Triple-negative Invasive Breast Carcinoma Research Articles

Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma

AimsSecretory carcinoma of breast (SCB) typically harbours ETV6-NTRK3 gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was...

Anti-transcription intermediary factor 1 gamma antibody-associated paraneoplastic dermatomyositis: A case report

Dermatomyositis (DM) is an inflammatory myopathy characterized by distinctive cutaneous manifestations. Recent advancements have led to the identification of a novel myositis-specific autoantibody called anti-transcription intermediary factor 1 gamma (anti-TIF-1-γ) which presents with unique cutaneous manifestations and a heightened risk for malignancy. We report a case of a 55-year-old female who presented with proximal muscle weakness, an erythematous rash over the face, blanching erythema over the nape of the neck, and red-on-white lesions over the chest. She was diagnosed with anti-TIF-1-γ positive DM and found to have a palpable mass in the right breast. Biopsy showed triple negative invasive breast carcinoma no special type (NST) grade 3. She showed poor response to steroids and was referred for cancer staging and treatment. The anti-TIF-1-γ antibody serves as a novel tool to identify a subset of DM patients at high risk for cancer. At present, its role in the prognosis or surveillance of cancer recurrence remains uncertain.

Relationship between Age, Histologic Grade, Tumour Size, Immunohistochemical Biomarkers Expressions and Molecular Subtypes of Invasive Breast Carcinoma in Ilorin, Nigeria

Background: Background: Invasive breast carcinoma causes the most cancer-related death in women, and age is an essential non-modifiable risk factor. This study determined the relationship between age and histopathologic grade, tumor size, immunohistochemical biomarkers (ER, PR, and HER-2) expressions, and subtypes of invasive breast carcinoma. Methods: This was a retrospective hospital-based study of patients with prior histopathological diagnoses of invasive breast carcinoma. Relevant data, including age, histologic type, grade, tumor size, and hormonal receptor status, were retrieved from the archival pathology request forms. Results: The mean age of study subjects was 52.14 ± 12.14 years. The peak age group was in the 5th decade, accounting for 37.0 (32.7%) cases. Nottingham grade III invasive breast carcinoma accounted for 47 (41.6 %) cases and predominated in the 6th decade, accounting for 17 (50.0%) cases. Majority of the study subjects presented with tumor size greater than 5.0 cm (75.9%). The mean tumor size was 6.87 ± 3.20 cm and ranged from 3.2 cm to 16.0 cm. The immunohistochemical expressions of ER, PR, and HER-2 biomarkers were 36.3%, 28.3%, and 41.6%, respectively, particularly in the 5th and 6th decades. Also, Luminal A, Luminal B, Triplenegative, and HER-2 enriched subtypes occurred in 16.8%, 20.4%, 42.4%, and 20.4% cases respectively in the 5th and 6th decades. However, the triple-negative subtype was found in the 4th to 6th decades in equal proportions. Conclusion: This study observed triple-negative invasive breast carcinoma immunohistochemical subtypes with age association from the 4th to 6th decade

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland–Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from −0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the ‘ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there is insufficient evidence for robust and reproducible sTILs-guided therapeutic decisions.

Prediction for pathological and immunohistochemical characteristics of triple-negative invasive breast carcinomas: the performance comparison between quantitative and qualitative sonographic feature analysis.

