Scholarlink

<p>Among breast cancer subtypes, basal-like breast cancer (BLBC) is a highly aggressive form characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor (HER2) expression and is associated with poor prognosis, leaving chemotherapy as the sole treatment option available. Loss-of-function mutations in <i>BRCA1</i> are strongly associated with the development of BLBC. Patients with this subtype are more likely to have grade III tumors and larger average tumor sizes than those with other subtypes of breast cancer. It is not known whether BRCA1 loss of function affects all cell types equally within breast tissue or if it has a preferential malignant impact on specific cell types, leading to the progression of lineage-specific tumorigenesis in the breast epithelium of women carrying <i>BRCA1</i> mutations. Lineage tracing experiments using genetically engineered mouse models have provided critical insights into how BRCA1 loss alters cellular hierarchy within the mammary gland. These studies have demonstrated that <i>BRCA1</i>-deficient luminal progenitors can aberrantly differentiate into basal-like cells, suggesting that BLBC may arise from a misregulated luminal compartment rather than pre-existing basal stem cells. Understanding the mechanisms underlying BRCA1-mediated lineage plasticity offers novel therapeutic avenues to target early-stage tumor initiation and progression in <i>BRCA1</i>-mutated breast cancer. This review perspective sheds light on the role of BRCA1 in lineage plasticity and highlights probable mechanisms by which BRCA1 could promote this lineage plasticity.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

BRCA1: An Unrecognized Modulator of Lineage Plasticity in Basal-like Breast Cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月3日

查看全文
  • Rahul Sanawar,
  • Satheesh Kumar Sengodan

摘要

Among breast cancer subtypes, basal-like breast cancer (BLBC) is a highly aggressive form characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor (HER2) expression and is associated with poor prognosis, leaving chemotherapy as the sole treatment option available. Loss-of-function mutations in BRCA1 are strongly associated with the development of BLBC. Patients with this subtype are more likely to have grade III tumors and larger average tumor sizes than those with other subtypes of breast cancer. It is not known whether BRCA1 loss of function affects all cell types equally within breast tissue or if it has a preferential malignant impact on specific cell types, leading to the progression of lineage-specific tumorigenesis in the breast epithelium of women carrying BRCA1 mutations. Lineage tracing experiments using genetically engineered mouse models have provided critical insights into how BRCA1 loss alters cellular hierarchy within the mammary gland. These studies have demonstrated that BRCA1-deficient luminal progenitors can aberrantly differentiate into basal-like cells, suggesting that BLBC may arise from a misregulated luminal compartment rather than pre-existing basal stem cells. Understanding the mechanisms underlying BRCA1-mediated lineage plasticity offers novel therapeutic avenues to target early-stage tumor initiation and progression in BRCA1-mutated breast cancer. This review perspective sheds light on the role of BRCA1 in lineage plasticity and highlights probable mechanisms by which BRCA1 could promote this lineage plasticity.