No Special Type Research Articles

Abstract PS6-36: The formation of GCs in cancer-free ALNs, a non-monotonic prognostic factor in HR-negative invasive breast cancer patients

Abstract Purpose: To assess the frequency and prognostic relevance of germinal centres (GC) in cancer-free axillary lymph nodes (ALNs), in relation to stromal tumour-infiltrating lymphocytes (sTILs) and the presence of tertiary lymphoid structures (TLS) in the primary carcinoma, in LN-positive Hormone Receptor (HR)-negative invasive breast cancer patients. Patients and methods: A cohort of 161 patients with HR-negative invasive breast cancer of no special type (NST) and LN-positive status treated between 2005-10 at Tianjin Medical University (China) was identified. sTILs and TLS at the primary tumour site and GC in 2,841 involved and cancer-free ALNs were evaluated on H&E stained sections. Markers were tested for prognostic value for invasive Disease-Free Survival (iDFS), distant Disease-Free Survival (dDFS) and Overall Survival (OS), using Cox regression models adjusted for clinico-pathological factors. Results: Among the 161 HR-negative breast cancers, 47% (n=75) had >=20% sTILs and 24% (n=38) peritumoural TLS. 75% (121/161) and 76% (122/161), respectively, displayed GCs in their cancer-free and involved ALNs. Significantly higher numbers of GCs were seen in both cancer-free and involved ALNs when the primary tumours showed >=20% sTILs. The presence of TLS was significantly associated with increased GC numbers in involved but to a lesser extend in cancer-free ALNs (Kruskal-Wallis rank sum test, p<0.001 and P_value=0.07, respectively). As expected, increased sTILs and presence of TLS were associated with improved outcome for all endpoints. Using an iterative process to determine an optimal cut off point by a minimal P value approach, a non-monotonic relationship between the frequency of GC in cancer-free ALNs and all endpoints was observed. Patients with >2 GC but less than the top 5% (= 62 GC) in cancer-free ALNs showed improved iDFS, dDFS and OS, whilst patients with <=2 GC or >62 GC across all assessed cancer-free ALNs had poorer iDFS, dDFS and OS (see Table). In the multivariate models, the frequency of GC in cancer-free ALNs added independent prognostic information for all endpoints across all patients. In patients with >=20% sTILS, cancer-free ALNs within the top 5% for GC remained associated with a worse dDFS and iDFS (see Table). Cancer-free ALNs with <=2 GC in total identified a subgroup of patients with <20% sTILs tumours having the worst iDFS, dDFS and OS in multivariate models. Five-year iDFS, dDFS and OS in patients with <20% sTILs were 39%, 39% and 48% respectively for those with <=2 GC in total, in comparison those with >2 GC whose five-year iDFS, dDFS and OS were 65%, 65% and 69%, respectively. Conclusions: The prognostic importance of GC assessment in cancer-free ALNs in women with LN-positive HR-negative breast cancers is demonstrated. A better outcome in patients with GC formation in their cancer-free ALNs, despite low sTILs in the primary carcinoma, may suggest a systemic anticancer immune response. High sTILs but with extreme GC formation in the cancer-free ALNs could potentially reflect an overdriving but less effective immune response. The assessment of the combination of primary and nodal immune response in HR-negative breast cancers is imperative in these high-risk patients. Table 1. Univariate and Multivariate Cox Regression Analysis of Outcome by GC in Cancer-Free ALNsiDFSUnivariateAll cases<20% sTIL>=20% sTILTotal GCs number - binnedModel PHRCIModel PHRCIModel PHRCI<=23.581.95 - 6.572.871.48 - 5.571.310.15 - 11.262>GC<624.86E-05reference7.64E-03reference4.66E-03reference>624.631.75 - 12.41.930.26 - 14.5612.793.34 - 48.97MultivariateCorrected for: pNstage, sTILS & TLSCorrected for: pTstage & TLSCorrected for: pNstageTotal GCs number - binnedCovariate PModel PHRCICovariate PModel PHRCICovariate PModel PHRCI<=22.90E-022.00E-082.102.08 - 4.103.13E-037.00E-042.831.42 - 5.658.45E-011.00E-031.240.14 - 10.622>GC<62NAreferenceNAreferenceNAreference>624.15E-059.583.25 - 28.201.94E-014.070.49 - 33.876.62E-038.861.83 - 42.82dDFSUnivariateAll cases<20% sTIL>=20% sTILTotal GCs number - binnedModel PHRCIModel PHRCIModel PHRCI<=24.762.48 - 9.143.681.82 - 7.432,130.22 - 20.442>GC<622.46E-06reference1.10E-03reference2.19E-03reference>625.872.14 - 16.082.490.32 - 19.0718.434.04 - 84.03MultivariateCorrected for: pTstage, pNstage, sTILS & TLSCorrected for: Age, pTstage, TLSCorrected for: pNstageTotal GCs number - binnedCovariate PModel PHRCICovariate PModel PHRCICovariate PModel PHRCI<=24.30E-033.00E-092.911.40 - 6.059.01E-042.00E-053.451.66 - 7.165.51E-011.00E-031.990.21 - 19.132>GC<62NAreferenceNAreferenceNAreference>622.49E-0615.304.91 - 47.635.19E-028.610.98 - 75.553.11E-0313.302.39 - 73.89OSUnivariateAll cases<20% sTIL>=20% sTILTotal GCs number - binnedModel PHRCIModel PHRCIModel PHRCI<=24.142.03 - 8.412.931.38 - 6.223.130.28 - 34.512>GC<622.62E-04reference1.78E-02reference7.52E-02reference>624.131.18 - 14.42.570.33 - 19.8311.891.65 - 85.45MultivariateCorrected for: Age, pTstage, pNstage, sTILS & TLSCorrected for: Age & TLSCorrected for: pNstage, LVI & TLSTotal GCs number - binnedCovariate PModel PHRCICovariate PModel PHRCICovariate PModel PHRCI<=21.50E-013.00E-091.820.80 - 4.122.28E-024.00E-042.411.13 - 5.12*3.00E-04**2>GC<62NAreferenceNAreferenceNAreference>628.62E-0516.064.02 - 64.247.01E-027.050.85 - 58.342.80E-012.970.41 - 21.43*too few events Citation Format: Fangfang Liu, Thomas Hardiman, Patrycja Gazinska, Jelmar Quist, Sarah Pinder, Anita Grigoriadis. The formation of GCs in cancer-free ALNs, a non-monotonic prognostic factor in HR-negative invasive breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-36.

