Inherited and acquired alterations in development of breast cancer

Rizzolo, Piera; Silvestri, Valentina; Falchetti, Mario; Ottini, Laura

doi:10.2147/tacg.s13226

Cited by 23 publications

(11 citation statements)

References 171 publications

(196 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although survival rates are improving, BC is still the fourth most common cause of death from cancer (627,000 deaths among women in 2018) [ 1 , 3 , 4 ]. Risk factors for developing BC include family history, age, environmental and lifestyle factors associated with carcinogen exposure, and hormonal changes [ 5 – 8 ]. The risk of developing BC is about two times higher if there is one first-degree relative affected by the disease and may be five times higher if the relative had BC at a young age [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

2021

View full text Add to dashboard Cite

Loss-of-function mutations in BRCA1 and BRCA2 are detected in at least 5% of unselected patients with breast cancer (BC). These BC susceptibility genes encode proteins critical for DNA homologous recombination repair (HRR). This review provides an update on oral poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of BC. Olaparib and talazoparib are PARP inhibitors approved as monotherapies for deleterious/suspected deleterious germline BRCA-mutated, HER2-negative BC. Olaparib is approved in the USA for metastatic BC and in Europe for locally advanced/metastatic BC. Talazoparib is approved for locally advanced/metastatic BC in the USA and Europe. In phase 3 trials, olaparib and talazoparib monotherapies demonstrated significant progression-free survival benefits compared with chemotherapy. Common toxicities were effectively managed by supportive treatment and dose interruptions/reductions. Veliparib combined with platinum-based chemotherapy has also shown promise for locally advanced/metastatic BC in a phase 3 trial. Differences in efficacy and safety across PARP inhibitors (olaparib, talazoparib, veliparib, niraparib, rucaparib) may relate to differences in potency of PARP trapping on DNA and cytotoxic specificity. PARP inhibitors are being investigated in early BC, in novel combinations, and in patients without germline BRCA mutations, including those with somatic BRCA mutations and other HRR gene mutations. Ongoing phase 2/3 studies include PARP inhibitors combined with immune checkpoint inhibitors for the treatment of triple-negative BC. Wider access to testing for BRCA and other mutations, and to genetic counseling, are required to identify patients who could benefit from PARP inhibitor therapy. The advent of PARP inhibitors has potential benefits for BC treatment beyond the locally advanced/metastatic setting.

show abstract

Section: Introductionmentioning

confidence: 99%

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

2021

View full text Add to dashboard Cite

show abstract

“…Interestingly, the genetic background fails to explain the molecular anomaly of breast cancer entirely due to the sporadicity often associated with breast cancer. The genomic causes responsible for breast cancer are acquired more often than inherited [7]. To date, epigenetic processes like DNA methylation, histone modification, and microRNAs (miRNAs) have been reported to be involved with every aspect of breast cancer pathophysiology, diagnosis, and treatment [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer

Rahman

Brane

Tollefsbol

2019

Cells

View full text Add to dashboard Cite

Breast cancer is a sporadic disease with genetic and epigenetic components. Genomic instability in breast cancer leads to mutations, copy number variations, and genetic rearrangements, while epigenetic remodeling involves alteration by DNA methylation, histone modification and microRNAs (miRNAs) of gene expression profiles. The accrued scientific findings strongly suggest epigenetic dysregulation in breast cancer pathogenesis though genomic instability is central to breast cancer hallmarks. Being reversible and plastic, epigenetic processes appear more amenable toward therapeutic intervention than the more unidirectional genetic alterations. In this review, we discuss the epigenetic reprogramming associated with breast cancer such as shuffling of DNA methylation, histone acetylation, histone methylation, and miRNAs expression profiles. As part of this, we illustrate how epigenetic instability orchestrates the attainment of cancer hallmarks which stimulate the neoplastic transformation-tumorigenesis-malignancy cascades. As reversibility of epigenetic controls is a promising feature to optimize for devising novel therapeutic approaches, we also focus on the strategies for restoring the epistate that favor improved disease outcome and therapeutic intervention.

show abstract

“…Overall, the 5-year survival rate is around 99% for localized BC, 86% for regional disease, and 27% for metastatic BC (BC stage IV) [ 4 ]. Around 5–10% of BC cases are hereditary, 85% of which are related to mutations in the two high penetrance tumor suppressor genes BRCA1 and BRCA2 [ 5 ], whereas the majority of breast tumors are sporadic and due to somatic, genetic, and epigenetic alterations acquired during life [ 6 ]. Non-hereditary risk factors include age, body mass index, sex, density of the breast, early menarche, age at first birth, late menopause, alcohol consumption, exposure to radiation, and smoking habits.…”

Section: Introductionmentioning

confidence: 99%

The Tumor Microenvironment as a Driving Force of Breast Cancer Stem Cell Plasticity

Fico

Santamaria-Martínez

2020

Cancers

View full text Add to dashboard Cite

Tumor progression involves the co-evolution of transformed cells and the milieu in which they live and expand. Breast cancer stem cells (BCSCs) are a specialized subset of cells that sustain tumor growth and drive metastatic colonization. However, the cellular hierarchy in breast tumors is rather plastic, and the capacity to transition from one cell state to another depends not only on the intrinsic properties of transformed cells, but also on the interplay with their niches. It has become evident that the tumor microenvironment (TME) is a major player in regulating the BCSC phenotype and metastasis. The complexity of the TME is reflected in its number of players and in the interactions that they establish with each other. Multiple types of immune cells, stromal cells, and the extracellular matrix (ECM) form an intricate communication network with cancer cells, exert a highly selective pressure on the tumor, and provide supportive niches for BCSC expansion. A better understanding of the mechanisms regulating these interactions is crucial to develop strategies aimed at interfering with key BCSC niche factors, which may help reducing tumor heterogeneity and impair metastasis.

show abstract

Inherited and acquired alterations in development of breast cancer

Cited by 23 publications

References 171 publications

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer

The Tumor Microenvironment as a Driving Force of Breast Cancer Stem Cell Plasticity

Contact Info

Product

Resources

About