Assessment of Breast Cancer Response to Neoadjuvant Chemotherapy: a Radiologist’s Perspective

Panagiotis Kapetas, Katja Pinker, Thomas Helbich


Neoadjuvant chemotherapy (NAC) plays a central role in the management of breast cancer (BC) patients, especially (but not exclusively) in cases of locally advanced cancers, to achieve operability. A wide spectrum of imaging modalities is used to evaluate BC response to NAC (mammography, digital breast tomosynthesis, ultrasound, magnetic resonance imaging, nuclear medicine imaging, optical imaging, etc.), providing not only morphological, but also functional and molecular information. This review aims to provide radiologists with an overview of the current knowledge and perspectives regarding the role of different imaging techniques in the assessment and prediction of BC response to NAC.


breast cancer; chemotherapy; neoadjuvant therapies; diagnostic imaging; multimodal imaging

Full Text:



Fumagalli D, Bedard PL, Nahleh Z, et al. A common language in neoadjuvant breast cancer clinical trials: proposals for standard definitions and endpoints. Lancet Oncol 2012; 13(6): e240-248.

Thompson AM, Moulder-Thompson SL. Neoadjuvant treatment of breast cancer. Ann Oncol 2012; 23 Suppl 10: x231-236.

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45(2): 228-247.

Rauch GM, Adrada BE, Kuerer HM, et al. Multimodality imaging for evaluating response to neoadjuvant chemotherapy in breast cancer. AJR Am J Roentgenol 2016: 1-10.

Gampenrieder SP, Rinnerthaler G, Greil R. Neoadjuvant chemotherapy and targeted therapy in breast cancer: past, present, and future. J Oncol 2013; 732047.

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Breast Cancer (Version 2.2017- April 6, 2017) [27.07.2017]. Available from:

Cain H, Macpherson IR, Beresford M, et al. Neoadjuvant Therapy in Early Breast Cancer: Treatment considerations and common debates in practice. Clin Oncol (R Coll Radiol) 2017; 29. doi: 10.1016/j.clon.2017.06.003.

Morigi C. Highlights from the 15th St Gallen International Breast Cancer Conference 15-18 March, 2017, Vienna: tailored treatments for patients with early breast cancer. Ecancermedicalscience 2017; 11: 732.

Mieog JS, van der Hage JA, van de Velde CJ. Pre¬operative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev 2007; (2): CD005002.

Santa-Maria CA, Camp M, Cimino-Mathews A, et al. Neoadjuvant therapy for early-stage breast cancer: Current practice, controversies, and future directions. Oncology (Williston Park) 2015; 29(11): 828-838.

Hylton NM, Blume JD, Bernreuter WK, et al. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy-results from ACRIN 6657/I-SPY TRIAL. Radiology 2012; 263(3): 663-672.

Martincich L, Montemurro F, De Rosa G, et al. Monitoring response to primary chemotherapy in breast cancer using dynamic contrast-enhanced magnetic resonance imaging. Breast Cancer Res Treat 2004; 83(1): 67-76.

Partridge SC, Gibbs JE, Lu Y, et al. MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival. AJR Am J Roentgenol 2005; 184(6): 1774-1781.

U.S. Department of health and human services food and drug administration center for drug evaluation and research. Guidance for Industry: Pathological complete response in neoadjuvant treatment of high-risk early-stage breast cancer: Use as an endpoint to support accelerated approval. Available via Published October 2014. Updated 21.11.2016.

Kong X, Moran MS, Zhang N, et al. Meta-analysis confirms achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur J Cancer 2011; 47(14): 2084-2090.

Mazouni C, Peintinger F, Wan-Kau S, et al. 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 2007; 25(19): 2650-2655.

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(15): 1796-1804.

Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol 2013; 24(9): 2206-2223.

Houssami N, Macaskill P, von Minckwitz G, et al. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer 2012; 48(18): 3342-3354.

