Type Of Invasive Breast Cancer Research Articles

Detection of TROP2: Ushering in a new choice in the treatment of patients with special types of invasive breast cancer.

1106 Background: TROP2 has become an attractive new therapeutic target in breast cancer (BC). TROPiCS-02 trial shows that the sacituzumab govitecan(SG) which is the TROP2 ADC drug can significantly benefit the survival of patients with TNBC and HR+/HER2- BC, and the 2023 ASCO guideline recommends that TROP2 detection is not necessary before the SG treatment. However, less than 5% BC patients of special subtype were included in clinical trials, and the TROP2 expression of them is not yet known. The aim of our study is to compare the expression of TROP2 in different special types of BC, and provide reference for targeted treatment of these patients. Methods: We retrospectively retrieved tissues from 383 patients diagnosed with special type of BC and undergoing surgical resection at our institution from 2018 to 2023. Including metaplastic carcinoma (MBC), mucinous carcinoma (MC), adenoid cystic carcinoma, cribriform carcinoma, carcinoma with apocrine differentiation, neuroendocrine carcinoma and tubular carcinoma. Classify them as TNBC or HR+/HER2- BC. Applying H-score to evaluate the TROP2 expression, H-score<100, 100~200, and 201~300 classified as low, moderate and high expression. Results: Expression of TROP2 is higher in tubular and cribriform carcinoma, while in MBC and MC is significantly lower (χ2=66.756, P<0.001) (Table). Low expression of TROP2 is associated with low clinical staging ( P<0.05), no lymph node metastasis ( P<0.05), and high-grade tumor infiltrating lymphocytes ( P<0.05). Moreover, TROP2 had the lowest expression in MBC, with a median H-score of 45. There are 78.13% (43/55) cases showed H-score<100, with 27.3% (15/55) of cases showing no expression of TROP2 at all. It is worth noting that MBC is highly invasive and has a poor prognosis, but the expression level of TROP2 is very low in mesenchymal cells, while in squamous differentiated tumor tissue, the expression level of TROP2 is high, and the overall H-Score score is low ( P<0.001). Conclusions: This study is the first preliminary study on the TROP2 expression in special types of breast cancer. Although the current ASCO guideline recommends not testing TROP2, but our study shows it is pretty low or even not expressed in MBC and MC. Notably, the lack of expression in the mesenchymal and spindle cell subtypes may be highly indicates that they lack epithelial tumor cells expressing TROP2 as vectors, resulting in the inability to exert the therapeutic effect of ADC, we suggest routine testing of TROP2. [Table: see text]

Clinicopathological characteristics and prognosis of metaplastic breast cancer versus triple-negative invasive ductal carcinoma: a retrospective analysis

BackgroundMetaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to analyse the differences in clinicopathological characteristics and prognosis between Metaplastic breast cancer and triple-negative invasive ductal carcinoma (TN-IDC).MethodsWe retrospectively compared the clinicopathological characteristics of patients diagnosed with MBC and TN-IDC at the Fourth Hospital of Hebei Medical University between 2011 and 2020 in a 1:2 ratio. The log-rank test was used to compare the two groups’ disease-free survival (DFS) and overall survival (OS). For MBCs, we performed univariate and multivariate analyses using the Cox proportional hazards model to determine the characteristics that impacted OS and DFS.ResultsA total of 81 patients with MBC and 162 patients with TN-IDC were included in this study. At initial diagnosis, MBC patients had larger tumour diameters(P = 0.03) and fewer positive lymph nodes (P = 0.04). Patients with MBC were more likely to have organ metastases after surgery (P = 0.03). Despite receiving the same treatment, MBC patients had worse DFS (HR = 1.66, 95%CI 0.90–3.08, P = 0.11) and OS (HR = 1.98, 95% CI 1.03–3.81, P = 0.04), and OS was statistically significant. Positive lymph nodes at initial diagnosis were associated with worse DFS (HR = 3.98, 95%CI 1.05–15.12, P = 0.04) and OS (HR = 3.70, 95%CI 1.03–13.34, P = 0.04) for patients with MBC. The efficacy of platinum-based agents is insensitive for MBC patients receiving chemotherapy. In addition, patients treated with preoperative chemotherapy had worse DFS compared to patients treated with postoperative chemotherapy (HR = 3.51, 95%CI 1.05–11.75, P = 0.04).ConclusionsThe clinicopathological characteristics and prognosis of MBC and TN-IDC differ in many ways. Further studies are required to determine suitable treatment guidelines for patients with MBC.

