Biological and clinical features of early triple-negative invasive lobular carcinomas of the breast.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Fabio Conforti ◽  
Laura Pala ◽  
Elena Guerini Rocco ◽  
Eleonora Pagan ◽  
Vincenzo Bagnardi ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Luminal A ◽  
Median Percentage ◽  
Biological Features ◽  
Mutational Status ◽  
Erbb2 Gene

e12570 Background: Hormone receptors and HER2 negative (triple negative, TN) invasive lobular carcinomas (ILCs) are very rare, accounting for 1-2% of all TN breast cancers (BCs). Methods: We extracted data from our prospectively collected institutional database on all consecutive patients (pts) with early stage TN ILC operated at the European Institute of Oncology (IEO) between June 1994 and December 2012. Invasive disease-free survival (iDFS) and cumulative incidence of distant metastases (CI-DM) were calculated. Biological features of these tumors, including molecular intrinsic subtypes based on PAM50 assay, expression of androgen receptor (AR) and mutational status of c-erbB2 gene were also evaluated. Additionally, NGS data of 45 TN ILCs were obtained from 3 large public databases, to confirm mutations in c-erbB2 gene and to identify other recurrently mutated genes. Results: Among 2952 ILCs treated at IEO, 44 (1.5%) were TN and were included in the analysis. All pts received adjuvant chemotherapy. The iDFS rates at 5 and 10 years of follow-up were 47.4% (95% CI, 31.1-62.0) and 29.5% (95% CI, 14.8-45.8), respectively. The corresponding CI-DM percentages were 17.6% (95% CI, 7.6-31.2) and 20.8% (95% CI, 9.5-35.1). The molecular intrinsic subtype was defined through PAM50 for 31 out of 44 TN ILCs: 48% were classified as luminal A, 3% luminal B, 32% HER2-enriched, and only 16% basal-like. The group of pts with luminal A or B tumors had a significantly better CI-DM as compared with pts with non-luminal tumors (i.e. HER2-enriched and basal-like; p=0.003). Luminal tumors expressed AR more frequently than non-luminal tumors (AR≥1% in 96% of luminal tumors versus 53% in non-luminal tumors; p=0.001), and at significantly higher levels (median percentage of AR-positive cells was 80% in luminal tumors versus 15% in non-luminal tumors; p=0.01). Higher AR expression was associated with significantly better iDFS in the whole cohort of TN ILCs (p=0.01), as well as in the group of luminal tumors (p=0.05). 27 TN ILCs of the IEO cohort were analyzed for mutations in c-erbB2 gene, and 9 (33%) harbored mutations. Analysis of the 3 public databases, confirmed c-erbB2 mutations in 9 out of 45 (20%) TN ILCs. All the c-erbB2 mutations found were previously reported to be pathogenetic in BCs and to predict response to neratinib. ErbB signaling and DNA damage response were among the top 10 pathways significantly enriched for mutated genes in TN ILCs. Conclusions: TN ILCs are rare tumors with dire prognosis. Their specific biological features require newly defined targeted therapeutic strategies.

scholarly journals Practical Approach to Triple-Negative Breast Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Management Strategies ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Proven Method

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.

scholarly journals Immunohistochemical Profile of Molecular Markers of Mammary Carcinomas in Libreville

2021 ◽  
Vol 2 (2) ◽  
pp. 55-62
Author(s):  
Barthélemy Mabika ◽  
Nicole Josiane Andeme ◽  
Sidonie Solange Nguizi Ogoula ◽  
Guy Joseph Lémamy
Keyword(s):  
Molecular Markers ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Progesterone Receptors ◽  
Molecular Classification ◽  
Breast Cancers ◽  
Luminal A ◽  
Mammary Carcinomas ◽  
Luminal B ◽  
Immunohistochemical Profile

