Molecular Subtypes Of Breast Carcinoma Research Articles

MCM2 Expression in Different Molecular Subtypes of Epithelial Breast Cancers and its Association with Clinicopathological Parameters and Ki-67 Expression

Introduction: Breast cancer is one of the most common malignancies, with few subtypes having a more aggressive outcome and resistance to conventional therapies, Triple Negative Breast Cancers (TNBCs) being one such variant. The Ki-67 lacks reproducibility and a standardised cut-off. MCM2 (Minichromosome Maintenance 2) has role in DNA repair and replication and its role as alternate marker for prognosis has been studied in this case. Aim: To study MCM2 expression with respect to histologic grade, stage, nodal status and molecular subtypes of breast carcinoma. Also, to look for any correlation between Ki-67 and MCM2 expressions. Materials and Methods: A cross-sectional, observational study conducted on a group of 20 patients who underwent mastectomy in a Tertiary Care Centre, R.G. Kar Medical College and Hospital, Kolkata, West Bengal, India, for a total duration of six months. Histologic grading, staging, nodal status was evaluated from Haematoxylin and Eosin (H&E) stained sections. Formalin-Fixed Paraffin-Embedded (FFPE) blocks suitable for Immunohistochemistry (IHC) were selected and MCM2, Estrogen Receptor (ER), Human Epidermal Growth Factor Receptor 2 (HER2), Progesterone Receptor (PR)/neu and Ki-67 were performed. Scores given based on visual examination under light microscope. Analysis was done using IBM Statistical Package for the Social Sciences (SPSS) version 25.0 software. Results: Most of the subjects belonged to 41-55 years age group. Statistical significance was seen between high MCM2 and Ki- 67 expressions (p-value=0.0171) and high histologic grade and TNBCs (p-value=0.009). High MCM2 and Ki-67 expressions also come with increased risk for advanced disease. High Ki-67 is also a risk predictor for lymph node positive cases. Positive correlation was seen between MCM2 and (R)= 0.4318. Conclusion: The MCM2 is a predictor for adverse outcomes in breast carcinoma cases. It may serve as an alternative to Ki-67 as a proliferation marker, to guide clinicians in treatment strategies. Its role as a therapeutic target in aggressive breast carcinomas may be evaluated with larger study population in the future.

Molecular subtypes of breast carcinoma and its relation with clinicopathological features: A single-center initial experience

Molecular subtypes of breast carcinoma and its relation with clinicopathological features: A single-center initial experience

Abstract P4-10-30: PD-L1 expression in tumor infiltrating lymphocytes (TILs) inversely correlates with androgen receptor (AR) expression in HER2-positive breast cancer