Neuroendocrine Breast Carcinoma: a Case Series

Neuroendocrine breast carcinoma (NEBC) is histologically a rare type of invasive breast cancer. It constitutes only 0.2–0.5% of all invasive breast cancers. In this case series, we are presenting five cases having primary neuroendocrine breast cancers that had been reported at a high-volume cancer centre in Pakistan. In this study, neuroendocrine breast cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Centre Peshawar were evaluated. We had retrospectively collected information on demographic characteristics of our patients, physical examination, radiological findings, surgical procedures with their outcomes, histopathological and immuno-histochemical characteristics, systemic adjuvant/neoadjuvant therapy and follow-up.

HER2 Low Breast Cancer: A New Subtype or a Trojan for Cytotoxic Drug Delivery?

Despite the great progress made in the understanding of the biological behavior of certain types of invasive breast cancer, there is still no single histological or molecular classification that encompasses such diversity and accurately predicts the clinical course of distinct breast cancer subtypes. The long-lasting classification of breast cancer as HER2-positive vs. HER2-negative has recently come into question with the discovery of new antibody drug conjugates (ADC), which are proven to be remarkably efficient in treating HER2-low breast cancer. The HER2-low paradigm has challenged the traditional understanding of HER2 overexpression and emphasized the need for more robust HER2 testing in order to encompass HER2 intratumoral heterogeneity and spatial distribution more accurately. It is yet to be seen if low HER2 will remain merely a marker of HER2-equipped tumors targetable with ADCs or if distinctive molecular and phenotypic groups within HER2-low tumors will eventually be discerned.

Axillary lymph node status and invasive lobular breast cancer : Analysis of the Clinical Tumor Register of the AGO Austria.

Invasive lobular carcinoma (ILC) represents the second most common type of invasive breast cancer (BC). Although ILC generally have good prognostic properties (positive estrogen receptor, ER, low tumor grade), they are generally diagnosed at amore advanced stage. The data on the axillary lymph node status in ILC compared to invasive ductal carcinoma (IDC) are considered controversial. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register. Data of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO) were retrospectively analyzed. Patients with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were included. Atotal of 2127 tumors were evaluated and compared in 2groups, ILC n = 303, IDC n = 1824. Atotal of 2095patients were analyzed in the study. In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (odds ratio, OR 1.93; 95% confidence interval, CI 1.19-3.14; p = 0.008 and OR 3.22; 95% CI: 1.47-7.03; p = 0.003; respectively). Other factors associated with ILC were tumor grades2 and3, positive ER, and pathological tumor stage (pT) 2 and pT3. In contrast, concomitant ductal carcinoma in situ, overexpression of the human epidermal growth factor receptor2 (HER2), and amoderate and high proliferation rate (Ki67) were found less frequently in ILC. The data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.

The association between KRAS gene expression and breast tumors in a sample of Iraqi women

In Iraq, breast cancer is considered one of the most widespread cancer types causing death in women due to changes in the genes that control cell growth and proliferation. KRAS gene plays a role in 30% of human cancers. This study aims to evaluate the expression of the KRAS gene and its role in women with breast tumours. A total of 120 women (60 women with breast tumours and 60 samples from apparently healthy women) were enrolled in this study to determine the expression of the KRAS gene. The RT-qPCR was used for this purpose. Fibroadenoma (FA) was the most common tumours, accounting for 53% of cases, followed by fibrocystic change (26%). Other benign tumours accounted for 20% of the cases; however, IDC is the most common type of invasive breast cancer, accounting for 70% of all breast cancers. Moreover, KRAS gene expression in women with breast tumours (benign and malignant) was not- significantly different from that seen in normal healthy women.

Metaplastic Breast Carcinoma (MBC), Primary Squamous Cell Carcinoma Subtype in A 49-Year-Old Woman: A Case Report

Introduction: Metaplastic Breast Carcinoma (MBC) is quite a challenging case because metaplastic breast cancer is one of the rarest subtypes of invasive breast cancer. It is reported that MBC occurs only 0.2 to 1% throughout the world. The metaplastic changes can be squamous cells or other mesenchymal cell types. Clinically, MBC presents as a large palpable mass and may be associated with rapid growth. The size of MBC tends to be larger compared with other types of invasive breast cancer ranging from 1 to more than 10 cm. Although there are several main categories of MBC, some carcinoma can be difficult to classify due to their unusual histologic patterns. This case report study is to provide a clinicopathological overview and approach to MBC.Case Presentation: We reported a 49-year-old woman who suffered from a breast mass that rapidly grew for less than one year. The microscopic findings showed squamous cell carcinoma. While molecular studies revealed triple negative results for hormone receptors although Human Epidermal Growth Factor Receptor 2 (HER2) overexpression was unusual (< 5%). Then, we confirmed with chromogen in situ hybridization (CISH) and there was no gen amplification for HER2. Microscopically, we found ductal carcinoma in situ and this finding supported breast origin.Conclusions: Metaplastic carcinoma did not have any specific and distinctive signs clinically. Metaplastic carcinoma can be monophasic (with only a metaplastic component) or biphasic with two or more components. As treatment options, our patient received conventional chemotherapy. Metaplastic breast cancer is reported to have a lower response rate to conventional adjuvant chemotherapy and worse clinical outcome after chemotherapy than other forms of triple-negative breast cancer.

