Adjuvant chemotherapy in T1a/bN0 HER2-positive or triple-negative breast cancers: Application and outcomes

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.

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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

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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

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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.

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Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal Growth Factor Receptor 2 (HER2) –Negative and Adjuvant Targeted Therapy for HER2-Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline

Journal of Clinical Oncology ◽

10.1200/jco.2016.67.0182 ◽

2016 ◽

Vol 34 (20) ◽

pp. 2416-2427 ◽

Cited By ~ 67

Author(s):

Neelima Denduluri ◽

Mark R. Somerfield ◽

Andrea Eisen ◽

Jamie N. Holloway ◽

Arti Hurria ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Clinical Practice ◽

Targeted Therapy ◽

Adjuvant Chemotherapy ◽

Growth Factor Receptor ◽

Breast Cancers ◽

Her2 Positive ◽

Epidermal Growth ◽

American Society ◽

Selection Of

Purpose A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)–positive breast cancers was identified for adaptation. Methods The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability. Results On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members. Recommendations Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline- and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available.

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