Cases Of Invasive Breast Carcinoma Research Articles

Identification of Luminal Subtypes of Breast Carcinoma Using Surrogate Immunohistochemical Markers and Ascertaining Their Prognostic Relevance

BackgroundTherapeutic decisions in breast carcinoma are being made on the basis of tumor cell proliferation using exorbitant genomic tests. The 2013 St Gallen meeting advocated surrogate definitions for classifying tumors into luminal subtypes on the basis of immunohistochemical (IHC) markers. We studied the classification of estrogen receptor (ER)-positive tumors using these definitions as well as different methods for Ki-67 labeling index (LI) estimation. Patients and MethodsA total of 541 ER+ invasive breast carcinoma cases from January 2012 to December 2012 were evaluated for Ki-67 LI by the average and hot spot methods. The IHC results of ER, PR, and human epidermal growth factor receptor 2 (HER2) were noted. HER2 IHC equivocal (2+) samples were subjected to HER2 fluorescence in-situ hybridization testing. Luminal subgroups created on the basis of the 2013 St Gallen meeting guidelines were correlated with clinicopathologic variables and disease-free survival. ResultsThe distribution of luminal subtypes was as follows: luminal A–like, 13.3%; luminal B–like (HER2−), 57.9%; and luminal B–like (HER2+), 28.8%. Approximately 6% of cases were recategorized into different subgroups when the average method was used instead of the hot spot method for Ki-67 LI assessment. Younger patients (≤ 50 years), grade 3 tumors, positive axillary nodes, recurrence, and distant metastasis had a positive statistical correlation with luminal B–like (HER2−) subtype. Patients with luminal B–like (HER2−) tumors had a shorter disease-free survival compared to patients with luminal A–like tumors. ConclusionKi-67 LI, irrespective of the method of assessment, along with PR, can be efficiently used to divide ER+ tumors into prognostic subgroups in Indian patients.

Breast Cancer Subtypes Based on ER, PR and HER2/neu Expression and Its Clinico-pathological Correlation

Background: Carcinoma of the breast is one of the most common cancer in women and it is the second cause of cancer deaths only to lung cancer. Recent attention has been directed singularly at molecular classifications of breast cancer. Molecular subtypes have different prognostic and therapeutic implications.
 Objective: The aim of this study was to assess the ER, PR, and HER-2/neu reactivity pattern in breast carcinomas and to correlate this reactivity pattern with stage tumor size and lymph node metastasis.
 Methodology: This is a prospective analytical observational study was conducted in the North East Cancer Hospital and Department of Pathology of North East Medical College, Sylhet, Bangladesh during a 42 months period from July 2015 to December 2018.
 Result: Among 67 Cases of primary invasive breast carcinoma only one case was male and 66 were female. In aspect of tumor size most of the patient presented with 2 to 5cm tumor, 47(70.2%) cases and (80.6%) presented with more than 2cm tumor size. In our study 38(56.7%) cases of breast cancer found ER positive, 38.8%(26 cases) PR positive and 22.4% (15 cases) HER2/neu positive, most common presentation of the disease was at stage llB(29 cases,45%), lymph node positivity 46(68.7%) cases and lymph node negative 21(31.3%) cases, 5(7.5%)cases. In aspect of molecular subtyping we found luminl A 29 (43.3%) cases Luminal B 11.9% (8 cases) basal like 22(32.8%) cases and HER-2/neu over expressed 8(11.9%) cases.
 Conclusion: Cancer screening and early detection program can improve our scenario.
 Journal of Current and Advance Medical Research 2020;7(1): 30-35

Quantitative digital imaging analysis of HER2 immunohistochemistry predicts the response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma.