Factors Associated with Lymph Node Metastasis in Special Types of Invasive Breast Cancer at National Cancer Hospital in the Period of 2018 - 2021

This paper assesses the rate of lymph node metastasis and the correlation between lymph node metastasis and some pathological characteristics in special types of invasive breast cancer. In the paper, a descriptive cross‐sectional study was conducted on 200 patients with special types of invasive breast cancer at the Institute of Molecular Biology and Pathology - National Cancer Hospital from August 2020 to April 2021. The study results show that 32% of the 200 cases had nodal metastases. The factors associated with the increased risk of lymph node metastasis were of histological types (invasive lobular, invasive micropapillary carcinomas) (p = 0.000), high tumour grade (p = 0.000), the presence of lymphovascular invasion (p = 0.000), tumor-infiltrating lymphocytes (TILs) < 10% (p = 0.000), the presence of tumor necrosis (p = 0.001), Her-2/neu overexpression (p = 0.01), Ki-67 ≥ 20% (p = 0.036), HER2-positive breast cancer (p = 0.015). Overall, the rate of lymph node metastasis was 32%. Histological type, tumour grade, the presence of lymphovascular invasion, TILs, tumor necrosis, Her-2/neu and Ki-67 expression, and molecular subtype were factors related to lymph node metastasis in special types of invasive breast cancer.
 Keywords:
 Lymph node metastasis, invasive breast cancer, special types.
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Survival Outcomes After Breast-Conserving Therapy Compared With Mastectomy for Patients With Early-Stage Invasive Micropapillary Carcinoma of the Breast: A SEER Population-Based Study.

BackgroundInvasive micropapillary breast carcinoma (IMPC) is a relatively rare pathological type of invasive breast cancer. Little is currently known on the efficacy and safety of breast-conserving treatment (BCT, lumpectomy plus postsurgical radiation) compared with mastectomy in women diagnosed with early-stage IMPC. Accordingly, we sought to investigate the long-term prognostic differences between BCT and mastectomy in patients with T1-3N0-3M0 invasive micropapillary breast carcinoma using data from the Surveillance, Epidemiology, and End Results (SEER) database.Materials and MethodsWe retrospectively analyzed 1,203 female patients diagnosed with early-stage IMPC between 2004 and 2015 from the SEER database. The impact of different surgical approaches on patient prognosis was assessed by the Kaplan-Meier method and Cox proportional risk models.ResultsA total of 609 and 594 patients underwent mastectomy and BCT, respectively. Compared with patients who underwent a mastectomy, patients in the BCT group were older and had lower tumor diameters, lower rates of lymph nodes metastasis, and higher rates of ER receptor positivity and PR receptor positivity (p < 0.05). Kaplan-Meier plots showed that the overall survival (OS) and breast cancer-specific survival (BCSS) were higher in the BCT group than in the mastectomy group. In subgroup analysis, patients with T2 stage in the BCT group had better OS than the mastectomy group. Multivariate analysis showed no statistical difference in OS and BCSS for patients in the mastectomy group compared with the BCT group (hazard ratio (HR) = 0.727; 95% confidence interval (95% CI) 0.369–1.432, p = 0.357; HR = 0.762; 95% CI 0.302–1.923, p = 0.565; respectively). During the multivariate analysis and stratifying for the T stage, a better OS was found for patients with T2 stage in the BCT group than the mastectomy group (HR = 0.333, 95% CI: 0.149–0.741, p = 0.007). There was no significant difference in OS for patients with T1 and T3 stages between the BCT and mastectomy groups (p > 0.05).ConclusionIn women with early-stage IMPC, BCT was at least equivalent to mastectomy in terms of survival outcomes. When both procedures are feasible, BCT should be recommended as the standard surgical treatment, especially for patients with T2 disease.

Effect of axillary lymph node status on prognosis of different types of invasive breast cancer