Sonographic features are associated with pathological and immunohistochemical characteristics of triple-negative breast cancer (TNBC). To predict the biological property of TNBC, the performance using quantitative high-throughput sonographic feature analysis was compared with that using qualitative feature assessment. We retrospectively reviewed ultrasound images, clinical, pathological, and immunohistochemical (IHC) data of 252 female TNBC patients. All patients were subgrouped according to the histological grade, Ki67 expression level, and human epidermal growth factor receptor 2 (HER2) score. Qualitative sonographic feature assessment included shape, margin, posterior acoustic pattern, and calcification referring to the Breast Imaging Reporting and Data System (BI-RADS). Quantitative sonographic features were acquired based on the computer-aided radiomics analysis. Breast cancer masses were manually segmented from the surrounding breast tissues. For each ultrasound image, 1688 radiomics features of 7 feature classes were extracted. The principal component analysis (PCA), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) were used to determine the high-throughput radiomics features that were highly correlated to biological properties. The performance using both quantitative and qualitative sonographic features to predict biological properties of TNBC was represented by the area under the receiver operating characteristic curve (AUC). In the qualitative assessment, regular tumor shape, no angular or spiculated margin, posterior acoustic enhancement, and no calcification were used as the independent sonographic features for TNBC. Using the combination of these four features to predict the histological grade, Ki67, HER2, axillary lymph node metastasis (ALNM), and lymphovascular invasion (LVI), the AUC was 0.673, 0.680, 0.651, 0.587, and 0.566, respectively. The number of high-throughput features that closely correlated with biological properties was 34 for histological grade (AUC 0.942), 27 for Ki67 (AUC 0.732), 25 for HER2 (AUC 0.730), 34 for ALNM (AUC 0.804), and 34 for LVI (AUC 0.795). High-throughput quantitative sonographic features are superior to traditional qualitative ultrasound features in predicting the biological behavior of TNBC. • Sonographic appearances of TNBCs showed a great variety in accordance with its biological and clinical characteristics. • Both qualitative and quantitative sonographic features of TNBCs are associated with tumor biological characteristics. • The quantitative high-throughput feature analysis is superior to two-dimensional sonographic feature assessment in predicting tumor biological property.

Ultrasonographic appearance of triple-negative invasive breast carcinoma is associated with novel molecular subtypes based on transcriptomic analysis.

BackgroundVarious sonographic features of triple-negative invasive breast carcinomas (TNBC) expected to be associated with the molecular subtypes based on transcriptomic analysis were examined. The effects of clinical, sonographic, pathological, and molecular features on survival outcome was also studied.MethodsOne hundred and fourteen patients with breast cancer with negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor 2 (HER2) were included in our retrospective study. Based on the transcriptomic profiles, four stable clusters named immunomodulatory (IM), luminal androgen receptor (LAR), mesenchymal-like (MES), and basal-like and immune-suppressed (BLIS) were identified. Ultrasound (US) images were reviewed by two US physicians according to Breast Imaging Reporting and Data System (BI-RADS). Multivariate Cox regression was used to determine the variables associated with recurrence-free survival (RFS) and overall survival (OS).ResultsThere were 21 IM, 18 LAR, 36 MES, and 39 BLIS cases. The four molecular subtypes showed significant differences in terms of tumor shape (P=0.008) and posterior acoustic pattern (P=0.028). Compared with the subtypes LAR and MES, the IM and BLIS subtypes had higher probability of presenting benign-like sonographic features, such as regular shape, no angular/spiculated margin, and posterior acoustic enhancement (P<0.05). The independent risk factors for RFS events and death were axillary lymph node metastasis (P<0.05) and BLIS subtype (P<0.05). BLIS subtype showed worse OS than other subtypes (log rank P=0.05). TNBCs with benign sonographic features tended to have less death events (3.3% vs. 15.2%, P=0.088).ConclusionsSonographic appearance of TNBCs is associated with transcriptome-based molecular subtypes, and tends to correlate with the survival outcome.

The association between molecular biomarkers and ultrasonographic radiomics features for triple negative invasive breast carcinoma

