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BACKGROUND: Current guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician's decisions. RESULTS: High-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29-2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32-4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS. CONCLUSIONS: Frequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments.
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BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.
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Adenocarcinoma Mucinoso , Neoplasias da Mama , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Receptor ErbB-2/metabolismo , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Idoso , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Prognóstico , Receptores de Estrogênio/metabolismo , Adulto , Receptores de Progesterona/metabolismo , Estadiamento de Neoplasias , Carcinoma Ductal de Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Estudos de Coortes , Carcinoma Lobular/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologiaRESUMO
Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor ß diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion: Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
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BACKGROUND: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. METHODS: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. RESULTS: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486). CONCLUSIONS: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.
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Neoplasias da Mama , Calcinose , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante/efeitos adversos , Prognóstico , Mama/patologia , Calcinose/diagnóstico por imagem , Calcinose/tratamento farmacológico , Calcinose/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Estudos RetrospectivosRESUMO
PURPOSE: Fertility preservation (FP) is an important issue for young survivors of breast cancer. Although international guidelines recommend pre-treatment fertility counseling for women with breast cancer, there is no standardized protocol or referral system for FP in South Korea. There are also barriers to discussing FP that make patient-centered decision making difficult. This study aimed to develop a shared decision making program for FP and compare the rates of FP procedures between the usual care and shared decision making groups. We hypothesized that multidisciplinary shared decision making for FP would increase the rate of FP procedures and patient satisfaction. METHODS: The multidisciplinary shared decision making for FP in young women with breast cancer (MYBC) is a multicenter, clustered, stepped-wedge, randomized trial. A total of 1100 patients with breast cancer, aged 19-40 years, from nine hospitals in South Korea, will be enrolled. They will be randomized at the institutional level and assigned to usual care and shared decision making groups. Four institutions, each of which can recruit more than 200 patients, will each become a cluster, whereas five institutions, each of which can recruit more than 50 patients, will become one cluster, for a total of five clusters. The shared decision making groups will receive multidisciplinary programs for FP developed by the investigator. The primary outcome is the rate of FP procedures; secondary outcomes include fertility results, satisfaction, and quality of life. Outcomes will be measured at enrollment, treatment initiation, and the 1-, 3-, and 5-year follow-ups after starting breast cancer treatment. DISCUSSION: A multidisciplinary shared decision making program for FP is expected to increase fertility rates and satisfaction among young patients with breast cancer. This study will provide the evidence to implement a multidisciplinary system for patients with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05139641. Registered on December 1, 2021.
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BACKGROUND: Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis. AIM: To evaluate the outcomes of young hormone receptor (HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy (NAC), and the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonists. METHODS: This retrospective study involved a prospectively enrolled cohort. We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017. Among patients with HR-positive and human epidermal grow factor 2 (HER2)-negative breast cancer, we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years. RESULTS: Among 431 patients with NAC and HR-positive/HER2-negative breast cancer, 78 were 35 years old or younger, and 353 patients were older than 35 years. The median follow-up was 71.0 months. There was no statistically significant difference in disease free survival (DFS, P = 0.565) and overall survival (P = 0.820) between the patients equal to or younger than 35 years and the patients older than 35 years. The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group (52.4% vs 11.2%, P < 0.001). Interestingly, for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years, patients treated with the GnRH agonist had better DFS (P = 0.037). CONCLUSION: Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.
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Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.
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PURPOSE: Cancer antigen 15-3 (CA15-3) is a serum tumor marker for breast cancer (BC) extensively used in clinical practice. CA15-3 is non-invasive, easily available, and a cost-effective tumor marker for immediate diagnosis, monitoring and prediction of BC recurrence. We hypothesized that an elevation of CA15-3 may have prognostic impact in patients with early BC with normal serum CA15-3 level. METHODS: This was a retrospective cohort study, which included patients with BC who received curative surgery at a comprehensive single institution between 2000 and 2016. CA15-3 levels from 0 to 30 U/mL were considered normal, and patients who had CA15-3 > 30 U/mL, were excluded from the study. RESULTS: The mean age of study participants (n = 11,452) was 49.3 years. The proportion of participants with elevated CA15-3 ≥ 1 standard deviation (SD) compared with the previous examination during follow-up was 23.3% (n = 2,666). During the follow-up (median follow-up 5.8 years), 790 patients experienced recurrence. The fully-adjusted hazard ratio (HR) for recurrence comparing participants with stable CA15-3 level to subjects with elevated CA15-3 level was 1.76 (95% confidence interval [CI], 1.52-2.03). In addition, if the CA15-3 was elevated ≥ 1 SD, the risk was much higher (HR, 6.87; 95% CI, 5.81-8.11) than in patients without elevated CA15-3 ≥ 1 SD. In sensitivity analysis, the recurrence risk was consistently higher in participants with elevated CA15-3 levels than in participants without elevated CA15-3 levels. The association between elevated CA15-3 levels and incidence of recurrence was observed in all subtypes and the association was stronger in patients with N+ than in patients with N0 stage (p-value for interaction < 0.01). CONCLUSION: The results of the present study demonstrated that elevation of CA15-3 in patients with early BC and initial normal serum CA15-3 levels has a prognostic impact.