Objective: To investigate the effect of axillary lymph node status on the prognosis of different types of invasive breast cancer. Methods: Patients with invasive breast cancer of different molecular subtypes diagnosed in the breast cancer prevention and treatment center of Beijing Cancer Hospital from January 2000 to July 2011 were collected as a historical cohort, and the influence of lymph node status on the prognosis of different types of breast cancer was analyzed. Results: A total of 4 269 female breast cancer patients with molecular subtypes [aged (50.8±11.2) years] information and 3 824 female breast cancer patients with complete axillary lymph node status information [aged (50.5±10.9) years] were included in the study, including 3 135 cases with both molecular subtypes and lymph node status information. The 10-year event free survival (EFS) rates of hormone receptor (HR)+/human epidermal growth factor receptor-2(HER2)-, HR-/HER2-and HER2+were 82.2%, 79.0% and 76.8%, respectively; the 10-year overall survival (OS) rates were 88.1%, 83.1% and 84.4%, respectively, and the differences of 3 molecular subtypes in EFS and OS were statistically significant (both P<0.001). The 10-year EFS rate of lymph node positive and negative patients was 68.8% and 88.2%, respectively; the 10-year OS rate was 76.7% and 92.5%, respectively, and the differences of lymph node status in EFS and OS were statistically significant (both P<0.001). In lymph node negative subgroup, 3 subtypes showed similar EFS and OS rate (both P>0.05); In lymph node positive subgroup, 3 subtypes showed significantly different EFS and OS (both P<0.05). No modification effect was detected of lymph node status on the correlation of molecular subtypes and EFS, DDFS and OS(all Pinteractive>0.1). Conclusions: Different molecular subtypes of breast cancer have different prognosis. Compared with molecular subtype, lymph node status may be a more important prognostic factor.

Identifying Clinicopathological Risk Factors of the Regional Lymph Node Metastasis in Patients with T1-2 Mucinous Breast Cancer: A Population-Based Study.

Background Pure mucinous breast cancer (PMBC) has a better prognosis than other types of invasive breast cancer. However, regional lymph node metastasis (LNM) might reverse this outcome. We aim to determine the independent predictive factors for regional LNM and further develop a nomogram model for clinical practice. Method Data of PMBC patients from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to determine the risk factors for LNM in T1-2 MBC. The nomogram was constructed and further evaluated by an internal validation cohort. The receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves were performed to evaluate the accuracy of this model. Result Five variables, including age, race, tumor size, grade, and breast subtype, were identified to be significantly associated with regional LNM in female patients with T1-2 PMBC. A nomogram was successfully established with a favorable concordance index (C-index) of 0.780, supported by an internal validation cohort with a C-index of 0.767. Conclusion A nomogram for predicting regional LNM in female patients with T1-2 PMBC was successfully established and validated via an internal cohort. This visualized model would assist surgeons to make appropriate clinical decisions in the management of primary PMBC, especially in terms of whether axillary lymph node dissection (ALND) is warranted.

Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study.

Background: In recent years, great progress has been made in the treatment of breast cancer, but it is still one of the ten leading causes of death in women. The aim of the study was to evaluate the heparanase concentration of invasive breast cancer (IBrC) patients, before and after cancer adjuvant treatment. Methods: Eighty patients with stage IA to IIB IBrC receiving adjuvant treatment were included prospectively in this study. The heparanase concentrations were determined by an enzyme-linked immunosorbent assay. A univariate analysis was used to estimate the factors influencing the low or high pre-treatment concentration of heparanase and the low or high numerical decrease in heparanase concentration after completion of adjuvant treatment. Results: Treatment reduced the concentration of heparanase by almost four times in the general IBrC cohort. Higher levels of pre- and post-treatment heparanase were noted in oestrogen receptor-negative cancers than in positive ones. A higher post-treatment concentration of heparanase was found in patients with a triple-negative tumour compared to patients with a luminal B HER2 negative type of IBrC. Overweight IBrC subjects and those with a tumour diameter of ≥2 cm demonstrated a lower chance of a lower pre-treatment heparanase concentration. Interestingly, a pre-treatment heparanase concentration is the main predictor of the changes in heparanase concentration after adjuvant treatment. Follow-up revealed significantly lower progression-free survival (PFS) rates in IBrC patients with a pre-treatment concentration of heparanase higher than 181.46 pg/mL (PFS = 80%). Conclusions: Our findings provide supporting evidence that IBrC therapy reduced the heparanase levels, regardless of treatment patterns and a pre-treatment concentration of heparanase may serve as a prognostic indicator for future outcomes.

Magnetic Resonance Imaging Features in Different Types of Invasive Breast Cancer: A Systematic Review of the Literature.

Breast cancer is the most common malignancy affecting women worldwide, and early diagnosis of breast cancer is the key to its successful and effective treatment. Traditional imaging techniques such as mammography and ultrasound are used to detect and configure breast abnormalities; unfortunately, these modalities have low sensitivity and specificity, particularly in young patients with dense breast tissue, breast implants, or post-surgical scar/architecture distortions. Therefore, breast magnetic resonance imaging (MRI) has been superior in the characterization and detection of breast cancer, especially that with invasive features. This review article explores the importance of breast MRI in the early detection of invasive breast cancer versus traditional tools, including mammography and ultrasound, while also analyzing the use of MRI as a screening tool for high-risk women. We will also discuss the different MRI features for invasive ductal carcinoma and lobular carcinoma and the role of breast MRI in the detection of ductal carcinoma in situ with a focus on the utilization of new techniques, including MR spectroscopy and diffusion-weighted imaging.