Objective To evaluate the association between quantitative ultrasonographic features and clinical, pathological and immunohistochemical features of triple negative invasive breast carcinoma(TNBC). Methods With the ethical approval, 96 patients who were pathologically confirmed as TNBC were retrospectively reviewed. All patients were sub-grouped according to age, tumor size, pathological grade, Ki67 expression level and human epidermal growth factor receptor 2 (HER-2) score.Ultrasound images were segmented for the breast carcinoma mass using a phase-based active contour model. The high-throughput radiomics features were extracted based on the two-dimensional sonographic features. There were 460 features extracted from each ultrasound image. A series of computer aided algorithms including K-svd algorithm, sparse representation, support vector machine (SVM) and radial basis function were used to determine the high-throughput sonographic features that were highly correlated to clinical, pathological and immunohistochemical features of TNBC. The performance efficacy was expressed by accuracy and area under curve (AUC) of the ROC curve. Results The high-throughput ultrasonographic features of invasive TNBC could predict its pathological grade, Ki67 level and HER-2 score with the accuracy 92.2%-96.9% and AUC 98.7%-99.9%. There were 82 radiomics features selected for predicting the pathological grade of TNBC, the feature with the maximum weight was the elliptic-normalized eccentricity based on morphological features. There were 100 features selected for predicting the Ki67 expression level, the feature with the maximum weight was the standard deviation of the annular region based on the boundary texture features. There were 85 features selected for the prediction of HER-2 score, the most powerful parameter was the intensity based on NGTDM texture features. Conclusions Quantitative high-throughput ultrasonographic features are correlated with the pathological and immunohistochemical characteristics of invasive TNBC. High-throughput ultrasonographic features are valuable in predicting biological behavior of TNBC. Key words: Ultrasonography; Breast neoplasms; Pathology; Radiomics; Immunohistochemistry

A Clinical Perspective on Triple Negative Invasive Breast Carcinomas with Comedo Necrotic Features

Abstract Triple-negative breast carcinomas are characterized by its unique molecular profile, histological and clinical features and distinct patterns of metastasis, and lack of targeted therapies. Most, but not all, triple negative

Management and prognosis of pure primary squamous cell carcinoma of the breast

PurposeThe aim of the study was to investigate the management and prognosis of Pure primary squamous cell carcinoma (PPSCC) of the breast. Materials and methodsThis study is a multicentre retrospective cohort from three French tertiary referral hospitals (Rennes, Orléans and Tours) including all women treated for a PPSCC of the breast defined by squamous cells that could contain a minority of sarcomatoid component. We excluded carcinomas with a ductual component. Clinicopathologic, radiological and therapeutic patterns were described. Demographic, histological and therapeutic characteristics were compared to a population of women with triple negative invasive breast carcinomas. ResultsTwelve patients were included, with a mean age of 71.6 years. All lesions were unifocal, with a cystic complex ultrasound mass in 50% of cases. Mean tumor size was 43mm, with axillary lymph node metastasis in 25% of patients.The comparison with a population of women with triple negative breast carcinomas revealed that women with PPSCC were older (71 versus 57 years, p=0.003), tumor size was larger (43mm versus 25mm, p=0.032) and local recurrence occurred earlier (three months versus 38 months, p=0.014). ConclusionPPSCC is a rare entity with a worse prognosis in comparison with triple negative invasive carcinoma.

Triple-negative invasive breast carcinoma: the association between the sonographic appearances with clinicopathological feature

In this study, we aimed to evaluate the clinical and pathological factors that associated with sonographic appearances of triple-negative (TN) invasive breast carcinoma. With the ethical approval, 560 patients who were pathologically confirmed as invasive breast carcinoma were reviewed for ultrasound, clinical, and pathological data. Logistic regression analysis was used to identify the typical sonographic features for TN invasive breast carcinomas. The effect of clinical and pathological factors on the sonographic features of TN invasive breast carcinoma was studied. There were 104 cases of TN invasive breast carcinoma. The independent sonographic features for the TN subgroup included regular shape (odds ratio, OR = 1.73, p = 0.033), no spiculated/angular margin (OR = 2.09, p = 0.01), posterior acoustic enhancement (OR = 2.09, p = 0.004), and no calcifications (OR = 2.11, p = 0.005). Higher pathological grade was significantly associated with regular tumor shape of TN breast cancer (p = 0.012). Higher Ki67 level was significantly associated with regular tumor shape (p = 0.023) and absence of angular/spiculated margin (p = 0.005). Higher human epidermal growth factor receptor 2 (HER2) score was significantly associated with the presence of calcifications (p = 0.033). We conclude that four sonographic features are associated with TN invasive breast carcinoma. Heterogeneity of sonographic features was associated with the pathological grade, Ki67 proliferation level and HER2 score of TN breast cancers.

Evaluation of cMET aberration by immunohistochemistry and fluorescence in situ hybridization (FISH) in triple negative breast cancers.

