Recent developments and translational aspects in targeted therapy for metastatic breast cancer

Biologically distinct subtypes of metastatic breast cancer (MBC) have been defined by multiple efforts in recent years, showing broad heterogeneity at the molecular level of disease. Throughout this endeavour, oncogenic drivers within MBC were identified as potential therapeutic targets. With recent results from clinical trials targeting these well-known cancer-promoting pathways, this review is trying to elucidate as well as summarise current new therapeutic aspects in MBC and shed light on translational aspects within this entity.

• Publication year

  2016

• Venue

  ESMO Open

• Publication date

  2016-05-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1136/esmoopen-2016-000036PMID 27843605PMCID 5070263
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

  2017cited by this paper
• First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors

  2017cited by this paper
• Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial.

  2016cited by this paper
• Abstract S5-07: Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive, estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028

  2016cited by this paper
• Abstract S6-01:PIK3CAstatus in circulating tumor DNA (ctDNA) predicts efficacy of buparlisib (BUP) plus fulvestrant (FULV) in postmenopausal women with endocrine-resistant HR+/HER2– advanced breast cancer (BC): First results from the randomized, phase III BELLE-2 trial:

  2016cited by this paper
• Abstract S1-04: Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial

  2016cited by this paper
• Afatinib alone or afatinib plus vinorelbine versus investigator's choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial.

  2015cited by this paper
• Updated findings of a first-in-human, phase I study of margetuximab (M), an Fc-optimized chimeric monoclonal antibody (MAb), in patients (pts) with HER2-positive advanced solid tumors.

  2015cited by this paper
• Phase I study of HER3 targeted antibody patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).

  2015cited by this paper
• Phase 1b study of ONT-380, an oral HER2-specific inhibitor, in combination with capecitabine (C) and trastuzumab (T) in third line + treatment of HER2+ metastatic breast cancer (MBC).

  2015cited by this paper
• Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.

  2015cited by this paper
• Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer.

  2015cited by this paper
• Cabozantinib (XL184) Inhibits Growth and Invasion of Preclinical TNBC Models

  2015influential reference
• Abstract CT234: A phase I study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2+ metastatic breast cancer

  2015cited by this paper
• Abstract 2859: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC)

  2015cited by this paper
• Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.

  2015cited by this paper
• Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer.

  2015cited by this paper
• Abstract P5-19-01: Randomized Phase III trial of afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one prior trastuzumab treatment: LUX-Breast 1

  2015cited by this paper
• Abstract P5-19-04: A phase I/II study of neratinib plus temsirolimus in HER2+ metastatic breast cancer reveals ongoing HER2 pathway dependence in many patients despite several lines of HER2 targeted therapy

  2015cited by this paper
• Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer.

  2015cited by this paper
• Abstract S1-09: A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer

  2015cited by this paper
• Neratinib after adjuvant chemotherapy and trastuzumab in HER2-positive early breast cancer: Primary analysis at 2 years of a phase 3, randomized, placebo-controlled trial (ExteNET).

  2015cited by this paper
• The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

  2015cited by this paper
• Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation.

  2015cited by this paper
• Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients.

  2014cited by this paper
• Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors.

  2014cited by this paper
• Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial.

  2014cited by this paper
• Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.

  2014cited by this paper
• Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial.

  2014cited by this paper
• Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study)

  2014cited by this paper
• Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival

  2014cited by this paper
• Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors.

  2014cited by this paper
• A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer.

  2013cited by this paper
• Neoadjuvant Therapy as a Platform for Drug Development and Approval in Breast Cancer

  2013cited by this paper
• Targeting FGFR with Dovitinib (TKI258): Preclinical and Clinical Data in Breast Cancer

  2013cited by this paper
• Incorporating Genomics into Breast Cancer Clinical Trials and Care

  2013cited by this paper
• The genomic landscape of breast cancer as a therapeutic roadmap.

  2013cited by this paper
• Emerging targeted agents in metastatic breast cancer

  2013cited by this paper
• Correlation of molecular alterations with efficacy of everolimus in hormone receptor-positive, HER2-negative advanced breast cancer: Results from BOLERO-2.

