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Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer

Breast Cancer volume 22, pages 185–191 (2015)Cite this article

Abstract

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.

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Abbreviations

ER:

Estrogen receptor

PgR:

Progesterone receptor

HER2:

Human epidermal growth factor receptor type 2

ER+:

Estrogen receptor-positive

ER−:

Estrogen receptor-negative

HER2+:

HER2-positive

HER2−:

HER2-negative

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

IHC:

Immunohistochemistry

Ki67 LI:

Ki67 labeling index

pCR:

Pathologic complete response

cCR:

Clinical complete response

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Conflict of interest

All authors have no conflict of interest to disclose.

Author information

Affiliations

  1. Breast and Endocrine Surgery, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, 060-8648, Japan

    Tatsuya Yoshioka, Mitsuchika Hosoda, Mitsugu Yamamoto, Kazunori Taguchi & Hiroko Yamashita

  2. Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Tatsuya Yoshioka

  3. Department of Surgical Pathology, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, 060-8648, Japan

    Kanako C. Hatanaka, Emi Takakuwa, Yutaka Hatanaka & Yoshihiro Matsuno

  4. Research Division of Companion Diagnostics, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, 060-8648, Japan

    Emi Takakuwa, Yutaka Hatanaka & Yoshihiro Matsuno

Authors
  1. Tatsuya Yoshioka
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  2. Mitsuchika Hosoda
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  3. Mitsugu Yamamoto
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  4. Kazunori Taguchi
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  5. Kanako C. Hatanaka
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  6. Emi Takakuwa
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  7. Yutaka Hatanaka
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  8. Yoshihiro Matsuno
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  9. Hiroko Yamashita
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Corresponding author

Correspondence to Hiroko Yamashita.

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Yoshioka, T., Hosoda, M., Yamamoto, M. et al. Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer. Breast Cancer 22, 185–191 (2015). https://doi.org/10.1007/s12282-013-0474-2

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  • DOI: https://doi.org/10.1007/s12282-013-0474-2

Keywords

  • Breast cancer
  • Neoadjuvant chemotherapy
  • Pathologic complete response
  • Ki67