Early-stage Invasive Ductal Carcinoma Research Articles

Unraveling malignant phenotype of peritumoral tissue: transcriptomic insights into early-stage breast cancer

BackgroundEarly-stage invasive ductal carcinoma displays high survival rates due to early detection and treatments. However, there is still a chance of relapse of 3–15% after treatment. The aim of this study was to uncover the distinctive transcriptomic characteristics and monitoring prognosis potential of peritumoral tissue in early-stage cases.MethodsRNA was isolated from tumoral, peritumoral, and non-tumoral breast tissue from surgical resection of 10 luminal early-stage invasive ductal carcinoma patients. Transcriptome expression profiling for differentially expressed genes (DEGs) identification was carried out through microarray analysis. Gene Ontology and KEGG pathways enrichment analysis were explored for functional characterization of identified DEGs. Protein-Protein Interactions (PPI) networks analysis was performed to identify hub nodes of peritumoral tissue alterations and correlated with Overall Survival and Relapse Free Survival.ResultsDEGs closely related with cell migration, extracellular matrix organization, and cell cycle were upregulated in peritumoral tissue compared to non-tumoral. Analyzing PPI networks, we observed that the proximity to tumor leads to the alteration of gene modules involved in cell proliferation and differentiation signaling pathways. In fact, in the peritumoral area were identified the top ten upregulated hub nodes including CDK1, ESR1, NOP58, PCNA, EZH2, PPP1CA, BUB1, TGFBR1, CXCR4, and CCND1. A signature performed by four of these hub nodes (CDK1, PCNA, EZH2, and BUB1) was associated with relapse events in untreated luminal breast cancer patients.ConclusionsIn conclusion, our study characterizes in depth breast peritumoral tissue providing clues on the changes that tumor signaling could cause in patients with early-stage breast cancer. We propose that the use of a four gene signature could help to predict local relapse. Overall, our results highlight the value of peritumoral tissue as a potential source of new biomarkers for early detection of relapse and improvement in invasive ductal carcinoma patient’s prognosis.

Abstract PO1-22-02: Optimal intra-fraction PTV margins for patients receiving stereotactic partial breast radiation (SPBI) using cone beam adaptive radiation therapy

Abstract Objectives To quantify the intra-fraction tumor bed motion using image guidance and fiducial markers to determine optimal PTV margins in early-stage breast cancer patients receiving adaptive radiation therapy SPBI after partial mastectomy. Methods A retrospective cohort of five patients with pT1a-pT2N0, grade 1-2, ER+/PR+ early-stage invasive ductal carcinoma of either the right breast or left breast underwent partial mastectomy and adjuvant five-fraction SPBI using cone beam based online adaptation. A total of 62 CBCTs and 22 total fractions were analyzed after post-processing with an average time span of 39.1±8.9 minutes. Two methods were utilized to determine optimal CTV to PTV margins: one contouring-based and another fiducial-based. Our contouring-based method involved independently contouring on each fraction’s CBCTs including pre-treatment CBCT, intra-treatment CBCT, and post-treatment CBCT. After image registration with the original simulation CT image, these contours were propagated to and combined to create a new union CTV. Using the original CTV on the simulation CT, optimal PTV margin was determined to achieve 95% overlap of the union CTV created from fractionated CBCTs. In addition to the contouring-based method, our fiducial-based method utilized an in-house script to calculate the centroid of all fiducials per CBCT. The average and maximum anterior-posterior, medial-lateral, superior-inferior shifts of fiducials between intra-fraction CBCTs were recorded. Results Using our contouring-based method, we calculated and determined that a uniform 3.5 mm expansion around the original CT simulation CTV is needed to achieve 95% PTV overlap encompassing the pre-treatment, intra-treatment, and post-treatment union CTV. Furthermore, with our fiducial-based method, we calculated average centroid anterior-posterior, medial-lateral and superior-inferior shifts to be the following: 1.51±0.79mm, 1.04±0.55 mm, 1.78±0.94 mm respectively. Average maximum shifts were determined to be 2.13±1.18mm anterior-posterior, 1.45±0.76mm medial-lateral and 2.47±1.40mm superior-inferior shifts. Conclusion With our contouring-based analysis, this preliminarily study suggests CTV to PTV margin of 3.5mm is adequate. On the other hand, our fiducial-based method suggests decreased movement and smaller asymmetric margin. Further CBCT adaptation images will be analyzed. In conjunction with these two methods, we currently recommend utilizing a 3.5mm uniform margin for intrafraction motion and to assess adequate coverage with image guidance during daily adaptation for patients with early-stage breast cancer receiving SPBI. Citation Format: Meng-Lun Hsieh, Justin Visak, Sean Domal, Gabrielle Gard, Steven Montalvo, Liyuan Chen, Xinran Zhong, Zohaib Iqbal, Tingliang Zhuang, Bin Cai, Heejung Kim, Mona Arbab, Prasanna Alluri, Nathan Kim, Mu-Han Lin, David Parsons, Asal Rahimi. Optimal intra-fraction PTV margins for patients receiving stereotactic partial breast radiation (SPBI) using cone beam adaptive radiation therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-02.

