Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments DOI Creative Commons
Ugo Testa, Germana Castelli, Elvira Pelosi

et al.

Medical Sciences, Journal Year: 2020, Volume and Issue: 8(1), P. 18 - 18

Published: March 23, 2020

Breast cancer is the most commonly occurring in women. There were over two-million new cases world 2018. It second leading cause of death from western countries. At molecular level, breast a heterogeneous disease, which characterized by high genomic instability evidenced somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The caused defects DNA damage repair, transcription, replication, telomere maintenance mitotic segregation. According to features, cancers are subdivided subtypes, according activation hormone receptors (estrogen receptor progesterone receptor), human epidermal growth factors 2 (HER2), or BRCA mutations. In-depth analyses features primary metastatic have shown great heterogeneity genetic alterations their clonal evolution during disease development. These studies contributed identify repertoire numerous disease-causing genes that altered through different mutational processes. While early-stage curable about 70% patients, advanced largely incurable. However, develop therapeutic approaches targeting HER2, CDK4/6, PI3K, involving poly(ADP-ribose) polymerase inhibitors for mutation carriers immunotherapy.

Language: Английский

Breast Cancer Treatment DOI
Adrienne G. Waks, Eric P. Winer

JAMA, Journal Year: 2019, Volume and Issue: 321(3), P. 288 - 288

Published: Jan. 22, 2019

Importance

Breast cancer will be diagnosed in 12% of women the United States over course their lifetimes and more than 250 000 new cases breast were 2017. This review focuses on current approaches evolving strategies for local systemic therapy cancer.

Observations

is categorized into 3 major subtypes based presence or absence molecular markers estrogen progesterone receptors human epidermal growth factor 2 (ERBB2; formerlyHER2): hormone receptor positive/ERBB2 negative (70% patients),ERBB2positive (15%-20%), triple-negative (tumors lacking all standard markers; 15%). More 90% cancers are not metastatic at time diagnosis. For people presenting without disease, therapeutic goals tumor eradication preventing recurrence. Triple-negative likely to recur other subtypes, with 85% 5-year cancer–specific survival stage I tumors vs 94% 99% positive andERBB2positive. Systemic nonmetastatic determined by subtype: patients receptor–positive receive endocrine therapy, a minority chemotherapy as well; withERBB2-positive receiveERBB2-targeted antibody small-molecule inhibitor combined chemotherapy; alone. Local consists surgical resection, consideration postoperative radiation if lumpectomy performed. Increasingly, some delivered before surgery. Tailoring treatment preoperative response under investigation. Metastatic treated according subtype, prolonging life palliating symptoms. Median overall approximately 1 year 5 years subtypes.

Conclusions Relevance

expression andERBB2gene amplification. The have distinct risk profiles strategies. Optimal each patient depends anatomic stage, preferences.

Language: Английский

Citations

3701
3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3) DOI Creative Commons
Fátima Cardoso, A. Costa, Elżbieta Senkus

et al.

Annals of Oncology, Journal Year: 2016, Volume and Issue: 28(1), P. 16 - 33

Published: Oct. 11, 2016

Advanced Breast Cancer (ABC) comprises both locally advanced (LABC) and metastatic breast cancer (MBC) [1]. Although treatable, MBC remains an incurable disease with a median overall survival of ∼2–3 years 5-year only ∼25% [2–4]. Some more recent series seem to indicate improvement in [5, 6].

Language: Английский

Citations

1940
2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS) DOI
Alexander R. Lyon, Teresa López‐Fernández, Liam S. Couch

et al.

European Heart Journal, Journal Year: 2022, Volume and Issue: 43(41), P. 4229 - 4361

Published: Aug. 26, 2022

65-74 years, Sex category (female) CIED Cardiac implantable electronic device CML Chronic myeloid leukaemia CMR magnetic resonance COMPASS-CAT Prospective COmparison of Methods for thromboembolic

Language: Английский

Citations

1620
Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology DOI Open Access
William J. Gradishar, Benjamin O. Anderson, Jame Abraham

et al.

Journal of the National Comprehensive Cancer Network, Journal Year: 2020, Volume and Issue: 18(4), P. 452 - 478

Published: April 1, 2020

Several new systemic therapy options have become available for patients with metastatic breast cancer, which led to improvements in survival. In addition patient and clinical factors, the treatment selection primarily depends on tumor biology (hormone-receptor status HER2-status). The NCCN Guidelines specific workup of recurrent/stage IV cancer are discussed this article.

Language: Английский

Citations

1452
5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5) DOI Creative Commons
Fátima Cardoso, Shani Paluch–Shimon, Elżbieta Senkus

et al.