Expression of Survivin in Basal-Like and Triple Negative Breast Carcinoma and Associations with Clinicopathological Parameters

INTRODUCTION: Triple negative breast carcinoma (TNBC) molecular subtype and its variant; basal-like triple negative (BLTN) carcinoma is an established poor prognostic indicator. The aim of this study is to analyse the survivin expression in TNBC and BLTN, and relating the results with clinicopathological parameters. MATERIALS AND METHODS: We conducted a cross sectional study using 94 archived formalin-fixed paraffin embedded tissue blocks of invasive breast carcinoma, no special type (NST). Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2) were used as surrogate markers to classify the cases into molecular subtypes. Samples with triple negative phenotype (ER, PR and HER2 negative) were stained with CK 5/6 to identify the BLTN subtype. All the samples were also immunostained for survivin. RESULT: Out of 94 cases, 41.5% (39 cases) were TNBC. Among the TNBC cases, only 41.0% (16 cases) were BLTN subtype when they found to be positive for CK 5/6. Among 94 cases of invasive breast carcinoma, 28.7% (27 cases) were survivin positive with (53.8%) 21 cases were TNBC and (11%) 6 cases were non-TNBC (p< 0.001). Among 16 cases of BLTN subtype, only 8 cases were survivin positive (p = 0.752). Survivin expression was also statistically significant with tubule formation (p=0.029), nuclear pleomorphism (p=0.008), tumour grade (p=0.010), ER status (p< 0.001) and PR status (p=0.001). CONCLUSION: Survivin expression was statistically significant in invasive breast carcinoma. Even though the expression was significantly high in TNBC, it is not related to whether it is a basal-like or non-basal-like variant.

Clinicopathological relation of CD10 and cyclooxygenase-2 expression in invasive breast cancer no special type

Background In breast cancer, which is the most frequent female cancer, new histopathologic parameters, such as tumor-infiltrating lymphocytes and stromal factors, are now introduced for prognosis and new strategies of therapy. This study was designed to explore CD10 and cyclooxygenase-2 (COX2) expression levels in invasive duct carcinoma (IDC) no special type (NST) and their relations with clinicopathological data. Methods This work was conducted on 40 cases of IDC of NST that were collected as paraffin-embedded blocks. For each case, sections of paraffin-embedded blocks were submitted to be stained with routine hematoxylin and eosin and other sections were stained using the immunohistochemistry technique with CD10 and COX2 antibodies and then evaluated and scored. Results CD10 was expressed in nearly half of the cases (45%), whereas COX2 was detected in all of the cases (100%). COX2 was strongly expressed in more than two-thirds of the cases. A significant association was detected between CD10 and lymph node status (P=0.017). Although no significant association could be detected, about one-fourth and one-third of cases with marked estrogen receptor and progesterone receptor expressions, respectively, had strong CD10. No significant association could be detected between COX2 and all studied clinical and histological data, including CD10 expression. However, COX2 was expressed more frequently in negative human epidermal growth factor receptor 2/neu and high Ki-67 cases. Cases with associated carcinoma in situ, detected vascular emboli, and lymph node positivity expressed COX2 score 4. Conclusion A significant association was found between CD10 and lymph node staging. COX2 was detected in all studied cases, with tendency to be associated with bad prognostic indicators. These findings suggest that CD10 and COX2 could contribute to tumor aggressiveness and progression in IDC NST.