Matrix Metalloproteinase as Predictors of Local Recurrence in Early-Stage Breast Cancer After Mastectomy and Chemotherapy A Cross-Sectional Study in Single Centre

Introduction: The prognosis for early-stage breast cancer is generally favourable. However, in cases when a recurrence manifests after therapy, the prognosis becomes significantly poor. To determine early breast cancer recurrence risk, a marker is needed. Currently, previous tumour markers are used to predict general breast cancer, lacking specificity in the context of early breast cancer. Matrix Metalloproteinase1 (MMP1) is already acquainted with the local recurrence process of invasive ductal carcinoma (IDC). MMP1 expression may better predict early recurrence in early-stage IDC than other approaches. This research examined the potential predictive value of MMP1 expression in early-stage IDC for early local recurrence and its correlation with clinicopathological factors. Methods: This study was a cross-sectional analysis of a single center's medical records. The sample size was 25 subjects for the group without recurrence and 25 subjects with recurrence. Mastectomy and chemotherapy were performed from January 2014 through December 2019. Using immunohistochemistry, paraffin blocks of surgical specimens were examined for MMP1. The data processing was done utilising the trial version of IBM SPSS 25. and Openepi 3.0 programs and analysed using Bivariate, which is performed using the Chi-square test or Fisher's exact test. Result: The statistic test showed a significant difference (p < 0.000) in the average expression of MMP1 for non-recurrence cases (3,95±5,36) compared to recurrence cases (14,95±5,36). We also found a statistically significant correlation between recurrence and high expression of MMP1 (odd ratio [OR]= 60.38, 95% confidence interval [CI]=10.01-364.3, p<0.001). Clinicopathological variables and MMP1 expression did not have a significant correlation. Conclusions: In early-stage IDC, MMP1 expression had the potential to predict and could be an independent prognostic factor for early recurrence.

Breast Edema of Early-stage Invasive Ductal Carcinoma: Correlation with Axillary Lymph Node Metastasis and Clinical-pathological Characteristics.

This study aimed to evaluate the association of different patterns of breast edema and clinical-pathological features and axillary lymph node (ALN) status in early invasive ductal carcinoma (IDC) for simple and readily available assessment and to guide surgeons to perform sentinel lymph node biopsy for selected patients. This retrospective analysis involved 207 individuals with clinical T1-T2 stage IDC. The clinical-pathological features of the patients were compared with different breast edema and ALN statuses. Independent risk factors for ALN metastasis were verified using multivariate logistic regression analysis. ALN metastasis was confirmed in 100 of 207 patients (48.3%) with early-stage IDC. Significant differences were found between different ALN states for tumour size, clinical T stage, and breast edema (P <0.05). The clinical T2 stage (odds ratio-1.882, p=0.043) and moderate to severe edema (odds ratio-10.869, p=0.004) were independent risk factors for ALN metastasis. Moreover, better prognostic factors, including smaller tumour size, lower Ki-67 index and histologic grade, luminal A subtype, and lower incidence of lymph node metastasis, were more frequently found in patients with no breast edema (p<0.05). Breast edema can be considered a promising feature to improve the predictive performance of pathological ALN status in patients with early-stage breast cancer and thus may contribute to preoperative treatment planning.