  2013cited by this paper
• Activating ESR 1 mutations in hormone-resistant metastatic breast cancer

  2013cited by this paper
• Predictive markers of everolimus efficacy in hormone receptor positive (HR+) metastatic breast cancer (MBC): Final results of the TAMRAD trial translational study.

  2013cited by this paper
• Comprehensive molecular portraits of human breast tumours

  2013cited by this paper
• Activating ESR1 mutations in hormone-resistant metastatic breast cancer

  2013cited by this paper
• Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer.

  2013cited by this paper
• Phase III, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and vinorelbine in trastuzumab-resistant, advanced breast cancer (BOLERO-3).

  2013cited by this paper
• The influence of treatment response on the impact of resection margin status after preoperative chemoradiotherapy in rectal cancer.

  2013cited by this paper
• A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab

  2012cited by this paper
• Activity of cabozantinib (XL184) in metastatic breast cancer (MBC): Results from a phase II randomized discontinuation trial (RDT).

  2012cited by this paper
• Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.

  2012cited by this paper
• Trastuzumab emtansine for HER2-positive advanced breast cancer.

  2012cited by this paper
• The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups

  2012cited by this paper
• Comprehensive molecular portraits of human breast tumors

  2012cited by this paper
• Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study

  2012cited by this paper
• A phase II study of foretinib in triple-negative, recurrent/metastatic breast cancer: NCIC CTG trial IND.197 (NCT01147484).

  2012cited by this paper
• Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study.

  2012cited by this paper
• Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.

  2012cited by this paper
• Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study.

  2012cited by this paper
• The clonal and mutational evolution spectrum of primary triple-negative breast cancers

  2012cited by this paper
• Whole Genome Analysis Informs Breast Cancer Response to Aromatase Inhibition

  2012cited by this paper
• Sequence analysis of mutations and translocations across breast cancer subtypes

  2012cited by this paper
• A multicenter, open-label phase II trial of dovitinib, an FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer.

  2011cited by this paper
• Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study.

  2011cited by this paper
• Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer

  2011cited by this paper
• Randomized phase II trial of first-line trastuzumab plus docetaxel and capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer.

  2010cited by this paper
• Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer.

  2010cited by this paper
• Poly(ADP-Ribose) Polymerase Inhibitors in Triple-Negative Breast Cancer

  2010cited by this paper
• Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer.

  2009cited by this paper
• Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study.

  2009cited by this paper
• Trastuzumab Beyond Progression in Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: A German Breast Group 26/Breast International Group 03-05 Study

  2009cited by this paper
• Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer.

  2008influential reference
• Acquired Resistance to Small Molecule ErbB2 Tyrosine Kinase Inhibitors

  2008cited by this paper
• Escape from HER family tyrosine kinase inhibitor therapy by the kinase inactive HER3

  2007cited by this paper
• Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer.

  2007cited by this paper
• Lapatinib plus capecitabine for HER2-positive advanced breast cancer.

  2006cited by this paper
• Dual Inhibition of mTOR and Estrogen Receptor Signaling In vitro Induces Cell Death in Models of Breast Cancer

  2005cited by this paper
• Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.

  2005cited by this paper
• The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine kinase receptors and the consequences for therapeutic approaches.

  2005cited by this paper
• Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

  2005cited by this paper
• Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group.

  2005cited by this paper
• Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer.

  2005cited by this paper
• High Frequency of Mutations of the PIK3CA Gene in Human Cancers

  2004cited by this paper
• Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression.

  2004cited by this paper
• NCCN breast cancer clinical practice guidelines in oncology: an update.

  2003cited by this paper
• Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.

  2001cited by this paper
• The n e w e n g l a n d j o u r n a l of m e d i c i n e

  2001cited by this paper
• Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer.

  1997cited by this paper
• Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer.

  1996cited by this paper
• Expression and amplification of cyclin genes in human breast cancer.

  1993cited by this paper
• Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.

  1987cited by this paper
• On the Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a New Method of Treatment, with Illustrative Cases

  1896cited by this paper

• What is known about melatonin, chemotherapy and altered gene expression in breast cancer

  2017cites this paper