the first case of a gasless robot-assisted nipple-sparing mastectomy and immediate reconstruction in a patient with early breast cancer.
Subject(s)
Humans , Artificial Limbs , Breast , Breast Neoplasms , Freedom , Imaging, Three-Dimensional , Joints , Mastectomy , Robotic Surgical ProceduresABSTRACT
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
PURPOSE: Breast-conserving surgery (BCS) shows no difference in survival rates compared with total mastectomy. So, BCS is considered standard breast surgery with modified radical mastectomy. But in patients who received BCS, there is a risk of local recurrence in their long term follow up periods. Especially, BCS of young age is controversial regarding oncologic safety because of local recurrence. In this study, we struggle to confirm the oncologic safety of BCS compared with total mastectomy under the age of 35 in South Korea.METHODS: All patients who underwent surgery for breast cancer were 5,366 at Severance Hospital, Yonsei University Health System, from January 1981 to April 2008. Of them, patients younger than 35 years old were 547. We excluded patients who received chemotherapy before surgery and included only stage 1 and 2 patients who identified through the pathology after surgery. Finally, we got 367 patients; total mastectomy was performed in 245 and BCS, in 122. We compared clinicopathological characteristics and oncologic outcomes between two groups using SPSS program.RESULTS: In patients received BCS, a local recurrence rate was 7.7% at 5 years and up to 20.3% at 10 years. In patients received total mastectomy, a local recurrence rate was 1.9% over 10 years (P<0.001). However, there was no difference in 5-year and 10-year overall survival rates between two groups (P=0.689). Adjuvant chemotherapy decreased local recurrence rate in BCS patients (P=0.019).CONCLUSION: So, we concluded that BCS under the age of 35 has oncologic safety with undergoing chemotherapy.
Subject(s)
Humans , Age Factors , Breast Neoplasms , Breast , Chemotherapy, Adjuvant , Drug Therapy , Follow-Up Studies , Korea , Mastectomy, Modified Radical , Mastectomy, Segmental , Mastectomy, Simple , Neoplasm Recurrence, Local , Pathology , Recurrence , Survival RateABSTRACT
PURPOSE: We evaluated the clinical role of rapid next-generation sequencing (NGS) for identifying BRCA1/2 mutations compared to traditional Sanger sequencing. METHODS: Twenty-four paired samples from 12 patients were analyzed in this prospective study to compare the performance of NGS to the Sanger method. Both NGS and Sanger sequencing were performed in 2 different laboratories using blood samples from patients with breast cancer. We then analyzed the accuracy of NGS in terms of variant calling and determining concordance rates of BRCA1/2 mutation detection. RESULTS: The overall concordance rate of BRCA1/2 mutation identification was 100%. Variants of unknown significance (VUS) were reported in two cases of BRCA1 and 3 cases of BRCA2 after Sanger sequencing, whereas NGS reported only 1 case of BRCA1 VUS, likely due to differences in reference databases used for mutation identification. The median turnaround time of Sanger sequencing was 22 days (range, 14–26 days), while the median time of NGS was only 6 days (range, 3–21 days). CONCLUSION: NGS yielded comparably accurate results to Sanger sequencing and in a much shorter time with respect to BRCA1/2 mutation identification. The shorter turnaround time and higher accuracy of NGS may help clinicians make more timely and informed decisions regarding surgery or neoadjuvant chemotherapy in patients with breast cancer.
Subject(s)
Humans , Breast Neoplasms , Breast , Clinical Decision-Making , Drug Therapy , High-Throughput Nucleotide Sequencing , Methods , Prospective StudiesABSTRACT
The Korean clinical practice guideline recently developed by the Korean Breast Cancer Society to address the national clinical situation is currently under revision ahead of a seventh recommendation. A second consensus conference was held to further develop this guideline by soliciting opinions regarding important issues related to surgery, radiotherapy, and medical oncology. Several issues were discussed, and the discussion progressed to pros and cons in the context of cases in various clinical situations. The panels discussed and voted on issues regarding surgical treatment for non-axillary regional lymph nodes, regional nodal irradiation of pN1 disease, and ovarian functional suppression (OFS) as an adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Regarding the surgical treatment of non-axillary regional lymph node, most panelists agreed with the recommendation of preoperative chemotherapy and postoperative radiotherapy for patients with biopsy-diagnosed metastases, whereas surgery or radiotherapy of non-axillary regional lymph nodes was suggested for clinical partial responders. Discussions on radiotherapy addressed the need for adjuvant radiotherapy and radiation field of regional lymph node in the context of various N1 breast cancer cases. The participants reached a consensus to recommend that N1 patients should receive regional nodal irradiation for a large tumor burden (e.g., three positive nodes, perinodal extension, or large primary tumor). Finally, the panels favored OFS in addition to endocrine therapy for premenopausal women with high risk factors such as a large tumor size, involvement of more than three nodes, and a high histologic grade.
Subject(s)
Female , Humans , Breast Neoplasms , Breast , Consensus , Drug Therapy , Interdisciplinary Communication , Korea , Lymph Nodes , Medical Oncology , Neoplasm Metastasis , Radiotherapy , Radiotherapy, Adjuvant , Risk Factors , Tumor BurdenABSTRACT
PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. RESULTS: CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). CONCLUSION: A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs.
Subject(s)
Female , Humans , Biomarkers, Tumor/blood , Breast Neoplasms/blood , Keratin-19/blood , Neoplastic Cells, Circulating , Prognosis , Prospective Studies , RNA, Messenger/blood , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction/methodsABSTRACT
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
PURPOSE: The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. METHODS: A total of 954 patients who had T1–2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. RESULTS: Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. CONCLUSION: Preoperative MRI did not influence survival outcomes in T1–2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1–2 breast cancer may not translate into longer RFS and OS.