Abstract PS17-27: Molecular evaluation of immunogenicity and genomic alterations in invasive lobular breast cancer

Abstract Background: Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer and accounts for 10-15% of all cases. Though ILC has distinct clinical, prognostic and molecular features, studies are limited and include few patients. ILCs show a decreased response to neoadjuvant chemotherapy and an increased resistance to endocrine therapy. Thus, there is a great need to identify alternative therapies, such as immunotherapy, that could improve overall survival. Success of immunotherapy largely depends on tumor immunogenicity which varies with histologic type. Determination of predictive and prognostic biomarkers for ILC will help determine who can benefit the most. Our study investigates canonical markers of immunogenicity - PD-L1 expression and Tumor Mutational Burden (TMB) - in patients with ILC compared to invasive ductal carcinoma (IDC). We further correlate these markers in different subtypes i.e. hormone receptor positive (HR+), HER2 positive (HER2+), and in triple negative breast cancers (TNBC). We also analyze differences in immune cell profiles constituting the tumor microenvironment (TME) and differences in genomic alterations between ILC and IDC. Methods: A retrospective data analysis was performed to identify breast cancer tumors with ILC or IDC histology profiled at Caris Life Sciences (Phoenix, AZ) that were tested for PD-L1 by SP142 assay and had whole transcriptome sequencing data available. ILC and IDC cases were further subtyped as HR+ and HER2+ and TNBC. PD-L1 expression in immune cell was assessed using Ventana PD-L1 (SP142) histochemical assay and PD-L1 expression in tumor cell was assessed by laboratory developed test using SP142 clone with staining higher than 2+ considered positive. TMB was measured by counting somatic non-synonymous missense mutations on the 592 gene panel (Nextseq) next generation sequencing (NGS) assay, and ≥ 10 mutations/megabase (mut/Mb) was considered high. Using the whole transcriptome RNA sequencing (NovaSeq) data we analyzed the difference in immune cell profiles constituting the TME using a computational RNA deconvolution approach. NGS was used to identify significant differences in genomic alterations between ILC and IDC. Results: We identified 1,359 breast cancer patients (ILC: 194 vs IDC: 1,165). Among ILC, 79% were HR +, 11% TNBC, &amp;lt;2% HER2+ and the rest were of unclear subtype, compared to 55% HR +, 31% TNBC, 10% HER2+ in the IDC group. PD-L1 expression in immune cells was lower in ILC (PD-L1≥ 1% ILC: 13% vs. IDC: 35% p &amp;lt;0.0001; PD-L1&amp;gt;10% ILC: 1% vs. IDC: 5% p=0.017). PD-L1 expression in tumor cells was also lower in ILC (ILC 1% vs IDC 5%; p =0.0136). All subtypes of ILC had lower PD-L1 expression in immune and tumor cells when compared to IDC. TMB was similar and comparable in IDC and ILC (median TMB 7 mut/Mb). Assessment of TME showed a significantly increased abundance of cytotoxic lymphocytes and monocytic cells in IDC, and stromal endothelial cells in ILC. Androgen receptor (AR) expression, and mutations in CDH1 (ILC 76% vs IDC 2%) and PIK3CA (ILC 44% vs IDC 30%) were more common in ILC. CDH1 mutation was significantly higher in both TN ILC (ILC 60% vs IDC 1%; p&amp;lt;0.05) and HR+ ILC (77% vs IDC 2%; p&amp;lt;0.05) subtypes of ILC. TP53 mutation was lower in ILC (ILC 26% vs IDC 65%) irrespective of subtype. Conclusion: In summary, PD-L1 expression in immune cells and tumor cells was lower in ILC, however TMB was comparable between ILC and IDC. Immune cell profiling supports a cold or less immunogenic TME for ILC. A composite immune biomarker may be able to better characterize immunogenicity of ILC. Citation Format: Upama Giri, Joanne Xiu, Tatiana Karadimitriou, Sofi Castanon, Foluso Ademuyiwa, Paula Pohlmann, Elias Obeid, Jasgit Sachdev, Elisa Krill-Jackson, Michael Simon, Antoinette Tan, Neelima Denduluri, Lee Schwartzberg, Michael Korn, Evanthia T Roussos Torres. Molecular evaluation of immunogenicity and genomic alterations in invasive lobular breast cancer [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 PS17-27.