Evaluation of Pathological Response in Post-Neoadjuvant Chemotherapy Breast Carcinoma Specimens using Residual Cancer Burden System

Introduction: Many systems have been proposed to classify the degree of tumour response to therapy in post-neoadjuvant Chemotherapy (NACT) breast cancers. The Residual Cancer Burden (RCB) developed by MD Anderson cancer hospital is an online tool for the quantification of residual disease that is easy to practice, reproducible, and the RCB score has been clinically validated as independent prognostic factor for long-term survival. Aim: To evaluate the methodology for grossing and microscopic examination for assessing pathologic response in postNACT breast cancer specimens using RCB system developed by MD Anderson cancer institute and its feasibility for routine practice. Materials and Methods: The present cross-sectional study was conducted in Basavatarakam Indo American Cancer Hospital and Research Institute Hyderabad over a duration of three months from May 2018 to July 2018. Histologically proven breast carcinoma patients who were treated with both NACT and surgery were included in the study. Before surgery, these patients were treated with either anthracycline-based chemotherapy regimen with or without additional taxanes or targeted therapy with transtuzumab. RCB score and class were calculated to assess pathologic response to NACT. Analysis was performed individually by two senior pathologists, who has expertise in breast pathology and a junior pathologist. Consensus opinion was noted in case of discrepancies. Results: The study included 50 carcinoma breast specimens. All the cases werefemales. 49 cases were diagnosed as invasive carcinoma, No Special Type (NST) and one was lobular carcinoma. pCR (Pathological complete response) was seen in 9 (18%) and residual disease was seen in 41 (82%) patients. Conclusion: The present study highlights feasibility of application of RCB system in assessing pathological response following NACT in breast cancer. Incorporating RCB score and class in the reporting helps the surgical pathologist to overcome sampling errors caused by heterogeneously variable cellularity commonly encountered in these type of specimens.

One year of breast cancer in Ibadan, Southwestern Nigeria: a histopathological review

Background: Breast cancer is a major public health problem in most low- to medium-income countries of the world because of its high morbidity and mortality rate. Histopathological features are vital in risk assessment, selection of treatment and prognostication in breast cancer patients. This study aimed to assess the histopathological features of all breast cancer cases seen in a tertiary hospital in the year 2018. Methods: This is a retrospective review of all breast cancer cases histologically diagnosed and confirmed by three Pathologists at the University College Hospital (UCH), Ibadan over a one-year period from 1st January 2018 to 31st December, 2018. Results: A total of 236 breast cancer cases were seen during this period, 234 (99.2%) were females while only 2 (0.8%) were male. 163 (69.7%) patients were between the fourth and sixth decades of life, 65 (27.8%) patients were above sixth decade while 6 (2.5%) patients were below fourth decade. Invasive ductal carcinoma of No Special Type (NST) was the commonest histological subtype 212 (89.8%). Grade 1 cases were 25(10.6%), Grade 2 129 (54.7%) and Grade 3 cases were 40 (16.9%) while 42 (17.8%) were not graded. Lymphovascular invasion observed in 98 (41.5%) of the cases. 54 (22.9%) had immunohistochemistry out of which 23 (43.4%) were triple negative while 8 (3.4%) were triple positive. Conclusion: Histopathological features suggesting aggressive disease was predominantly observed. Efforts should be made towards early diagnosis, adequate evaluation and prompt treatment. Cancer care should be fully incorporated in the National Health Insurance Scheme (NHIS).

