Annals of Surgical Oncology

, Volume 21, Issue 10, pp 3317–3323 | Cite as

Tumor Response Ratio Predicts Overall Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

  • Marian Miller
  • Rebecca A. Ottesen
  • Joyce C. Niland
  • Laura Kruper
  • Steven L. Chen
  • Courtney VitoEmail author
Breast Oncology



Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods.


Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I–III breast cancer who had NAC and pretreatment imaging at City of Hope (1997–2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0–0.4 (strong partial response, SPR), TRR > 0.4–1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan–Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders.


There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016).


TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.


Overall Survival National Comprehensive Cancer Network Pathologic Stage National Comprehensive Cancer Network Residual Cancer Burden 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Nicola Solomon, PhD, for editorial assistance.


The authors declare no conflict of interest.


  1. 1.
    Kaufmann M, von Minckwitz G, Bear HD, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives, 2006. Ann Oncol. 2007;18:1927–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Edge SB, Compton CC, Fritz AG, et al. American Joint Committee on Cancer (AJCC) cancer staging manual. 7th ed. Chicago: Springer; 2010.Google Scholar
  3. 3.
    Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460–9.PubMedGoogle Scholar
  4. 4.
    Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Jeruss JS, Mittendorf EA, Tucker SL, et al. Staging of breast cancer in the neoadjuvant setting. Cancer Res. 2008;68:6477–81.PubMedCrossRefGoogle Scholar
  6. 6.
    Weeks JC. Outcomes assessment in the NCCN. Oncology (Williston Park). 1997;11(11A):137–40.PubMedGoogle Scholar
  7. 7.
    Weeks J. Outcomes assessment in the NCCN: 1998 update. Oncology (Williston Park). 1999;13(5A):69–71.PubMedGoogle Scholar
  8. 8.
    Niland JC. NCCN outcomes research database: data collection via the Intranet. Oncology (Williston Park). 2000;14(11A):100–3.PubMedGoogle Scholar
  9. 9.
    von Minckwitz G, Untch M, Blohmer JU, 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.CrossRefGoogle Scholar
  10. 10.
    Chollet P, Amat S, Cure H, et al. Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer. 2002;86:1041–6.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–74.PubMedCrossRefGoogle Scholar
  12. 12.
    Bonadonna G, Valagussa P, Brambilla C, et al. Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol. 1998;16:93–100.PubMedGoogle Scholar
  13. 13.
    Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.Google Scholar
  14. 14.
    Green MC, Buzdar AU, Smith T, et al. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol. 2005;23:5983–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379(9816):633–40 (Erratum in: Lancet. 2012;379(9816):616).Google Scholar
  16. 16.
    Steger GG, Greil R, Lang A, et al. Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24). Ann Oncol. 2014;25:366–71.PubMedCrossRefGoogle Scholar
  17. 17.
    von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol. 2010;28:2015–23.CrossRefGoogle Scholar
  18. 18.
    Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12:320–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995;180:297–306.PubMedGoogle Scholar
  20. 20.
    Corben AD, Abi-Raad R, Popa I, et al. Pathologic response and long-term follow-up in breast cancer patients treated with neoadjuvant chemotherapy: a comparison between classifications and their practical application. Arch Pathol Lab Med. 2013;137:1074–82.PubMedCrossRefGoogle Scholar
  21. 21.
    von Minckwitz G, Schmitt WD, Loibl S, et al. Ki67 measured after neoadjuvant chemotherapy for primary breast cancer. Clin Cancer Res. 2013;19:4521–31.CrossRefGoogle Scholar
  22. 22.
    Varga Z, Diebold J, Dommann-Scherrer C, et al. How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists. PLoS One. 2012;7:e37379.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Marian Miller
    • 1
  • Rebecca A. Ottesen
    • 2
  • Joyce C. Niland
    • 2
  • Laura Kruper
    • 1
  • Steven L. Chen
    • 1
  • Courtney Vito
    • 1
    Email author
  1. 1.Department of Surgical OncologyCity of HopeDuarteUSA
  2. 2.Department of Information SciencesCity of HopeDuarteUSA

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