Abstract Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for 20-30% of breast carcinomas and is associated with a poor prognosis. While anti-HER2 targeted therapies have improved outcomes within this group, a subset of these tumors eventually develop resistance urgently requiring novel therapeutic options. In addition to classic HER2+ subtype, estrogen receptor (ER)-positive and HER2-positive tumors (luminal B) are another subtype of HER2 expressing breast carcinomas which could also benefit from additional therapies. Targeting the androgen receptor (AR) pathway and the PD-L1 axis may represent potential new therapeutic strategies in breast cancer. Our group previously reported that AR expression is seen in ¾ of HER2+ carcinomas and is more common in luminal B compared to classic HER2+ tumors. In this report, we evaluated expression of PD-L1 in tumor infiltrating lymphocytes (TILs) in both classic HER2 + and Luminal B subtypes of breast carcinomas and correlated the expression of PD-L1 with AR expression in these tumors. Methods: The study population consisted of 114 patients with HER2-positive invasive breast carcinoma diagnosed from 2009-2014 at Northwestern Memorial Hospital. Electronic medical records were reviewed for patient demographics (mean age 54, range 23-80). Pathologic tumor characteristics (histologic type, size, and grade) and tumor marker profile (ER and HER2) were evaluated. Tissue microarrays were constructed (3 cores from each case to account for tumor heterogeneity) for immunohistochemical evaluation of AR and PD-L1. AR was graded as positive when at least 1% of tumor cells showed nuclear immunoreactivity. For PD-L1, the extent of staining (0%=0, 1-10%=1, 11-50%=2, and 51-100%=3) and staining intensity (0, 1+, 2+, 3+) were assessed in TILs. Then a composite score (CS) was calculated by multiplying extent and intensity results (range 0-9; 0-3=negative, 4-9=positive). Results: Of the 114 studied breast carcinoma cases, 54 were classic HER2+ tumors (47%) and 60 were luminal B (53%) tumors. Approximately 69% of classic HER2+ and 87% of luminal B cases were positive for AR. Of interest, in classic HER2+ cases, the expression of PD-L1 in TILs was inversely correlated with the expression of AR, with 82% (14/17) of AR- tumors being positive for PD-L1 in TILs compared to only 46% (17/37) of AR+ tumors with PD-L1 expression in TILs (p<0.01). No association of expression of PD-L1 in TILs with AR expression was observed in luminal B cases (62% in AR+ versus 50% in AR- tumors; p=0.70). Moreover, in classic HER2+/AR- group, grade 3 tumors were seen almost exclusively in the PD-L1 expressing group (13 versus 3), in contrast to the equal number of grade 3 tumors in classic HER2+/AR+ group regardless of PD-L1 expression in TILs (14 versus 14). No association of the PD-L1 expression with age, race, and tumor histologic types was observed in classic HER2+/AR+ or classic HER2+/AR- cases. Conclusions: Our results demonstrated that the expression of PD-L1 in TILs was inversely correlated with the expression of AR in classic HER2 positive tumors but not in luminal B tumors. We also found that in classic HER2+/AR- group, grade 3 tumors were seen almost exclusively in the PD-L1 expression group. Our findings add to the body of knowledge of the molecular mechanisms that drive the different molecular subtypes of breast carcinomas and raise the interesting possibility that new treatment strategies such as targeting the PD-L1 axis may show more benefit against the AR negative subtype of the classic HER2 positive carcinomas. Citation Format: Tiansheng Shen, Jennifer L. Pincus, Kalliopi P. Siziopikou. PD-L1 expression in tumor infiltrating lymphocytes (TILs) inversely correlates with androgen receptor (AR) expression in HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-30.

Clinicopathologic implications of epithelial cell adhesion molecule expression across molecular subtypes of breast carcinoma.

Epithelial cell adhesion molecule (EpCAM), a type I transmembrane protein of the epithelial tissues and known cell adhesion molecule, has been demonstrated to have critical role in carcinogenesis. In breast cancer, EpCAM expression has been associated with poor prognosis. The expression pattern of EpCAM across molecular subtypes of breast carcinoma has been studied in patients reporting to a South Indian multispecialty tertiary care hospital. The prognostic significance of EpCAM expression pattern and probable response to therapy has also been addressed. EpCAM expression was assessed by immunohistochemical studies on 200 breast carcinoma tissue samples of different molecular subtypes, including luminal A, luminal B, Her2Neu, and triple-negative breast cancer (TNBC). The expression was scored using the standard scoring system. A correlation was drawn with detailed clinicopathologic annotation and available outcomes data to analyze the influence of EpCAM on prognosis. EpCAM expression varied significantly in the different intrinsic subtypes of breast carcinoma. Differential expression was also established with different grades of breast carcinoma with varying levels of differentiation. We observed strong EpCAM expression in TNBC among other subtypes. The differential expression of EpCAM among intrinsic subtypes of breast cancer and the correlation of EpCAM expression with high-grade breast carcinoma shown in the study have important implications in understanding the role of EpCAM and might form the basis for developing targeted therapies in breast cancer in the future.