Abstract PS11-16: Rare patients in routine care: Treatment and outcome in advanced invasive lobular breast cancer in the prospective German research platform OPAL

Abstract Introduction Invasive lobular breast cancer (ILC) is with 5-10% the second most common histologic type of invasive breast cancer after invasive ductal breast cancer (IDC). ILC differs from IDC, for example in its metastatic pattern. However, guidelines do not provide special treatment recommendations for this subtype and specific clinical studies are rare. Here we present prospective data on characteristics, treatment and outcome of patients (pts) with advanced ILC in routine care in Germany. Methods The Tumor Registry Breast Cancer (TMK) has prospectively documented data of pts with breast cancer by oncologists in Germany since 2007. Since 2017 OPAL continues the TMK work with representation of all specialists (medical and gynecologic oncologists) treating advanced breast cancer (ABC). Both projects are prospective, observational, open, longitudinal multicenter cohort studies (clinical registries). Pts at the start of their treatment can be included after signing informed consent. Together over 7500 pts (4250 with ABC) will be recruited from over 150 sites in Germany. There is no treatment specification. Details on all (sequential) treatments, patient and tumor characteristics, clinical and patient-reported outcomes are documented. Follow-Up is until death or up to 5 years. Here, data as of March, 31st 2020 are presented. Results Pts with advanced ILC (n=372) were older at start of first-line treatment (median 68 vs. 63 years) while ECOG performance status (ECOG 0 25% vs 29%) and Charlson Comorbidity Index (CCI 0: 82% vs 84%) were similar compared to pts with IDC (n=1745). The lobular tumor was more often hormone receptor (HR) positive (87% vs 74%) and less often HER2 positive (14% vs 27%). The percentage of primary metastatic disease (M1) was 34% in both groups, while grade at diagnosis was more frequently G1/2 in the ILC group (73% vs 51%). The metastatic pattern was more often non-visceral only for the ILC group (26% vs 19%), and metastases were found more often in bone (52% vs 42%) and peritoneum (9% vs 2%) and less often in liver (20% vs 25%) and lung (7% vs 25%). Overall, pts with ILC were treated more often with endocrine therapy (ET) +/- CDK4/6-inhibitors (CDK4/6i) than pts with IDC (52% vs 33%), yet, ILC is more often HR-positive than IDC. Of pts receiving chemotherapy (CT) 53% of ILC and 56% of IDC tumors were treated with taxanes as first-line treatment. 20% of ILC vs. 24% of IDC tumors received a combination-CT. First-line treatment strategy was analyzed for the HR-positive, HER2-negative subgroup. From 2007-16 pts with ILC received more often ET (ILC (n=162) 54% vs IDC (n=696) 44%), while IDC were more often treated with CT first-line. Since approval of CDK4/6i, distribution of treatment strategies has been quite similar (ILC (n=123): CDK4/6i: 76%, ET: 15%, CT: 10% and IDC (n=311): CDK4/6i: 72%, ET: 12%, CT: 15%). Overall survival (OS) from start of first-line treatment was estimated for all pts recruited by 2016 (follow-up of at least 3 years). Median OS was comparable: ILC (n=224) 30.6 months (68% events, 95%-CI 26.1 - 36.9 months) and IDC (n=1217) 34.1 months (60% events, 95%-CI 30.6 - 38.4 months). For the HR-positive, HER2-negative subgroup, OS was also similar. A multivariate regression analysis on factors affecting OS will be presented. Conclusion Registries, like TMK/OPAL, can provide data on rare tumor subtypes. We show that ABC with an invasive lobular histology differs in receptor status (more often HR-positive) and metastatic pattern (e.g. more often non-visceral) from the invasive ductal subtype. Nevertheless, treatment strategies for first-line treatment are similar and median OS is comparable despite ILC pts being markedly older. Future research should focus on identifying pts who could benefit from personalized treatment approaches including tumor subtype as a factor to consider. Citation Format: Marc Thill, Mark-Oliver Zahn, Anja Welt, Elmar Stickeler, Arnd Nusch, Thomas Fietz, Jacqueline Rauh, Natalie Wetzel, Lisa Kruggel, Martina Jänicke, Norbert Marschner, Nadia Harbeck, Achim Wöckel, Thomas Decker, OPAL study group. Rare patients in routine care: Treatment and outcome in advanced invasive lobular breast cancer in the prospective German research platform OPAL [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 PS11-16.

LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with fewer treatment options than other types of invasive breast cancer due to the loss of the estrogen, progesterone receptors and low levels of the HER2 protein, resulting in a poor prognosis for these patients. Here, we found that the expression of the lncRNA, ZFAS1, was significantly downregulated (∼3.0-fold) in blood samples of TNBC patients (n=40) compared to matched healthy controls (n=40). Functionally, silencing of ZFAS1 promoted cell proliferation and colonization of human MDA-MB-231 TNBC cells by inhibiting the expression levels of the cyclin-dependent kinase (CDK) inhibitors p21 (CDKN1A) and p27 (CDKN1B) compared to the scrambled siRNA control cells. Further, we found that downregulation of ZFAS1 led to decreased protein levels of the epithelial markers, E-cadherin, Claudin-1, and Zo-1, with increased protein levels of the mesenchymal markers, Slug and ZEB1. In addition, by utilizing the bioinformatic tools such as RAID v2.0 (RNA Interactome Database Version 2.0), AnnoLnc (Annotate human lncRNA database), and GEPIA (Gene Expression Profiling Interactive Analysis), we identified a strong negative correlation between ZFAS1 and signal transducer and activator of transcription 3 (STAT3) gene expression (R = −0.11, p-value = 0.0002). Further, we observed that decreased ZFAS1 expression significantly (p < 0.05) increased STAT3 and phosphorylated STAT3 (at Ser727 residue) protein levels in TNBC cells. The composite data indicate that ZFAS1 may function as a tumor-suppressor lncRNA with potential as a diagnostic/prognostic marker and may offer a new target for the treatment of TNBC patients.