English

BACKGROUND Breast lesions have gained importance globally due to significant increase in mortality and morbidity associated with breast cancer which is now the commonest malignancy worldwide. Previously, cervical cancer was the most common cancer in Indian women but now the incidence of breast cancer has outnumbered cervical cancer and is the leading cause of death in women due to cancer. Although advances in imaging techniques and increased use of fine needle aspiration cytology have greatly assisted the preoperative evaluation of breast lesions, histopathology remains the gold standard in differentiating benign and malignant lesions. The present study was carried out to know the frequency, age distribution and histopathological profile of neoplastic as well as non-neoplastic lesions of breast. METHODS This retrospective one-year study was conducted in the Department of Pathology at a tertiary health care institute from January 2017 - December 2017. All specimens of mastectomy, lumpectomy, and Tru-Cut biopsies were studied except treated cases of malignancy. Detailed gross examination was done followed by thorough sampling and processing. Tissue sections were stained with haematoxylin and eosin. Different lesions were studied by microscopic examination. Neoplastic lesions were classified based on the WHO (World Health Organization) classification (2012). RESULTS A total of 980 cases was studied out of which 951 were females and 29 were males. The benign neoplasms constituted 329 cases (33.57 %), malignant neoplasms 521 cases (53.16 %) and non-neoplastic lesions 130 cases (13.26 %). In our study fibroadenoma was the most common benign neoplasm (n = 292) and fibrocystic disease formed the major population of non-neoplastic benign lesion (n = 66). Vast majority of cases with malignant neoplasms had invasive carcinoma of no special type (NST) (n = 479). Significantly higher incidence of malignancy was noted in the age group of 41 - 80 years and benign tumours were mostly seen in 2nd and 3rd decade. The ratio of malignant to benign lesions was slightly higher in our study. CONCLUSIONS Large number of carcinoma breast was seen in our study which is a serious concern. So, design and implementation of screening programs and control of the risk factors seem essential. This study emphasizes the importance of early and accurate histopathological diagnosis of breast lesions. KEYWORDS Neoplastic, Non-Neoplastic, Breast Lesions, Histopathology, Invasive Carcinoma Breast

Invasive carcinoma no special type, pleomorphic carcinoma: Case report of a rare variant of invasive breast carcinoma

Invasive breast carcinoma – No special type (NST), Pleomorphic carcinoma is a rare morphological variant of invasive carcinoma NST. This is a case report of a 30 year old nulliparous woman who presented with a tender palpable mass in her right breast. Microscopic examination of the breast lump was predominantly composed of pleomorphic and bizarre cells. No positive lymph nodes or distant metastasis was present. This case report is to emphasise on the importance of identifying this variant of breast carcinoma because of its prognostic significance. Keywords: Carcinoma breast, Pleomorphic carcinoma, Pleomorphic bizarre tumor cells.

Clinicopathologic characteristics of HER2-positive metaplastic squamous cell carcinoma of the breast

AimsThe aim of this study was to analyse the clinicopathological features and prognosis of human epidermal growth factor receptor-2 (HER2)-positive metaplastic squamous cell carcinoma (MSCC).MethodsFifty-eight patients with MSCC of the...

Tumor-infiltrating lymphocyte abundance and programmed death-ligand 1 expression in metaplastic breast carcinoma: implications for distinct immune microenvironments in different metaplastic components.

Both stromal tumor-infiltrating lymphocytes (sTILs) and programmed death-ligand 1 (PD-L1) affect responses to immunotherapy; however, the extent of sTIL and PD-L1 expression within various metaplastic components in metaplastic breast carcinoma (MBC), which are critical for the characterization of immune microenvironments, remains unreported. We profiled sTIL infiltration and PD-L1 expression in different metaplastic components of specimens from 82 MBC patients. The overall positivity for high or intermediate (H/I) sTIL, immune cell-PD-L1 (IcPD-L1), and tumor cell-PD-L1 (TcPD-L1) was 34.1%, 47.6%, and 17.1%, respectively, but differences specific to MBC subtypes and each metaplastic component existed. Squamous cell carcinoma exhibited the highest positivity rates of sTIL(H/I) (50.0%) and IcPD-L1 (66.7%), while matrix-producing carcinoma had the lowest respective rates (14.3% and 28.6%). The positivity rates of sTIL(H/I) and IcPD-L1 were the highest in squamous component (Sq) and the lowest in chondroid component (Ch). All cases that had discordant sTIL categories between carcinoma of no special type (NST) and metaplastic components showed sTIL(H/I) positivity higher in Sq, but lower in spindled component (Sp) and Ch. While there was no pattern of higher IcPD-L1-positivity in Sp, six of the seven cases that were TcPD-L1-discordant between NST and Sp were TcPD-L1-positive in Sp, suggesting a trend for higher TcPD-L1 in Sp. The diagnostic predictability of total tumor IcPD-L1 positivity based on IcPD-L1 positivity in Sq and Ch was 95.2% and 33.3%, respectively. Multivariate analysis showed that sTIL(H/I) positivity, but not PD-L1 positivity, correlated with better survival. Our data implicate distinct immune microenvironments in different metaplastic components in MBC, which may have immunopathologic, diagnostic, and therapeutic significance.