Short- and long-term recurrence of early-stage invasive ductal carcinoma in middle-aged and old women with different treatments

Most new cases and the highest mortality rates of breast cancer occur among middle-aged and old women. The recurrence rate of early-stage invasive ductal carcinoma (IDC) among women aged ≥ 50 years and receiving different treatments remains unclear. Therefore, this study was conducted to determine these rates. We used Surveillance, Epidemiology, and End Results (SEER) data for this nationwide population-based cohort study. All women aged ≥ 50 years and diagnosed with early-stage IDC between 2000 and 2015 were identified and divided into three treatment groups, namely, breast conservation therapy (BCT), mastectomy alone (MAS), and mastectomy with radiation therapy (MAS + RT). The recurrence rates of IDC among these groups were then compared. The BCT group had a lower short-term recurrence risk than the MAS and MAS + RT groups (hazard ratio [HR]: 1.00 vs. 2.90 [95% CI 1.36–2.66] vs. 2.07 [95% CI 0.97–4.44]); however, the BCT group also had a higher long-term recurrence risk than MAS and MAS + RT groups (HR 1.00 vs. 0.30 [95% CI 0.26–0.35] vs. 0.43 [95% CI 0.30–0.63]). The high long-term recurrence rate of the BCT group was especially prominent at the 10- and 15-year follow-ups. The results provide valuable evidence of the most reliable treatment strategy for this population. Further studies including more variables and validation in other countries are warranted to confirm our findings.

Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality Using Genes Commonly Involved in Breast Cancer: A Retrospective Study

Introduction: Invasive ductal carcinoma (IDC) of the breast is a heterogeneous disease characterized by multiple subtypes. IDC survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on IDC prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC to provide further understanding of the genetic characteristics associated with poor survival. Methods: The gene mutation profiles, baseline demographics, clinicopathologic variables, and treatment characteristics of the early-stage IDC subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 40 genes commonly involved in IDC were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes. Results: The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates of low-risk, control, and high-risk patients were 97.4%, 96.1%, and 73.0%, respectively. The high-risk group had a significantly higher risk of poor overall ­survival (adjusted hazard ratio = 6.57, 95% confidence interval = 1.51–28.7, p = 0.012) than that of the control group, and the low-risk group did not have a significant survival difference compared with control group. Conclusions: This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 14 candidate genes selected are particularly involved in cell-cycle processes, deoxyribonucleic acid repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor overall survival outcomes in IDC.

Comparing the effect of distance to treatment facility on reconstruction and breast conservation therapy for early-stage invasive ductal carcinoma between the nation and the mountain region

BackgroundOur objective is to evaluate the effect of distance to facility on the use of breast conservation therapy and reconstruction for early stage breast cancer. MethodsUtilizing the National Cancer Database, we identified females, age <65, with Stage I invasive ductal carcinoma from 2004 to 2015. Using logistic regression, we compared radiation, mastectomy, and reconstruction treatment patterns. A subgroup analysis was performed within the mountain region (MR). ResultsNationwide, there are decreasing odds of radiation, increasing odds of mastectomy, and increasing odds of reconstruction. Patients living farther were less likely to receive radiation, more likely to undergo mastectomy, with no effect on reconstruction. Within the MR, patients living farther from their facility were less likely to receive radiation, more likely to undergo mastectomy, however, they were less likely to undergo reconstruction. ConclusionsNationwide and within the MR, patients living farther from their facility are less likely to receive radiation and more likely to undergo mastectomy. There is a disparity between the MR and the nation in use of reconstruction for this population.

