Faverly D R, Hendriks J H, Holland R
Department of Pathology, Radboud University Hospital, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Cancer. 2001 Feb 15;91(4):647-59. doi: 10.1002/1097-0142(20010215)91:4<647::aid-cncr1053>3.0.co;2-z.
Clinical trials established the value of breast-conserving treatment (BCT) including the macroscopic removal of the tumor followed by local radiation therapy (RT) for Stage I and II invasive carcinomas. The occurrence of local tumor recurrence is related to the extent and multifocality of the tumor. Various studies aim to identify those tumors that could be proper candidates for conventional BCT. Furthermore, recent studies have focused on the identification of tumors that may be treated by breast-conserving surgery alone without RT. Small, localized tumors theoretically should be the potential candidates for this type of treatment. The mammographic and pathologic criteria for the identification of tumors with limited extent are not yet established; furthermore, the optimal extent of the surgical excision and the method for margin examination are controversial.
Surgical breast-conserving procedures were simulated in a review of 135 mastectomy specimens of patients treated for an invasive carcinoma (> or = 4 cm in size, all pathologic types except invasive lobular carcinoma) who were theoretically eligible for conservative treatment. Tumor spread including possible multifocality and multicentricity was studied by the technique of correlated specimen radiography and pathology. Breast carcinoma of limited extent (BCLE), the proper tumor profile for BCT, was defined as having no invasive carcinoma, ductal carcinoma in situ, and lymphatic emboli foci beyond 1 cm from the edge of the dominant mass.
Fifty-three percent of the patients in this series had a BCLE. No statistically significant relation was found between BCLE and patient age, pathologic size, type and grade of the tumor, lymph node status, mode of detection, and mammographic aspect of the index tumor. Based on mammography, the absence of calcification or tumor density beyond the edge of index tumor appears to be the best predictor for BCLE (P < 0.0001). A 1-cm microscopically tumor free margin as the outer rim of a macroscopic surgical margin of 2 cm gives the best positive predictive value based on pathology (P < 0.0001). By applying the above conditions, 72 of the 135 cancers were identified as being potential BCLE cases in this series. However, whereas 64 of these 72 tumors (89%) were correctly identified as being true BCLE, 8 (11%) were erroneously identified as such (non-BCLE cases), having "residual" tumor foci beyond 2 cm from the edge of the dominant tumor.
We conclude, that approximately 50% of invasive ductal carcinomas may have limited extent. The accuracy of identifying this group of cancers, the proper candidates for BCT, by applying state-of-the-art mammography and pathology may be as high as 90%. A subset of these tumors might represent the potential candidates for treatment with surgery alone without RT. As a result, the routine application of BCT complemented by RT would have led to the overtreatment of 89% of the patients with a BCLE in this series; conversely, 11% of the tumors may have recurred without the use of RT. Considering that these conclusions are based on a theoretic morphologic model, further clinical studies with facilities for high quality team approach in diagnosis and therapy are needed to evaluate the impact of BCLE on BCT strategies. The results of this study should not justify the withholding of RT outside the context of clinical trials.
临床试验证实了保乳治疗（BCT）的价值，包括对I期和II期浸润性癌进行肿瘤的宏观切除，随后进行局部放射治疗（RT）。局部肿瘤复发的发生与肿瘤的范围和多灶性有关。各种研究旨在确定哪些肿瘤可能是传统保乳治疗的合适候选者。此外，最近的研究集中在识别那些可能仅通过保乳手术而无需放疗即可治疗的肿瘤。理论上，小的局限性肿瘤应该是这类治疗的潜在候选者。目前尚未确立用于识别范围有限肿瘤的乳腺X线摄影和病理标准；此外，手术切除的最佳范围和切缘检查方法仍存在争议。
对135例接受浸润性癌（大小≥4cm，除浸润性小叶癌外的所有病理类型）治疗的患者的乳房切除标本进行回顾，模拟保乳手术。通过相关标本放射摄影和病理学技术研究肿瘤扩散情况，包括可能的多灶性和多中心性。将范围有限的乳腺癌（BCLE）定义为距主要肿块边缘1cm以外无浸润性癌、原位导管癌和淋巴栓子灶，这是保乳治疗的合适肿瘤特征。
本系列中53%的患者患有BCLE。未发现BCLE与患者年龄、肿瘤的病理大小、类型和分级、淋巴结状态、检测方式以及索引肿瘤的乳腺X线摄影表现之间存在统计学显著关系。基于乳腺X线摄影，索引肿瘤边缘以外无钙化或肿瘤密度似乎是BCLE的最佳预测指标（P<0.0001）。基于病理学，以2cm的宏观手术切缘的外边缘为1cm的显微镜下无肿瘤切缘具有最佳的阳性预测价值（P<0.0001）。应用上述条件，本系列135例癌症中有72例被确定为潜在的BCLE病例。然而，在这72例肿瘤中，有64例（89%）被正确识别为真正的BCLE，8例（11%）被错误识别，在距主要肿瘤边缘2cm以外有“残留”肿瘤灶（非BCLE病例）。
我们得出结论，大约50%的浸润性导管癌可能范围有限。通过应用先进的乳腺X线摄影和病理学来识别这组癌症（保乳治疗的合适候选者）的准确性可能高达90%。这些肿瘤的一个子集可能代表仅通过手术而无需放疗即可治疗的潜在候选者。因此，在本系列中，常规应用保乳治疗并辅以放疗会导致89%患有BCLE的患者受到过度治疗；相反，11%的肿瘤可能在未使用放疗的情况下复发。鉴于这些结论是基于理论形态学模型，需要进一步开展高质量团队诊断和治疗设施的临床研究，以评估BCLE对保乳治疗策略的影响。本研究结果不应成为在临床试验背景之外拒绝放疗的理由。