Patients with HER2-positive breast cancer commonly receive anti-HER2 neoadjuvant chemotherapy and pathologic complete response (pCR) can be achieved in up to half of the patients. HER2 protein expression detected by immunohistochemistry (IHC) can be quantified using digital imaging analysis (DIA) as a value of membranous connectivity. We aimed to investigate the association HER2 IHC DIA quantitative results with response to anti-HER2 neoadjuvant chemotherapy. Digitized HER2 IHC whole slide images were analyzed using Visiopharm HER2-CONNECT to obtain quantitative HER2 membranous connectivity from a cohort of 153 HER2+ invasive breast carcinoma cases treated with anti-HER2 neoadjuvant chemotherapy (NAC). HER2 connectivity and other factors including age, histologic grade, ER, PR, and HER2 fluorescence in situ hybridization (FISH) were analyzed for association with the response to anti-HER2 NAC. Eighty-three cases (54.2%) had pCR, while 70 (45.8%) showed residual tumor. Younger age, negative ER/PR, higher HER2 DIA connectivity, higher HER2 FISH ratio and copy number were significantly associated with pCR in univariate analysis. Multivariate analysis demonstrated only age, HER2 DIA connectivity, PR negativity, and HER2 copy number was significantly associated with pCR, whereas HER2 DIA connectivity had the strongest association. HER2 IHC DIA connectivity is the most important factor predicting pCR to anti-HER2 neoadjuvant chemotherapy in patients with HER2-positive breast cancer.

Importance of endothelial markers in detection of lymphovascular invasion in carcinoma breast and its correlation with axillary lymph node metastasis

Background: Lymphovascular invasion (LVI) is one of the important prognostic factors in carcinoma breast and its accurate diagnosis is important, particularly in node-negative cases for making the decision regarding aggressive adjuvant chemotherapy. Sometimes, it becomes very difficult to diagnose LVI on routine hematoxylin and eosin (H and E) stained tissue sections. Staining with endothelial immunomarkers makes the identification easy. Aim of the Study: This study aims to compare LVI detection on H and E and immunohistochemistry (IHC) stained sections and its correlation with axillary lymph node metastasis. Materials and Methods: A total of 45 cases of invasive breast carcinoma were studied. LVI was evaluated in routine H and E and IHC stained sections. The results were compared. The LVI status on IHC was correlated with axillary lymph node status. Results: The accuracy of H and E stained sections in detection of LVI was 75.6% with a false-positive and false-negative rate of 20% and 4.4%, respectively. There was no significant association between LVI on IHC and axillary lymph node status. Conclusions: The detection of LVI on routine H and E sections can be erroneous. IHC should be done in cases with confusing focus on routine H and E stained sections, particularly in node-negative cases.

Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.

The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters. We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas. In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion. Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.

Tumor budding in invasive breast cancer - An indispensable budding touchstone.

Tumor budding denotes a phenomenon in which the tumor cells, singly or in small aggregates, become detached from the neoplastic glands at the invasive front of adenocarcinoma. Tumors with budding cells have a significantly more aggressive clinical course. Significance of tumor budding has mainly been examined in the field of colorectal cancer. To document the number tumor buds at the invasive front of invasive breast cancer. To correlate the number of tumor buds with other histopathological parameters, and available clinical details. Analytical study at a rural tertiary care referral institute. It was a retrospective study of invasive breast cancer cases from January 2012 to April 2015. Tumor buds were counted in H and E stained sections in 10 High Power Fields (HPFs). Association of tumor budding with histological parameters and available clinical details were analyzed statistically. Frequencies, Chi-Square Test and Crosstabs were used for calculation. 50 cases of invasive breast carcinoma were analyzed. Invasive ductal carcinoma constituted predominant histological type (92%). Low tumor budding (tumor buds ≤20/10HPFs) constituted 20 cases. High tumor budding (tumor buds >20/10HPFs) constituted 30 cases. Association of high tumor budding with lympho-vascular invasion, lymph node metastasis, primary tumor staging, regional lymph node staging, necrosis and Monckeberg medial sclerosis was statistically significant. Tumor budding may be incorporated as a new parameter in reporting protocols. Tumor budding serves as an indispensable touchstone in evaluating cases of invasive breast cancer.

Utility of PHH3 in Evaluation of Mitotic Index in Breast Carcinoma and Impact on Tumor Grade.