The effect of breast MRI on disease-free and overall survival in breast cancer patients: a retrospective population-based study

PurposeTo evaluate the effect of breast MRI on overall survival (OS) and disease-free survival (DFS) of patients with invasive breast cancer in the Netherlands.MethodsWe selected all women from the Netherlands Cancer Registry diagnosed with invasive breast cancer (a) between 2011 and 2013 for the OS-cohort and (b) in the first quarter of 2012 for the DFS-cohort. The study population was subdivided into an MRI and non-MRI group. In addition, subgroups were created according to breast cancer subtype: invasive carcinoma of no special type (NST) versus invasive lobular carcinoma (ILC). OS and DFS were compared between the MRI and non-MRI group using the Kaplan–Meier method and the log-rank test. Cox proportional hazard regression analysis was performed to estimate hazard ratios (HR) with a 95% confidence interval (CI). To account for missing data, multiple imputation was performed.ResultsOf the 31,756 patients included in the OS-cohort (70% non-MRI and 30% MRI), 27,752 (87%) were diagnosed with invasive carcinoma NST and 4004 (13%) with ILC. Of the 2464 patients included in the DFS-cohort (72% non-MRI and 28% MRI), 2161 (88%) were diagnosed with invasive carcinoma NST and 303 (12%) with ILC. The distribution of breast MRI use was significantly lower over different age categories, from 49.0% aged < 50 to 16.5% aged > 70. Multivariable Cox regression showed that breast MRI was not significantly associated with OS overall (HR 0.91, 95%-CI 0.74–1.11, p = 0.35), nor in the different histological subtypes. Multivariable Cox regression analysis showed that breast MRI was also not significantly associated with DFS (HR 1.16, 95%-CI 0.81–1.67), nor in the different histological subtypes.ConclusionUse of breast MRI was not significantly associated with an improved OS or DFS in patients treated with primary surgery.

Role of p53 as a prognostic marker in breast carcinoma and its correlation with tumor size, tumor grade and lymph node metastasis

Breast cancer is the most frequently diagnosed cancer among females worldwide. p53 tumor suppressor gene regulates the cell cycle and DNA repair and its over-expression in breast cancer is associated with a worse prognosis. This study was done to correlate p53 over-expression with histopathological parameters such as tumor size, tumor grade and lymph node metastasis in breast carcinoma. This retroprospective study was conducted in a tertiary care centre, western U.P. retroprospectively from July 2014 to June 2019. Immuno-histochemical evaluation of 50 histologically confirmed cases of breast carcinoma was done. A total of 50 patients of breast carcinoma were analysed. Most common was Invasive carcinoma of no special type (NST). Most common age group involved was 40-49 years and majority were of age more than 45 years of age. Majority of breast carcinoma cases were of left breast and involving upper outer quadrant. In majority of cases, the tumor size was of more than 2 to 5cms. Majority of cases of breast carcinoma were of grade II according to Nottingham Modified Bloom Richardson System. More than half of patients with lymph nodes showed metastatic deposits. Majority of cases were in moderate prognostic index group. Out of 50 cases, 24(48%) cases showed p53 expression (≥5%). High p53 expression (&amp;#62;50%) was seen in 8(16%) cases of breast carcinoma. A statistically significant association was found between p53 expression, tumor size and lymph node metastasis. No statistically significant association was found between p53 overexpression and tumor grade. Overall, p53 overexpression was found to be poor prognostic factor and its detection may help in risk catergorization and designing future target therapies.

Characteristics and prognosis of 17 special histologic subtypes of invasive breast cancers according to World Health Organization classification: comparative analysis to invasive carcinoma of no special type.

Breast cancer is a heterogeneous disease with various histopathologic subtypes. Except for invasive carcinoma of no special type (NST), other subtypes are rare with limited data. The purpose of this study was to analyze the characteristics and prognosis of special histopathologic subtypes of breast cancer compared to NST. A total of 136,140 patients were analyzed using the Korean Breast Cancer Society Registry database between January 1996 and March 2019. The clinicopathologic features and survival outcomes of special type breast carcinoma were compared with those of NST. The prevalence of special subtypes other than NST was 13.7% (n = 18,633). Compared to NST, patients with lobular, medullary, metaplastic, and micropapillary carcinoma had larger tumors (p < 0.001). Patients with mucinous, tubular, medullary, metaplastic, and cribriform carcinoma presented with less node metastasis (p < 0.001), contrary to patients with micropapillary carcinoma. Patients with lobular, mucinous, tubular, papillary, and cribriform carcinoma presented as luminal A subtype much more often (p < 0.001). Micropapillary carcinoma included more luminal B subtype (p < 0.001). Typically, medullary and metaplastic carcinoma included more triple-negative subtypes (p < 0.001). In survival analysis, only medullary (Hazard Ratio (HzR) 0.542, 95% CI 0.345 to 0.852, p = 0.008) and metaplastic carcinoma (HzR 1.655, 95% CI 1.317 to 2.080, p < 0.001) showed significantly different overall survival from NST by multivariate analysis. Breast cancer had distinct clinicopathologic features according to histopathologic subtype. However, special types of breast cancer had similar survival outcomes compared to NST when adjusting for other prognostic factors, except for metaplastic carcinoma and medullary carcinoma.

