AbstractSevere calorie restriction, in the form of cyclic fasting or fasting‐mimicking diets (FMDs), boosts the antitumor activity of cytotoxic chemotherapy in mouse models of triple‐negative breast cancer (TNBC). This effect is mostly mediated by fasting/FMD‐induced reduction of plasma glucose concentration and by a boost in antitumor immunity. However, clinical evidence that cyclic FMD may impact on the outcomes of advanced TNBC (aTNBC) patients is lacking. We compared the overall survival (OS) of 14 aTNBC patients receiving first‐line carboplatin‐gemcitabine plus cyclic FMD in the context of the NCT03340935 trial with the OS of 76 consecutive aTNBC patients treated with carboplatin‐based chemotherapy alone at Fondazione IRCCS Istituto Nazionale dei Tumori. Multivariable Cox regression models were used to adjust the prognostic impact of FMD for other prognostic variables. Patients undergoing cyclic FMD in combination with carboplatin‐gemcitabine had better OS when compared to patients receiving chemotherapy alone (median OS 30.3 months, 95% CI 18‐NR, vs 17.2 months, 95% CI 15.3‐25.1, log‐rank P value .041). Multivariable analysis confirmed an association between FMD use and better OS (HR: 0.40; 95% CI: 0.19‐0.86; P = .019) also after propensity score‐based matching according to patient ECOG PS and the presence of de novo metastatic disease (HR: 0.41; 95% CI: 0.21‐0.83; P = .013). Cyclic FMD in combination with first‐line chemotherapy may improve clinical outcomes in aTNBC patients. Our study paves the way for conducting phase II trials to investigate if cyclic FMD can increase the antitumor activity/efficacy of chemotherapy or chemoimmunotherapy in patients with early‐stage TNBC or aTNBC.