Background:Mitotic activity index is considered as the most important grading component to predict prognosis in invasive breast carcinoma. But it is believed that it is also the cause of discordance in grade estimation based on Bloom-Richardson system. Thus, reproducible methods such as immunohistochemistry (IHC) based analysis methods appears to be of great value in facilitating mitotic count. Materials and Methods:In the present study, we examined the utility of Phosphohistone H3 by IHC in various grades of breast carcinoma and compared it with traditional mitotic count by hematoxylin and eosin (H and E) staining and probable changes in tumor grading. Results:Total 90 cases of invasive breast carcinoma were evaluated. Mean mitotic count were 8.6 and 6.4/10HPF in IHC and HandE groups, respectively. Although , mean average count was higher by IHC method , good correlation was observed(R=0.914). Using PHH3 IHC, two out of 33 cases of grade I tumors were upgraded in to grade II and three cases of grade II were upgraded in to grade III. None of the tumors were down graded. Conclusion:Similar to some other previous studies, we found PHH3 a robust sensitive and practical marker for mitotic count in breast carcinoma. Especially it is helpful to identify the most proliferating area. However, further studies are required to confirm the superiority of this biomarker for including in grading system.

Correlation between the presence of androgenic receptors and molecular and histopathological variables in breast cancer

Introduction: The expression of androgenic receptors (AR) is a new predictive marker of response and prognosis in invasive breast carcinoma (BC). It emerges as a potential therapeutic target. Objective: To evaluate the frequency of AR positivity and its correlation with molecular and histopathological parameters in infiltrative BC. Method: Retrospective cohort study, analyzing 119 cases of invasive non-metastatic BC, seen at a private clinic. Hormonal receptors were screened by immunohistochemical reaction, and AR were considered positive when present in at least 10% of cells, ER and PR from 1%. This finding was correlated with pathological staging, histological grade (HG), vascular-lymphatic invasion (VLI), estrogen (ER) and progesterone receptors (RP), HER2 and Ki 67. Results: Androgen receptors were positive in 80.6% of cases. In the assessment of pathological staging, of the 63 patients with stage I, 81% showed positive androgen receptors, while among the 28 patients with stage II, 75% had positive androgen receptors, and 88% of the 17 patients with stage III presented the positivity of the recipient. Regarding the histological parameters of the tumor, 16 patients had grade 1 tumors, 93.7% of them with positive androgen receptors, while among the 63 with grade 2 tumors 90.4% had androgen receptor positivity, and only 59, 3% of the 27 tumors evaluated as grade 3 had a positive androgen receptor. The vascular-lymphatic invasion was negative in 57 patients, 78.9% of the tumors with positive androgen receptor. Among the 56 tumors with positive vascular-lymphatic invasion, 85.7% had an androgen receptor positivity. In the immunohistochemical evaluation of tumors, among the 95 patients with positive estrogen receptors, 91.5% also had positive androgen receptor, which was positive in only 37.5% of the 24 patients with negative estrogen receptors. Of the 21 patients who had tumors with overexpressed HER, 85.7% also had positive androgen receptors, which were also positive in 86.4% of 96 without overexpression of HER2. In the evaluation of cell proliferation by the Ki67 antigen, among the 50 tumors with Ki67 <20%, 94% had positive androgen receptors, while 83.7% were positive among the 49 tumors with Ki67 between 20 and 50% and only 35% positivity of androgen receptors in 17 tumors with Ki67> 50%. Conclusions: AR positivity is associated with more differentiated hormone-dependent tumors with a lower proliferation rate.

Stem cells in ductal breast cancer: immunohistochemical expression of CD44, CD24, CD133, and ALDH-1 markers in 104 cases

Objective: The aim of this study was to evaluate the immunohistochemical expression of stem cell markers CD44, CD24, CD133, and ALDH-1 in breast carcinomas and investigate any correlation with stage, degree of tumor differentiation, cell proliferation index, and hormone receptors status. Materials and Methods: One hundred and four cases of invasive ductal breast carcinomas were studied and classified according to grade and stage, hormonal status, and C-erbB2 expression. A semi-automatic Ventana method was used to examine by semi-quantitative method the immunohistochemical expression of anti-CD133, CD24, CD44, and ALDH1 antibodies. Results: CD44, CD24, and ALDH1 markers demonstrated a statistically significant correlation with higher disease stage and triple negative cancers (94%-55.5%). CD133 correlated with triple negative cancers (55.5%). No correlation with other clinical data or tumor differentiation was observed. Conclusion: Triple negative breast cancers express specific stem cell markers responsible for cell/stroma interaction and this is a useful tool in predicting tumor progression and developing specific targeted therapies.