To establish the immunohistochemical profile of the molecular markers of free-ranging breast carcinomas. Descriptive retrospective study over 3 years from July 2014 to September 2017. The tumour samples came from the Anatomical Pathology Laboratories of the Omar Bongo Ondimba Army Instruction Hospital and the University of Health Sciences. In total, the records of 60 patients with histologically proven breast carcinoma with the immunohistochemical study were included in the study. The following molecular markers, hormone receptors (estrogen receptors, progesterone receptors), the HER2/Neu oncogene, and the Ki67 cell proliferation marker, was identified using the Immunohistochemistry technique.The average age was 47.6 years, with extremes of 15 and 69 years. Depending on the location, the right breast was most commonly affected (50%). Histologically, there was a predominance of infiltrating ductal carcinomas (66.6%) and a majority SBR III grade (50%). This study revealed an immunohistochemical profile of positive hormone receptors: ERs + (13.3%); PRs + (8.3%) and a Ki67 profile positive in 10% of tumors. The molecular classification into 4 subtypes (Luminal A, Luminal B, HER2 and Triple Negative) places the Luminal A group in the first rank (33.3%) followed by the Luminal B (15%), Triple Negative (11.6%) and HER2 (8.3%). The present work is the first study reporting the immunohistochemical profile of molecular markers of mammary carcinomas in Gabon. It would be necessary to continue this study on a larger and wider cohort throughout Gabon because the knowledge of the immunohistochemical profile gives an indication of the origin of breast cancers and allows to consider better management of patients by a targeted therapy to avoid unnecessary toxic effects resulting from ineffective treatment.

scholarly journals The Roles of DNA Demethylases in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (7) ◽  
pp. 628
Author(s):  
Shoghag Panjarian ◽  
Jean-Pierre J. Issa
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Breast Cancers ◽  
Therapeutic Implications ◽  
High Propensity ◽  
Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

scholarly journals Epigenetic Regulation of Immunotherapy Response in Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4139
Author(s):  
Pere Llinàs-Arias ◽  
Sandra Íñiguez-Muñoz ◽  
Kelly McCann ◽  
Leonie Voorwerk ◽  
Javier I. J. Orozco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Regulatory Elements ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Cancer Subtypes

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor and progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression. This malignancy, representing 15–20% of breast cancers, is a clinical challenge due to the lack of targeted treatments, higher intrinsic aggressiveness, and worse outcomes than other breast cancer subtypes. Immune checkpoint inhibitors have shown promising efficacy for early-stage and advanced TNBC, but this seems limited to a subgroup of patients. Understanding the underlying mechanisms that determine immunotherapy efficiency is essential to identifying which TNBC patients will respond to immunotherapy-based treatments and help to develop new therapeutic strategies. Emerging evidence supports that epigenetic alterations, including aberrant chromatin architecture conformation and the modulation of gene regulatory elements, are critical mechanisms for immune escape. These alterations are particularly interesting since they can be reverted through the inhibition of epigenetic regulators. For that reason, several recent studies suggest that the combination of epigenetic drugs and immunotherapeutic agents can boost anticancer immune responses. In this review, we focused on the contribution of epigenetics to the crosstalk between immune and cancer cells, its relevance on immunotherapy response in TNBC, and the potential benefits of combined treatments.

scholarly journals Influence of Germline BRCA Genotype on the Survival of Patients with Triple-Negative Breast Cancer

2021 ◽  
Vol 1 (3) ◽  
pp. 140-147
Author(s):  
Cynthia Villarreal-Garza ◽  
Ana S. Ferrigno ◽  
Alejandro Aranda-Gutierrez ◽  
Paul H. Frankel ◽  
Nora H. Ruel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Point Mutations ◽  
Treatment Resistance ◽  
Cancer Center ◽  
Breast Cancers ◽  
Entire Cohort ◽  
Pathogenic Variants ◽  
Mutational Status