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Purpose: The use of absorbable skin staplers (ASS) for skin closure has been increasing due to their convenience and time-saving effect. In this study, we evaluated the effectiveness of ASS in reducing skin closure time and its safety regarding surgical site infection (SSI), comparing it to conventional hand sewing (HS) in patients who underwent mastectomy. Methods: A single-center, retrospective study was conducted. The electronic medical records of patients who underwent mastectomy between July 2015 and June 2020 in Samsung Medical Center were reviewed. The data included previously known risk factors for SSI. We compared the time expended on skin closure and the occurrence rate of SSI between the ASS group and the HS group. Results: We included 4,311 patients in the analysis. Among them, 520 patients were treated with ASS and 3,791 patients with HS. The average time for skin closure was 16.2 ± 10.1 minutes in the ASS group and 36.5 ± 29.0 minutes in the HS group (P < 0.001). The SSI rate was 0.38% (2 of 520) in the ASS group and 0.36% (14 of 3,791) in the HS group (P > 0.999). Conclusion: The use of ASS in mastectomy reduced the time for skin closure significantly but did not increase the SSI. Therefore, it can be an effective and safe choice to use ASS instead of HS for skin closure in mastectomy.
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Due to the rarity of primary angiosarcoma of the breast, optimal management is based on expert opinion. The aim of this study was to review all primary angiosarcomas of the breast obtained from a single center in terms of clinicopathologic characteristics, treatment, and survival outcomes. From 1997 to 2020, 15 patients with primary angiosarcoma of the breast underwent either mastectomy or wide excision. We analyzed the clinicopathologic data to assess disease-free survival and overall survival. Fifteen women with primary angiosarcoma of the breast were identified. The mean age at diagnosis was 33 years (range: 14-63 years). The overall mean tumor size was 7.7 cm (range 3.5-20 cm). Upon histological grading, there were three cases of low grade, five intermediate grade, six high grade, and one unidentified grade. The five-year disease-free survival rate was 24.4%, and the five-year survival rate was 37.2%. The survival rate of the low-grade patient group was statistically higher than that of the intermediate- or high-grade patient groups (p = 0.024). Primary angiosarcoma of the breast is a rare aggressive tumor characterized by high grade and poor outcome. Histologic grade appears to be a reliable predictor of survival. There are no standard treatment guidelines; thus, optimal R0 surgical resection remains the best approach. The roles of neoadjuvant, adjuvant chemotherapy, and radiotherapy remain unclear.
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Neoplasias da Mama , Hemangiossarcoma , Neoplasias da Mama/cirurgia , Feminino , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/cirurgia , Humanos , Mastectomia , República da Coreia , Estudos RetrospectivosRESUMO
The American Society of Clinical Oncology and College of American Pathologists guidelines for HER2 testing in breast cancer (BC) have been updated with more stringent criteria regarding immunohistochemistry (IHC) 2 + interpretation. The aim of our study was to determine HER2 status in IHC 2 + cases based on 2013 and 2018 guidelines and to investigate specific histologic characteristics that might predict HER2 status in tumors with equivocal IHC staining. Two hundred eighty BC cases reported as IHC 2 + and 24 cases reported as non-IHC 2 + were reviewed with 12 histologic characteristics. Of the IHC 2 + cases based on 2013 guideline, 21% were reclassified to IHC 1 + when applying the 2018 guidelines. Consequently, it led to an 8% increase of HER2 amplification rate in 2018 IHC 2 + group. Seven characteristics were significantly associated with prediction of HER2 amplification in IHC 2 + BCs, including high tumor-infiltrating lymphocytes (TILs), distinct cellular membrane, no apical snout, large nuclear size, nuclear size variation, high nuclear grade, and tubule formation < 10%. Using these criteria, the presence of four or more characteristics significantly indicates HER2 amplification. Moreover, four characteristics among them, including high TILs, distinct cellular membrane, nuclear size variation, and high nuclear grade, were also associated with HER2 amplification in non-IHC 2 + cases, demonstrating their predictive value as complements to IHC. In conclusion, we provide specific morphologic features that will improve pathologist performance in identifying more HER2-positive BCs. We further suggest an algorithm for trastuzumab therapy decisions using a combination of histomorphologic evaluation and the updated 2018 guidelines.