Pre-surgical level of von Willebrand factor as an evident indicator of breast cancer recurrence.

Endothelial and platelet activation as well as a disruption of haemostatic balance are crucial in cancer-dependent venous thromboembolism development. The aim of this study was to investigate the influence of von Willebrand factor (VWF), sE-selectin, sP-selectin as well as VWF/sE-selectin and sP-selectin/sE-selectin ratios on the probability of disease relapse in invasive breast carcinoma (IBrC) cases. Eighty-four patients with IA-IIB stage of IBrC who passed a comprehensive clinicopathologic evaluation were included in the study. Follow-up was completed in all patients with a 15.48 % recurrence rate. An immunoassay of VWF antigen, sE-selectin, sP-selectin, as well as an immunohistochemistry of oestrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2) and Ki67 was performed in all cases. The VWF/sE-selectin ratio was significantly higher in patients with poorly differentiated tumours than in those with high-differentiated tumours. A positive correlation between VWF concentration and tumour grade was noted. Eleven of 13 events happened in patients with VWF value below 600 mU/mL with recurrence rate of 25%, but only two events occurred in subject with VWF values above the 600 mU/mL (5%; P= 0.0028). Our study show that VWF could be considered as a suitable biomarker of breast cancer relapse.

Combined use of SOX10 and GATA3 in mammary carcinoma

The complementary coverage of different subsets of breast cancer by GATA3 and SOX10 makes their use in combination appealing for routine clinical use, but study of these markers has been largely limited to cases with high or absent ER expression. Here we report SOX10 and GATA3 immunostaining in parallel using a tissue microarray containing 246 invasive breast carcinoma cases with a range of ER expression. GATA3 and SOX10 were positive in 93 % (229/246) and 15 % (38/246) of cases overall and in 63 % (24/38) and 74 % (28/38) of triple negative breast carcinomas (TNBC), respectively; SOX10 was positive in 15 of the 17 cases that lacked GATA3 expression (88 %). SOX10 was also positive in 3 % (6/196) of ER + cases, including 50 % of cases with low ER (3/6), 20 % with intermediate ER (3/15), and 0 % with high ER (n = 175), so that ER-low cases more strongly resembled TNBC than those with high ER expression. GATA3 expression was lower in cases that co-expressed SOX10 in comparison to those that were positive for GATA3 alone. Less than 1 % (2/246) of cases were negative for both GATA3 and SOX10. Therefore, SOX10 is a useful adjunct to GATA3 in the detection of TNBC and cases with low ER expression and/or reduced GATA3 intensity relative to that typical of breast cancers with higher ER expression. Moreover, given such high sensitivity, metastatic tumors lacking either GATA3 or SOX10 are unlikely to be of breast origin. Additional study is necessary to determine the extent to which SOX10 may also improve specificity and to characterize its biologic significance in breast cancers with low ER expression.

HER2 immunohistochemistry inter-observer reproducibility in 205 cases of invasive breast carcinoma additionally tested by ISH