To evaluate the incidence of cMET proto-oncogene aberration in a cohort of triple negative breast cancers using immunohistochemistry and fluorescence in situ hybridization (FISH) methods and correlated with patient outcome. One hundred and six female patients with diagnosis of triple negative invasive breast carcinoma at The University of Texas-M D Anderson Cancer Center from 1983 to 2009 were included in the study. Expression of cMET was assessed by IHC using rabbit monoclonal anti-total cMET antibody (SP44 from Ventana). Staining intensity was scored on a scale of 0, 1+, 2+ and 3+. cMET overexpression was defined as at least moderate membranous/cytoplasmic staining in ≥50% of tumor cells (score ≥ 2+). FISH analysis was performed using MET (7q31) specific probe (BAC clone RP11-95i20, Abbott Molecular Inc.) and the centromere probe (CEP7/D7Z1, Abbott Molecular Inc.) as internal control. cMET amplification was defined as gene copy numbers ≥4 per cell or cMET/CEP7 ratio ≥ 2. cMET status was tested for correlation using Fisher's exact test with other clinicopathological parameters. The Kaplan-Meier product limit method was used to estimate the survival outcomes. Cox proportional hazards models were fit to determine the association of cMET status by IHC, or by FISH, or by copy number with survival outcomes after adjustment for other patient and disease characteristics. Medium follow up is 69.4 months (range 9-317 months). cMET was successfully evaluated by both IHC and FISH methods in ninety-six patients. There were 13 patients whose tumors overexpressed cMET was by IHC. Two patients had cMET amplification by FISH using definitive of cMET/CEP7 ratio of ≥2 and four patients had cMET copy number >4. Only one patient showed cMET/CEP7 ratio of 2.53 and one was positive for cMET overexpression by IHC. No significant association between cMET overexpression by IHC and by FISH using cut-off of with either cMET/CEP7 ratio of ≥2 or cMET copy number of >4 (P = 1.0). There was no significant correlation between the cMET overexpression and other clinicopathological characteristics, such as patient demographics, tumor grade, stage, or chemotherapy treatment history. cMET overexpression and gene amplification did not correlate with the prognosis of TNBC regarding OS or DFS. MET amplification is a rare incidence in TNBCs. cMET overexpression is infrequent in TNBCs and may not be driven by gene amplification. Neither have significant prognostic value nor do they correlate with other clinicopathological characteristics in this TNBC cohort.

Extent of ductal carcinoma in situ according to breast cancer subtypes: a population-based cohort study

Ductal carcinoma in situ (DCIS) is a precursor of invasive breast carcinoma (IBC). The DCIS component is often more extensive than the invasive component, which affects local control. The aim of our study was to analyze features of DCIS within different IBC subtypes, which may contribute to the optimization of personalized approaches for patients with IBC. Patients with IBC reported according to the synoptic reporting module in the Netherlands between 2009 and 2015 were included. Data extraction included characteristics of the invasive component and, if present, several features of the DCIS component. Resection margin status analyses were restricted to patients undergoing breast-conserving surgery (BCS). Differences between subtypes were tested by a Chi-square test, spearman’s Rho test or a one-way ANOVA test. Overall, 36.937 cases of IBC were included. About half of the IBCs (n = 16.014; 43.4 %) were associated with DCIS. Her2+ IBC (irrespective of ER status) was associated with a higher prevalence of adjacent DCIS, a larger extent of DCIS and a higher rate of irradicality of the DCIS component as compared to ER+/Her2− and triple-negative subtypes (P < 0.0001 for all variables). The prevalence of DCIS in triple-negative IBC on the other hand was lowest. In this large population-based cohort study, we showed significant differences between the prevalence and extent of DCIS according to IBC subtypes, which is also reflected in the resection margin status in patients treated with BCS. Our data provide important information regarding the optimization of local therapy according to IBC subtypes.

Neuroendocrine tumor of the breast: Is it primary or metastatic?

