Medical Oncology

, Volume 29, Issue 5, pp 3222–3231 | Cite as

Pre-treatment hormonal receptor status and Ki67 index predict pathologic complete response to neoadjuvant trastuzumab/taxanes but not disease-free survival in HER2-positive breast cancer patients

  • Guo-Chun Zhang
  • Xue-Ke Qian
  • Zi-Bai Guo
  • Chong-Yang Ren
  • Meng Yao
  • Xue-Rui Li
  • Kun Wang
  • Jian Zu
  • Ning LiaoEmail author
Original Paper


Trastuzumab-containing neoadjuvant chemotherapy achieves a pathologic complete response (pCR) rate of about 40 % in HER2-positive breast cancers, and pCR predicts better survival. A cohort of 102 consecutive Chinese HER2-positive stage II/III patients with neoadjuvant trastuzumab/taxanes were retrospectively analyzed, to evaluate the role of hormonal receptor (HR) status and Ki67 index, along with other parameters, in pCR and survival prediction. pCR rate of the cohort was 44.1 % (45/102). Fifty-three patients were HR-positive and 49 were HR-negative. Median Ki67 index was 40 %, and 49 patients had a high Ki67 index (>40 %) whereas 53 had a low Ki67 index (≤40 %). HR status and Ki67 index were confirmed as the only two parameters associated with pCR in multivariate analysis (hazard ratio = 2.952; 95 % CI, 1.227–7.105; P = 0.016 for HR status and hazard ratio = 2.583, 95 % CI 1.107–6.026, P = 0.028 for Ki67 index). Patients with coexisting HR-negative and high Ki67 index had higher pCR rate (69.2 %), compared to those with either HR-negative alone or high Ki67 alone (hazard ratio = 3.038; 95 % CI, 1.102–8.372; P = 0.029), and to those with coexisting HR-positive and low Ki67 index as well (hazard ratio = 7.071; 95 % CI, 2.150–23.253; P = 0.001). In a median follow-up duration of 25.9 months, 11 disease-free survival events (DFS) were recorded. pCR predicted better DFS (log rank P = 0.018) and was the only significant factor in Cox regression analysis (hazard ratio = 0.184; 95 % CI, 0.038–0.893; P = 0.036). Our study indicates that HR status and Ki67 index are predictors for pCR but not for DFS in HER2-positive patients with neoadjuvant trastuzumab/taxanes, which deserves further investigations.


HER2-positive Breast cancer Trastuzumab Neoadjuvant chemotherapy Pathologic complete response Disease-free survival 



Human epidermal growth factor receptor 2


Hormonal receptor


Estrogen receptor


Progesterone receptor


Disease-free survival


Overall survival


Pathologic complete response


Partial response


Stable disease


Progressed disease


Ductal carcinoma in situ



This work has been supported by two grants encoded as 81001189 and 81071851 from the National Natural Science Foundation of China. We thanked Dr. Xu Fang-Ping for performing the Ki67 re-examination in our study as well as for kindly providing us the delicate pathologic photos.

