By the use of IGFBP7 as a predictor of ganitumab efficacy, we identified a substantial proportion of HER2 negative breast cancers (approximately 25%) including both poor prognosis ER/PgR-positive HER2-negative cancers and TNBC where the addition of ganitumab/metformin plus chemotherapy substantially improves pCR rates. This evidence concerns the gene ESR1 and breast carcinoma.