Bodini M, Berruti A, Bottini A, et al. Magnetic resonance imaging in comparison to clinical palpation in assessing the response of breast cancer to epirubicin primary chemotherapy. Breast Cancer Res Treat 2004; 85(3): 211-218.

Croshaw R, Shapiro-Wright H, Svensson E, et al. Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining postneoadju¬vant pathologic tumor response in operable breast cancer patients. Ann Surg Oncol 2011; 18(11): 3160-3163.

Marinovich ML, Houssami N, Macaskill P, et al. Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst 2013; 105(5): 321-333.

Marinovich ML, Macaskill P, Irwig L, et al. Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy. Br J Cancer 2013; 109(6): 1528-1536.

Cocconi G, Di Blasio B, Alberti G, et al. Problems in evaluating response of primary breast cancer to systemic therapy. Breast Cancer Res Treat 1984; 4(4): 309-313.

Vinnicombe SJ, MacVicar AD, Guy RL, et al. Primary breast cancer: Mammographic changes after neoadjuvant chemotherapy, with pathologic correlation. Radiology 1998; 98(2): 333-340.

Keune JD, Jeffe DB, Schootman M, et al. Accuracy of ultrasonography and mammography in predicting pathologic response after neoadjuvant chemotherapy for breast cancer. Am J Surg 2010; 199(4): 477-484.

Londero V, Bazzocchi M, Del Frate C, et al. Locally advanced breast cancer: comparison of mammography, sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy. Eur Radiol 2004; 14(8): 1371-1379.

Huber S, Wagner M, Zuna I, et al. Locally advanced breast carcinoma: evaluation of mammography in the prediction of residual disease after induction chemotherapy. Anticancer Res 2000; 20(1B): 553-558.

Li JJ, Chen C, Gu Y, et al. The role of mammographic calcification in the neoadjuvant therapy of breast cancer imaging evaluation. PLoS One 2014; 9(2): e88853.

Weiss A, Lee KC, Romero Y, et al. Calcifications on mammogram do not correlate with tumor size after neoadjuvant chemotherapy. Ann Surg Oncol 2014; 21(10): 3310-3316.

Adrada BE, Huo L, Lane DL, et al. Histopathologic correlation of residual mammographic microcalcifications after neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol 2015; 22(4): 1111-1117.

Arasaki A UN, Uchiyama N, Kinoshita T. Usefulness of digital breast tomosynthesis (DBT) in evaluation of pathological response after neoadjuvant chemotherapy (NAC) for breast cancer. J Clin Oncol 2015;

Uchiyama N, Kinoshita T, Hojo T, et al. Usefulness of adjunction of digital breast tomosynthesis (DBT) to full-field digital mammography (FFDM) in evaluation of pathological response after neoadjuvant chemotherapy (NAC) for breast cancer. In: Maidment ADA, Bakic PR, Gavenonis S, editors. Breast Imaging: 11th International Workshop, IWDM 2012, Philadelphia, PA, USA, July 8-11, 2012. Proceedings. Springer Berlin Heidelberg; 2012. pp 354-361.

Berg WA, Gutierrez L, NessAiver MS, et al. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 2004; 233(3): 830-849.

Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft e.V. (DKG). Diagnosis and treatment of patients with primary and metastatic breast cancer: Neoadjuvant (Primary) systemic therapy. Available via Published March 2014. Updated March 2016 Accessed 17.02.2017.

Vriens BE, de Vries B, Lobbes MB, et al. Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer. Eur J Cancer 2016; 52: 67-76.

Lee SH, Chang JM, Han W, et al. Shear-wave elastography for the detection of residual breast cancer after neoadjuvant chemotherapy. Ann Surg Oncol 2015; 22 Suppl 3: S376-384.

Falou O, Sadeghi-Naini A, Prematilake S, et al. Evaluation of neoadjuvant chemotherapy response in women with locally advanced breast cancer using ultrasound elastography. Transl Oncol 2013; 6(1): 17-24.

