Galli Giulia, Bregni Giacomo, Cavalieri Stefano, Porcu Luca, Baili Paolo, Hade Amash, Di Salvo Francesca, Sant Milena, Agresti Roberto, Gennaro Massimiliano, Folli Secondo, De Santis Maria C, Paolini Biagio, Carcangiu Maria L, de Braud Filippo, Di Cosimo Serena
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Unit of Medical Oncology 1, IRCCS AOU San Martino-IST, Genova, Italy.
Breast Care (Basel). 2017 Dec;12(6):391-394. doi: 10.1159/000479582. Epub 2017 Dec 12.
Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy.
We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions.
Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation.
The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.
新辅助化疗（NAC）后的乳腺癌（BC）表型尚未得到广泛描述，关于原发性肿瘤激素受体、HER2和Ki-67的表达是否因化疗而改变的数据也很少。
我们分析了2010年1月至2015年3月期间在本机构接受蒽环类/紫杉类NAC治疗的所有BC患者的标本（n = 325）。在NAC前后的标本中测定雌激素受体（ER）、孕激素受体（PR）、HER2和Ki-67的表达。采用McNemar检验比较配对比例。
在NAC后有残留疾病的患者中，基底样表型在管腔A型、管腔B型、HER2阳性和三阴性中分别有44例、111例、74例和27例。PR阳性肿瘤从初始活检样本中的68.0%降至手术标本中的61.7%（p = 0.024）。Ki-67<20%的比例从23.6%增加到45%（p<0.001）。ER表达在5%的病例中从阳性变为阴性，在16.7%的病例中从阴性变为阳性。总体而言，30%的病例发生了亚型改变，其中79%向管腔分化。
向管腔表型的转变提示NAC有某种内分泌效应。我们的发现重新引发了对联合细胞毒性化疗与同步或序贯内分泌治疗（单独或与靶向药物联合）的兴趣。
