Yoshioka Tatsuya, Hosoda Mitsuchika, Yamamoto Mitsugu, Taguchi Kazunori, Hatanaka Kanako C, Takakuwa Emi, Hatanaka Yutaka, Matsuno Yoshihiro, Yamashita Hiroko
Breast and Endocrine Surgery, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, 060-8648, Japan.
Breast Cancer. 2015 Mar;22(2):185-91. doi: 10.1007/s12282-013-0474-2. Epub 2013 May 5.
Recent studies have indicated that response to chemotherapy and the prognostic impact of a pathologic complete response (pCR) after neoadjuvant chemotherapy differ among breast cancer subtypes.
Women with Stage I to III breast cancer treated with anthracycline and taxane-based neoadjuvant chemotherapy (four cycles of docetaxel every 3 weeks followed by four cycles of FEC every 3 weeks) between 2006 and 2011 were retrospectively analyzed. Trastuzumab was concurrently added to docetaxel for HER2-positive breast cancer. Expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 was examined by immunohistochemistry in pre- and post-treatment specimens. Predictive factors for neoadjuvant chemotherapy and prognosis were analyzed by breast cancer subtype.
Of 64 patients, 30 (47 %) were ER-positive (ER+) HER2-negative (HER2-), including eight as luminal A (Ki67 labeling index (LI) <14 %) and 22 as luminal B (Ki67 LI ≥ 14 %) subtypes, 11 (17 %) were ER+ HER2-positive (HER2+), 12 (19 %) were ER-negative (ER-) HER2+, and 11 (17 %) were ER- HER2-. The clinical response rates were significantly higher in luminal B, ER+ HER2+, and ER- HER2+ subtypes compared with luminal A subtype. Patients whose tumors contained high Ki67 expression effectively responded to neoadjuvant chemotherapy. Ki67 LI was a predictive marker for pCR, and all patients whose tumors achieved pCR are currently disease-free. Furthermore, high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free and overall survival regardless of subtype.
It is necessary to establish additional strategies to improve survival for patients whose residual tumors show high Ki67 expression after neoadjuvant chemotherapy.
近期研究表明，乳腺癌各亚型对化疗的反应以及新辅助化疗后病理完全缓解（pCR）对预后的影响有所不同。
对2006年至2011年间接受蒽环类和紫杉类新辅助化疗（每3周一次多西他赛共4个周期，随后每3周一次FEC共4个周期）的Ⅰ至Ⅲ期乳腺癌女性患者进行回顾性分析。对于HER2阳性乳腺癌，曲妥珠单抗与多西他赛同时使用。通过免疫组织化学检测治疗前和治疗后标本中雌激素受体（ER）、孕激素受体（PgR）、HER2和Ki67的表达。按乳腺癌亚型分析新辅助化疗的预测因素和预后。
64例患者中，30例（47%）为ER阳性（ER+）HER2阴性（HER2-），其中8例为腔面A型（Ki67标记指数（LI）<14%），22例为腔面B型（Ki67 LI≥14%）；11例（17%）为ER+HER2阳性（HER2+）；12例（19%）为ER阴性（ER-）HER2+；11例（17%）为ER-HER2-。与腔面A型相比，腔面B型、ER+HER2+型和ER-HER2+型的临床缓解率显著更高。肿瘤Ki67表达高的患者对新辅助化疗有效反应。Ki67 LI是pCR的预测标志物，所有肿瘤达到pCR的患者目前均无病生存。此外，无论亚型如何，治疗后肿瘤中高Ki67表达与无病生存期和总生存期差密切相关。
有必要制定额外策略以提高新辅助化疗后残留肿瘤Ki67表达高的患者的生存率。
