Skip to main content
Erschienen in: Breast Cancer 2/2015

01.03.2015 | Original Article

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

verfasst von: Tatsuya Yoshioka, Mitsuchika Hosoda, Mitsugu Yamamoto, Kazunori Taguchi, Kanako C. Hatanaka, Emi Takakuwa, Yutaka Hatanaka, Yoshihiro Matsuno, Hiroko Yamashita

Erschienen in: Breast Cancer | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012;19:1508–16.CrossRefPubMed Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012;19:1508–16.CrossRefPubMed
2.
Zurück zum Zitat Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22:1736–47.CrossRefPubMedCentralPubMed Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22:1736–47.CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat von Minckwitz G. Neoadjuvant chemotherapy in breast cancer-insights from the German experience. Breast Cancer. 2012;19:282–8.CrossRef von Minckwitz G. Neoadjuvant chemotherapy in breast cancer-insights from the German experience. Breast Cancer. 2012;19:282–8.CrossRef
4.
Zurück zum Zitat Houssami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012;48:3342–54.CrossRefPubMed Houssami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012;48:3342–54.CrossRefPubMed
5.
Zurück zum Zitat von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef
6.
Zurück zum Zitat Jones RL, Salter J, A’Hern R, Nerurkar A, Parton M, Reis-Filho JS, et al. Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat. 2010;119:315–23.CrossRefPubMed Jones RL, Salter J, A’Hern R, Nerurkar A, Parton M, Reis-Filho JS, et al. Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat. 2010;119:315–23.CrossRefPubMed
7.
Zurück zum Zitat Lips EH, Mulder L, de Ronde JJ, Mandjes IA, Vincent A, Vrancken Peeters MT, et al. Neoadjuvant chemotherapy in ER+ HER2− breast cancer: response prediction based on immunohistochemical and molecular characteristics. Breast Cancer Res Treat. 2012;131:827–36.CrossRefPubMed Lips EH, Mulder L, de Ronde JJ, Mandjes IA, Vincent A, Vrancken Peeters MT, et al. Neoadjuvant chemotherapy in ER+ HER2− breast cancer: response prediction based on immunohistochemical and molecular characteristics. Breast Cancer Res Treat. 2012;131:827–36.CrossRefPubMed
8.
Zurück zum Zitat Montagna E, Bagnardi V, Rotmensz N, Viale G, Pruneri G, Veronesi P, et al. Pathological complete response after preoperative systemic therapy and outcome: relevance of clinical and biologic baseline features. Breast Cancer Res Treat. 2010;124:689–99.CrossRefPubMed Montagna E, Bagnardi V, Rotmensz N, Viale G, Pruneri G, Veronesi P, et al. Pathological complete response after preoperative systemic therapy and outcome: relevance of clinical and biologic baseline features. Breast Cancer Res Treat. 2010;124:689–99.CrossRefPubMed
9.
Zurück zum Zitat Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010;11:174–83.CrossRefPubMed Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010;11:174–83.CrossRefPubMed
10.
Zurück zum Zitat Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30:3242–9.CrossRefPubMedCentralPubMed Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30:3242–9.CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat Burcombe R, Wilson GD, Dowsett M, Khan I, Richman PI, Daley F, et al. Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer. Breast Cancer Res. 2006;8:R31.CrossRefPubMedCentralPubMed Burcombe R, Wilson GD, Dowsett M, Khan I, Richman PI, Daley F, et al. Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer. Breast Cancer Res. 2006;8:R31.CrossRefPubMedCentralPubMed
12.
Zurück zum Zitat Jones RL, Salter J, A’Hern R, Nerurkar A, Parton M, Reis-Filho JS, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2009;116:53–68.CrossRefPubMed Jones RL, Salter J, A’Hern R, Nerurkar A, Parton M, Reis-Filho JS, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2009;116:53–68.CrossRefPubMed
13.
Zurück zum Zitat Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486.CrossRefPubMedCentralPubMed Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486.CrossRefPubMedCentralPubMed
14.