Fecal expression of Escherichia coli lysine decarboxylase (LdcC) is downregulated in E-cadherin negative lobular breast carcinoma.

Breast cancer is characterized by oncobiosis, the abnormal composition of the microbiome in neoplastic diseases. The biosynthetic capacity of the oncobiotic flora in breast cancer is suppressed, as suggested by metagenomic studies. The microbiome synthesizes a set of cytostatic and antimetastatic metabolites that are downregulated in breast cancer, including cadaverine, a microbiome metabolite with cytostatic properties. We set out to assess how the protein expression of constitutive lysine decarboxylase (LdcC), a key enzyme for cadaverine production, changes in the feces of human breast cancer patients (n = 35). We found that the fecal expression of Escherichia coli LdcC is downregulated in lobular cases as compared to invasive carcinoma of no special type (NST) cases. Lobular breast carcinoma is characterized by low or absent expression of E-cadherin. Fecal E. coli LdcC protein expression is downregulated in E-cadherin negative breast cancer cases as compared to positive ones. Receiver operating characteristic (ROC) analysis of LdcC expression in lobular and NST cases revealed that fecal E. coli LdcC protein expression might have predictive values. These data suggest that the oncobiotic transformation of the microbiome indeed leads to the downregulation of the production of cytostatic and antimetastatic metabolites. In E-cadherin negative lobular carcinoma that has a higher potential for metastasis formation, the protein levels of enzymes producing antimetastatic metabolites are downregulated. This finding represents a new route that renders lobular cases permissive for metastasis formation. Furthermore, our findings underline the role of oncobiosis in regulating metastasis formation in breast cancer.

A ten-year, single-center experience: Concordance between breast core needle biopsy/vacuum-assisted biopsy and postoperative histopathology in B3 and B5a cases.

PurposeTo determine the concordance rate between core needle biopsy/vacuum-assisted biopsy (CNB/VAB) and postoperative histopathology in B3 (lesions of uncertain malignant potential) and B5a (in situ) lesions found on mammograms or ultrasound.Material and methods2,029 consecutive biopsies performed over 10 years for patients who underwent mammograms or ultrasounds. For CNB 14G needle and for VAB 8G/10G needles were used. In all biopsies, we identified the age, BI-RADS®, histopathological biopsy results, B-category, nuclear grade for DCIS and postoperative histopathology results in B3 and B5a cases from the biopsy.ResultsThe B-categories from CNB/VAB were as follows: B2 42.2 percent (n = 856), B3 4.5 percent (n = 91), B5a 5.7 percent (n = 115), and B5b 47.6 percent (n = 967). In the B3-category, 72/91 patients underwent surgical excision, with a concordance rate of 83.3 percent (n = 60/72) and a discordance rate of 16.7 percent (n = 12/72) to postoperative histopathology. From the discordant cases, 67.7 percent (n = 8/12) showed DCIS and 32.3 percent (n = 4/12) showed invasive breast cancer. The BIRADS of the discordant cases was 4b in 41.7 percent (n = 5/12) and 5 in 58.3 percent (n = 7/12). The PPVs for malignancy of B3 lesions were 0.21, with no statistical significance between subgroups. In the B5a-category, 101 of 115 patients underwent surgery in our hospital, with a concordance rate of 80.2 percent (n = 81/101) and a discordance rate of 19.8 percent (n = 20/101) to postoperative histopathology. From the discordant cases, 55 percent (n = 11/20) showed invasive breast carcinoma of no special type (NST).ConclusionOur concordance rate for B3 (83.3 percent) and B5a (80.2 percent) lesions in the biopsies to postoperative histopathology is matching to previously published literature. Surgical excision is our recommendation for lesions biopsied with a B3 category in the histopathology and a BIRADS category of (4b, 4c and 5). The PPVs for malignancy of B3 lesions showed no statistical significance between subgroups. Also, the nuclear grade of DCIS was not statistically significant in terms of upgrade into invasive breast cancer.

Multiplatform Investigation of Plasma and Tissue Lipid Signatures of Breast Cancer Using Mass Spectrometry Tools.

Plasma and tissue from breast cancer patients are valuable for diagnostic/prognostic purposes and are accessible by multiple mass spectrometry (MS) tools. Liquid chromatography-mass spectrometry (LC-MS) and ambient mass spectrometry imaging (MSI) were shown to be robust and reproducible technologies for breast cancer diagnosis. Here, we investigated whether there is a correspondence between lipid cancer features observed by desorption electrospray ionization (DESI)-MSI in tissue and those detected by LC-MS in plasma samples. The study included 28 tissues and 20 plasma samples from 24 women with ductal breast carcinomas of both special and no special type (NST) along with 22 plasma samples from healthy women. The comparison of plasma and tissue lipid signatures revealed that each one of the studied matrices (i.e., blood or tumor) has its own specific molecular signature and the full interposition of their discriminant ions is not possible. This comparison also revealed that the molecular indicators of tissue injury, characteristic of the breast cancer tissue profile obtained by DESI-MSI, do not persist as cancer discriminators in peripheral blood even though some of them could be found in plasma samples.

