RESPONDER AI - Reliable exclusion of residual cancer after neoadjuvant systemic treatment for women with breast cancer by an intelligent vacuum-assisted biopsy

近年来，新辅助全身治疗已获得临床意义，目前推荐用于三阴性、HER2阳性或（高增殖）B腔乳腺癌的妇女。新辅助全身治疗（NAST）的使用越来越多，治疗方案的疗效也越来越好，这使得越来越多的患者在手术后没有任何可检测到的残留肿瘤（病理完全缓解、pCR、ypT0和ypN0）。对于这些对NAST有特殊反应的患者，手术可能是过度治疗：所有局部肿瘤已经被NAST根除了。保乳手术（BCS）与前哨淋巴结活检（SLNB）是目前的标准护理。使用NAST代替辅助治疗促进了更多的BCS而不是乳房切除术，生存率相同。尽管与其他肿瘤手术相比，BCS是一种低发病率的手术，但它会引起与患者相关的发病率：(1)大约30%的BCS和SLNB患者在术后2年报告中度持续疼痛(2)患者报告的术后8年生活质量下降与BCS或乳房切除术患者相当。因此，尽管被诊断患有乳腺癌的妇女比以往任何时候都更有可能在诊断后存活下来，但许多人必须与治疗对生活质量的长期影响作斗争。鉴于ypT0率的增加，目前的研究评估了替代BCS的诊断程序，以确定这些对NAST有特殊反应的达到ypT0的患者。为此，我们的研究小组开发了一种所谓的智能真空辅助活检（VAB）。诊断智能VAB的使用可能会在未来为这些女性省去诊断性腋窝和乳房手术。量化这一主题的相关性，我们估计约有10%的乳腺癌患者可能在未来免于手术。在这项多中心、前瞻性、验证性试验中，我们旨在证明智能VAB与手术一样准确，可靠地排除NAST术后残留肿瘤。如果能够获得这一证据，后续的随机对照试验可能会评估这些对NAST有特殊反应的患者不进行乳房和腋窝手术的长期肿瘤学安全性。因此，这项试验可能会导致大约10%的乳腺癌女性的临床实践发生根本性的变化。

In recent years, neoadjuvant systemic treatments have gained clinical relevance and are nowadays recommended for women with triple-negative, HER2 positive, or (high proliferative) Luminal B breast cancers. Increasing use of neoadjuvant systemic treatment (NAST) and improved efficacy of treatment regimens have led to increasing numbers of patients without any detectable residual cancer upon surgery (pathologic complete response, pCR, ypT0 and ypN0). For these exceptional responders to NAST, surgery may be overtreatment: all local tumor has already been eradicated by NAST. Breast conserving surgery (BCS) with Sentinel Lymph Node Biopsy (SLNB) is the current standard of care. The use of NAST instead of adjuvant treatment has facilitated more BCS instead of mastectomy with equal survival. Although BCS is a low morbidity procedure compared to other oncologic surgeries, it causes morbidity relevant to patients: (1) About 30% of patients undergoing BCS and SLNB report moderate, persistent pain two years after surgery (2) the reduction in patient-reported quality of life up to 8 years after surgery is comparable between patients undergoing BCS or mastectomy. Thus, although women diagnosed with breast cancer are more likely than ever to survive their diagnosis, many must contend with the long-term effects of their treatment on quality of life. In the light of increasing ypT0 rates, current research evaluates alternative diagnostic procedures than BCS to identify these exceptional responders to NAST who achieve ypT0. For this purpose, our research group has developed a so-called intelligent vacuum-assisted biopsy (VAB). The use of a diagnostic intelligent VAB may potentially spare these women diagnostic axillary and breast surgery in the future. Quantifying the relevance of this topic, we estimate that about 10% of all breast cancer patients might be spared surgery in the future. In this multicenter, prospective, confirmatory trial we aim to prove that an intelligent VAB is as accurate as surgery to reliably exclude residual cancer after NAST. If this evidence could be obtained, a subsequent randomized controlled trial may evaluate the long-term oncologic safety of omitting breast and axillary surgery for these exceptional responders to NAST. The trial could therefore lead to a fundamental change of clinical practice for about 10% of all women with breast cancer.