Immunotherapy and targeted therapy combinations in metastatic breast cancer

Esteva, Francisco J.; Hubbard-Lucey, Vanessa M.; Tang, Jun; Pusztai, Lajos

doi:10.1016/s1470-2045(19)30026-9

Cited by 343 publications

(256 citation statements)

References 72 publications

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“…For example, among patients with metastatic HR‐negative/HER2‐negative breast cancer, the PD‐L1 checkpoint inhibitor, atezolizumab, in combination with nanoparticle albumin‐bound paclitaxel, has been shown to prolong progression‐free survival . Clinical trials are currently evaluating combinations of immunotherapies and targeted therapies in all subtypes of breast cancer …”

Section: Selected Findingsmentioning

confidence: 99%

“…54 Clinical trials are currently evaluating combinations of immunotherapies and targeted therapies in all subtypes of breast cancer. 55 Most patients with stage IV breast cancer are managed with palliative/noncurative-intent treatment: 56% received radiation/chemotherapy alone, and 26% received no treatment (although some of these patients received hormonal therapy). However, the expanded spectrum of targeted systemic therapies for breast cancer, especially for HR-positive and HER2-positive disease, has improved survival for metastatic disease over the past 3 decades.…”

Section: Treatmentmentioning

confidence: 99%

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Breast cancer statistics, 2019

DeSantis

Gaudet

et al. 2019

CA A Cancer J Clinicians

2,306

1,727

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This article is the American Cancer Society’s biennial update on female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Over the most recent 5‐year period (2012‐2016), the breast cancer incidence rate increased slightly by 0.3% per year, largely because of rising rates of local stage and hormone receptor‐positive disease. In contrast, the breast cancer death rate continues to decline, dropping 40% from 1989 to 2017 and translating to 375,900 breast cancer deaths averted. Notably, the pace of the decline has slowed from an annual decrease of 1.9% during 1998 through 2011 to 1.3% during 2011 through 2017, largely driven by the trend in white women. Consequently, the black–white disparity in breast cancer mortality has remained stable since 2011 after widening over the past 3 decades. Nevertheless, the death rate remains 40% higher in blacks (28.4 vs 20.3 deaths per 100,000) despite a lower incidence rate (126.7 vs 130.8); this disparity is magnified among black women aged <50 years, who have a death rate double that of whites. In the most recent 5‐year period (2013‐2017), the death rate declined in Hispanics (2.1% per year), blacks (1.5%), whites (1.0%), and Asians/Pacific Islanders (0.8%) but was stable in American Indians/Alaska Natives. However, by state, breast cancer mortality rates are no longer declining in Nebraska overall; in Colorado and Wisconsin in black women; and in Nebraska, Texas, and Virginia in white women. Breast cancer was the leading cause of cancer death in women (surpassing lung cancer) in four Southern and two Midwestern states among blacks and in Utah among whites during 2016‐2017. Declines in breast cancer mortality could be accelerated by expanding access to high‐quality prevention, early detection, and treatment services to all women.

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Section: Selected Findingsmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Breast cancer statistics, 2019

DeSantis

Gaudet

et al. 2019

CA A Cancer J Clinicians

2,306

1,727

View full text Add to dashboard Cite

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“…Indeed, the landscape of clinical trials exploring combination treatment regimens coupling checkpoint blockade with other therapies is rapidly expanding. [53][54][55][56][57] Quantifying the molecular consequences of these combination regimes with our platform could provide novel insights into these trials and enable the informed design of new therapeutic combinations, potentially with targeted immunotherapies. Taken together, our relative and absolute quantitative immunopeptidomic data demonstrate the utility of quantitative immunopeptidomics in evaluating the pMHC repertoire response to therapy.…”

Section: Repertoire Changes Induced By Ifn-g Stimulation Are Distinctmentioning

confidence: 99%

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

Stopfer

Mesfin

Joughin

et al. 2020

Preprint

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Peptides bound to class I major histocompatibility complexes (MHC) play a critical role in immune cell recognition and can trigger an antitumor immune response in cancer. Surface MHC levels can be modulated by anticancer agents, altering immunity. However, understanding the peptide repertoire's response to treatment remains challenging and is limited by quantitative mass spectrometry-based strategies lacking robust normalization controls. We describe a novel approach that leverages recombinant heavy isotope-coded peptide MHCs (hipMHCs) and multiplex isotope tagging to quantify peptide repertoire alterations using low sample input.HipMHCs improve quantitative accuracy of peptide repertoire changes by normalizing for variation across analyses and enable absolute quantification using internal calibrants to determine copies per cell of MHC antigens, which can inform immunotherapy design. Applying this platform in melanoma to profile the immunopeptidome response to CDK4/6 inhibition and interferon gamma, known modulators of antigen presentation, we uncovered treatment-specific alterations, connecting the intracellular response to extracellular immune presentation.

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“…Because of this, there is an intensive effort in testing the efficacy of new therapies, to be used alone or in combination with hormone therapy, for the treatment of ER + BC. Not surprisingly, there is particular interest in exploring the potential of therapies targeting immune checkpoints such as those mediated by cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1) (4), although initial evidence indicate that ER + tumors are not very responsive due to low numbers of infiltrating lymphocytes and a low mutational burden (5).…”

Section: Introductionmentioning

confidence: 99%

Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells

Hühn

Martí‐Rodrigo

Mourón³

et al. 2019

Preprint

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Estrogen receptor (ER)-positive breast tumors are routinely treated with estrogen-depriving therapies. Despite their effectiveness, patients often progress into a more aggressive form of the disease. Through a chemical screen oriented to identify chemicals capable of inducing the expression of the immune-checkpoint ligand PD-L1, we found antiestrogens as hits. Subsequent validations confirmed that estrogen deprivation or ERa depletion induces PD-L1 expression in ER-positive breast cancer cells, both in vitro and in vivo. Likewise, PD-L1 expression is increased in metastasis arising from breast cancer patients receiving adjuvant hormonal therapy for their local disease. Transcriptome analyses indicate that estrogen deprivation triggers a broad immunosuppressive program, not restricted to PD-L1. Accordingly, estrogen deprived MCF7 cells are resistant to T-cell mediated cell killing, in a manner that can be reverted by estradiol. Our study reveals that while antiestrogen therapies effectively limit tumor growth in ER-positive breast cancers, they also trigger a transcriptional program that favors immune evasion.

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Immunotherapy and targeted therapy combinations in metastatic breast cancer

Cited by 343 publications

References 72 publications

Breast cancer statistics, 2019

Breast cancer statistics, 2019

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells

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