Correlation between HER2 Expression and Clinicopathological Features of Breast Cancer: A Cross- Sectional Study in Vietnam.

Background: HER2 is the target of the therapeutic agents which are used to treat HER2-positive breast cancer. Reports have shown that the HER2 oncogene expression and its association with clinicopathological factors remain unclear in breast cancer (BC) patients. This study aimed to determine the correlation between HER2 expression and clinicalpathological characteristics of breast cancer in Vietnamese women. Methods:Between June 2016 and August 2018, paraffin-embedded specimens from 237 patients with primary invasive breast carcinoma in Hue University Hospital and Hue Center Hospital, Hue city, Vietnam were examined for pathological features. The gene expression of HER2, ER, PR and Ki-67 were determined by immunohistochemistry (IHC). The gene amplification of Her2 was assessed by using Dual color in situ hybridization (DISH). Results:The most frequent histological type was invasive carcinoma of no special type (NST) with 77.35%, the highest percentage of patients with Grade II was detected (59.36%), tumor size > 2 cm accounted for 71.31% of cases, Lymph node metastases were available in 57.86% cases. Most patients were diagnosed at stage II (59.18%). The majority of patients were classified as moderate Nottingham prognostic index (54.9%). Estrogen receptor and Progesterone receptor were positive in 53.16% and 50.63%, respectively. 76.37% of cases were in high expression group of Ki-67 (≥14%). HER2 IHC 2+, 3+ were accounted for 28.69% and HER2 gene amplification was detected in 31% cases. HER2 gene amplification and/or overexpression was significantly associated with cell proliferation index Ki67. Furthermore, HER2 gene expression tended to be more frequently found in tumors with large tumor size, high grade, high stage and high Nottingham prognostic index and confirmed their prognostic independent role. Conclusions: Our data indicated that HER2 gene expression was significantly correlated with cell proliferation index Ki67, but not significantly associated with another clinicopathological factors in breast cancer of Vietnamese women.

Histological subtypes in triple negative breast cancer are associated with specific information on survival

Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC.A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed.Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18–3.03; p = 0.008; OS HR 1.94; 95% CI 1.28–2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes.In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.

Is the presence of edema and necrosis on T2WI pretreatment breast MRI the key to predict pCR of triple negative breast cancer?

Given that a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic factor, evaluating pretreatment imaging findings is important. Outcomes for triple negative breast cancer (TNBC) vary with the histological classification, indicating that this classification is clinically significant. In this study, we focus on the most common histological subtype of TNBC, invasive carcinoma of no special type (NST), to evaluate whether intramammary edema (intra-E) and intratumoral necrosis (intra-N) on T2-weighted magnetic resonance imaging (T2WI) is a useful predictor of pCR. We retrospectively included patients with biopsy-diagnosed TNBC-NST who received NAC between January 2014 and December 2017. Intra-E and intra-N were evaluated on T2WI before NAC. We grouped intra-E into no edema, peritumoral edema, prepectoral edema, and subcutaneous edema, and we defined intra-N as water-like signal intensity without enhancement on T2WI. We also evaluated tumor size, Ki-67 expression, and histological/nuclear grade, as well as their correlation with intra-E and intra-N. Fifty-seven patients with TNBC-NST were enrolled. There was no correlation with the rate of pCR and the presence of either intra-E or intra-N before NAC. Only intra-E and tumor size showed a positive correlation. In patients with TNBC-NST, intra-E and intra-N did not correlate with pCR, but intra-E did positively correlate with tumor size. NST may exhibit a greater response to NAC, regardless of whether intra-E or intra-N is present or not on the pretreatment MRI. • Pathological complete response in TNBC-NST had no correlation with intramammary edema or intratumoral necrosis. • NAC may be justified in TNBC-NST even in the presence of edema or necrosis. • The extension of edema correlated with tumor size of TNBC-NST.