Conflict of interest



  1. 1.
    Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5(1):63–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Guarneri V, Barbieri E, Dieci MV, Piacentini F, Conte P. Anti-HER2 neoadjuvant and adjuvant therapies in HER2 positive breast cancer. Cancer Treat Rev. 2010;36(Suppl 3):S62–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Bullock K, Blackwell K. Clinical efficacy of taxane–trastuzumab combination regimens for HER-2-positive metastatic breast cancer. Oncologist. 2008;13(5):515–25.PubMedCrossRefGoogle Scholar
  5. 5.
    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(8):1736–47.PubMedCrossRefGoogle Scholar
  6. 6.
    Chang HR. Trastuzumab-based neoadjuvant therapy in patients with HER2-positive breast cancer. Cancer. 2010;116(12):2856–67.PubMedCrossRefGoogle Scholar
  7. 7.
    Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375(9712):377–84.PubMedCrossRefGoogle Scholar
  8. 8.
    Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28(12):2024–31.PubMedCrossRefGoogle Scholar
  9. 9.
    Untch M, Fasching PA, Konecny GE, Hasmuller S, Lebeau A, Kreienberg R, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29(25):3351–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Precht LM, Lowe KA, Atwood M, Beatty JD. Neoadjuvant chemotherapy of breast cancer: tumor markers as predictors of pathologic response, recurrence, and survival. Breast J. 2010;16(4):362–8.PubMedGoogle Scholar
  11. 11.
    Huober J, von Minckwitz G, Denkert C, Tesch H, Weiss E, Zahm DM, et al. Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat. 2010;124(1):133–40.PubMedCrossRefGoogle Scholar
  12. 12.
    Fasching PA, Heusinger K, Haberle 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(1):486.PubMedCrossRefGoogle Scholar
  13. 13.
    Wang Y, Yin Q, Yu Q, Zhang J, Liu Z, Wang S, et al. A retrospective study of breast cancer subtypes: the risk of relapse and the relations with treatments. Breast Cancer Res Treat. 2011;130(2):489–98.PubMedCrossRefGoogle Scholar
  14. 14.
    Liao N, Zhang GC, Liu YH, Li XR, Yao M, Xu FP, et al. HER2-positive status is an independent predictor for coexisting invasion of ductal carcinoma in situ of the breast presenting extensive DCIS component. Pathol Res Pract. 2011;207(1):1–7.PubMedCrossRefGoogle Scholar
  15. 15.
    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(1):53–68.PubMedCrossRefGoogle Scholar
  16. 16.
    Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American society of clinical oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287–312.PubMedCrossRefGoogle Scholar
  17. 17.
    Burstein HJ, Harris LN, Gelman R, Lester SC, Nunes RA, Kaelin CM, et al. Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study. J Clin Oncol. 2003;21(1):46–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Chevallier B, Roche H, Olivier JP, Chollet P, Hurteloup P. Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in a high histologic response rate. Am J Clin Oncol. 1993;16(3):223–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, Aura C, De Azambuja E, et al. First results of the NeoALTTO trial (BIG 01-06/EGF 106903): a phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. (meeting abstract) Abstract S3-3 of the 2010 San Antonio Breast Cancer Symposium. (
  20. 20.
    Gianni L, Pienkowski T, Im Y-H, Roman L, Tseng L-M, Liu M-C, et al. Neoadjuvant Pertuzumab (P) and Trastuzumab (H): antitumor and safety analysis of a randomized phase II study (‘NeoSphere’). (meeting abstract) Abstract S3-2 of the 2010 San Antonio Breast Cancer Symposium. (
  21. 21.
    Querzoli P, Albonico G, Ferretti S, Rinaldi R, Magri E, Indelli M, et al. MIB-1 proliferative activity in invasive breast cancer measured by image analysis. J Clin Pathol. 1996;49(11):926–30.PubMedCrossRefGoogle Scholar
  22. 22.
    de Azambuja E, Cardoso F, De Castro G Jr, Colozza M, Mano MS, Durbecq V, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96(10):1504–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Stuart-Harris R, Caldas C, Pinder SE, Pharoah P. Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast. 2008;17(4):323–34.PubMedCrossRefGoogle Scholar
  24. 24.
    Darb-Esfahani S, Loibl S, Muller BM, Roller M, Denkert C, Komor M, et al. Identification of biology-based breast cancer types with distinct predictive and prognostic features: role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/taxane-based chemotherapy. Breast Cancer Res. 2009;11(5):R69.PubMedCrossRefGoogle Scholar
  25. 25.
    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. 2009;119(2):315–23.PubMedCrossRefGoogle Scholar
  26. 26.
    Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101(10):736–50.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Guo-Chun Zhang
    • 1
  • Xue-Ke Qian
    • 1
    • 2
  • Zi-Bai Guo
    • 1
    • 2
  • Chong-Yang Ren
    • 1
    • 3
  • Meng Yao
    • 1
  • Xue-Rui Li
    • 1
  • Kun Wang
    • 1
  • Jian Zu
    • 1
  • Ning Liao
    • 1
    Email author
  1. 1.Department of Breast Cancer, Cancer Center, Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouChina
  2. 2.Shantou University Medical SchoolShantouChina
  3. 3.Southern Medical UniversityGuangzhouChina

Personalised recommendations