Clinical and imaging presentation of molecular types of breast cancer

Introduction: Breast cancer is the second most common malignant neoplasm among women in Brazil and worldwide. Its incidence increases with age, especially in individuals older than 50 years. Mammography is the main screening test, has high sensitivity, and is the only method that has made an impact on mortality rate. Breast cancer is classified into molecular subtypes, based on immunohistochemical markers. The luminal A subtype (LA) presents estrogen receptor (ER) and progesterone receptor (PR) positive, HER2 negative, and low Ki-67 index. Luminal B (LB) shows ER and/or PR positive, HER2 negative, high Ki-67 index, or HER2 positive (luminal HER2). HER2 has HER2 overexpression and ER and PR negative. Triple-negative (TN) has ER, PR, and HER2 negative and high histological grade. Objective: To evaluate patient characteristics according to the molecular subtypes of breast carcinoma among individuals treated at the Hospital São Paulo – Universidade Federal de São Paulo. Method: This is a retrospective study based on the analysis of medical records of breast cancer cases from the Hospital São Paulo between 2013 and 2016. During this period, 235 patients were treated. Among them, 40% were classified as LA, 34% as LB, 8% as luminal HER2, 15% as TN, and 3% as HER2. The mean age was 57.6 years. The incidence of breast carcinoma was higher in women over 50 years of age in all subtypes: 75.2% for LA, 65% for LB, 58% for luminal HER2, 100% for HER2 overexpression, and 75.1% for TN. Regarding ethnicity, most women were white in all subtypes, accounting for 66.5% of cases. In all subtypes, the most common clinical complaint was nodule: 86% for LA, 86% for LB, 100% for HER2 overexpression, and 96% for TN. Among the mammographic findings, nodule was the most frequent in all subtypes. Luminal subtypes presented other findings, such as suspicious calcifications (14% for LA and 21% for LB), focal asymmetries (14% for LA and 5% for LB), and distortions (2% for LA and 3% for LB). Conclusion: Breast cancer has a higher incidence among Caucasian individuals and those aged 50 to 60 years. The clinical and imaging presentation of tumors is influenced by their molecular subtype: luminal subtypes have a greater diversity of findings and non-palpable lesions, while TN tumors usually manifest as palpable nodules.

High Expression of Trophoblast Cell Surface Antigen 2 in Triple-negative Breast Cancer Identifies a Novel Therapeutic Target

Abstract Objectives Patients with triple-negative breast cancer (TNBC) respond poorly to current therapeutic modalities. The newly FDA-approved drug conjugate, Sacituzumab Govitecan, targeting antitrophoblastic cell surface antigen 2 (Trop-2), offers a new modality to treat these subtypes of breast carcinoma (BC). Our study examines expression of Trop-2 by immunohistochemistry (IHC) in TNBC. Methods Forty cases of TNBC were selected from our files (34 ductal, 4 pleomorphic lobular, 1 metaplastic, and 1 mixed ductal and lobular carcinoma). A control group included 11 luminal A-like, 11 luminal B-like, and 8 HER2-like BC. Immunostaining for Trop-2 was performed on 4-micron-thick tissue sections using goat polyclonal antibody (R&D Systems). Three pathologists individually scored the % and intensity of membranous staining. The % of staining was defined as <10%, 10%-50%, and >50%. The intensity of staining was scored as 3+ (crisp circumferential membranous staining), 2+ (medium membranous staining), 1+ (patchy weak membranous staining), and 0 (no staining). A Kruskal-Wallis H-test and pairwise comparison with Bonferroni correction was performed to compare % and intensity of staining in TNBC to control group. Results TNBC exhibited stronger Trop-2 staining in both intensity and extent when compared to the control. The result was significantly different, χ2 (4) = 17.427, P = .001. A pairwise comparison with Bonferroni correction found significant difference between TNBC (42.55) and luminal A (16.65) (P < .001). There was significant agreement (P < .001) among 3 independent pathologists for assessing % and intensity of staining. Conclusion The extent and intensity of staining for Trop-2 is higher in TNBC than in other molecular subtypes of BC. These findings suggest that patients with TNBC may potentially benefit from this targeted therapy. Furthermore, identification of Trop-2 in other molecular subtypes may expand the therapeutic potential of this new drug. Further studies are needed to determine the efficacy of this marker.

Luminal B is the Most Common Intrinsic Molecular Subtypes of Invasive Ductal Breast Carcinoma Patients in East Kalimantan, Indonesia.