Annals of Oncology, Journal Year: 2020, Volume and Issue: 31(12), P. 1623 - 1649

Published: Sept. 23, 2020

Language: Английский

Citations

1089
Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer DOI Open Access
Nicholas C. Turner, Dennis J. Slamon, Jungsil Ro

et al.

New England Journal of Medicine, Journal Year: 2018, Volume and Issue: 379(20), P. 1926 - 1936

Published: Oct. 20, 2018

The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis overall survival. randomly assigned HER2-negative cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus placebo fulvestrant. analyzed survival; effect according stratification factors presence absence sensitivity visceral metastatic disease, menopausal status; efficacy subsequent therapies after disease progression; safety. Among 521 underwent randomization, median was 34.9 months (95% confidence interval [CI], 28.8 40.0) palbociclib-fulvestrant group 28.0 CI, 23.6 34.6) placebo-fulvestrant (hazard ratio for death, 0.81; 95% 0.64 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 treatment completion trial regimen occurred 16% group. 410 39.7 34.8 45.7) 29.7 23.8 37.9) ratio, 0.72; 0.55 0.94; 10.0 duration similar two groups, time receipt chemotherapy 17.6 group, as compared 8.8 0.58; 0.47 0.73; P<0.001). No new safety signals were observed 44.8 follow-up. resulted longer than placebo-fulvestrant. differences entire not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .).

Language: Английский

Citations

1006
Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer DOI Open Access
Seock‐Ah Im, Yen‐Shen Lu, Aditya Bardia

et al.

New England Journal of Medicine, Journal Year: 2019, Volume and Issue: 381(4), P. 307 - 316

Published: June 4, 2019

An earlier analysis of this phase 3 trial showed that the addition a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided greater benefit with regard progression-free survival than alone in premenopausal or perimenopausal patients advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report results protocol-specified interim key secondary end point overall survival.We randomly assigned receive either ribociclib placebo (goserelin nonsteroidal aromatase tamoxifen). Overall was evaluated use stratified log-rank test summarized Kaplan-Meier methods.A total 672 were included intention-to-treat population. There 83 deaths among 335 (24.8%) group 109 337 (32.3%) group. The resulted significantly longer alone. estimated at 42 months 70.2% (95% confidence interval [CI], 63.5 76.0) 46.0% CI, 32.0 58.9) (hazard ratio for death, 0.71; 95% 0.54 0.95; P = 0.00973 by test). seen subgroup 495 who received an consistent population 0.70; 0.50 0.98). percentage subsequent antineoplastic balanced between groups (68.9% 73.2% group). time from randomization disease progression during receipt second-line death also 0.69; 0.55 0.87).This CDK4/6 plus HER2-negative No new concerns regarding toxic effects emerged follow-up. (Funded Novartis; MONALEESA-7 ClinicalTrials.gov number, NCT02278120.).

Language: Английский

Citations

842
Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer DOI Open Access
Dennis J. Slamon, Patrick Neven,

Stephen Chia

et al.

New England Journal of Medicine, Journal Year: 2019, Volume and Issue: 382(6), P. 514 - 524

Published: Dec. 11, 2019

In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than alone in postmenopausal patients hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. Here we report the results protocol-specified second interim overall survival.

Language: Английский

Citations

678
Genomic characterization of metastatic breast cancers DOI
François Bertucci, Charlotte K.Y. Ng, Anne Patsouris

et al.

Nature, Journal Year: 2019, Volume and Issue: 569(7757), P. 560 - 564

Published: May 1, 2019

Language: Английский

Citations

600
The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer DOI Open Access
Lei Ding,

Jiaqi Cao,

Wen-Shan Lin

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(6), P. 1960 - 1960

Published: March 13, 2020

Cyclin-dependent kinases (CDKs) are serine/threonine whose catalytic activities regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints transcriptional events response to extracellular intracellular signals. Not surprisingly, the dysregulation of is a hallmark cancers, inhibition specific members considered an attractive target cancer therapy. In breast (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, abemaciclib, combined other agents, were approved Food Drug Administration (FDA) recently for treatment hormone receptor positive (HR+) advanced or metastatic (A/MBC), as well sub-types cancer. Furthermore, ongoing studies identified more selective promising clinical targets. this review, we focus on roles driving progression, checkpoints, regulation, highlight dysregulated activation BC. We also discuss most relevant currently BC trials, special emphasis used estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2−) M/ABC patients, emerging precise therapeutic strategies, such combination therapies microRNA (miRNA)

Language: Английский

Citations

460