Abstract P1-14-07: Association between quantitative values of estrogen receptor expression level and pathological complete response in human epidermal growth factor 2-negative breast cancer: Should the clinical definition of triple-negative breast cancer be redefined?

Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC is a genetically diverse, highly heterogeneous, and rapidly evolving disease that challenges our ability to individualize treatment for incomplete responders and relapsed patients. Currently, the frontline standard chemotherapy, composed of anthracyclines, alkylating agents, and taxanes, is commonly used to treat high-risk and locally advanced TNBC. Several FDA-approved drugs that target programmed cell death protein-1 (Keytruda) and programmed death ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise in improving clinical outcomes for a subset of TNBC. These inhibitors that target key genetic mutations and specific molecular signaling pathways that drive malignant tumor growth have been used as single agents and/or in combination with standard chemotherapy regimens. Here, we review the current TNBC treatment options, unmet clinical needs, and actionable drug targets, including epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERβ), phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with chemo-resistance, aggressive dissemination, and early relapse, we hope to design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic strategy to control and eradicate incurable TNBC in the future.

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MLTI-16. SYSTEMIC THERAPY FOLLOWING CRANIOTOMY IN PATIENTS WITH A SOLITARY BREAST CANCER BRAIN METASTASIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.075 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i17-i17

Author(s):

Alexander Hulsbergen ◽

Logan Cho ◽

Marco Mammi ◽

Nayan Lamba ◽

Timothy Smith ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Epidermal Growth Factor Receptor ◽

Targeted Therapy ◽

Growth Factor ◽

Brain Metastasis ◽

Triple Negative ◽

Growth Factor Receptor ◽

Breast Cancer Brain Metastasis ◽

Epidermal Growth

Abstract INTRODUCTION: Between 15–50% of patients with metastatic breast cancer will develop brain metastases, with the frequency more common in patients with HER2-positive or triple-negative subtypes. Surgical resection is often indicated for diagnostic and/or therapeutic intent for patients presenting with a solitary lesion and/or symptomatic lesion(s) with mass effect. Practice patterns and patient outcomes with respect to the use of postoperative systemic therapy (ST) after resection of a solitary breast cancer brain metastasis (BCBM) have not been previously well-described, particularly in the modern era. METHODS: A multi-institutional retrospective review of 44 patients was performed to assess the impact of types of ST on site of recurrence, progression-free survival (PFS) and overall survival (OS) after resection of solitary BCBM. RESULTS: Stratified estimated survival was 15, 24 and 23 months for patients with triple negative, estrogen receptor positive (ER+), and human epidermal growth factor receptor 2 positive (HER2+) BCBMs. Patients receiving postoperative ST had a longer median PFS (8 versus 4 months) and OS (32 versus 15 months). Nine patients (20%) had extracranial progression, 23 (52%) had intracranial progression, three (8%) had both, and nine (20%) did not experience progression at last follow-up. Multivariate analysis showed that postoperative hormonal therapy was associated with longer OS in estrogen receptor (ER) positive patients (HR = 0.26; CI = 0.08 – 0.89; p = 0.03), but not with longer PFS. Postoperative human epidermal growth factor receptor 2 (HER2)-targeted therapy was not associated with longer PFS or OS in HER2+ patients. CONCLUSIONS: Disease progression occurred intracranially more often than extracranially following resection of a solitary BCBM. In ER+ patients, postoperative hormonal therapy was associated with longer OS. Postoperative HER2-targeted therapy did not show survival benefits in HER2+ patients. These results should be validated in larger cohorts.

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