Obesity (BMI ≥ 30 kg/m2), which has been spreading at a fast pace during the last decades and exerting a negative impact on the health and life quality of women worldwide3, is an established risk factor of estrogen receptor-positive (ER+) BC in post-menopausal women4,5 and has also been associated with a higher incidence of triple-negative breast cancer (TNBC)6,7. Here, ESR1 is linked to obesity due to melanocortin 4 receptor deficiency.