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Neoplasias da Mama , Receptor ErbB-2 , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Genes erbB-2 , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Receptor ErbB-2/análise , Receptor ErbB-2/genéticaRESUMO
OBJECTIVE: This study aimed to investigate the impact of baseline values and temporal changes in body composition parameters, including skeletal muscle index (SMI) and visceral adipose tissue area (VAT), measured using serial computed tomography (CT) imaging on the prognosis of operable breast cancers in Asian patients. MATERIALS AND METHODS: This study retrospectively included 627 Asian female (mean age ± standard deviation [SD], 53.6 ± 8.3 years) who underwent surgery for stage I-III breast cancer between January 2011 and September 2012. Body composition parameters, including SMI and VAT, were semi-automatically calculated on baseline abdominal CT at the time of diagnosis and follow-up CT for post-treatment surveillance. Serial changes in SMI and VAT were calculated as the delta values. Multivariable Cox regression analysis was used to evaluate the association of baseline and delta SMI and VAT values with disease-free survival. RESULTS: Among 627 patients, 56 patients (9.2%) had breast cancer recurrence after a median of 40.5 months. The mean value ± SD of the baseline SMI and baseline VAT were 43.7 ± 5.8 cm²/m² and 72.0 ± 46.0 cm², respectively. The mean value of the delta SMI was -0.9 cm²/m² and the delta VAT was 0.5 cm². The baseline SMI and VAT were not significantly associated with disease-free survival (adjusted hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.937-1.031; p = 0.475 and adjusted HR, 1.001; 95% CI, 0.995-1.006; p = 0.751, respectively). The delta SMI and VAT were also not significantly associated with disease-free survival (adjusted HR, 0.894; 95% CI, 0.766-1.043; p = 0.155 and adjusted HR, 1.001; 95% CI, 0.989-1.014; p = 0.848, respectively). CONCLUSION: Our study revealed that baseline and early temporal changes in SMI and VAT were not independent prognostic factors regarding disease-free survival in Asian patients undergoing surgery for breast cancer.
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Neoplasias da Mama , Obesidade Abdominal , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Esquelético , Recidiva Local de Neoplasia/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The aim of this study was to investigate the relationship between changes in breast density during menopause and breast cancer risk. METHODS: This study was a retrospective, longitudinal cohort study for women over 30 years of age who had undergone breast mammography serially at baseline and postmenopause during regular health checkups at Samsung Medical Center. None of the participants had been diagnosed with breast cancer at baseline. Mammographic breast density was measured using the American College of Radiology Breast Imaging Reporting and Data System. RESULTS: During 18,615 person-years of follow-up (median follow-up 4.8 years; interquartile range 2.8-7.5 years), 45 participants were diagnosed with breast cancer. The prevalence of dense breasts was higher in those who were younger, underweight, had low parity or using contraceptives. The cumulative incidence of breast cancer increased 4 years after menopause in participants, and the consistently extremely dense group had a significantly higher cumulative incidence (CI) of breast cancer compared with other groups [CI of extremely dense vs. others (incidence rate per 100,000 person-years): 375 vs. 203, P < 0.01]. CONCLUSION: Korean women whose breast density was extremely dense before menopause and who maintained this density after menopause were at two-fold greater risk of breast cancer. PREVENTION RELEVANCE: Extremely dense breast density that is maintained persistently from premenopause to postmenopause increases risk of breast cancer two fold in Korean women. Therefore, women having risk factors should receive mammography frequently and if persistently extremely dense breast had been detected, additional modalities of BC screening could be considered.
