Abstract
Neoadjuvant systemic therapy (NST) has become part of the standard treatment of patients with locally advanced breast cancer. Patients who achieve a pathologically complete response (pCR) after NST have improved outcomes compared with patients with residual disease at the primary tumor site or the lymph nodes. Achieving a pCR after NST correlates with improved disease-free and overall survival; therefore the amount of residual disease is a prognostic predictor, and it is an area of ongoing research. In this article, we review the literature on NST to highlight the importance of pCR as a prognostic indicator. We also review the definition of pCR and describe the association between different patient and tumor characteristics, including the breast cancer subtype classification, and its response to chemotherapy. We expand on the clinical impact of residual disease and comment on the importance of quantifying it and the current treatment recommendations for patients with residual disease after NST.
Similar content being viewed by others
References
Jemal A, Siegel R, Ward E et al (2008) Cancer statistics. CA Cancer J Clin 58:71–96
American Cancer Society (2009) Breast cancer facts and figures 2007–2008 Atlanta: American Cancer Society. http://www.cancer.org/downloads/stt/bcff-final.pdf
SEER (2009) Cancer statistics review 1975–2006: National Cancer Institute, DC-CPS, Surveillance Research Program, Cancer Statistics Branch.
NCCN (2009) Clinical practice guidelines in oncology. Breast cancer V.I: National Comprehensive Cancer Network. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685
Rastogi P, Anderson SJ, Bear HD et al (2008) Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol 26:778–785
Kuerer HM, Newman LA, Smith TL et al (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469
Hennessy BT, Hortobagyi GN, Rouzier R et al (2005) Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol 23:9304–9311
Rouzier R, Extra JM, Klijanienko J et al (2002) Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol 20:1304–1310
Jones RL, Lakhani SR, Ring AE et al (2006) Pathological complete response and residual DCIS following neoadjuvant chemotherapy for breast carcinoma. Br J Cancer 94:358–362
Mazouni C, Peintinger F, Wan-Kau S et al (2007) Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol 25:2650–2655
Pusztai L (2008) Preoperative systemic chemotherapy and pathologic assessment of response. Pathol Oncol Res 14:169–171
Symmans WF, Peintinger F, Hatzis C et al (2007) Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25:4414–4422
Smith IC, Heys SD, Hutcheon AW et al (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20:1456–1466
Thomas E, Holmes FA, Smith TL et al (2004) The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol 22:2294–2302
von Minckwitz G, Kummel S, Vogel P et al (2008) Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 100:542–551
Caudle AS, Gonzalez-Angulo AM, Hunt KK et al (2010) Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:1821–1828
von Minckwitz G, Kummel S, Vogel P et al (2008) Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 100:552–562
Early Breast Cancer Trialists’ Collaborative Group (1992) Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Lancet 339(8785):71–85
Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168
Nemoto T, Vana J, Bedwani RN et al (1980) Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer 45:2917–2924
Cristofanilli M, Gonzalez-Angulo A, Sneige N et al (2005) Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol 23:41–48
Dawood S, Broglio K, Kau SW et al (2008) Prognostic value of initial clinical disease stage after achieving pathological complete response. Oncologist 13:6–15
Buzdar AU, Ibrahim NK, Francis D et al (2005) Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23:3676–3685
Ravdin PM, Chamness GC (1995) The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers—a review. Gene 159:19–27
Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182
Huber KE, Carey LA, Wazer DE (2009) Breast cancer molecular subtypes in patients with locally advanced disease: impact on prognosis, patterns of recurrence, and response to therapy. Semin Radiat Oncol 19:204–210
Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752
Sorlie T, Perou CM, Tibshirani R et al (2010) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874
Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 100:8418–8423
Sotiriou C, Neo SY, McShane LM et al (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 100:10393–10398
Fan C, Oh DS, Wessels L et al (2006) Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 355:560–569
Carey LA, Perou CM, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502
Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374
Cheang MC, Chia SK, Voduc D et al (2009) Ki-67 index, HER-2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101:736–750
Guarneri V, Broglio K, Kau SW et al (2006) Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 24:1037–1044
Carey LA, Dees EC, Sawyer L et al (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13:2329–2334
Liedtke C, Mazouni C, Hess KR et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26:1275–1281
Rouzier R, Perou CM, Symmans WF et al (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11:5678–5685
Sawaki M, Ito Y, Akiyama F et al (2006) High prevalence of HER-2/neu and p53 overexpression in inflammatory breast cancer. Breast Cancer 13:172–178
Gianni L, Zambetti M, Clark K et al (2005) Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23:7265–7277
Lee JK, Coutant C, Kim YC et al (2010) Prospective comparison of clinical and genomic multivariate predictors of response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res 1:711–718
Lee JK, Havaleshko DM, Cho H et al (2007) A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery. Proc Natl Acad Sci U S A 104:13086–13091
Rouzier R, Pusztai L, Delaloge S et al (2005) Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol 23:8331–8339
Hess KR, Anderson K, Symmans WF et al (2006) Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol 24:4236–4244
Guarneri V, Piacentini F, Ficarra G et al (2009) A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy. Ann Oncol 20:1193–1198
Jones RL, Salter J, A’Hern R et al (2009) The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 116:53–68
Mittendorf EA, Wu Y, Scaltriti M et al (2009) Loss of HER2 amplification following trastuzumabbased neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 15:7381–7388
Creighton CJ, Li X, Landis M et al (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A 106:13820–13825
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chávez-MacGregor, M., González-Angulo, A.M. Breast cancer, neoadjuvant chemotherapy and residual disease. Clin Transl Oncol 12, 461–467 (2010). https://doi.org/10.1007/s12094-010-0538-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-010-0538-0