Objective:Breast carcinoma has no longer been considered as a single and standalone disease. Its subtypes have been known to vary in terms of risk factors, natural histories, and responses to therapies. In particular, intrinsic molecular subtypes based on St. Gallen International Expert Consensus 2013 have classified breast carcinoma into luminal A, luminal B, HER2+, and triple-negative, depending on the expression of ER, PgR, HER2, and Ki-67. Research on intrinsic molecular subtypes of breast carcinoma in Indonesia, however, are rarely conducted, which then triggers the intention to conduct this study. Methods:In this work, a retrospective study was conducted on 92 formalin-fixed paraffin-embedded samples of invasive ductal breast carcinoma patients. These samples were from patients at Abdul Wahab Sjahranie County General Hospital Samarinda, East Kalimantan, Indonesia, in 2016. Next, immunohistochemical staining using anti-ER, PgR, HER2, and Ki-67 antibodies was applied to classify intrinsic molecular subtypes. Then, an association between clinical and immunohistochemical factors with intrinsic molecular subtypes of breast carcinoma were analyzed using Chi-square test. Results:Looking at results of the retrospective study, luminal B was discovered as the most common intrinsic molecular subtypes of breast carcinoma (42.39%) in East Kalimantan, Indonesia. The next ranks of breast carcinoma subtypes in the region included HER2+ (39.13%), triple-negative (10.87%), and luminal A (7.61%). In fact, there was a significant association between age (p = 0.019) with intrinsic molecular subtypes of breast carcinoma. Conclusion:The study found luminal B as the most common intrinsic molecular subtypes of Indonesian breast carcinoma in the region under investigation. In the future, the higher positivity rate of luminal B in breast carcinoma patients compared to prior studies would require further investigations.

Surrogate Molecular Classification of Invasive Breast Carcinoma: A Comparison Between Core Needle Biopsy and Surgical Excision, With and Without Neoadjuvant Therapy.

Surrogate molecular classification identifies different subtypes of invasive breast carcinoma on the basis of their immunohistochemical markers. The purpose of the study is to verify whether the immunohistochemical markers and surrogate molecular subtypes can be correctly assessed on the core needle biopsy (CNB) when compared with the corresponding surgical excision (SE), with or without neoadjuvant treatment (NAT). Cases with invasive carcinomas identified on both CNB and SE were retrospectively selected. With immunohistochemistry for estrogen receptors (ER), progesterone receptors (PgR), Ki67, human epidermal growth factor receptor 2 (Her2), and molecular analysis for Her2, surrogate molecular classification was determined in 4 and 5 groups, according to the 2013 St Gallen consensus. A total of 1067 cases was considered and complete data for surrogate molecular classification were available for 988 cases (655 without NAT, 333 with NAT). Without NAT, concordance was strong for ER and Her2, moderate for PgR, and weak for Ki67; concordance for surrogate molecular classification was moderate. After NAT, lower concordance rates were recorded, with significant reduction of PgR (P<0.001) and Ki67 (P<0.001). Without NAT, the surrogate molecular subtypes of breast carcinoma can be reliably assessed on CNB; Ki67 and/or PgR may be repeated on SE when values are close to cutoffs to avoid tumor subtype misclassification. After NAT, it seems advisable to repeat at least Ki67 and PgR.

EGF (epidermal growth factor) receptor expression in blood: Prognostic biomarker in overall survival (OS) of patients with non-metastatic triple negative (TN) breast carcinoma.

e14518 Background: EGF acts on tumor progression and its receptor can be measured by immunohistochemistry, or in the blood by immunoenzymatic method. This study quantified the expression of blood EGF receptors (bEGFR) in the molecular subtypes of breast carcinoma and their impact on OS. Methods: Prospective study with 125 patients (pts) and 89 healthy women (controls). All of them signed the free and detailed consent form. The blood collection was performed before the surgery (stages I–10pts; II–59pts) and before neoadjuvant chemotherapy (stage III-41pts) or palliative (stage IV–15pts). All the patients have made the protocol of a public service treatment. Measurement of bEGFR expression was done by the ELISA method. The statistical significance was set at p &lt; 0.05. Results: In a follow-up of 29.9 months (8-44m) 23 deaths occurred at 15.8 months (8-34.5m); 58pt had bEGFR &lt; 40ng/mL (E40-) and 67pt ≥40ng/mL (E40 +). TNs (28pt) had lower OS than Luminal (A = 29pts; B = 44pts) and HER2 (24pts) (p = 0.0020). But in TN E40- the significant difference in OS disappeared (TN versus Luminal A: p = 0.0785; TN versus Luminal B: p = 0.1995; TN versus HER2: p = 0.3017); which did not occur in TN E40 + (TN versus Luminal A: p = 0.0009; TN versus Luminal B: p = 0.0241; TN versus HER2: p = 0.0014). In OS of non-metastatic 24 TN (3pts stages 0/I; 13pts II; 8pts III) there was significant difference according to bEGFR expression (E40+ with lower OS than E40-, HR:5.49; 95%CI:1.26–15.07;p = 0.0159). In binary logistic regression, bEGFR was considered to be a significant predictor of death in TN non-metastatic, p = 0.008 (bEGFR of 30ng/mL = death probability of 6.7% until bEGFR of 80ng/mL = probability of death of 99.8%). There were no significant differences in bEGFR between patients and controls, among grades of histological differentiation, or in those with ki67 &gt; 14%. There was no difference in OS according to bEGFR in stages I, III or IV, except in stage II (E40+ with lower OS than E40-, HR:4.248;95% CI:1.229–14.68; p = 0.0460). Conclusions: Increased expression of bEGFR in non-metastatic TNs is a predictor of lower OS, with statistical significance.