Introduction: Neuroendocrine breast carcinoma is a rare form of tumor that may be either primary or metastatic. Case Report: We present the case of a patient who was referred to our outpatient office with the diagnosis of a triple negative invasive breast carcinoma on an ultrasound-guided core needle biopsy. The patient subsequently underwent a lumpectomy with sentinel lymph node biopsy. Postoperative pathology revealed neuroendocrine carcinoma of the breast with sentinel lymph node biopsy negative for carcinoma. The tumor cells were positive for AE1/AE3, chromogranin, synaptophysin and CD-56 but negative for estrogen, progesterone and HER2. To exclude a primary carcinoma elsewhere, we obtained a whole body PET scan which showed a mildly hypermetabolic mesenteric mass in the midline with curvilinear calcification. Computed tomography scan of the abdomen and pelvis with oral and IV contrast showed a mass-like soft tissue within the terminal ileum with thickening of the cecum. An octreotide scan of the whole body revealed

Abstract P3-05-01: Accurate assessment of HER2 status in “triple-negative” breast cancer requires both IHC and FISH testing

Abstract Introduction: Triple-negative invasive breast carcinoma (TNBC) does not over-express estrogen, progesterone receptors and HER2/neu. Approximately 15% breast cancers are “triple negative” and have poor overall survival with no targeted therapeutic options. HER2 positive patients also have a poor prognosis which is markedly improved with anti-HER2 therapy. ASCO/CAP guidelines have made substantial improvement in biomarker assessment by standardizing pre-analytic, analytic and post-analytic variables. Since 2009, we have performed HER2 fluorescence in situ hybridization (FISH) analysis in addition to immunohistochemistry (IHC) on all triple negative patients in an effort to accurately assess HER2 status. Materials and Methods: Pathology database at our institute was queried for triple negative breast cancer cases 2009-2012. 175 cases were identified with ER(SP1; Ventana)&amp;lt; = 1%, PR(1E2; Ventana)&amp;lt; = 1% and HER2 IHC (HercepTest® DAKO 2009-2011; 4B5-Ventana- 2012)&amp;lt; = 1+. FISH for Her2 was also performed on these cases. HER2/CEP17&amp;gt; = 2 was classified as HER2 positive. FISH for HER2 amplification was performed using the FDA-approved HER2 DNA Probe Kit (Vysis, Inc.). The hybridization results were recorded and analyzed by BioView Duet system (Allegro Plus Automated Scanner) with HER2 application software (BV-HER2-AF). Fisher's exact test was performed to correlate HER2 amplification with clinico-pathological parameters. Results: 175 breast cancers were classified as “triple-negative” by IHC between 2009-2012. The patients’ age ranged from 25 to 93 years old (mean = 58); 109 were Caucasian (62%), 33 African American (19%), 9 Asian (5%) and 4 Hispanic (2%). The majority of the cases (152, 86%) were invasive ductal carcinoma. The rest include 9 cases of medullary carcinoma, 3 cases of metaplastic carcinoma, 3 cases of apocrine carcinoma, 2 cases of papillary carcinoma and 2 cases of invasive lobular carcinoma. 34 had regional lymph node (axillary) metastasis (19%) and 9 had distant metastasis (5%). 23 of the 175 “triple-negative” cases (13%) showed HER2 amplification by HER2 FISH analysis (HER2/CEP17&amp;gt; = 2). 14.9% (20/134) TNBC cases were FISH positive 2009-11 (HercepTest®, DAKO) and 7.3% (3/41) cases were FISH positive in 2012 (4B5, Ventana). 14 of the 23 patients were Caucasian (61%), 4 African American (17%), 2 Asian and 1 Hispanic. 20 of the 23 cases (87%) had invasive ductal carcinoma, of which 18 (78%) were poorly differentiated. 8 of the 23 cases (35%) had lymph node metastasis and 1 case had distant metastasis. No statistically significant correlation was observed between the HER2 gene amplification and clinicopathological factors analyzed, including race (P = 1), age (P = 1), tumor size (P = 0.6), pathologic stage (P = 0.6), lymph node status (P = 0.08), and Ki-67 index (P = 0.8 with 20% cutoff; P = 0.1 with 70% cutoff). Conclusion: In this cohort, 13% TNBC were re-classified as HER2 positive by performing HER2 FISH test in addition to immunohistochemistry analysis. Rate of FISH positivity in TNBC declined over the four year study period. No clinicopathological variables are correlated with HER2 FISH amplification. These data suggest that dual testing of HER2 should be considered routinely in TNBC for accurate classification to guide therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-05-01.

