Changing frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers

Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

Download Full-text

Genomic Insights into Triple-Negative and HER2-Positive Breast Cancers Using Isogenic Model Systems

PLoS ONE ◽

10.1371/journal.pone.0074993 ◽

2013 ◽

Vol 8 (9) ◽

pp. e74993 ◽

Cited By ~ 5

Author(s):

Prakriti Mudvari ◽

Kazufumi Ohshiro ◽

Vasudha Nair ◽

Anelia Horvath ◽

Rakesh Kumar

Keyword(s):

Triple Negative ◽

Model Systems ◽

Breast Cancers ◽

Her2 Positive

Download Full-text

Epigenetic Regulation of Immunotherapy Response in Triple-Negative Breast Cancer

Cancers ◽

10.3390/cancers13164139 ◽

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.

Download Full-text

Practical Approach to Triple-Negative Breast Cancer

Journal of Oncology Practice ◽

10.1200/jop.2017.022632 ◽

2017 ◽

Vol 13 (5) ◽

pp. 293-300 ◽

Cited By ~ 24

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.

Download Full-text

Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy

Annals of Oncology ◽

10.1093/annonc/mdz395 ◽

2019 ◽

Vol 30 (12) ◽

pp. 1941-1949 ◽

Cited By ~ 28

Author(s):

J H Park ◽

S F Jonas ◽

G Bataillon ◽

C Criscitiello ◽

R Salgado ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Prognostic Value ◽

Triple Negative ◽

Early Stage ◽

Tumor Infiltrating Lymphocytes ◽

Breast Cancers ◽

Infiltrating Lymphocytes

Download Full-text

Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy

The Breast ◽

10.1016/j.breast.2015.03.002 ◽

2015 ◽

Vol 24 (4) ◽

pp. 397-405 ◽

Cited By ~ 9

Author(s):

Anna Miquel-Cases ◽

Lotte M.G. Steuten ◽

Valesca P. Retèl ◽

Wim H. van Harten

Keyword(s):

Cost Effectiveness ◽

Triple Negative ◽

Early Stage ◽

Cost Effectiveness Analysis ◽

High Dose ◽

Breast Cancers ◽

Effectiveness Analysis

Download Full-text

Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

BioMed Research International ◽

10.1155/2020/8970340 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Xiao-Xiao Li ◽

Li-Juan Wang ◽

Jie Hou ◽

Hong-Yang Liu ◽

Rui Wang ◽

...

Keyword(s):

Breast Cancer ◽

Network Analysis ◽

Molecular Mechanisms ◽

Triple Negative ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Breast Cancers ◽

Luminal A ◽

Her2 Positive ◽

Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

Download Full-text