Gump Frank E, Parmar Priyanka, Feldman Sheldon, Gupta Anjuli M
Department of Surgery, Columbia University, New York, NY, USA.
Department of Surgery, Montefiore Medical Center, Bronx, NY, USA.
Breast Cancer (Dove Med Press). 2024 Dec 17;16:973-980. doi: 10.2147/BCTT.S476416. eCollection 2024.
Early detection is a relative newcomer in medicine, with its efficacy relying not only on therapy but also on the availability of evidence supporting the advantage of treatment at an earlier stage. Late 19th century histologic evidence that cancer begins as a single primary focus and Halsted's centrifugal theory of stepwise spread (breast, regional nodes, and systemic distribution) provided the rationale for both en bloc surgery and the lifesaving benefit of early detection. Clinicians soon noticed exceptions to this ordered timeline, and pathologists identified histological features that questioned its primacy; however, Bernard Fisher spearheaded the initial challenge. His groundbreaking hypothesis that breast cancer was systemic from its inception was supported indirectly by the 3rd arm of National Surgical Adjuvant Breast and Bowel Project (NSABP) B04 and B06. These trials bolster his contention that a patient's fate was dependent on shed cells rather than the extent of the operation; however, the breast cancer wars of the 1970s focused on competing local treatments. When follow-up data revealed equivalent survival results, it established lumpectomy/radiation as equal to mastectomy, but overlooked Fisher's attack on Halsted's theory. Two mid-20th century medical innovations also played a role in the history of early detection: population-based screening by detecting cancer before it became clinically evident, and repurposing systemic treatment designed for metastatic recurrence into adjuvant chemotherapy. This review illustrates how these advances have led to the incremental acceptance of Fisher's hypothesis and recognition that invasive cancer cannot be equated with localized disease, regardless of how early it might be detected.
早期检测在医学领域是一个相对较新的概念,其有效性不仅依赖于治疗,还依赖于支持早期治疗优势的证据的可得性。19世纪末的组织学证据表明癌症始于单个原发灶,以及霍尔斯特德的逐步扩散的离心理论(乳房、区域淋巴结和全身扩散)为整块切除手术和早期检测的救命益处提供了理论依据。临床医生很快注意到了这个有序时间线的例外情况,病理学家也发现了质疑其首要地位的组织学特征;然而,伯纳德·费希尔率先发起了最初的挑战。他具有开创性的假设,即乳腺癌从一开始就是全身性的,这一假设得到了国家外科辅助乳腺和肠道项目(NSABP)B04和B06的第三组试验的间接支持。这些试验支持了他的观点,即患者的命运取决于脱落的细胞,而不是手术范围;然而,20世纪70年代的乳腺癌之战聚焦于相互竞争的局部治疗方法。当随访数据显示出相同的生存结果时,保乳手术/放疗被确立为与乳房切除术等效,但却忽略了费希尔对霍尔斯特德理论的抨击。20世纪中叶的两项医学创新也在早期检测的历史中发挥了作用:通过在癌症临床显现之前进行检测的基于人群的筛查,以及将针对转移性复发设计的全身治疗重新用于辅助化疗。这篇综述阐述了这些进展是如何导致费希尔的假设逐渐被接受,以及人们认识到浸润性癌不能等同于局限性疾病,无论它被检测得有多早。