Expression of Basal-like Biomarkers in Triple-Negative Invasive Breast Carcinoma in Puerto Rico

Expression of Basal-like Biomarkers in Triple-Negative Invasive Breast Carcinoma in Puerto Rico

Decreased Androgen Receptor Expression Is Associated With Distant Metastases in Patients With Androgen Receptor–Expressing Triple-Negative Breast Carcinoma

To characterize prognostic values of androgen receptor (AR) in triple-negative (TN) breast cancers, we investigated AR expression status and levels, explored an association of AR expression with metastatic disease, and correlated AR expression with Ki-67 in TN invasive breast carcinomas. AR expression was analyzed with immunohistochemistry in 121 cases of TN tumors. Thirty-nine cases had distant metastatic disease and 82 had locoregional disease only. AR was positive in 38 (31.4%) of the 121 cases. Our results indicate that among the AR-positive TN tumors, distant metastases are significantly associated with lower expression of AR compared with cases with only locoregional disease, and that AR expression negatively correlates with Ki-67 expression. These findings suggest that decreased intratumoral AR expression may be predictive of distant metastatic disease and AR expression levels may have potential prognostic value in AR-expressing TN tumors.

CD44+/CD24−/low cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome

Women classified as having triple-negative tumors have a poor prognosis. The importance of CD44(+)/CD24(-/low) (stem/progenitor cell-phenotype) in breast cancer patients has also been appreciated. However, correlation between triple negativity and CD44(+)/CD24(-/low) with tumor recurrence remains elusive. In the present study, we evaluated tumor specimens of 50 breast cancer patients with known hormone receptor status for whom we had follow-up information and outcome data available, and performed immunohistochemistry analysis to determine CD44 and CD24 expression. Gene expression arrays were also independently performed on 52 breast cancer specimens with banked frozen tissue. Lastly, we used FVBN202 transgenic mouse model of breast carcinoma and determined the hormone receptor status, the proportion of CD44(+)/CD24(-/low) breast cancer stem-like cells, and the behavior of the tumor. We determined that patients with triple-negative tumors had significantly higher incidence of recurrence or distant metastasis associated with increased frequency of breast cancer stem cell phenotypes compared with those with non-triple-negative tumors. Preclinical studies in FVBN202 transgenic mice confirmed these findings by showing that relapsed tumors were triple negative and had significantly higher frequency of breast cancer stem cells compared with their related primary tumors. Unlike non-triple-negative primary tumors, relapsed triple-negative tumors were tumorigenic at low doses when inoculated into FVBN202 transgenic mice. These findings suggest that CD44(+)/CD24(-/low) breast cancer stem-like cells play an important role in the clinical behavior of triple-negative breast cancer and that development of therapeutic targets directed to breast cancer stem-like cells may lead to reduction in the aggressiveness of triple-negative breast cancers.

Triple Negative Invasive Breast Carcinoma: Incidence and Clinical - Pathological Characteristics