Loss of Nuclear ARID-1A Expressions Is Associated with Hormone Receptor Status in Breast Cancers.

Breast cancer is the most common cancer among women worldwide. Adenine thymine-rich interactive domain 1A (ARIDIA) is a tumor suppressor gene involved in chromatin remodeling and it encodes the ARIDIA protein. Recent studies have shown the loss of ARIDIA protein expression in different carcinomas may have a prognostic significance. In the present study, we aimed to evaluate the interactions between ARIDIA loss and molecular subtypes of breast carcinomas. ARIDIA expressions were studied in 292 formalin- fixed, paraffin- embedded breast carcinoma specimens and its association with different pathological and clinical parameters was evaluated. Loss of ARIDIA expression was detected in 123 cases. There was no statistically significant association between ARID-1A expression and molecular subtype of breast carcinomas (p=0.110) or HER2 amplification (p=0.909). Contrarily, there was a significant association between ARIDIA expression and presence of estrogen (p=0.047) or progesterone receptors (p=0.023). Besides a statistically significant relationship was found between loss of ARID1A, and the presence of both in situ component (p=0.016) and lymph node metastasis (p=0.001). In this study, we have demonstrated that loss of ARID1A expression positively correlates with hormone receptor status as well as tumor aggressiveness.

P176 - The impact of molecular subtypes of breast carcinoma on response to neo-adjuvant chemotherapy in Asian population

P176 - The impact of molecular subtypes of breast carcinoma on response to neo-adjuvant chemotherapy in Asian population

Molecular Subtypes of Indonesian Breast Carcinomas - Lack of Association with Patient Age and Tumor Size

Objective:Breast carcinoma (BC) is a heterogeneous disease that exhibits variation in biological behaviour, prognosis and response to therapy. Molecular classification is generally into Luminal A, Luminal B, HER2+ and triple negative/basal-like, depending on receptor characteristics. Clinical factors that determined the BC prognosis are age and tumor size. Since information on molecular subtypes of Indonesian BCs is limited, the present study was conducted, with attention to subtypes in relation to age and tumor size.Methods:A retrospective cross-sectional study of 247 paraffin-embedded samples of invasive BC from Dr. Sardjito General Hospital Yogyakarta in the year 2012- 2015 was performed. Immunohistochemical staining using anti- ER, PR, HER2, Ki-67 and CK 5/6 antibodies was applied to classify molecular subtypes. Associations with age and tumor size were analyzed using the Chi Square Test.Results:The Luminal A was the most common subtype of Indonesian BC (41.3%), followed by triple negative (25.5%), HER2 (19.4%) and luminal B (13.8%). Among the triple negative lesions, the basal-like subtype was more frequent than the non basal-like (58.8 % vs 41.2%). Luminal B accounted for the highest percentage of younger age cases (< 40 years old) while HER2+ was most common in older age (> 50 years old) patients. Triple negative/basal-like were commonly large in size. Age (p = 0.080) and tumor size (p = 0.462) were not significantly associated with molecular subtypes of BC.Conclusion:The most common molecular subtype of Indonesian BC is luminal A, followed by triple-negative, HER2+ and luminal B. The majority of triple-negative lesions are basal-like. There are no association between age and tumor size with molecular subtypes of Indonesian BCs.

Correlations of aldehyde dehydrogenase-1 (ALDH1) expression with traditional prognostic parameters and different molecular subtypes of breast carcinoma.