The presence of BRCA pathogenic variants (PV) in triple-negative breast cancer (TNBC) is associated with a distinctive genomic profile that makes the tumor particularly susceptible to DNA-damaging treatments. However, patients with BRCA PVs can develop treatment resistance through the appearance of reversion mutations and restored BRCA expression. As copy-number variants (CNV) could be less susceptible to reversion mutations than point mutations, we hypothesize that carriers of BRCA CNVs may have improved survival after treatment compared with carriers of other BRCA PVs or BRCA wild-type. Women diagnosed with stage I–III TNBC at ≤50 years at a cancer center in Mexico City were screened for BRCA PVs using a recurrent PV assay (HISPANEL; 77% sensitivity). Recurrence-free survival (RFS) and overall survival (OS) were compared according to the mutational status. Among 180 women, 17 (9%) were carriers of BRCA1 ex9–12del CNVs and 26 (14%) of other BRCA PVs. RFS at ten years for the whole cohort was 79.2% [95% confidence interval (CI), 72.3–84.6], with no significant differences according to mutational status. 10-year OS for the entire cohort was 85.3% (95% CI, 78.7–90.0), with BRCA CNV carriers demonstrating numerically superior OS rates other PV carriers and noncarriers (100% vs. 78.6% and 84.7%; log-rank P = 0.037 and P = 0.051, respectively). This study suggests that BRCA1 ex9–12del CNV carriers with TNBC may have a better OS, and supports the hypothesis that the genotype of BRCA PVs may influence survival by limiting treatment resistance mediated by reversion mutations among CNV carriers. Significance: Large CNV BRCA carriers in a cohort of young Mexican patients with TNBC had superior OS rates than carriers of other BRCA pathogenic variants (i.e., small indels or point mutations). We hypothesize that this is due to the resistance of CNVs to reversion mutations mediating resistance to therapy. If validated, these findings have important prognostic and clinical treatment implications for BRCA-associated breast cancers.

Tubular Carcinoma of the Breast: Further Evidence to Support Its Excellent Prognosis

2010 ◽  
Vol 28 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Emad A. Rakha ◽  
Andrew H.S. Lee ◽  
Andrew J. Evans ◽  
Sindhu Menon ◽  
Nancy Y. Assad ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Disease Free Survival ◽  
Distinct Type ◽  
Second Primary ◽  
Low Grade ◽  
Breast Cancers ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Tubular Carcinoma ◽  
Molecular Features

Purpose Although tubular carcinoma (TC) is known to have a favorable prognosis, it is still unknown whether this subtype represents a distinct type of breast carcinoma or whether it behaves like other low-grade luminal A–type breast carcinomas. Methods In this study, we performed a retrospective analysis of a large well-characterized series of breast cancers (2,608 carcinomas) to assess the clinicopathologic and molecular features and prognostic value of TC compared with grade 1 ductal carcinomas of the breast. Results When compared with grade 1 ductal carcinoma (n = 212), TC (n = 102) was more likely to be detected on mammographic screening, had smaller median size, and less frequently showed lymphovascular invasion. Compared with grade 1 ductal carcinoma, TC was associated with longer disease-free survival (χ2 = 13.25, P < .001) and breast cancer–specific survival (χ2 = 8.8, P = .003). In this study, none of the patients with TC developed distant metastasis or died from the disease without an intervening recurrence as invasive carcinoma of different histologic type. Conclusion We conclude that the biologic behavior of TC is excellent and is more favorable than that of grade 1 ductal carcinoma. Patients with TC may be at risk of developing second primary carcinomas in the contralateral breast, which may be of higher grade and poorer potential prognostic outcome. In addition, patients with TC seem to have a close to normal life expectancy, and as a consequence, adjuvant systemic therapy may not be justified in their routine management.

Abstract 1697: Gadd45A expression is high in luminal A and her2 human breast cancers, but frequently absent in triple negative breast cancers

2012 ◽  
Author(s):  
Jennifer S. Tront ◽  
Alliric Willis ◽  
Yajue Huang ◽  
Geoffery Smith ◽  
Benjamin Powers ◽  
...  
Keyword(s):  
Triple Negative ◽  
Breast Cancers ◽  
Human Breast ◽  
Luminal A

scholarly journals Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers

2019 ◽  
Vol 37 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Sherene Loi ◽  
Damien Drubay ◽  
Sylvia Adams ◽  
Giancarlo Pruneri ◽  
Prudence A. Francis ◽  
...  
Keyword(s):  
Triple Negative ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cox Proportional Hazards ◽  
Prognostic Information ◽  
Free Survival ◽  
Node Negative ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Purpose The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%). Conclusion This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .

Sign in / Sign up

Export Citation Format

Share Document