Bottini A, Berruti A, Brizzi M P, Bersiga A, Generali D, Allevi G, Aguggini S, Bolsi G, Bonardi S, Tondelli B, Vana F, Tampellini M, Alquati P, Dogliotti L
Breast Unit and Anatomia Patologica Azienda Ospedaliera Istituti Ospitalieri, Cremona, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Oncologia Medica, Azienda Ospedaliera San Luigi, Orbassano, Italy.
Endocr Relat Cancer. 2005 Jun;12(2):383-92. doi: 10.1677/erc.1.00945.
This study was designed to address whether simultaneous primary chemo-hormonal therapy provides additional activity compared with chemotherapy alone in breast cancer patients with operable or locally advanced disease. Between January 1997 and January 2002, 211 consecutive patients with T2-4, N0-1, M0 breast cancer were randomized to receive either epirubicin alone (EPI) or epirubicin plus tamoxifen (EPI-TAM). Ki67 expression was evaluated immunohistochemically in tumor specimens obtained before chemotherapy by incision biopsy and at definitive surgery. Tumor shrinkage of >50% was obtained in 76% of patients randomized in the EPI arm and 81.9% of patients randomized in the EPI-TAM arm (not significant). The corresponding rates of clinical and pathological complete response were 20.2 and 21.9% (not significant), and 4.8 and 6.7% (not significant), respectively. Pathologically complete response was more frequently observed in estrogen receptor (ER)-negative (ER-) tumors (P=0.04) and correlated with elevated baseline Ki67 expression (P<0.01). Both EPI and EPI-TAM treatments resulted in a significant reduction in Ki67 expression, either in overall patients (P=0.000) or in patients with ER+ breast cancer (P=0.000). The reduction in Ki67 immunostaining in the EPI-TAM arm was greater than in the EPI arm, leading to a lower Ki67 expression at post-operative residual histology (P=0.0041). The addition of tamoxifen to epirubicin chemotherapy did not improve the response rate but led to a significantly higher reduction in the Ki67 expression. Baseline elevated Ki67 expression and the ER- status were both associated with a greater chance of obtaining a pathological complete response at residual histology.
本研究旨在探讨对于可手术或局部晚期乳腺癌患者，同步进行的原发性化疗联合激素治疗与单纯化疗相比是否具有额外的疗效。1997年1月至2002年1月期间，211例连续的T2-4、N0-1、M0乳腺癌患者被随机分为两组，分别接受单纯表柔比星（EPI）治疗或表柔比星联合他莫昔芬（EPI-TAM）治疗。通过手术切取活检在化疗前获取肿瘤标本，并在根治性手术时对肿瘤标本进行免疫组织化学评估Ki67表达。EPI组76%的随机分组患者和EPI-TAM组81.9%的随机分组患者实现了>50%的肿瘤缩小（无显著差异）。临床和病理完全缓解的相应比例分别为20.2%和21.9%（无显著差异），以及4.8%和6.7%（无显著差异）。在雌激素受体（ER）阴性（ER-）肿瘤中更常观察到病理完全缓解（P=0.04），且与基线Ki67表达升高相关（P<0.01）。EPI和EPI-TAM治疗均导致Ki67表达显著降低，无论是总体患者（P=0.000）还是ER+乳腺癌患者（P=0.000）。EPI-TAM组中Ki67免疫染色的降低幅度大于EPI组，导致术后残留组织学中的Ki67表达更低（P=0.0041）。在表柔比星化疗中添加他莫昔芬并未提高缓解率，但导致Ki67表达显著降低。基线Ki67表达升高和ER-状态均与残留组织学中获得病理完全缓解的可能性更大相关。
