Kuerer H M, Newman L A, Buzdar A U, Dhingra K, Hunt K K, Buchholz T A, Binkley S M, Strom E A, Ames F C, Ross M I, Feig B W, McNeese M D, Hortobagyi G N, Singletary S E
Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer J Sci Am. 1998 Jul-Aug;4(4):230-6.
Neoadjuvant chemotherapy is becoming the standard of care for locally advanced breast cancer. This study was performed to determine whether pathologic primary tumor response to neoadjuvant chemotherapy might predict axillary lymph node status and so be used to identify patients in whom surgery could be effectively limited to biopsy of the previous primary tumor site without axillary dissection.
Between 1992 and 1996, 170 consecutive patients with locally advanced breast cancer were treated in a prospective trial with four preoperative cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Disease was staged before initiation of preoperative chemotherapy and before surgery. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed first, followed by postoperative chemotherapy and radiation therapy of the breast (or chest wall) and regional lymphatics. Patient and tumor characteristics associated with complete versus incomplete pathologic primary tumor response to neoadjuvant chemotherapy and correlation between primary breast tumor pathologic response and axillary lymph node status found at surgery were analyzed.
Of 156 evaluable patients, 30 patients (19%) had primary breast tumors that were completely eliminated after induction chemotherapy based on histologic assessment. Nineteen of those 30 patients (63%) had negative axillary lymph nodes at dissection, compared with 13 patients (33%) of the 40 who had a near-complete pathologic primary tumor response (< or = 1 cm3 remaining) and only 15 patients (17%) of the 86 who had > 1 cm3 tumor remaining in the pathology specimen of the breast primary. Of the 22 patients with a complete pathologic response in the breast and a clinically negative axilla after induction chemotherapy, axillary dissection revealed positive lymph nodes in four. These four patients had only one or two positive lymph nodes.
Because initial clinical regression of primary tumor with neoadjuvant chemotherapy is considered an excellent prognostic indicator and because patients with locally advanced breast cancer routinely receive local and regional radiation treatment followed by additional chemotherapy, the role of breast and axillary surgery has been questioned. In this study, a complete pathologic response of the primary tumor to induction chemotherapy is highly predictive of negative axillary lymph node status. Therefore, axillary lymph node dissection may be omitted in certain subsets of patients who have a biopsy-proven complete pathologic response in the primary tumor and a clinical negative axillary examination. Further prospective, randomized investigation is needed to confirm this finding.
新辅助化疗正成为局部晚期乳腺癌的标准治疗方法。本研究旨在确定新辅助化疗后原发性肿瘤的病理反应是否可预测腋窝淋巴结状态，从而用于识别那些手术可有效局限于先前原发性肿瘤部位活检而无需腋窝清扫的患者。
1992年至1996年间，170例连续的局部晚期乳腺癌患者参加了一项前瞻性试验，接受四个周期的术前5-氟尿嘧啶、阿霉素和环磷酰胺治疗。在术前化疗开始前及手术前对疾病进行分期。首先进行腋窝淋巴结清扫的节段性切除或改良根治性乳房切除术，随后进行乳房（或胸壁）及区域淋巴结的术后化疗和放疗。分析了与新辅助化疗后原发性肿瘤病理反应完全或不完全相关的患者和肿瘤特征，以及手术时原发性乳腺肿瘤病理反应与腋窝淋巴结状态之间的相关性。
在156例可评估患者中，30例（19%）患者的原发性乳腺肿瘤在诱导化疗后根据组织学评估完全消除。这30例患者中有19例（63%）在清扫时腋窝淋巴结阴性，相比之下，40例原发性肿瘤病理反应接近完全（残留≤1 cm³）的患者中有13例（33%）腋窝淋巴结阴性，而86例乳腺原发性病理标本中残留肿瘤＞1 cm³的患者中只有15例（17%）腋窝淋巴结阴性。在诱导化疗后乳房病理反应完全且临床腋窝阴性的22例患者中，腋窝清扫发现4例淋巴结阳性。这4例患者只有一两个阳性淋巴结。
由于新辅助化疗后原发性肿瘤的初始临床退缩被认为是一个良好的预后指标，并且由于局部晚期乳腺癌患者常规接受局部和区域放疗，随后进行额外化疗，乳房和腋窝手术的作用受到质疑。在本研究中，原发性肿瘤对诱导化疗的完全病理反应高度预测腋窝淋巴结阴性状态。因此，对于原发性肿瘤经活检证实病理反应完全且临床腋窝检查阴性的某些患者亚组，可能无需进行腋窝淋巴结清扫。需要进一步的前瞻性随机研究来证实这一发现。