Abstract P2-18-06: Value of PAM50 risk of recurrence score in patients with HR positive HER2 negative early breast cancer and intermediate risk: A single cancer center institution prospective observational study

Abstract Background: Currently, clinico-pathological characteristics (CPC) such as tumor size, lymph node status, tumor grade, proliferation, lympho-vascular invasion and percentage of cells expressing estrogen (ER) and progesterone receptors (PR) are usually considered in order to guide decisions on adjuvant systemic therapy for women with early-stage breast cancer (EBC). The indication of adjuvant chemotherapy (ACT) or not is relatively easy in women with ER+/HER2- EBC with either poor or very good CPC. However, this decision is much more difficult in those with intermediate CPC (essentially defined by grade II tumor with low PR expression and/or intermediate proliferation). The PAM50-based Prosigna risk of recurrence (ROR) is one of the multigene assays that have been evaluated and recommended for guiding treatment decision. We report here our experience on the impact of ROR in treatment decision-making in women with intermediate CPC. Patients and methods: Between March 2016 and May 2019, ROR was performed in 200 consecutive women with intermediate CPC ER+/HER2- EBC. The clinical decision (ACT or not) was prospectively recorded before and after ROR assessment and finally after the consultation with each patient. Data were summarized by frequency and percentage for categorical variables and by median and range for continuous variables. Associations between variables will be assessed using Chi-square or Fisher’s exact test for qualitative variables and the Mann-Whitney for continuous variables. All reported p-values were two-sided. For all statistical tests, differences were considered significant at the 5% level. Statistical analysis was performed using STATA v13 software. Results: Median age at diagnostic was 57 years [30-79] and 119 (59.5%) were post-menopausal. Median tumor size was 18mm [8-70mm]. Most tumors were PR+ (n=153, 76.5%), no special type (NST) carcinomas (n=172, 86%), Elston and Ellis grade II (n=183, 91.5%), with Ki67 value between 10 and 20 % (n=117, 62.6%). Lympho vascular invasion was observed in 38 tumors (19%), 124 patients were pN0 (62%), 20 pNmi (10%) and 55 pN1a (27.5%). Using the immunohistochemical (IHC)-based definition proposed by Prat et al. (JCO 2013), 90 tumors were luminal A (45%) and 110 luminal B (55%). There was 59.5% of concordance between IHC subtype classification and PAM50. ROR distribution was as follows: ROR-low (n=33; 16.5%); ROR-intermediate (n=75; 37.5%); and ROR-high (n=92; 46%). The clinical decision of modalities of adjuvant medical therapy switched after ROR assessment for 74 patients (37%): -26 patients from ACT plus endocrine therapy (ET) to ET only (13%); 9 and 17 have respectively a ROR-low or -intermediate and 23 a luminal A tumor according to PAM50, -48 patients from ET only to ACT plus ET (24%); 7 and 41 have respectively a ROR-intermediate or high and 44 a luminal B tumor. Importantly, 8 of them don’t received ACT at the issue of the consultation with the medical oncologist. Conclusion: In our experience, the use of ROR leads us more often to escalate than de-escalate adjuvant therapy, proving that the definition of the group with intermediate prognosis remains uncertain and variable according medical teams. Citation Format: Vincent Nicolaï, Julia Gilhodes, Jean Louis Lacaze, Mony Ung, Eleonora De Maio, Raphaelle Duprez-Paumier, Charlotte Vaysse, Thomas Filleron, Eva Jouve, Gabrielles Selmes, Camille Franchet, Carole Massabeau, Cyprian Chira, Francoise Izar, Henri Roché, Anne Pradines, Florence Dalenc. Value of PAM50 risk of recurrence score in patients with HR positive HER2 negative early breast cancer and intermediate risk: A single cancer center institution prospective observational study [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 P2-18-06.

Breast carcinoma: A clinicopathological study of 90 cases.

Objective: To describe the clinicopathological features of breast carcinoma in the local population based on age, menopausal status, laterality, tumor site, tumor size, histological subtype, and histological grading of breast carcinoma. Study Design: Descriptive cross-sectional study. Setting: University of Health Sciences (U.H.S), Lahore. Period: 6 months (June 2017-Dec 2017) after approval from the ethical committee of U.H.S. Material &amp; Methods: In this study, the clinicopathological profile of 90 female patients of breast carcinoma was evaluated from different tertiary care hospitals and U.H.S, Lahore. Histological diagnosis and histological grading was then carried out and were analyzed statistically through SPSS 21.0. Associations between the histological grade and other parameters were established using the Chi-square test. Results: The mean age of patients was 48.44±11.64 with 33.3% of patients younger than 40 years of age and 58.9% of women were found pre-menopausal. The left breast was more involved (65.6%) than the right side, upper outer quadrant of the breast was the commonest site (64.4%), and the majority of the tumors (76%) were more than 2 cm in size. All 90 cases were histologically diagnosed as invasive carcinoma of no special type (NST). Nottingham histological grade-II was observed as the commonest grade (54.4%) followed by grade- III (31.1%). Histological grade was significantly associated with the tumor size (p-value=0.000, Chi-square value= 29.17). Conclusions: Breast cancer is mostly reported in younger premenopausal women in our region. Delay in the diagnosis is most likely related to larger tumor sizes and moderate to poor histological grades.