The genomic landscape of metastatic histologic special types of invasive breast cancer

Histologic special types of breast cancer (BC) account for ~20% of BCs. Large sequencing studies of metastatic BC have focused on invasive ductal carcinomas of no special type (IDC-NSTs). We sought to define the repertoire of somatic genetic alterations of metastatic histologic special types of BC. We reanalyzed targeted capture sequencing data of 309 special types of BC, including metastatic and primary invasive lobular carcinomas (ILCs; n = 132 and n = 127, respectively), mixed mucinous (n = 5 metastatic and n = 14 primary), micropapillary (n = 12 metastatic and n = 8 primary), and metaplastic BCs (n = 6 metastatic and n = 5 primary), and compared metastatic histologic special types of BC to metastatic IDC-NSTs matched according to clinicopathologic characteristics and to primary special type BCs. The genomic profiles of metastatic and primary special types of BC were similar. Important differences, however, were noted: metastatic ILCs harbored a higher frequency of genetic alterations in TP53, ESR1, FAT1, RFWD2, and NF1 than primary ILCs, and in CDH1, PIK3CA, ERBB2, TBX3, NCOR1, and RFWD2 than metastatic IDC-NSTs. Metastatic ILCs displayed a higher mutational burden, and more frequently dominant APOBEC mutational signatures than primary ILCs and matched metastatic IDC-NSTs. ESR1 and NCOR mutations were frequently detected in metastatic mixed mucinous BCs, whereas PIK3CA and TP53 were the most frequently altered genes in metastatic micropapillary and metaplastic BCs, respectively. Taken together, primary and metastatic BCs histologic special types have remarkably similar repertoires of somatic genetic alterations. Metastatic ILCs more frequently harbor APOBEC mutational signatures than primary ILCs and metastatic IDC-NSTs.

Establishing Correlations between Breast Tumor Response to Radio-Immunotherapy and Radiomics from Multi-Parametric Imaging: An Animal Study

Triple-negative breast cancer (TNBC), which is a type of invasive breast cancer, is characterized by severe disease progression, poor prognosis, high recurrence rate, and short survival. We sought to gain new insight into TNBC by applying computed tomography (CT) and magnetic resonance (MR) quantitative imaging (radiomics) approaches to predict the outcome of radio-immunotherapy treatments in a syngeneic subcutaneous murine breast tumor model. Five Athymic Nude mice were implanted with breast cancer cell lines (4T1) tumors on the right flank. The animals were CT- and MRI-imaged, tumors were contoured, and radiomics features were extracted. All animals were treated with radiotherapy (RT), followed by the administration of PD1 inhibitor. Approximately 10 days later, the animals were sacrificed, tumor volumes were measured, and histopathology evaluation was performed through Ki-67 staining. Linear regression modeling between radiomics and Ki-67 results was performed to establish a correlation between quantitative imaging and post-treatment histochemistry. There was no correlation between tumor volumes and Ki-67 values. Multiple CT- and MRI-derived features, however, correlated with histopathology with correlation coefficients greater than 0.8. MRI imaging helps in tumor delineation as well as an additional orthogonal imaging modality for quantitative imaging purposes. This is the first investigation correlating simultaneously CT- and MRI-derived radiomics to histopathology outcomes of combined radio-immunotherapy treatments in a preclinical setting applied to treatment naïve tumors. The findings indicate that imaging can guide discrimination between responding and non-responding tumors for the combined RT and ImT treatment regimen in TNBC.