Assessment of HER2 biomarker in invasive breast carcinoma patients allows a specific therapeutic approach. Clinical guidelines indicate immunohistochemistry (IHC) and in situ hybridization (ISH) to test HER2, however both have drawbacks which results in low reproducibility of results especially in equivocal cases. Our main objective is to quantify inter-observer IHC reproducibility and cross it with the ISH result. Our series includes 205 invasive breast carcinoma cases sent for ISH retest from 14 hospitals, 5 observers to assess the IHC and 2 observers for the ISH of each case. We found that the observers only achieve an absolute agreement for IHC in 1 out of 3 cases. The inter-observer concordance for IHC is low (0.2 ≤ k ≤ 0.4) or moderate (0.41 ≤ k ≤ 0.6). In ISH positive cases the concordance for IHC is higher than in the ISH negative cases. In conclusion, the study shows low and moderate IHC inter-observer concordance, finding the more worrying values among the ISH negative cases which are the most part of this particular sample. Subjective interpretation of the techniques, among other factors, has negative impact in HER2 evaluation. To offset this limitation we have checked that reaching a consensus from different observers for HER2 IHC assessment improves the results.

A comparison of Ki67 index in carcinoma breast by digital image analysis with manual method

A comparison of Ki67 index in carcinoma breast by digital image analysis with manual method - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.107, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

The Correlation of Nottingham Prognostic Index with Immunoexpression of ER, PR, HER2, and Ki67 in Breast Cancer Tissue

Abstract Background In the underdeveloped and developing countries, the application of immunohistochemistry (IHC) to assess the status of oestrogen receptor (ER), progesterone receptor (PR), HER2 receptor, and Ki67 proteins in formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma is utterly hindered by high cost, long procedure, and need for both skilled operator and pathologist. The objective of this study was to evaluate the correlation of Nottingham prognostic index (NPI) with immunoexpression of ER, PR, HER2, and Ki67 proteins in the formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma. The ethical approval reference number is IRBRTA 306/2560. Methods Two hundred and forty primary invasive breast carcinoma cases were determined their NPI which was calculated as [0.2 × maximum tumour diameter in cm] + tumour grade + axillary lymph node score. Tumour grade was given a score 1 to 3 based on the Nottingham Combined Histologic Grade system (Elston-Ellis modification of Scarff-Bloom-Richardson grading system) of primary invasive breast carcinoma. Axillary lymph node metastasis (ALNM) was given a score 1 if no ALNM, a score 2 if 1 to 3 metastatic nodes, and a score 3 if at least 4 nodal involvement. The correlation between NPI and the IHC status of ER, PR, HER2, and Ki67 was analysed at the 95% confidence interval. Results The NPI had a significant association with the immunoexpression of ER, PR, and Ki67 proteins. There was no correlation with HER2 immunohistochemical reactivity. The proposed NPI score less than 4.5 will significantly correlate with positive immunoexpression of ER and PR. The NPI score greater than or equal to 4.5 will correlate with high Ki67. Conclusion The NPI might have a role in predicting the results of ER, PR and Ki67 expression in the formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma, if immunohistochemical method is unavailable.

Hormone Receptor and Human Epidermal Growth Factor Receptor 2 Detection in Invasive Breast Carcinoma: A Retrospective Study of 12,467 Patients From 19 Chinese Representative Clinical Centers

IntroductionWe evaluated the current status of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detection in invasive breast carcinoma (IBC) in various laboratories across China. Materials and MethodsThe Breast Pathology Study Group of the Chinese Society of Pathologists collected HR and HER2 data from 12,467 IBC cases from 19 representative clinical centers in China. The data from every center were compared with the pooled data from the other centers. ResultsThe assessment of HR status showed that the overall positive estrogen receptor (ER) and progesterone receptor (PR) rates were 71.7% and 63.7% (range, 60.9%-87.9% and 43.9%-84.8%), respectively. The ER results in 3 centers and the PR results in 6 centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). Of the 12,467 cases, 62.4% were ER+/PR+, 9.3% were ER+/PR−, 1.3% were ER−/PR+, and 27.0% were ER−/PR−. The assessment of HER2 status showed that the overall positive rate of HER2 (with a definition of immunohistochemistry [IHC] 3+ or IHC2+/ in situ hybridization-positive) was 24.7% (range, 13.7%-35.7%) in each center. Three centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). The proportion of HER2 IHC3+ was 21.1%. The positive rates of HER2 gene amplification in IHC 0/1+, 2+, 3+ cases were 2.0%, 17.6%, and 85.9%, respectively. ConclusionsAs the largest study of HR and HER2 status in Chinese patients with IBC, the data from the present study have indicated that the overall rates of HR and HER2 were comparable to those reported in previous studies. However, the rates varied among the laboratories. Individual centers had not met the target values, and they need to improve the detection.