Athanasiou A, Latorre-Ossa H, Criton A, et al. Feasibility of imaging and treatment monitoring of breast lesions with three-dimensional shear wave elastography. Ultraschall Med 2017; 38(1): 51-59.

Hatzis C, Pusztai L, Valero V, et al. A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. JAMA 2011; 305(18): 1873-1881.

Evans A, Armstrong S, Whelehan P, et al. Can shear-wave elastography predict response to neoadjuvant chemotherapy in women with invasive breast cancer? Br J Cancer 2013; 109(11): 2798-2802.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-674.

Makris A, Powles TJ, Kakolyris S, et al. Reduction in angiogenesis after neoadjuvant chemoendocrine therapy in patients with operable breast carcinoma. Cancer 1999; 85(9): 1996-2000.

Singh S, Pradhan S, Shukla RC, et al. Color Doppler ultrasound as an objective assessment tool for chemotherapeutic response in advanced breast cancer. Breast Cancer 2005; 12(1): 45-51.

Cao X, Xue J, Zhao B. Potential application value of contrast-enhanced ultrasound in neoadjuvant chemotherapy of breast cancer. Ultrasound Med Biol 2012; 38(12): 2065-2071.

Amioka A, Masumoto N, Gouda N, et al. Ability of contrast-enhanced ultrasonography to determine clinical responses of breast cancer to neoadjuvant chemotherapy. Jpn J Clin Oncol 2016; 46(4): 303-309.

Wang JW, Zheng W, Liu JB, et al. Assessment of early tumor response to cytotoxic chemotherapy with dynamic contrast-enhanced ultrasound in human breast cancer xenografts. PLoS One 2013; 8(3): e58274.

Schuster A HA, Knauer M, Lang A, et al. Monitoring of neoadjuvant chemotherapy by contrast-enhanced ultrasound in patients with breast carcinoma: Preliminary results. European Congress of Radiology 2011; doi: 10.1594/ecr2011/C-2285.

Kaiser WA. False-positive results in dynamic MR mammography. Causes, frequency, and methods to avoid. Magn Reson Imaging Clin N Am 1994; 2(4): 539-555.

Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic accuracy, and transfer to clinical practice. Radiology 2007; 244(2): 356-378.

Morris EA. Rethinking breast cancer screening: ultra FAST breast magnetic resonance imaging. J Clin Oncol 2014; 32(22): 2281-2283.

Benndorf M, Baltzer PA, Vag T, et al. Breast MRI as an adjunct to mammography: Does it really suffer from low specificity? A retrospective analysis stratified by mammographic BI-RADS classes. Acta Radiol 2010; 51(7): 715-721.

Balasubramanian P, Murugesan VK, Boopathy V. The Role of MR mammography in differentiating benign from malignant in suspicious breast masses. J Clin Diagn Res 2016; 10(9): TC05-TC08.

De Los Santos JF, Cantor A, Amos KD, et al. Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017. Cancer 2013; 119(10): 1776-1783.

Hayashi Y, Takei H, Nozu S, et al. Analysis of complete response by MRI following neoadjuvant chemotherapy predicts pathological tumor responses differently for molecular subtypes of breast cancer. Oncol Lett 2013; 5(1): 83-89.

Ko ES, Han BK, Kim RB, et al. Analysis of factors that influence the accuracy of magnetic resonance imaging for predicting response after neoadjuvant chemotherapy in locally advanced breast cancer. Ann Surg Oncol 2013; 20(8): 2562-2568.

Chen JH, Bahri S, Mehta RS, et al. Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology. J Surg Oncol 2014; 109(2): 158-167.

Bouzon A, Acea B, Soler R, et al. Diagnostic accuracy of MRI to evaluate tumour response and residual tumour size after neoadjuvant chemotherapy in breast cancer patients. Radiol Oncol 2016; 50(1): 73-79.

