| Title | Protocol to Establish Estrogen Receptor-Negative Heterozygous BRCA1 Organoids. |
| Publication Type | Journal Article |
| Year of Publication | 2025 |
| Authors | Deshpande M, Gerhardt J |
| Journal | Methods Protoc |
| Volume | 8 |
| Issue | 6 |
| Date Published | 2025 Nov 01 |
| ISSN | 2409-9279 |
| Abstract | Cancer development in BRCA1 carriers is a multi-step process, which is triggered by several factors and mechanisms that are not clearly understood. Most BRCA1 carriers develop triple-negative breast cancer (TNBC)-estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2 -negative cancers-which originates from ER/PR/HER2-negative breast progenitor cells. Due to a lack of ER/PR/HER2-negative cell models with BRCA mutations, the processes inducing cancer development in BRCA carriers have not been comprehensively studied. Thus, studies characterizing ER/PR/HER2-negative cells carrying a BRCA1 germline mutation are needed to gain more in-depth knowledge about the steps leading to cancer initiation in BRCA1 carriers. To study the cancer development in these patients, we established a protocol for the generation of human ER/PR/HER2-negative breast organoids carrying a BRCA1 germline mutation. We confirmed that these organoids are unresponsive to estrogen, can self-renew, and express the stem/progenitor marker CD44. In addition, we observed that these organoids contain outgrowths that resemble the mature ductal and lobular units of the mammary gland, thus making it a suitable model system to study how cancer develops in ER/PR/HER2-negative mammary cells that carry a BRCA1 germline mutation. |
| DOI | 10.3390/mps8060127 |
| Alternate Journal | Methods Protoc |
| PubMed ID | 41283387 |
| PubMed Central ID | PMC12641787 |
| Grant List | R01ES034733 / ES / NIEHS NIH HHS / United States |