Abstract 3541: Characterization of olfactory receptor upregulation in invasive breast cancer

Abstract Despite some progress in early detection and new therapies, breast cancer remains the second most common cause of cancer-related deaths among women. Majority of deaths occur due to invasion and metastasis among triple-negative breast cancer (TNBC) patients. Gene profiling of mammary tumors has enabled identification of novel genes with potential roles in cancer invasion using next generation sequencing technologies. This study is the first to examine upregulation of olfactory receptors (ORs) among a large invasive breast carcinoma population and begins to establish a correlation of OR genes in breast cancer invasion. Invasive breast carcinoma cases from the TCGA database were used. Among data from 1100 unique patients, 960 cases of invasive breast carcinoma had RNAseq of their primary tumors in addition to exome sequencing data. The abundance of all 408 human coding OR genes among the 960 cases were analyzed using a three-factor stratification algorithm, and 30 OR genes were identified as highly abundant among 198 breast invasive carcinoma patients. Supervised clustering of the 198 patients based on the similarity of OR upregulation levels identified five subpopulations among the invasive carcinoma patients in which only one OR gene (OR2A7, OR2B6, OR2C1, OR2W3) was significantly upregulated. Abundance of OR2W3 was significantly elevated in two subpopulations with 30- and 19-fold increase compared to their level of abundance in normal mammary tissue. These two subpopulations were composed of 74% and 70% TNBC tumor subtypes and included all the stage iv cancer patients in the study. Transcript abundance of 21 genes included in the Oncotype DX gene expression diagnostic test was measured for each patient subpopulation. The subpopulation with abundance in OR2W3 was correlated with significant upregulation of invasion genes (CTSV, MMP-11) and the subpopulation with abundance of OR2B6 was correlated with significant upregulation of proliferation genes (MKI67, AURKA, BIRC67, CCNB1, MYBL2). Interestingly, only the cases with significant upregulation of OR2W3 were correlated with significantly reduced survival probability compared to invasive breast carcinoma patients not expressing OR2W3. Furthermore, analysis of OR transcript abundance levels among 56 human breast cancer cell lines showed that 3 ORs (OR2A7, OR2B6, OR2W3) were exclusively upregulated in one cell group with 2, 1.3 and 2.1-fold increase compared to their upregulation levels in a human mammary epithelial cell line (MCF10A). The cell group with significant upregulation of OR2W3 was composed of 83% TNBC cell lines. These results show a consistent elevated upregulation of the OR2W3 gene in all the invasive breast tumors and cell lines. Our ongoing discovery research suggests that OR2W3 may be an indicator of breast cancer invasion. It is also possible that OR2W3 has signaling or other mechanistic roles in breast cancer progression, metastasis and reduced survival. Citation Format: Shirin Masjedi, Laurence J. Zwiebel, Todd D. Giorgio. Characterization of olfactory receptor upregulation in invasive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3541.

Thymidylate Synthase, a New Myoepithelial Biomarker for Breast Lesions.

Background. The identification of myoepithelial cells (MECs) can facilitate the differential diagnosis of breast lesions. We previously found thymidylate synthase (TS) expression in the nuclei of MECs in breast tissues, which prompted us to investigate the usefulness of TS as a sensitive and specific biomarker in the differential diagnosis of breast lesions, similar to other MEC biomarkers (ie, tumor protein [P63] and cluster of differentiation 10 [CD10]). Methods. Immunohistochemistry for TS, P63, and CD10 was performed on paraffin sections from 189 breast specimens. Results. The results showed the intensity of the immunoreactive TS signal to be comparable with that of P63 in the nuclei of MECs. Furthermore, the nuclei of MECs stained strongly for TS and P63 in normal breast tissues (obtained adjacent to invasive breast lesions), benign breast lesions, and carcinoma in situ, whereas the cytoplasm of MECs stained strongly for CD10. The immunoreactive TS signal in the cytoplasm of MECs was variable in 22 out of 32 (65.6%) cases of invasive breast carcinoma and 4 out of 20 cases (20.0%) of ductal carcinoma in situ. We found no immunoreactive TS signal in the nuclei of luminal and stromal cells in breast lesions, although there was a weak positive signal in the cytoplasm of luminal and stromal cells. Conclusions. TS is a sensitive and specific MEC biomarker in the differential diagnosis of breast lesions.