Background and aimBreast cancer, a heterogeneous disease, is the most common cause of cancer-related death in women worldwide. Despite considerable developments in treatment modalities, a subset of patients with advanced-stage breast carcinoma display poor prognosis. Breast cancer heterogeneity and risk of recurrence could be explained with the help of cancer stem cell hypothesis. Stem cells have the capacity to self-renew and differentiate into multiple cell types. Aldehyde dehydrogenase-1 (ALDH1), an enzyme responsible for the oxidation of intracellular aldehydes, contributes to normal and tumor stem cell differentiation. Invasion and metastasis in breast cancer are found to be mediated by a subpopulation of tumor cells which exhibit stem cell-like features and express ALDH1.The aim was to document ALDH1 expression in breast carcinoma and find its association with other clinico-pathologic prognostic parameters.Study designThis was a cross-sectional observational study.MethodsA total of 62 patients with breast carcinoma undergoing mastectomy were included in this study. The tumors were classified into molecular subtypes by assessing immunohistochemical (IHC) expression of ER, PgR, HER2 and Ki-67 according to St. Gallen Consensus Conference 2013. ALDH1 expression was studied by IHC and correlated with clinicoathological parameters.Statistical analysisStatistical analysis was done using Graph Pad software (Prism 5 version) for Windows 7. A p-value <0.05 was considered statistically significant.Results and analysisOut of 62 tumors, 35 tumors (56.4%) showed ALDH1 positivity. ALDH1 expression was significantly associated with larger size, lymph node involvement, higher grade, higher stage and HER2+ or triple negative tumors.ConclusionThis study suggests that ALDH1 expression is associated with poor prognostic parameters and aggressive tumor behavior. Larger population-based prospective trials on Indian patients are required to validate these results.

The Association between Molecular Subtypes of Breast Cancer with Histological Grade and Lymph Node Metastases in Indonesian Woman

Objective:Breast carcinoma is a heterogeneous disease which is rich in diversity. Molecular subtypes of breast cancer, histological grade and lymph node metastases are strong prognostic and predictive factors. In Indonesia, only a limited number of studies have investigated the correlation between molecular subtypes with histological grade and lymph node metastases.Methods:We analyzed 247 invasive breast carcinoma cases from the Anatomic Pathology Installation of Dr. Sardjito General Hospital Yogyakarta between 2012-2015. The slides were stained for estrogen receptors (ER), progesterone receptors (PR), HER2, Ki-67 and CK5/6 for classification into breast cancer subtypes (BCS). Histological grade using the Nottingham system and lymph node status were obtained from anatomic pathology records. The association between histological grade and lymph node status with BCS was examined with Chi-square tests.Results:The immunohistochemical features of 247 cases of women with invasive breast carcinoma were examined. There were 102 (41.3%) patients with Luminal A, 34 (13.8%) patients with Luminal B, 48 (19.4%) patients with HER2-positive, and 63 (25.5%) patients with triple negative breast cancer (TNBC). There were 148 (59.9%) patients with negative lymph node status and 99 (40.1%) with positive status. Among 63 TNBC cases, 37 (58.7%) patients were positive for CK5/6 staining (basal-like). Statistically, there were significant differences between histological grade and subtypes (p=0.013). However, no significant differences were found for lymph node metastases (p=0.540).Conclusion:Among subtypes, Luminal A has the highest frequency, followed by TNBC, HER2-positive and Luminal B. Histological grade was associated with molecular subtypes of breast carcinoma in Yogyakarta. Grade I was associated with Luminal A, while Grade III was associated with Luminal B, HER2 and TNBC subtypes.

Relationship between clinicopathological features and molecular subtypes of invasive breast ductal carcinoma in young women

Objective To analyze the association between clinicopathological features and molecular subtypes of breast carcinoma in women aged under 35 years old. Methods The clinicopathological data of 385 women aged under 35 years old who had complete data and were diagnosed as breast cancer from July 2009 to May 2016 were retrospectively analyzed. The relationship between clinicopathological features and molecular subtypes was analyzed by using nonparametric Kruskal-Wallis H test. Results In 415 cases, 385 cases were invasive ductal carcinoma, 22 cases were ductal carcinoma in situ, 4 cases were mucinous adenocarcinoma, 3 cases were invasive lobular carcinoma, 1 case was lobular carcinoma in situ. In invasive ductal carcinoma, luminal B type was the most [218 cases (56.6%)], and 60 cases (15.6%) were triple negative breast cancer (TNBC). There were significant differences in tumor mass, N stage, histological grade and clinical stage between the different molecular subtypes (all P < 0.05). Conclusions Tumor size, histological grade, lymph node staging and clinical stage of young female patients with breast carcinoma are closely associated with different molecular subtypes. The ratio of molecular subtypes with poor prognosis, higher histological grade and later clinical stage is high in all cases, which is related to the poor prognosis of young women breast carcinoma and should be paid more attention to the early diagnosis. Key words: Breast neoplasms; Female; Young adult; Molecular typing; Pathological conditions, signs and symptoms