Abstract PS14-24: Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results

Abstract Purpose: To report on the technique of intra-operative electronic brachytherapy, local control, side effects and complications after a single fraction of 2000 cGy at the time of partial mastectomy. Material &amp; Methods: 1200 patients with early stage invasive ductal carcinoma and carcinoma in situ were enrolled in the Multi-Center Trial. 246 (20.5%) patients among these 1200 patients had carcinoma in situ and were treated by a single fraction of 2000 cGy dose by intra-operative irradiation to the lumpectomy cavity using Xoft system of electronic brachytherapy at the time of partial mastectomy. 80% of the patients were Caucasian, 7% African American, 7% Hispanic and 6% others. Estrogen receptor was positive in 211 patients, negative in 28 patients and unknown/not assessed in 7 patients. Progesterone receptor was positive in 190 patients, negative in 45 patients and unknown/not assessed in 11 patients. All patients were BRCA negative. 34 (14%) patients had low grade tumors, 109 (44%) intermediate grade tumors, and 103 (42%) high grade tumors. Seroma occurred in 9.8%, induration in 7.6%, and significant fibrosis in 3.5% of the patients. 2/246 (1%) developed ipsilateral recurrence and one patient developed a gastrointestinal cancer. 118 (48%) patients had characteristics of ASTRO criteria being suitable, 108 (44%) cautionary and 20 (8%) unsuitable. Conclusion: The relatively early 2.3 year results of a single fraction of 2000 cGy by IORT to the lumpectomy cavity at the time of partial mastectomy using Xoft Axxent electronic brachytherapy in the treatment of carcinoma in situ of the breast is safe and associated with low morbidity and local recurrence with good to excellent cosmesis in 80% of the patients. Citation Format: Alam M.Nisar Syed. Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-24.

Background Parenchymal Enhancement on Breast MRI as a Prognostic Surrogate: Correlation With Breast Cancer Oncotype Dx Score.

PurposeBreast MRI background parenchymal enhancement (BPE) can potentially serve as a prognostic marker, by possible correlation with molecular subtype. Oncotype Dx, a gene assay, is a prognostic and predictive surrogate for tumor aggressiveness and treatment response. The purpose of this study was to investigate the association between contralateral non-tumor breast magnetic resonance imaging (MRI) background parenchymal enhancement and tumor oncotype score.MethodsIn this retrospective study, patients with ER+ and HER2− early stage invasive ductal carcinoma who underwent preoperative breast MRI, oncotype risk scoring, and breast conservation surgery from 2008–2010 were identified. After registration, BPE from the pre and three post-contrast phases was automatically extracted using a k-means clustering algorithm. Four metrics were calculated: initial enhancement (IE) relative to the pre-contrast signal, late enhancement, overall enhancement (OE), and area under the enhancement curve (AUC). Histogram analysis was performed to determine first order metrics which were compared to oncotype risk score groups using Mann–Whitney tests and Spearman rank correlation analysis.ResultsThis study included 80 women (mean age = 51.1 ± 10.3 years); 46 women were categorized as low risk (≤17) and 34 women were categorized as intermediate/high risk (≥18) according to Oncotype Dx. For the mean of the top 10% pixels, significant differences were noted for IE (p = 0.032), OE (p = 0.049), and AUC (p = 0.044). Using the risk score as a continuous variable, correlation analysis revealed a weak but significant correlation with the mean of the top 10% pixels for IE (r = 0.26, p = 0.02), OE (r = 0.25, p = 0.02), and AUC (r = 0.27, p = 0.02).ConclusionBPE metrics of enhancement in the non-tumor breast are associated with tumor Oncotype Dx recurrence score, suggesting that the breast microenvironment may relate to likelihood of recurrence and magnitude of chemotherapy benefit.

Oncoplastic breast-conserving therapy and intraoperative radiotherapy for management of carcinoma in situ of the breast: A single-center experience.

Intraoperative radiation therapy (IORT) has been shown to reduce local recurrence rates among women with early-stage invasive ductal carcinoma, but data regarding its use among women with in situ carcinoma are limited. In this single-institution study, 50 women with in situ carcinoma were treated with oncoplastic breast-conserving surgery (OPS) and single-dose IORT. All 50 patients had "no tumor on ink," but 9 (16%) had margins<2mm and required additional therapy. No local recurrences were observed after a median follow-up of 46months. Single-dose IORT is an efficacious treatment for well-selected patients with DCIS.

Muscular endurance and progression rates of early-stage invasive ductal carcinoma: A pilot study.

Muscular endurance and progression rates of early-stage invasive ductal carcinoma: A pilot study.

E-cadherin expression phenotypes associated with molecular subtypes in invasive non-lobular breast cancer: evidence from a retrospective study and meta-analysis

BackgroundThis retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC).MethodsA total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics.ResultsE-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P < 0.050); moreover, the molecular subtypes were an independent factor influencing E-cad expression in early-stage IDCs. A total of 12 observational studies (including our study) were included in the meta-analysis. The meta-analytical results show a significantly greater risk of E-cad expression loss in triple-negative breast cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79–4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49–3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24–3.07).ConclusionsEarly-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.

Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.

Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms. In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group ( p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group ( p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group ( p < 0.001). Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.

High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer

AimsBreast cancers are heterogeneous, making it essential to recognise several biomarkers for cancer outcome predictions. Ki67 proliferation index and B cell lymphoma 2 (BCL2) proteins are widely used as prognostic...

Excellent Long-term Breast Preservation Rate After Accelerated Partial Breast Irradiation Using a Balloon Device

BackgroundAccelerated partial breast irradiation (APBI) using a balloon device has been well tolerated. A recent retrospective population-based study showed an increase in the rate of subsequent mastectomy for patients who undergo APBI compared with whole breast radiation therapy. Our aim was to analyze the long-term results of patients treated with APBI at our institution to determine the salvage mastectomy and locoregional recurrence rates and cosmesis outcomes. Materials and MethodsAfter institutional review board approval, we conducted a retrospective review of 111 patients treated from June 2003 to October 2014 at our institution for early-stage breast cancer using a balloon device. After lumpectomy and nodal staging, the patients underwent APBI with high-dose rate iridium-192 brachytherapy. A computed tomography-based 3-dimensional plan was created, and a dose of 34 Gy in 10 fractions was given twice daily, 6 hours apart, over 5 days. Follow-up examinations were performed 2 to 3 times annually by either a surgeon and/or a radiation oncologist. Annual mammograms were obtained. The patients included postmenopausal women with node-negative early-stage invasive ductal carcinoma with a tumor size < 3 cm (n = 93) or ductal carcinoma in situ (n = 18). Cosmesis was evaluated using the Harvard criteria, as excellent, good, fair, or poor. ResultsAt a median follow-up period of 66 months (range, 1-139 months) after completing treatment, with a minimum of 5 years of follow-up data for 62 patients (55.9%), the incidence of ipsilateral breast tumor recurrence (IBTR) was 2.7% (n = 3) and the incidence of ipsilateral axilla nodal recurrence was 1.8% (n = 2). The ipsilateral breast preservation rate was 97.3%. The salvage mastectomy rate was 2.7% (n = 3), and the 5-year salvage mastectomy-free rate was 98.7% (95% confidence interval, 91.0%-99.8%). No distant failure developed, and no breast cancer-related deaths occurred. The 5-year overall survival rate was 91.7% (95% confidence interval, 83.2%-96.0%), and the 10-year breast cancer-specific survival rate was 100%. Of the 3 cases of IBTR, 2 were estrogen receptor negative (P = .076). The mean interval to IBTR was 78.7 ± 27.5 months from treatment completion. A significant association was noted between African-American ethnicity and IBTR (P = .0398). Excellent to good cosmesis was observed in 98.1% of the patients. The maximum skin dose (mean value) for patients with excellent, good, and fair cosmesis was 302.2 Gy, 315.4 Gy, and 372.5 Gy (88.9%, 92.7%, and 109.5% of the prescription dose), respectively. The maximum skin dose was < 340 Gy (100% of the prescribed dose) in 69.9% of patients with excellent to good cosmesis. ConclusionThe long-term follow-up data of patients receiving APBI with a balloon device showed a low salvage mastectomy rate with durable long-term breast preservation. Excellent local control with good cosmesis was noted in these postmenopausal patients treated with APBI.

Significance of Sentinel Lymph Nodes with Low Gamma Counts in Breast Cancer Patients via Radioisotopic Sentinel Lymph Node Biopsy