A simple immunohistochemical bio-profile incorporating Bcl2 curbs those cases of invasive breast carcinoma for which an Oncotype Dx characterization is needed.

AimOur goal has been to evaluate the importance that the incorporation of Bcl2 in the ER/PGR/Her2/Ki67 bio-profile can have as predictor of the Oncotype Dx categories.Material and methods156 consecutive cases of HR+/Her2- pN0/1 primary breast carcinoma were sent to the Oncotype Dx test. Immunohistochemical determination of Bcl2/ER/PGR/Ki67/Her2 expression was evaluated for each case. After the selection of the appropriate cut-off values for PGR and Ki67, explorative as well as confirmative statistical analyses were performed to build and validate predictive risk-of-recurrence immunohistochemical only bio-profiles.ResultsThe predictive capacity of these immunohistochemical profiles was compared with both traditional and TAILORx Oncotype Dx risk class classification. This comparison showed that immunohistochemical bio-profiles select those cases not associated with high risk-of-recurrence of disease (luminal-A/B and luminal A/B Bcl2) and those that are instead at high risk and therefore worthy of chemotherapy (luminal-B ki67 and luminal-B Bcl2/Ki67), strongly suggesting to only submit PGR-positive/Bcl2-Ki67 altered cases to Oncotype Dx, thus reducing the number of cases to be tested.ConclusionsOur results indicate that the addition of Bcl2 to an immunohistochemical bio-profile definitely improves its predictive capacity to correctly select which cases to send to the Oncotype Dx test. We have also suggested that institutions with a significant number of breast carcinomas sent to the Oncotype Dx test can use these latter to derive their own PGR and Ki67 cut-off values, overcoming the drawbacks of sharing common inter-laboratory values. Validation of these bio-profiles as predictors of the Oncotype Dx categories is ongoing in a prospective series of new cases.

215P - Male breast cancer, a heterogeneous entity: Experience from a cancer center

Background: Male Breast Cancer (MBC) represents 1% of all breast cancers, as well as less than 1% of malignant neoplasm in male. Methods: Describe male population with breast cancer (BC) in our institute from 2007 to 2017. Methods: Unicentric, retrospective and descriptive study with inclusion of all male individuals with diagnosis of invasive breast carcinoma. Data was obtained through clinical process review and analyzed with SPSS®. Results: There were included 66 cases of invasive male breast carcinoma with a median age at diagnosis of 66,5 years old, [24-88] and an initial ECOG PS of 0 in 73% (n = 48). Locally advanced disease was diagnosis on 47% (n = 30) of patients, meanwhile 44% of cases were early BC at the diagnosis. Stage IV disease occurred on 9% (n = 6), and 6 % (n = 4) of patients had bilateral BC. The most frequent molecular subtype was Luminal B-Like (67% n = 44), and cerB-2 overexpression occurred in 10,6% (n = 7). The most frequent symptom was breast lump (89% n = 59). At the time of diagnosis, clinical suspected axillary lymph nodes were detected on 68% of the cases and gynecomastia was present in 28%. The percentage of cases observed after 6 months of symptoms onset was 30%. Positive family history of neoplasms occurred on 71% of cases, including 26% with BC family history. Pre-existing neoplasia was observed in 20% of patients, namely prostate adenocarcinoma as the most frequent diagnosis. Near 53% of the cases were followed on familiar cancer risk appointment, with 4,5%, (n = 3) of cases positive for BRCA2 pathologic mutations. Neoadjuvant chemotherapy was performed in 33% (n = 22). Surgery was performed on 94% (n = 62) of the patients. The pathologic response rate was 90%. In adjuvant setting, 70% (n = 46) of patients received hormonotherapy and 47% (n = 31) radiotherapy. The median time to recurrence was 33 months, [11-147]. Near 23% (n = 15) of patients progressed and the most frequent secondary location was bone (60%). The median OS was 8 years, 95% CI[6,5 -9,5]. Conclusions: MBC is diagnosed later, presenting a more advanced stage, and the majority of patients had expression of hormonal receptors. Despite the late diagnosis, good disease control was achieved. This study in addition to being in accordance with literature reflects the importance of follow-up in family risk consultation. Legal entity responsible for the study: Joana Cunha Carvalho. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Abstract P4-02-09: Clinical and histopathologic characteristics of breast cancer in very young patients