Abstract 3743: Magnetic resonance imaging shrinkage patterns after neoadjuvant chemotherapy for breast carcinomas: Correlation with molecular subtypes

Abstract Background: Neoadjuvant chemotherapy (NAC) is widely performed for patients with locally advanced breast carcinomas. It is important to obtain precise information using imaging modalities about the distribution of residual carcinomas after NAC to predict the success of breast conserving surgery. However, the relationship between magnetic resonance imaging (MRI) shrinkage patterns and molecular subtypes of breast carcinomas has not yet been investigated. Methods: We analyzed the MRI shrinkage and pathological patterns of residual carcinomas after NAC in 54 consecutive breast carcinomas. The shrinkage patterns were classified into five categories: Type I and II (concentric shrinkage with or without any surrounding lesion), type III (shrinkage with residual multinodular lesions), type IV (diffuse contrast enhancement in the entire quadrant), and non-visualization. Results: The most common MRI shrinkage pattern was type I (39%) followed by non-visualization (26%). The most common pathological shrinkage pattern was type III (33%), followed by type II (28%) and non-visualization (22%). The concordance rates of the MRI patterns of non-visualization and type I were significantly lower than those of the MRI patterns of type II, III, and IV (p = 0.018). Moreover, in the luminal subtypes, the concordance rates of the MRI patterns of non-visualization and type I were significantly lower than those of the MRI patterns of type II, III, and IV (p = 0.026); however, in the non-luminal subtypes, this correlation was not significant. Conclusions: The results of the present study suggest that the cases with MRI shrinkage patterns of non-visualization and type I require caution regarding the surgical margins compared with the other types, especially the luminal subtypes. Citation Format: Tsuyoshi Mori, Kaori Tomida, Mina Kitamura, Sachiko Sakai, Yuki Kawai, Tomoharu Shimizu, Tomoko Umeda, Tomoyuki Ueki, Sachiko Kaida, Toru Miyake, Hiroya Iida, Hiroya Akabori, Naomi Kitamura, Tsuyoshi Yamaguchi, Hiromichi Sonoda, Shigeyuki Naka, Masaji Tani. Magnetic resonance imaging shrinkage patterns after neoadjuvant chemotherapy for breast carcinomas: Correlation with molecular subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3743. doi:10.1158/1538-7445.AM2017-3743

Expressions of HIF-1α and CA9 in breast carcinoma and their relationships with basal-like subtype

Objective To study the expressions of hypoxia inducible factor-1α (HIF-1α) and carbo-nic anhydrase 9 (CA9) in different molecular subtypes of breast carcinoma and their relationships with basal-like subtype. Methods The expressions of HIF-1α and CA9 were detected by immunohistochemistry in five subtypes of breast carcinoma (n=803). The relationships of the expressions of HIF-1α and CA9 with the clinicopathologic parameters of basal-like subtype and with the prognosis of patients were analyzed. Results The positive expression rates of HIF-1α and CA9 protein in breast carcinoma were much higher than those in para-tumor breast tissues (43.96% vs. 3.86%, χ2=354.858, P<0.001; 19.80% vs. 4.61%, χ2=86.495, P<0.001). The positive expression rates of HIF-1α in Luminal A, Luminal B, epidermal growth factor receptor-2 (HER-2) over-expression, basal-like and normal breast-like subtypes were 31.97%, 25.00%, 56.06%, 77.89% and 55.76% respectively, and the positive expression rates of CA9 were 7.48%, 5.56%, 60.61%, 40.00% and 27.88% respectively, with significant differences (χ2=88.628, P<0.001; χ2=147.128, P<0.001). The positive expression rates of HIF-1α and CA9 in estrogen receptor (ER)-negative breast carcinomas (HER-2 over-expression, basal-like and normal breast-like) were significantly higher than those in ER-positive subtypes (Luminal A and Luminal B, all P<0.005). There was a significant positive correlation between HIF-1α and CA9 (C=0.315, P=0.001), and both were correlated with the lymph node metastasis (χ2=4.542, P=0.033; χ2=7.025, P=0.008), pTNM stage (χ2=5.390, P=0.020; χ2=10.179, P=0.001) and poor prognosis (χ2=4.353, P=0.037; χ2=6.056, P=0.014) of basal-like subtype. Conclusion Over-expressions of HIF-1α and CA9 may be related to the ER-negative breast cancer more closely, and both may play important roles in the occurrence and development of basal-like subtype. Over-expressions of HIF-1α and CA9 may suggest the poorer prognosis of patients with basal-like breast carcinoma. Key words: Breast neoplasms; Hypoxia-inducible factor 1, alpha subunit; Carbonic anhydrases; Basal-like subtype