Kuzucan A, Chen JH, Bahri S, et al. Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile. Clin Breast Cancer 2012; 12(2): 110-118.

McGuire KP, Toro-Burguete J, Dang H, et al. MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol 2011; 18(11): 3149-3154.

Mukhtar RA, Yau C, Rosen M, et al. Clinically meaningful tumor reduction rates vary by prechemotherapy MRI phenotype and tumor subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol 2013; 20(12): 3823-3830.

Lobbes MB, Prevos R, Smidt M, et al. The role of magnetic resonance imaging in assessing residual disease and pathologic complete response in breast cancer patients receiving neoadjuvant chemotherapy: a systematic review. Insights Imaging 2013; 4(2): 163-175.

Chen JH, Feig BA, Hsiang DJ, et al. Impact of MRI-evaluated neoadjuvant chemotherapy response on change of surgical recommendation in breast cancer. Ann Surg 2009; 249(3): 448-454.

Cowen D, Houvenaeghel G, Bardou V, et al. Local and distant failures after limited surgery with positive margins and radiotherapy for node-negative breast cancer. Int J Radiat Oncol Biol Phys 2000; 47(2): 305-312.

Lobbes M, Prevos R, Smidt M: Response monitoring of breast cancer patientsreceiving neoadjuvant chemotherapy using breast MRI - a review of current knowledge. J Cancer Ther Res 2012; 1: 34.

Charehbili A, Wasser MN, Smit VT, et al. Accuracy of MRI for treatment response assessment after taxane-and anthracycline-based neoadjuvant chemotherapy in HER2-negative breast cancer. Eur J Surg Oncol 2014; 40(10): 1216-1221.

Tomida K, Ishida M, Umeda T, et al. Magnetic resonance imaging shrinkage patterns following neoadjuvant chemotherapy for breast carcinomas with an emphasis on the radiopathological correlations. Mol Clin Oncol 2014; 2(5): 783-788.

Price ER, Wong J, Mukhtar R, et al. How to use magnetic resonance imaging following neoadjuvant chemotherapy in locally advanced breast cancer. World J Clin Cases 2015; 3(7): 607-613.

Chen JH, Bahri S, Mehta RS, et al. Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR imaging. Radiology 2011; 261(3): 735-743.

McLaughlin R, Hylton N. MRI in breast cancer therapy monitoring. NMR Biomed 2011; 24(6): 712-720.

van la Parra RF, Kuerer HM. Selective elimination of breast cancer surgery in exceptional responders: Historical perspective and current trials. Breast Cancer Res 2016; 18(1): 28.

Esserman L, Kaplan E, Partridge S, et al. MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer. Ann Surg Oncol 2001; 8(6): 549-559.

Padhani AR, Hayes C, Assersohn L, et al. Prediction of clinicopathologic response of breast cancer to primary chemotherapy at contrast-enhanced MR imaging: initial clinical results. Radiology 2006; 239(2): 361-374.

Ah-See ML, Makris A, Taylor NJ, et al. Early changes in functional dynamic magnetic resonance imaging predict for pathologic response to neoadjuvant chemotherapy in primary breast cancer. Clin Cancer Res 2008; 14(20): 6580-6589.

Li SP, Makris A, Beresford MJ, et al. Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy. Radiology 2011; 260(1): 68-78.

Tudorica A, Oh KY, Chui SY, et al. Early prediction and evaluation of breast cancer response to neoadjuvant chemotherapy using quantitative DCE-MRI. Transl Oncol 2016; 9(1): 8-17.

Spick C, Pinker-Domenig K, Rudas M, Helbich TH, Baltzer PA. MRI-only lesions: application of diffusion-weighted imaging obviates unnecessary MR-guided breast biopsies. Eur Radiol 2014; 24(6): 1204-1210.