Aim: The epidemiological behavior of malignant tumors in Costa Rica has undergone an important change during the last years; breast carcinoma has increased its incidence, occupying the second place in malignancies in women and the first one in mortality. This type of tumor can be studied by several immunohistochemistry markers, such as the expression of different hormonal receptors by neoplastic cells (estrogen receptors, progesterone receptors and Human Epidermal Growth-Factor Receptor type 2, HER2). Carcinomas which do not express any of these three receptors have a worse prognosis. Objectives for this study were to determine the main characteristics of these tumors, named triple negative carcinomas, and to define their relevance within breast carcinomas.Methodology: Data was collected from all women with breast cancer diagnosed, with immunohistochemistry studies, from January 1st, to December 31st, 2006, at the Pathology Department of the San Juan de Dios Hospital. Patient´s age, histological type and degree of differentiation, were taken into account for each case. Triple negative carcinomas were considered separately, and statistical analysis was made with Epi Info 3.3.4 software.Results: During the above mentioned period, 221 patients were diagnosed with breast cancer, 40 of them were identified as having triple negative carcinomas, which meant an incidence of 18% (C.I. 95%, 12.79 – 23.40), and had an average of 54 years old (C.I. 95%, 50 - 58 ), a median of 52 years old and a mode of 48 years old. Triple-negative cancer was more related with ductal infiltrating histological type: 67.5% (C.I. 95%, 51.73-83.26), followed by infiltrating lobular, with 12.5% (C.I. 95%, 4.18 – 26.80), medullary, with 5%, and less related are papillary type and spindle cell metaplastic carcinoma. According to the degree of differentiation, there were 23 grade-3 cases, 8 grade-2 cases, and 3 grade-1 carcinomas.Conclusion: Triple negative breast cancers are an aggressive group of tumors, which manifest at younger ages, have larger tumor size, are of higher histological grade, and mostly are infiltrating ductal carcinomas. Due to the fact that this was based only on determination of hormonal receptors and HER2, other tests might be necessary such as CK5/6 and 17 stains to check basal-like carcinoma cases. Also, this study shows a higher prevalence for infiltrating lobular carcinomas than other studies, so that other tests could be done such as e-cadherin, to verify the cases of lobular carcinomas, thereby increasing reliability of results.

Abstract P6-01-04: Ductal Carcinoma In-Situ Associated with Triple-Negative Invasive Breast Carcinoma Is Often Immunohistochemically Distinct from Invasive Component

Abstract Background: Gene expression profiling studies have identified a sub-set of breast carcinoma known as basal-like carcinoma, which characteristically do not express estrogen receptor (ER), progesterone receptor (PR), or HER2neu (HER2). These triple negative invasive ductal carcinomas (TN-IDC) are associated with an aggressive clinical course and poor prognosis. Little information exists in the literature concerning ductal carcinoma in-situ (DCIS) associated with TN-IDC. We evaluated the frequency, histologic features, and receptor status of DCIS associated with TN-IDC. Design: From our institutional archives between July 2006 and August 2009, we retrieved all cases of intermediate and high grade invasive ductal breast carcinoma. Based on the immunoprofiling, invasive carcinomas were categorized into either TN-IDC or non triple-negative invasive carcinoma (non-TN-IDC). Immunohistochemistry for ER, PR, and HER2 was performed on the DCIS of the TN-IDC group and on some available cases from the non-TN-IDC group. The frequency, receptor status, and nuclear grade of DCIS associated with both groups were noted. Statistical analysis was performed using Fisher Exact Test. Results: Among a total of 224 cases, 56 (25%) were classified as TN-IDC and 168 (75%) as non-TN-IDC. DCIS was seen in 28 (50%) TN-IDC cases and in 150 (89.3%) non-TN-IDC cases (P&amp;lt;0.0001). Sufficient tumor was available for immunohistochemical staining in 23 of 28 cases with DCIS in the TN-IDC group. Within the 23 cases, the DCIS were triple negative in 15 cases (65%). Of the remaining 8 cases (35%), 4 were positive for ER and PR, but negative for HER2, while the other 4 cases were negative for ER and PR but positive for HER2. Ninety-six cases in the non-TN-IDC group had available immunostains for review, 7 of which (7.3%) displayed a different receptor status from their invasive counterparts (p=0.0016, compared with TN-IDC). Two cases of non-TN-IDC showed an associated TN-DCIS. Of the 28 cases of TN-IDC associated with DCIS, 4 (14.3%) showed lower nuclear grade in DCIS than in its invasive counterpart, compared with 22 of 150 (14.7%) non-TN-IDC cases (no significant difference). One TN-IDC case displayed two distinct morphologic patterns of DCIS; neither pattern was triple negative. Conclusion: Our study demonstrated the presence of DCIS in a considerable proportion of TN-IDC although at a significantly lower frequency than in non-TN-IDC. DCIS associated with TN-IDC was significantly more likely to display a different immunoprofile from its invasive counterpart than DCIS associated with non-TN-IDC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-04.