A genome-wide association study (GWAS) identified 65 new breast cancer risk loci in 122,977 European and 14,068 East Asian cases and controls. These loci were associated with breast cancer risk at P < 5 × 10⁻⁸. Most credible risk single-nucleotide polymorphisms (SNPs) in these loci are located in distal regulatory elements. Integration of in silico data predicted target genes in breast cells, showing strong overlap with somatic driver genes in breast tumors. Heritability of breast cancer due to regulatory features was 2–5-fold enriched compared to the genome-wide average, with strong enrichment for specific transcription factor binding sites. These results enhance understanding of genetic susceptibility to breast cancer and improve genetic risk scores for individualized screening and prevention. The study genotyped 61,282 European women with breast cancer and 45,494 controls using the OncoArray. Data from 68 studies in the Breast Cancer Association Consortium (BCAC) and Discovery, Biology and Risk of Inherited Variants in Breast Cancer Consortium (DRIVE) were used. After imputation, 11.8 million SNPs were analyzed, adjusting for country and ancestry-informative principal components. Results were combined with data from the Collaborative Oncological Gene-environment Study (iCOGS) and 11 other GWAS studies using a fixed-effect meta-analysis. Of 102 loci previously associated with breast cancer in Europeans, 49 showed association in the OncoArray dataset at P < 5 × 10⁻⁸, and 94 at P < 0.05. Five additional loci associated with breast cancer in Asian women also showed evidence in the European ancestry OncoArray dataset. The study found 65 new loci associated with breast cancer risk at P < 5 × 10⁻⁸. Of these, 21 showed differential association based on estrogen receptor (ER) status, with most SNPs more strongly associated with ER-positive disease. Forty-four loci showed evidence of association with ER-negative breast cancer. Credible risk variants (CRVs) were identified at the new loci, with 2,221 CRVs across 65 novel regions. These CRVs were enriched for genomic features such as DNase I hypersensitivity sites and transcription factor binding sites. Target genes were predicted using integrated genomic data, showing strong enrichment for established breast cancer drivers. Pathway gene set enrichment analysis identified several growth or development-related pathways, including fibroblast growth factor, platelet-derived growth factor, and Wnt signaling pathways. The study estimated that the newly identified susceptibility loci explain around 4% of the twofold familial relative risk of breast cancer, with common susceptibility variants explaining 18% of the familial relative riskA genome-wide association study (GWAS) identified 65 new breast cancer risk loci in 122,977 European and 14,068 East Asian cases and controls. These loci were associated with breast cancer risk at P < 5 × 10⁻⁸. Most credible risk single-nucleotide polymorphisms (SNPs) in these loci are located in distal regulatory elements. Integration of in silico data predicted target genes in breast cells, showing strong overlap with somatic driver genes in breast tumors. Heritability of breast cancer due to regulatory features was 2–5-fold enriched compared to the genome-wide average, with strong enrichment for specific transcription factor binding sites. These results enhance understanding of genetic susceptibility to breast cancer and improve genetic risk scores for individualized screening and prevention. The study genotyped 61,282 European women with breast cancer and 45,494 controls using the OncoArray. Data from 68 studies in the Breast Cancer Association Consortium (BCAC) and Discovery, Biology and Risk of Inherited Variants in Breast Cancer Consortium (DRIVE) were used. After imputation, 11.8 million SNPs were analyzed, adjusting for country and ancestry-informative principal components. Results were combined with data from the Collaborative Oncological Gene-environment Study (iCOGS) and 11 other GWAS studies using a fixed-effect meta-analysis. Of 102 loci previously associated with breast cancer in Europeans, 49 showed association in the OncoArray dataset at P < 5 × 10⁻⁸, and 94 at P < 0.05. Five additional loci associated with breast cancer in Asian women also showed evidence in the European ancestry OncoArray dataset. The study found 65 new loci associated with breast cancer risk at P < 5 × 10⁻⁸. Of these, 21 showed differential association based on estrogen receptor (ER) status, with most SNPs more strongly associated with ER-positive disease. Forty-four loci showed evidence of association with ER-negative breast cancer. Credible risk variants (CRVs) were identified at the new loci, with 2,221 CRVs across 65 novel regions. These CRVs were enriched for genomic features such as DNase I hypersensitivity sites and transcription factor binding sites. Target genes were predicted using integrated genomic data, showing strong enrichment for established breast cancer drivers. Pathway gene set enrichment analysis identified several growth or development-related pathways, including fibroblast growth factor, platelet-derived growth factor, and Wnt signaling pathways. The study estimated that the newly identified susceptibility loci explain around 4% of the twofold familial relative risk of breast cancer, with common susceptibility variants explaining 18% of the familial relative risk