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Densidade da Mama , Neoplasias da Mama , Adulto , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Estudos Longitudinais , Mamografia/métodos , Menopausa , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)-expressing invasive breast cancer. METHODS: This retrospective, non-interventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathological characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-low (1% to 10%) and ER-high (> 10%) according to the Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test. RESULTS: 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-low tumors: 63 (53.8%) of whom had HER2- tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-high/HER2- cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-low/HER2- (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS. CONCLUSION: Patients with ER-low/HER2- breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-low/HER2- disease.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Prevalência , Prognóstico , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , República da Coreia/epidemiologia , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
BACKGROUND: Increasing rates of breast cancer screening have been associated with an increasing frequency of non-palpable breast lesions detection. Preoperative breast lesion localization is essential for optimizing excision accuracy. This study aimed to evaluate the efficacy and safety of indocyanine green (ICG) hyaluronic acid injection as a novel mixture for localization. METHODS: We performed a prospective clinical trial with female patients who underwent surgery for non-palpable breast lesions. All patients were sequentially assigned to the control group (localization with activated charcoal), Test Group 1 (ICG-hyaluronic acid mixture 0.1 mL), or Test Group 2 (ICG-hyaluronic acid mixture 0.2 mL) by 1:1:1 ratio. RESULTS: A total of 44 patients were eligible for this study (Control Group = 14, Test Group 1 = 15, Test Group 2 = 15 patients). Fibroadenoma (n = 17, 38.6%) accounted for the largest proportion of diagnoses, and five patients (11.4%) were diagnosed with malignancies. There were no statistically significant differences in baseline characteristics among the three groups. The marking rate was over 86% in all groups, with no significant intergroup differences. Skin pigmentation was only observed in the control group. The mean accuracy of resection (the greatest diameter of the excised specimen divided by the greatest diameter of the preoperative lesion as observed using ultrasonography, with values closer to 1 reflecting a higher accuracy) was 3.7 in the control group, 2.2 in Test Group 1, and 2.1 in Test Group 2 (p = 0.037 between Controls and Test Group 1, p = 0.744 between Test Group 1 and Test Group 2, and p = 0.026 between Controls and Test Group 2). CONCLUSION: ICG-hyaluronic acid injection is a novel method that was shown to accurately localize non-palpable breast lesions and was associated with no skin pigmentation. Further research is required to apply this method to malignant breast lesions. Trial registration "A Multicenter Open-label, Parallel, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of LuminoMark™ Inj. (Conc. for Fluorescence) Localization in Patients with Non-palpable Breast Lesions" was prospectively registered as a trial (ClinicalTrials. gov Identifier: NCT03743259, date of registration: May 29, 2018, https://clinicaltrials.gov/ct2/show/NCT03743259 ).
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Neoplasias da Mama , Ácido Hialurônico , Verde de Indocianina , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Ácido Hialurônico/uso terapêutico , Verde de Indocianina/efeitos adversos , Verde de Indocianina/uso terapêutico , Estudos Prospectivos , Resultado do TratamentoRESUMO
To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.
