肥胖促进三阴性乳腺癌（TNBC），迫切需要有效干预措施来打破肥胖-TNBC之间的联系。流行病学研究表明，胃旁路手术降低TNBC风险，但低脂饮食（LFD）或卡路里限制（CR）通过减重的证据有限或相互矛盾。使用肥胖驱动的TNBC小鼠模型，我们比较了垂直袖状胃切除术（VSG）与LFD、慢性CR和间歇CR的抗肿瘤效果。每种干预措施均导致体重和脂肪减少，并相对于肥胖小鼠抑制肿瘤生长（CR抑制效果最大）。使用多组学方法评估，VSG和CR方案以不同程度的方式产生了相似和独特的效果，逆转了肥胖相关转录、表观遗传、分泌物和微生物组变化，并恢复了抗肿瘤免疫力。因此，在TNBC小鼠模型中，肥胖手术和CR通过共享和独特的抗肿瘤机制逆转了肥胖驱动的肿瘤生长，CR优于VSG逆转肥胖的促癌效果。

Obesity promotes triple-negative breast cancer (TNBC), and effective interventions are urgently needed to break the obesity-TNBC link. Epidemiologic studies indicate that bariatric surgery reduces TNBC risk, while evidence is limited or conflicted for weight loss via low-fat diet (LFD) or calorie restriction (CR). Using a murine model of obesity-driven TNBC, we compared the antitumor effects of vertical sleeve gastrectomy (VSG) with LFD, chronic CR, and intermittent CR. Each intervention generated weight and fat loss and suppressed tumor growth relative to obese mice (greatest suppression with CR). VSG and CR regimens exerted both similar and unique effects, as assessed using multi-omic approaches, in reversing obesity-associated transcriptional, epigenetic, secretome, and microbiota changes and restoring antitumor immunity. Thus, in a murine model of TNBC, bariatric surgery and CR each reverse obesity-driven tumor growth via shared and distinct antitumor mechanisms, and CR is superior to VSG in reversing obesity's procancer effects.