Abstract P2-14-13: Comparison of survival outcomes between treatment with endocrine therapy and chemoendocrine therapy in patients with invasive lobular carcinoma

Abstract Background: Invasive lobular breast cancer (ILC) is the second most common histological type of invasive breast cancer and accounts for 10-15% of all breast cancer cases. It is commonly strongly hormone receptor positive and, in general, is considered to be less chemo-sensitive compared with invasive ductal carcinoma (IDC). The aim of this study was to compare survival outcomes among ILC patients treated with adjuvant endocrine therapy (ET) compared with chemoendocrine therapy (CET). We also sought to assess utilization of Oncotype Dx testing and distribution of Recurrence Score results among ILC patients treated at our institution. Methods: We conducted an IRB approved retrospective study at Cleveland Clinic Taussig Cancer Institute of patients with non-metastatic ILC. Patient diagnosed with ILC and treated from January 2004 through December 2017 were identified from our tumor registry. Patient characteristics including demographics, pathologic features, hormone replacement therapy (HRT) use, Oncotype Dx recurrence score, treatment details and recurrence data were obtained through medical chart review. Recurrence-free and overall survival (OS) were compared between ET and CET using Kaplan-Meier method and Cox proportional hazard model with consideration of differences on age and prognostic factors. The outcomes between age and pathological stage propensity score matched treatment groups were also compared. Results: A total of 638 patients (Mean age 61.9±11.7, 99.1% estrogen receptor positive, 82.6% progesterone receptor positive) were identified. 406 (63.6%) patients received ET and 232 (36.4%) patients received CET. Compared to ET, patients who received CET were significantly younger (Mean 56.3 vs 65.0 years) and more likely to be premenopausal (40.1% vs 14.6%), however they had significant worse prognostic features including pathological stage (stage III: 38.9% vs 2.1%), grade (≥ II: 69.0% vs 55.9%) and Oncotype Dx score (≥18: 72.4% vs 36.2%). Patients were followed for median (IQR) time of 4 (2.0, 6.4) years for survival outcomes. Although recurrence-free survival (local or distant) was worse in CET (5-year recurrence-free: 81.9% vs 96.5%), age and clinical prognostic features adjusted recurrence risk was similar as ET (Adjusted HR and 95% CI: 0.83, 0.36-1.92) and risk of death was also similar (Adjusted HR and 95% CI: 0.68, 0.31-1.50). Only 222 patients had Oncotype Dx score (35%), with 59% falling in the low risk range, 39% intermediate risk range and 2% high risk range. The Oncotype Dx recurrence score was not associated with recurrence or death. The recurrence-free (5-year: 97.4% vs 90.4%, p=0.37) and OS (At 5-year OS: 94.3% vs 89.4%, p=0.08) were also similar between age and pathological stage matched CET and ET groups. Conclusion: Use of chemoendocrine therapy did not result in improved survival outcomes for patients with ILC compared to those treated with endocrine monotherapy in the adjuvant setting. The majority of ILC patients did not have Oncotype Dx testing sent however when it was ordered, most cases resulted in the low-intermediate risk range, suggesting limited benefit of chemotherapy as reflected by survival outcome results observed. Citation Format: Mathew Thomas, Hong Li, Jame Abraham, Halle CF Moore, G Thomas Budd, Alberto J Montero, Megan L Kruse. Comparison of survival outcomes between treatment with endocrine therapy and chemoendocrine therapy in patients with invasive lobular carcinoma [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 P2-14-13.

Clinicopathological characteristics of metaplastic breast cancer – analysis of the basic immunohistochemical profile and comparison with other invasive breast cancer types

IntroductionMetaplastic breast cancer (MpBC) is a rare but aggressive type of breast cancer accounting for 0.25–1% of all diagnosed invasive breast cancers. Morphologically, it is characterized by differentiation of the neoplastic epithelium into squamous cells and/or mesenchymal-looking tissue. Material and methodsWe analyzed 13 MpBCs selected from the group of 1122 invasive breast cancers. Histopathological examination and analysis of estrogen (ER), progesterone (PR) and HER2 receptors expression in MpBC patients and their comparison to other types of invasive breast cancer has been performed. Results13 MpBC cases represented 1.16% of the 1122 invasive breast cancers. The MpBC group presented with a significantly larger tumor size (≥T2, 69% versus 49%, p < 0.001) and with higher grade of histological malignancy (G1-G3) (p < 0.001). MpBC group had significantly more cases with no hormone receptors (ER, PR) and HER2 overexpression/gene amplification compared with the other invasive breast cancer types group (ER-, 69% versus 23%, p < 0.001; PR-, 69% versus 28%, p < 0.001; HER2 0/1+, 93% versus 82%, p = 0.019). Most MpBCs (62%) were triple-negative. We found a correlation between hormone receptors expression and lymph node metastasis (p < 0.001). The analysis of the HER2 expression allowed us to find correlation between its expression and tumor histological grade (G1-G3) (p < 0.001), tumor size (T1a-T4) (p < 0.001) and lymph node metastasis (pN0-pN4) (p < 0.001) in MpBCs. DiscussionMpBCs are usually larger at primary diagnosis and most of MpBCs present with other poor prognostic indicators and show lack of steroid hormone receptors expression as well as HER2. Hormone receptor status and HER2 expression seems to correlate with histological grade of malignancy (G1-G3), tumor size (T1a-T4) and regional lymph node involvement (pN0-pN4) and these features are directly related to MpBC malignancy.