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Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast
Tatsuya Yoshioka1, Mitsuchika Hosoda, Mitsugu Yamamoto
1Breast and Endocrine Surgery, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, 060-8648, Japan.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
It is necessary to establish additional strategies to improve survival for patients whose residual tumors show high Ki67 expression after neoadjuvant chemotherapy.