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Antígeno B7-H1/genética , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Terapia Neoadjuvante/métodos , Antraciclinas/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/mortalidade , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/imunologia , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Docetaxel/uso terapêutico , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Estudos Longitudinais , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Neoplasia Residual , Receptor ErbB-2/genética , Receptor ErbB-2/imunologia , Trastuzumab/uso terapêutico , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
gBRCA1/2 mutations increase the incidence of breast cancer by interrupting the homologous recombination repair (HRR) pathway. Although gBRCA1 and gBRCA2 breast cancer have similar clinical profiles, different molecular characteristics have been observed. In this study, we conducted comprehensive genomic analyses and compared gBRCA1/2 breast cancer. Sanger sequencing to identify gBRCA1/2 mutations was conducted in 2,720 patients, and gBRCA1 (n = 128) and gBRCA2 (n = 126) mutations were analyzed. Within this population, deep target sequencing and matched whole-transcriptome sequencing (WTS) results were available for 46 and 34 patients, respectively. An internal database of patients with breast cancer with wild-type gBRCA was used to compile a target sequencing (n = 195) and WTS (n = 137) reference dataset. Three specific mutation sites, p.Y130X (n = 14) and p.1210Afs (n = 13) in gBRCA1 and p.R294X (n = 22) in gBRCA2, were comparably frequent. IHC subtyping determined that the incidence of triple-negative breast cancer was higher among those with a gBRCA1 mutation (71.9%), and estrogen receptor-positive breast cancer was dominant in those with a gBRCA2 mutation (76.2%). gBRCA1/2 mutations were mutually exclusive with PIK3CA somatic mutations (P < 0.05), and gBRCA1 frequently cooccurred with TP53 somatic mutations (P < 0.05). The median tumor mutation burden was 6.53 per megabase (MB) in gBRCA1 and 6.44 per MB in gBRCA2. The expression of AR, ESR1, and PGR was significantly upregulated with gBRCA2 mutation compared with gBRCA1 mutation. gBRCA1 and gBRCA2 breast cancer have similar clinical characteristics, but they have different molecular subtypes, coaltered somatic mutations, and gene expression patterns. IMPLICATIONS: Even though gBRCA1 and gBRCA2 mutations both alter HRR pathways, our results suggest that they generate different molecular characteristics and different mechanisms of carcinogenesis.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Mutação em Linhagem Germinativa , Adulto , Idoso , Feminino , Genômica/métodos , Humanos , Pessoa de Meia-IdadeRESUMO
PURPOSE: We evaluated the clinical features and outcomes of invasive breast cancer (BC) among different age groups by analyzing a modern BC registry including subtypes and treatment information. METHODS: This was a retrospective cohort study of 6,405 women aged 18 years or older with pathologically confirmed stage I, II, or III BC who underwent curative surgery followed by adjuvant therapy at a university-based hospital in Seoul, South Korea, between January 2003 and December 2011. The study end point was all-cause mortality. We used Cox proportional hazards models and hazard ratios (HRs) with 95% CIs calculated after adjusting for age, body mass index, stage, subtype, and treatment, including type of surgery and use of chemotherapy, radiation therapy, hormone therapy, and targeted therapy. RESULTS: During 36,360 person-years of follow-up (median follow-up: 5.45 years; interquartile range, 4.3-7.1), 256 deaths were reported (mortality rate, 7.0/1,000 person-years). The adjusted HR for all-cause mortality was higher in patients older than 40 years (HR, 2.03; 95% CI, 1.44 to 2.87) and older than 60 years (HR, 2.35; 95% CI, 1.63 to 3.39) than in patients aged 40 to 49 years. Across age groups, advanced stage at diagnosis, luminal type as well as triple-negative BC, and not receiving adjuvant treatment were associated with increased risk of mortality. CONCLUSION: A strong J-shaped relationship was observed between age and mortality, indicating worse clinical outcomes in young and old patients. This study suggested a possible benefit of personalized BC screening examination and precise and active treatment strategies to reduce BC-related mortality.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Adulto , Fatores Etários , Idoso , Causas de Morte , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
After the publication of this work [1] errors were found in Figs. 1a and 5d.
RESUMO
The Ki-67 labeling index (LI) is an important prognostic factor in breast carcinoma. The Ki-67 LI is traditionally calculated via unaided microscopic estimation; however, inter-observer and intra-observer variability and low reproducibility are problems with this visual assessment (VA) method. For more accurate assessment and better reproducibility with Ki-67 LI, digital image analysis was introduced recently. We used both VA and automated digital image analysis (ADIA) (Ventana Virtuoso image management software) to estimate Ki-67 LI for 997 cases of breast carcinoma, and compared VA and ADIA results. VA and ADIA were highly correlated (intraclass correlation coefficient 0.982, and Spearman's correlation coefficient 0.966, p<0.05). We retrospectively analyzed cases with a greater than 5% difference between VA and ADIA results. The cause of these differences was: (1) tumor heterogeneity (98 cases, 56.0%), (2) VA interpretation error (32 cases, 18.3%), (3) misidentification of tumor cells (26 cases, 14.9%), (4) poor immunostaining or slide quality (16 cases, 9.1%), and (5) Estimation of non-tumor cells (3 cases, 1.7%). There were more discrepancies between VA and ADIA results in the group with a VA value of 10-20% compared to groups with <10% and ≥20%. Although ADIA is more accurate than VA, there are some limitations. Therefore, ADIA findings require confirmation by a pathologist.