Abstract Background: While breast cancer risk increases with age, about 7% of breast cancer cases in the US are diagnosed in women &amp;lt;40 years of age. Evidence suggests that young breast cancer patients tend to have more aggressive disease subtypes, less favorable tumor biomarker profiles, higher risk of relapse, and poorer survival. However, there is no universally accepted definition of "young patients," and most studies have focused on premenopausal women or those &amp;lt;40 years of age, with some studies using age &amp;lt;35. To date, very little is known on the clinical and histopathologic characteristics of breast cancer in very young women, namely those ≤30 years of age. In this study, we describe such features in a cohort of very young women treated for breast cancer at our academic institution. Methods: Our patient population consisted of all cases of invasive breast carcinoma at Northwestern Memorial Hospital in women &amp;lt;40 years of age at surgery between January 1, 2009, and December 31, 2015. Very young was defined as having an age ≤30. Histopathologic features including tumor size, grade, histologic type, presence of lymphovascular invasion (LVI), lymph node status, tumor markers (ER, PR, HER2) and Ki-67 proliferation rate were recorded. Cases in which specific histopathologic features could not be determined from available materials were excluded from the corresponding analysis. The use of neoadjuvant chemotherapy, type of surgery, and the use of prophylactic surgery on the contralateral side were also recorded and analyzed. Results: A total of 301 invasive breast carcinoma cases were identified (age range 18-39). 40 cases of very young (age ≤30) women with breast cancer (13%) were identified. Nearly all very young patients were diagnosed with tumors of ductal histology (39/40, 98%). Just under half of these patients (19/40, 48%) had a T1 (&amp;lt;2 cm), 16/40 (40%) had a T2 (2-5 cm), and 2/40 (5%) had a T3 (&amp;gt;5 cm) tumor at the time of surgery. The majority of these carcinomas were grade 3 (25/39, 64%), 14/39 (36%) were grade 2, and none were grade 1 tumors. Over half of the tumors were highly proliferative with a high Ki-67 count of &amp;gt;20% (17/31, 55%). ER was expressed in 34/40 (85%), PR in 25/40 (63%) and HER2 in 9/40 (23%). LVI was present in half of the cases (20/40, 50%), and positive lymph nodes were identified in over a third (15/40, 38%) of the cases. Neoadjuvant chemotherapy was used in 9/40 (23%). Three patients (8%) had no residual carcinoma at the time of surgery post chemotherapy. Most of these very young patients chose a mastectomy (28/40, 70%), and 19/40 (48%) also underwent a prophylactic mastectomy on the contralateral side. Conclusions: Our study is one of the largest to date to describe the characteristics of breast carcinomas in very young women (age ≤30). Poor pathologic features such as high tumor grade, high proliferation rate, and presence of LVI were seen in half or more of these very young patients. A high rate of positive lymph nodes was also seen. Mastectomy, often with contralateral prophylactic surgery, was the procedure of choice. Further studies evaluating the molecular characteristics of these tumors and the prevalence of underlying genetic mutations are under way in this unique population of very young breast cancer patients. Citation Format: Finkelman BS, Blanco LZ, Siziopikou KP. Clinical and histopathologic characteristics of breast cancer in very young patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-09.