Zurück zum Zitat Matsubara N, Mukai H, Fujii S, Wada N. Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer. Breast Cancer Res Treat. 2013;137:203–12.CrossRefPubMed Matsubara N, Mukai H, Fujii S, Wada N. Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer. Breast Cancer Res Treat. 2013;137:203–12.CrossRefPubMed
15.
Zurück zum Zitat Kurosumi M, Akashi-Tanaka S, Akiyama F, Komoike Y, Mukai H, Nakamura S, et al. Histopathological criteria for assessment of therapeutic response in breast cancer (2007 version). Breast Cancer. 2008;15:5–7.CrossRefPubMed Kurosumi M, Akashi-Tanaka S, Akiyama F, Komoike Y, Mukai H, Nakamura S, et al. Histopathological criteria for assessment of therapeutic response in breast cancer (2007 version). Breast Cancer. 2008;15:5–7.CrossRefPubMed
16.
Zurück zum Zitat Yamashita H, Takahashi S, Ito Y, Yamashita T, Ando Y, Toyama T, et al. Predictors of response to exemestane as primary endocrine therapy in estrogen receptor-positive breast cancer. Cancer Sci. 2009;100:2028–33.CrossRefPubMed Yamashita H, Takahashi S, Ito Y, Yamashita T, Ando Y, Toyama T, et al. Predictors of response to exemestane as primary endocrine therapy in estrogen receptor-positive breast cancer. Cancer Sci. 2009;100:2028–33.CrossRefPubMed
17.
Zurück zum Zitat Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95.CrossRefPubMedCentralPubMed Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95.CrossRefPubMedCentralPubMed
18.
Zurück zum Zitat Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.CrossRefPubMed Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.CrossRefPubMed
19.
Zurück zum Zitat Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst. 2011;103:1656–64.CrossRefPubMedCentralPubMed Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst. 2011;103:1656–64.CrossRefPubMedCentralPubMed
20.
Zurück zum Zitat Piccart-Gebhart MJ. New developments in hormone receptor-positive disease. Oncologist. 2010;15(Suppl 5):18–28.CrossRefPubMed Piccart-Gebhart MJ. New developments in hormone receptor-positive disease. Oncologist. 2010;15(Suppl 5):18–28.CrossRefPubMed
21.
Zurück zum Zitat Endo Y, Toyama T, Takahashi S, Sugiura H, Yoshimoto N, Iwasa M, et al. High estrogen receptor expression and low Ki67 expression are associated with improved time to progression during first-line endocrine therapy with aromatase inhibitors in breast cancer. Int J Clin Oncol. 2011;16:512–8.CrossRefPubMed Endo Y, Toyama T, Takahashi S, Sugiura H, Yoshimoto N, Iwasa M, et al. High estrogen receptor expression and low Ki67 expression are associated with improved time to progression during first-line endocrine therapy with aromatase inhibitors in breast cancer. Int J Clin Oncol. 2011;16:512–8.CrossRefPubMed
22.
Zurück zum Zitat Viale G, Regan MM, Mastropasqua MG, Maffini F, Maiorano E, Colleoni M, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst. 2008;100:207–12.CrossRefPubMed Viale G, Regan MM, Mastropasqua MG, Maffini F, Maiorano E, Colleoni M, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst. 2008;100:207–12.CrossRefPubMed
23.
Zurück zum Zitat Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, Dumontet C, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27:1168–76.CrossRefPubMedCentralPubMed Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, Dumontet C, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27:1168–76.CrossRefPubMedCentralPubMed
24.
Zurück zum Zitat Penault-Llorca F, Andre F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V, et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009;27:2809–15.CrossRefPubMed Penault-Llorca F, Andre F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V, et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009;27:2809–15.CrossRefPubMed
Metadaten
Titel
Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer
verfasst von
Tatsuya Yoshioka
Mitsuchika Hosoda
Mitsugu Yamamoto
Kazunori Taguchi
Kanako C. Hatanaka
Emi Takakuwa
Yutaka Hatanaka
Yoshihiro Matsuno
Hiroko Yamashita
Publikationsdatum
01.03.2015
Verlag
Springer Japan
Erschienen in
Breast Cancer / Ausgabe 2/2015
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-013-0474-2

Weitere Artikel der Ausgabe 2/2015

Breast Cancer 2/2015 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.