Abstract PD13-07: Subgroup analysis of patients with brain metastases from the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in metastatic triple-negative breast cancer

Abstract INTRODUCTION: Approximately 50% of patients with metastatic triple negative breast cancer (TNBC) will develop brain metastases (BM). Routinely treated with radiotherapy and/or surgery, survival is generally less than one year. There are no approved systemic therapies to treat TNBC BM. We characterized the genomic and immune landscape of TNBC BM to foster the development of effective brain permeable anti-cancer agents, including immunotherapy. EXPERIMENTAL PROCEDURES: A clinically-annotated BCBM biobank of archival tissues was created under IRB approval. DNA (tumor/normal) and RNA (tumor) were extracted from TNBC primaries and BM; whole exome (WES) and RNA sequencing (RNASeq) was performed. Mutations were determined from WES as those co-identified by two variant callers (Strelka|Cadabra). Immune gene signature expression, molecular subtype identification, and T cell receptor repertoires were inferred from RNAseq. RESULTS: 32 TNBC patient tissues (14 primaries, 18 BCBM, 6 primary-BCBM matched), characterized as basal-like by PAM50, were analyzed. Top exome mutation calls included ten genes in ≥19% of BCBMs including TP53, ATM, and PIK3R1, and four genes in ≥18% of primaries including TP53 and PIK3R1. Many immune gene signatures were lower in BM compared to primaries including B cell, dendritic cell, regulatory T cell, and IgG cluster (p< 0.05). A signature of PD-1 inhibition responsiveness was higher in BM compared with primaries (p< 0.05). BCBM T cell receptor repertoires showed higher evenness and lower read count (both p < 0.01) compared to primaries. CONCLUSIONS: TNBC BM compared to primaries that metastasize to the brain show lower immune gene signature expression, higher PD-1 inhibition response signature expression, and T cell receptor repertoire features less characteristic of an active antigen-specific response. Mutations common to TNBC BM and primaries include TP53 and PIK3R1. Given that non-BCBM (i.e. lung and melanoma) show response to checkpoint inhibitors, these findings collectively support further study of immunotherapy for TNBC BM.

Download Full-text

Abstract P6-16-12: Graded prognostic assessment for triple negative breast cancer brain metastases

10.1158/1538-7445.sabcs14-p6-16-12 ◽

2015 ◽

Author(s):

Ming Chi ◽

Vyshak Alva Venur ◽

Jame Abraham ◽

Thomas G Budd ◽

Paul Elson ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Prognostic Assessment ◽

Graded Prognostic Assessment ◽

Breast Cancer Brain Metastases

Download Full-text

Abstract OT3-02-10: Nordic trip, a randomized phase 3 study in early triple negative breast cancer

10.1158/1538-7445.sabcs15-ot3-02-10 ◽

2016 ◽

Cited By ~ 1

Author(s):

N Loman ◽

B Linderholm ◽

H Joensuu ◽

B Ejlertsen ◽

OT Johannsson ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Phase 3

Download Full-text

In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer

Clinical & Experimental Metastasis ◽

10.1007/s10585-016-9835-5 ◽

2017 ◽

Vol 34 (2) ◽

pp. 133-140 ◽

Cited By ~ 4

Author(s):

Amanda M. Hamilton ◽

Paula J. Foster

Keyword(s):

Breast Cancer ◽

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Brain Metastases ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Resonance Imaging

Download Full-text

The role of systemic treatment after whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases: Differences depending on biological subtype

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1027 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1027-1027

Author(s):

A. Niwinska ◽

M. Murawska ◽

I. Lemanska ◽

J. Milewska

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Median Survival ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Systemic Treatment ◽

Performance Status ◽

Poor Performance Status ◽

Breast Cancer Patients ◽

Her 2

1027 Background: The aim of the study was to analyze the efficacy of systemic treatment (chemotherapy [chth], endocrine therapy, targeted therapy) performed after WBRT in patients (pts) with breast cancer and brain metastases. Methods: The group of 222 consecutive breast cancer pts with brain metastases treated in one institution in the years 2003–2006 was divided into four biological subgroups based on ER, PR, and HER-2 receptors’ expression: HER-2(+++)ER/PR(-); HER-2(+++)ER/PR(+); ER(-)PR(-)HER-2(-); and ER/PR(+)HER-2(-). WBRT was performed in 219 (99%) pts. Systemic therapy after WBRT was continued in 160 (72%) pts. Clinically, patients with triple-negative breast cancer were more often in poor performance status (KPS<60%) than the others (51% vs. 28%, respectively). Survivals from brain metastases without and with systemic treatment were compared in four mentioned biological subgroups. Results: Median survival from brain metastases in the entire group was 7.5 months. In the group of ER/PR(+)HER-2(-) median survival without and with systemic therapy was 3 and 14 months, respectively (p = 0.007). In the group of HER-2(+++)ER/PR(+) median survival without further treatment, after chth and after chth with trastuzumab was 2, 8, and 13 months, respectively (p = 0.000) and in the group of HER-2(+++)ER/PR(-) median survival without further treatment, after chth and after chth with trastuzumab was 4, 8, and 10 months, respectively (p = 0.004). In triple-negative breast cancer patients median survival without and with chemotherapy was 3 and 4 months, respectively (p = 0.75). Conclusions: Systemic treatment (chth, endocrine therapy, targeted therapy) continued after WBRT in breast cancer pts with brain metastases prolongs survival in three of four biological subgroups. In the group of HER-2-positive breast cancer pts, trastuzumab added to chth had independent positive impact on survival. No benefit was observed in the subgroup of triple-negative breast cancer pts; it would be the result of refractory disease and the fact, that more pts were in poor performance status. No significant financial relationships to disclose.

Download Full-text

TBCRC 018: Phase II study of iniparib plus chemotherapy to treat triple-negative breast cancer (TNBC) brain metastases (BM).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.tps127 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. TPS127-TPS127 ◽

Cited By ~ 1

Author(s):

C. K. Anders ◽

R. Nanda ◽

M. C. Liu ◽

K. L. Blackwell ◽

C. H. Van Poznak ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Phase Ii ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Phase Ii Study

Download Full-text

ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early-stage triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps598 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS598-TPS598

Author(s):

Heather L. McArthur ◽

Michail Ignatiadis ◽

Sebastian Guillaume ◽

Andrew Bailey ◽

Jorge Luis Martinez ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Disease Free Survival ◽

Phase Iii ◽

Lymph Node Status ◽

Phase 3 ◽

Metastatic Setting

TPS598 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer and promising clinical activity has been reported with the anti–PD-L1 antibody, atezolizumab, in Phase 1/1b metastatic TNBC trials. Furthermore, the randomized phase 3 IMpassion130 study demonstrated enhanced anti-tumor activity when atezolizumab was co-administered with chemotherapy in the first line metastatic setting, with benefit mainly observed in PD-L1+ cohort. ALEXANDRA/IMpassion030 will evaluate the efficacy and safety of atezolizumab in combination with standard anthracycline/taxane adjuvant chemotherapy in early TNBC patients. Methods: ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard chemotherapy versus chemotherapy alone in early TNBC. In total, 2300 patients with operable stage II or III TNBC, confirmed by central pathology review, will be randomized. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant treatment will consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first patient was enrolled on August 2nd 2018, and approximately 430 sites are expected to be opened globally in 30 countries. Clinical trial information: NCT03498716.

Download Full-text