Objective: Sentinel lymph node biopsy (SLNB), a standard diagnostic procedure worldwide, uses blue dye and/or radioisotopic methods to detect clinically node-negative breast cancer. With the latter method, we often experience axillary lymph nodes with extremely low levels of radioactivity, compared with the maximum radioactive nodes. Here, we investigated the significance and possibility of metastasis in low radioactive SLNs in patients with and without metastasis in maximum radioactive SLNs. Patients and methods: Between 2003 and 2011, we subjected a total of 453 breasts in 443 patients with earlystage invasive ductal carcinoma to SLNB using a combination of blue dye and radioisotopic methods. All lymph nodes detected via gamma -probe were considered SLNs and resected. Results: SLNs were identified in 452 (99.8%) of 453 cases; of these, SLN metastasis was pathologically diagnosed in 118 cases (26.1%). Two or more SLNs were detected in 232 (51.2%) of 453 cases; of these, 46 cases (19.8%) had SLNs with gamma counts < 10% of the maximum detected values. Metastasis was detected in these low-gamma-count SLNs in 4 of 453 cases (0.9%), even though no metastasis had been detected in SLNs with maximum radioactivity levels. Macrometastasis was pathologically demonstrated in 3 of 4 cases. Conclusion: We identified several cases of metastatic SLNs with very low radioactivity, despite a lack of metastasis in SLNs with maximum radioactivity. These findings indicate that the evaluation of SLNs with gamma counts < 10% of the patient maximum would provide more precise information about the axillary status and help to maintain a low SLNB false-negative rate.

Early-stage invasive ductal carcinoma: Association of tumor apparent diffusion coefficient values with axillary lymph node metastasis

PurposeTo evaluate any association between tumor apparent diffusion coefficient (ADC) values and axillary lymph node metastasis (ALNM) in early-stage invasive ductal carcinoma. Materials and methodsRecords of 270 invasive ductal carcinoma patients with stages T1 and T2 disease who underwent breast magnetic resonance imaging, including diffusion-weighted imaging with b values of 0 and 1000s/mm2 were reviewed retrospectively. The tumor ADC values were analyzed for their utility in predicting ALNM using multivariate regression analysis and receiver operating characteristic (ROC) curve analysis. ResultsOf the 270 patients, 58 (21.5%) experienced ALNM. The mean tumor ADC values were significantly lower in patients with ALNM than in those without metastasis (0.880×10−3 vs. 0.999×10−3mm2/s, P<0.001). A ROC curve demonstrated a tumor ADC value of 0.991×10−3mm2/s to be the optimal cut-off for predicting ALNM. In a multivariate analysis, lower tumor ADC (≤0.991×10−3mm2/s; adjusted odds ratio (OR)=5.861, P<0.001), large tumor size (>2cm; adjusted OR=3.156, P=0.002) and the presence of lymphovascular invasion (adjusted OR=4.125, P<0.001) were independent variables associated with ALNM. When tumor ADC value was added to known risk factors (i.e., tumor size and lymphovascular invasion), a significant improvement in the accuracy of risk prediction for axillary node metastasis was shown (c-statistic=0.758 vs. 0.816, P=0.026). ConclusionIn early-stage invasive ductal carcinoma, lower tumor ADC values are associated with the presence of ALNM.

Proteomic Profiling of Invasive Ductal Carcinoma (IDC) using Magnetic Beads‐based Serum Fractionation and MALDI‐TOF MS

To reveal the serum proteomic profiling of intraductal carcinoma (IDC) patients in China, establish a serum proteome fractionation technique for choosing magnetic beads for proteomic analysis in breast cancer research; and identify differentially expressed peptides (m/z; P < 0.0001) as potential biomarkers of early IDCs. We used two different kinds of magnetic beads (magnetic bead-based weak cation exchange chromatography (MB-WCX) and immobilized metal ion affinity chromatography (MB-IMAC-Cu)) to analyze 32 patients with early stage (stages I-II) IDC and 32 healthy control serum samples for proteomic profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The mass spectra, analyzed using ClinProTools software, distinguished between IDC patients and healthy individuals based on k-nearest neighbor genetic algorithm. The serum samples purified in the MB-WCX group provided better proteomic patterns than the MB-IMAC-Cu group. The samples purified by MB-WCX had better average peak numbers, higher peak intensities, and better capturing ability of low abundance proteins or peptides in serum samples. In addition, the MB-WCX and MB-IMAC-Cu purification methods, followed MALDI-TOF MS identification and use of ClinProTools software accurately distinguished patients with early stage IDC from healthy individuals. Serum proteomic profiling by MALDI-TOF MS is a novel potential tool for the clinical diagnosis of patients with IDC in China.

Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer

To our knowledge, there are no recent studies that directly compare survival after breast conservation therapy (BCT) vs mastectomy. To compare the breast cancer-specific survival rates of patients undergoing BCT, mastectomy alone, or mastectomy with radiation using a contemporary cohort of patients. We performed univariate, multivariate logistic regression, and propensity analyses to compare the hazard of death for female patients with early-stage invasive ductal carcinoma treated with BCT, mastectomy alone, or mastectomy with radiation during the period from 1998 to 2008. The data were extracted from the Surveillance, Epidemiology, and End Results database. Early-stage breast cancer was defined as having a tumor size of 4 cm or smaller with 3 or less positive lymph nodes. Breast conservation therapy, mastectomy alone, or mastectomy with radiation. Hazard of death due to breast cancer for patients undergoing BCT, mastectomy alone, or mastectomy with radiation. A total of 132,149 patients were included in this analysis. Breast conservation therapy was used to treat 70% of patients, mastectomy alone was used to treat 27% of patients, and mastectomy with radiation was used to treat 3% of patients. The 5-year breast cancer-specific survival rates of patients who underwent BCT, a mastectomy alone, or a mastectomy with radiation were 97%, 94%, and 90%, respectively (P < .001); the 10-year breast cancer-specific survival rates were 94%, 90%, and 83%, respectively (P < .001). Multivariate analysis showed that women undergoing BCT had a higher survival rate than those undergoing mastectomy alone (hazard ratio, 1.31; P < .001) or mastectomy with radiation (hazard ratio, 1.47; P < .001). When propensity score stratification was used, the effect of treatment method on survival was similar. Patients who underwent BCT have a higher breast cancer-specific survival rate compared with those treated with mastectomy alone or mastectomy with radiation for early-stage invasive ductal carcinoma. Further investigation is warranted to understand what may be contributing to this effect.

Invasive breast cancer induces laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling

IntroductionAlthough development of anoikis-resistant myofibroblasts during tissue remodeling is known to be associated with tumor invasion, the mechanism by which myofibroblasts become resistant to anoikis is unknown. We previously demonstrated laminin-332 upregulation in the fibrosis around invasive ductal carcinoma (IDC). Because laminin-332 promotes cell survival through binding to integrins, we hypothesized that invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts by upregulating laminin-332 expression during tissue remodeling. Here, we demonstrate that invasive breast cancer cells induce laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype.MethodsThree types of fibroblasts were isolated from the tumor burden, the fibrosis, and normal tissue of patients with early stage IDC (less than 10 mm diameter), designated cancer-associated fibroblasts (CAFs), interface fibroblasts (InFs), and normal breast fibroblasts (NBFs), respectively. To investigate direct and indirect crosstalk with tumor cells, fibroblasts were co-cultured with invasive MDA-MB-231 or noninvasive MCF7 cells or in conditioned medium. Anoikis resistance of fibroblasts was measured by cell viability and caspase-3 activity after incubation on poly-HEMA coated plates for 72 hours. Involvement of laminin-332/integrin α3β1 or α6β4 signaling in anoikis resistance was confirmed by treatment with purified laminin-332 or blocking antibodies against laminin-332, integrin β1, or integrin β4.ResultsMDA-MB-231 cells induced laminin-332 upregulation and integrin β4 neoexpression in fibroblasts, leading to anoikis resistance. InFs showed a higher endogenous level of laminin-332 than did CAFs and NBFs. After stimulation with MDA-MB-231-conditioned medium, laminin-332 expression of InFs was dramatically increased and maintained under anoikis conditions. Laminin-332 upregulation was also observed in CAFs and NBFs, but at a lower level than in InFs. Laminin-332 induced Akt (Ser473) phosphorylation by binding to integrin α3β1. Integrin β4 neoexpression induced laminin-332-independent Rac1 activation and promoted anoikis resistance in fibroblasts approximately twofold more effectively than did laminin-332, regardless of the type of fibroblast. In addition, integrin β4 expression suppressed fibroblast aggregation in conditions of anoikis.ConclusionInvasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts during tissue remodeling by inducing laminin-332 upregulation and integrin β4 neoexpression. Interface fibroblasts appear to be the primary myofibroblasts that interact with invasive tumor cells during tissue remodeling.