Breast Cancer

2026-04-27 · A genome-wide association study on radiation induced fibrosis in breast cancer patients. Clinical and Translational Radiation Oncology. 2026. DOI:10.1016/j.ctro.2026.101180

A near-significant chromosome 10 signal for who gets scarring after breast cancer radiotherapy

Radiation-induced fibrosis (scarring) affects women to varying degrees after lumpectomy and radiotherapy for breast cancer, and remains a significant source of late-term morbidity, though its genetic basis is incompletely understood. This study analyzed 869 early breast cancer patients from two Danish Breast Cancer Group trials, testing genetic associations with grade 2-3 fibrosis. After correcting for population-structure outliers, it found a signal on chromosome 10 (lead variant rs75542274) at P=5.90x10^-8 -- just short of the standard 5x10^-8 genome-wide significance threshold, and no other variant reached significance. The authors themselves describe this as an exploratory finding requiring independent validation or meta-analysis before it can be considered established. This is included here as an honestly-caveated near-miss rather than a confirmed discovery: if replicated, a genetic marker for radiation fibrosis risk could eventually help personalize radiotherapy planning for breast cancer patients, but this single study alone does not establish that. This site does not currently have specific variant content on radiation-induced fibrosis to compare against.

2025-12-01 · Leveraging Genome-wide Association Studies to Identify Pathogenic Variants for Breast Cancer Among Multiple Continents. Anticancer Research. 2025. DOI:10.21873/anticanres.17873

Mining 1,219 known breast cancer SNPs for druggability turns up an unexpected repurposing candidate: MAPT

Rather than running a new GWAS, this study mined the existing GWAS Catalog for genome-wide significant breast cancer SNPs (1,219 total) and systematically re-scored them for biological and therapeutic relevance -- missense impact, eQTL evidence, CADD/SIFT/PolyPhen-2/AlphaMissense pathogenicity predictions, and druggability via DrugBank. Nine genes reached the maximum relevance score: SLCO1B1, ARHGEF38, EXO1, KDELC2, MAPT, PHLDA3, AKAP9, ATXN7 and DCLRE1B. SLCO1B1, EXO1 and ATXN7 are already on this site's breast cancer page from earlier studies; ARHGEF38, KDELC2, MAPT, PHLDA3, AKAP9 and DCLRE1B are new. The most actionable finding: among all nine, only MAPT had existing approved drugs already linked to its function -- paclitaxel and docetaxel, both established chemotherapy agents -- indirectly through its role in microtubule biology, since taxanes work by stabilizing microtubules and MAPT (better known as the tau protein in Alzheimer's research) also binds them. This is a drug-repurposing hypothesis derived from re-reading known genetic risk data through a druggability lens, not a discovery of new taxane efficacy -- the authors frame it as foundational for further study, not a clinical recommendation.

2026-09-04 · U.S. Food and Drug Administration (FDA), official approval summary

FDA approves camizestrant for breast cancer that develops resistance through an ESR1 mutation

Verified directly against the FDA's own approval summary. Accelerated approval (4 Sep 2026) for camizestrant (Etcamah, AstraZeneca) plus a CDK4/6 inhibitor, for HR-positive/HER2-negative advanced breast cancer that develops an ESR1 mutation *during* prior aromatase-inhibitor + CDK4/6-inhibitor treatment -- detected with the newly co-approved Guardant360 CDx companion diagnostic. In the SERENA-6 trial: 16-month median progression-free survival vs 9.2 months on continued aromatase-inhibitor therapy. Important distinction from this page's own genetics: the ESR1 mutations this drug targets are acquired/somatic, arising in the tumor during treatment -- a different category from the four germline ESR1 variants already on /conditions/breast-cancer (rs9383938, rs2046210, rs3757318, rs140068132), which are inherited common variants studied for population-level risk, not treatment-resistance mutations. Filed as a real, verified drug-approval event connected to the same gene this page already discusses, with that distinction stated plainly rather than blurred.

rs2180341 (6q22.33). Identified in a three-phase GWAS in Ashkenazi Jewish women: phase 1 compared 150,080 SNPs in 249 high-risk BRCA1/2 mutation-negative familial cases against 299 cancer-free controls; phase 2 genotyped 343 SNPs from the 123 most significant regions in 950 consecutive cases and 979 age-matched controls; phase 3 replicated in 243 cases and 187 controls. The same study confirmed the FGFR2 region (P = 1.5 x 10^-5, OR 1.26, 95% CI 1.13-1.40 at rs1078806 across all phases). The design — familial cases with the high-penetrance genes excluded — is what makes this locus a statement about polygenic background rather than about monogenic risk.

rs4973768 (near SLC4A7). Recorded against a 2011 genome-wide analysis that compared 296,114 tagging SNPs in 1,694 breast cancer cases — 92% with two primary cancers or at least two affected first-degree relatives — against 2,365 controls, with validation in three independent series totalling 11,880 cases and 12,487 controls. That study's own novel finding was 9q31.2 (rs865686, OR 0.89, 95% CI 0.85-0.92, P = 1.75 x 10^-10); rs4973768 is among the established loci carried in the same analysis.

Relation to high-penetrance testing. Pathogenic variants in BRCA1, BRCA2, PALB2, TP53, CDH1, STK11 and PTEN carry substantially elevated lifetime risk and drive management: earlier and more intensive surveillance, consideration of risk-reducing mastectomy or salpingo-oophorectomy, and eligibility for PARP inhibitors in the treatment setting. Common variants such as those recorded here are not diagnostic, are not a substitute for clinical testing, and do not modify eligibility for any of it. Polygenic risk scores combining hundreds of common variants have been studied for risk stratification and are not standard of care in most systems.