Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others have proposed that some aspect of surgical tumor resection triggers the outgrowth of otherwise-dormant metastases, leading to the synchronous pattern of relapse. Clinical data cannot distinguish between these hypotheses, and previous experimental approaches have not provided clear answers. Such uncertainty hinders the development and application of therapeutic approaches that could potentially reduce early metastatic relapse. We describe an experimental model system that definitively links surgery and the subsequent wound-healing response to the outgrowth of tumor cells at distant anatomical sites. Specifically, we find that the systemic inflammatory response induced after surgery promotes the emergence of tumors whose growth was otherwise restricted by a tumor-specific T cell response. Furthermore, we demonstrate that perioperative anti-inflammatory treatment markedly reduces tumor outgrowth in this model, suggesting that similar approaches might substantially reduce early metastatic recurrence in breast cancer patients.

接受手术切除原发性乳腺肿瘤的患者面临转移复发的风险，该风险在手术后12至18个月急剧上升。乳腺癌早期转移性复发的原因一直存在争议，许多人将这些复发归因于疾病的自然进展。其他人提出，外科肿瘤切除的某些方面会触发原本休眠的转移灶的生长，从而导致同步复发。临床数据无法区分这些假设，并且以前的实验方法还没有提供明确的答案。这种不确定性阻碍了可能潜在地减少早期转移性复发的治疗方法的开发和应用。我们描述了一个实验模型系统，该系统明确地将手术与随后的伤口愈合反应联系到远处解剖部位的肿瘤细胞。具体而言，我们发现手术后诱导的全身性炎症反应促进了肿瘤的出现，否则其生长受到肿瘤特异性T细胞反应的限制。此外，我们证明围手术期抗炎治疗显着降低了该模型中的肿瘤生长，表明相似的方法可能会大大减少乳腺癌患者的早期转移复发。我们发现，手术后诱导的全身性炎症反应促进了肿瘤的出现，而肿瘤的生长受到肿瘤特异性T细胞反应的限制。此外，我们证明围手术期抗炎治疗显着降低了该模型中的肿瘤生长，表明相似的方法可能会大大减少乳腺癌患者的早期转移复发。我们发现，手术后诱导的全身性炎症反应促进了肿瘤的出现，而肿瘤的生长受到肿瘤特异性T细胞反应的限制。此外，我们证明围手术期抗炎治疗显着降低了该模型中的肿瘤生长，表明相似的方法可能会大大减少乳腺癌患者的早期转移复发。