Breast cancer biomarkers at Niger delta university hospital: Comparisons with national and international trends and clinical significance

Breast cancer biology is heterogeneous and patients with the same diagnostic profile have markedly different clinical outcomes. Gene expression profiling and its surrogate IHC markers classified breast cancer into four molecular subtypes with different prognosis, targeted therapies, and/or clinical outcomes. The present study was conducted to investigate breast cancer subtypes among women in NDUTH Bayelsa state and compared them with similar studies in other populations of international and national origin. Archived formalin fixed paraffin embedded tissue blocks were retrieved from January 2010-December 2014 provided 20 cases of microscopically confirmed invasive ductal breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Cytokeratin 5/6) immunostain. All the patients were females and most of them were under 50 years at presentation. The molecular subtypes were luminal A (54.1%), luminal B (25.0%), HER2 (12.5%), basal-like (4.2%), and unclassified (4.2%). Triple negative carcinoma (basal-like and unclassified combined) was 4.2%, ER+ (65%) and (PR+70%).Breast carcinoma in Bayelsa state women presents at a younger age. We note that the prevalence of the molecular subtypes of breast carcinoma appears to have variation in geographical distribution. The reasons for these differences could be technical, quality of fixation and processing, varying staining techniques, and different criteria in scoring and reporting. This study indicates that the majority of breast cancer in NDUTH lies at the two ends of the molecular spectrum, that is, luminal A (54.1%), sensitive to hormonal therapy and with a good prognosis, and “triple negative” (4.2%) not hormonally sensitive and with a poor prognosis.

P248 - Cancer stem cell marker, CD44 expression in Indian breast carcinoma patients and its association with the molecular subtypes of breast carcinoma

P248 - Cancer stem cell marker, CD44 expression in Indian breast carcinoma patients and its association with the molecular subtypes of breast carcinoma

Expression of chemokine CXCL12 and its receptor (CXCR4 and CXCR7) in different molecular subtypes of human breast carcinoma and the clinical significance

To study the expressions and the clinical significance of chemokine CXCL12 and its receptor CXCR4, CXCR7 in the human breast carcinoma (BC) with different molecular subtypes. Methods: The mRNA expressions of CXCL12, CXCR4 and CXCR7 in tissues from 80 patients with different molecular subtype of BC were measured by qRT-PCR. The protein expressions of CXCL12, CXCR4 and CXCR7 in paraffin-embedded samples from 160 patients with different molecular subtypes were detected by immunohistochemical staining. Results: The mRNA expression levels of CXCL12, CXCR4 and CXCR7 in HER-2 positive BC and TNBC tissues were significantly higher than those in luminal A and luminal B subtype BC tissues (all P<0.05), but their expressions were not different between luminal A and luminal B subtype BC tissues or between HER-2 positive BC and TNBC tissues. The positive expression rates of CXCL12 protein in HER-2 positive BC and TNBC tissues were significantly higher than those in luminal A and luminal B subtype BC tissues (all P<0.05), while their expressions were not different between luminal A and luminal B subtype BC tissues or between HER-2 positive BC and TNBC tissues. High expressions of the gene CXCL12 and its receptor CXCR4 and CXCR7 in HER-2 positive BC and TNBC may be closely associated with their poor prognosis. Inhibition of their expressions in HER-2 positive BC and TNBC may provide a strategy for treating BC in clinic.