Sharma U, Danishad KK, Seenu V, et al. Longitudinal study of the assessment by MRI and diffusion-weighted imaging of tumor response in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. NMR Biomed 2009; 22(1): 104-113.

Park SH, Moon WK, Cho N, et al. Diffusion-weighted MR imaging: pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer. Radiology 2010; 257(1): 56-63.

Meisamy S, Bolan PJ, Baker EH, et al. Neoadjuvant Chemotherapy of Locally Advanced Breast Cancer: Predicting Response with in Vivo 1H MR Spectroscopy-A Pilot Study at 4 T. Radiology 2004; 233(2): 424-431.

Baek H-M, Chen J-H, Nie K, et al. Predicting pathologic response to neoadjuvant chemotherapy in breast cancer by using MR imaging and quantitative 1H MR spectroscopy. Radiology 2009; 251(3): 653-662.

Pinker K, Bogner W, Baltzer P, et al. Improved diagnostic accuracy with multiparametric magnetic resonance imaging of the breast using dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging, and 3-dimensional proton magnetic resonance spectroscopic imaging. Invest Radiol 2014; 49(6): 421-430.

Wu L-M, Hu J-N, Gu H-Y, et al. Can diffusion-weighted MR imaging and contrast-enhanced MR imaging precisely evaluate and predict pathological response to neoadjuvant chemotherapy in patients with breast cancer? Breast Cancer Res Treat 2012; 135(1): 17-28.

The Royal College of Radiologists, Royal College of Physicians of London, Royal College of Physicians and Surgeons of Glasgow, Royal College of Physicians of Edinburgh, British Nuclear Medicine Society, Committee AoRSA. Evidence-based indications for the use of PET-CT in the United Kingdom 2016. Clin Radiol 2016; 71(7): e171-e88.

Liu Y. Role of FDG PET-CT in evaluation of locoregional nodal disease for initial staging of breast cancer. World J Clin Oncol 2014; 5(5): 982-989.

Mghanga FP, Lan X, Bakari KH, et al. Fluorine-18 Fluorodeoxyglucose positron emission tomography & computed tomography in monitoring the response of breast cancer to neoadjuvant chemotherapy: A meta-analysis. Clin Breast Cancer; 13(4): 271-279.

Groheux D, Majdoub M, Sanna A, et al. Early metabolic response to neoadjuvant treatment: FDG PET/CT criteria according to breast cancer subtype. Radiology 2015; 277(2): 358-371.

Pengel KE, Koolen BB, Loo CE, et al. Combined use of 18F-FDG PET/CT and MRI for response monitoring of breast cancer during neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 2014; 41(8): 1515-1524.

Talbot JN, Gligorov J, Nataf V, et al. Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone. Q J Nucl Med Mol Imaging 2015; 59(1): 4-17.

Peterson LM, Mankoff DA, Lawton T, et al. Quantitative imaging of estrogen receptor expression in breast cancer with PET and 18F-fluoroestradiol. J Nucl Med 2008; 49(3): 367-374.

van Kruchten M, de Vries EG, Glaudemans AW, et al. Measuring residual estrogen receptor availability during fulvestrant therapy in patients with metastatic breast cancer. Cancer Discov 2015; 5(1): 72-81.

Yang Z, Sun Y, Xue J, et al. Can positron emission tomography/computed tomography with the dual tracers fluorine-18 fluoroestradiol and fluorodeoxyglucose predict neoadjuvant chemotherapy response of breast cancer? A pilot study. PLoS One 2013; 8(10): e78192.

Evangelista L, Ruggieri D, Pescarini L, et al. MRI and 18F-FDG PET/CT in monitoring the response to neoadjuvant chemotherapy: is it necessary to appropriately select the patients? Eur J Nucl Med Mol Imaging 2014; 41(8): 1511-1514.

Cheng J, Lei L, Xu J, et al. 18F-Fluoromisonidazole PET/CT: A potential tool for predicting primary endocrine therapy resistance in breast cancer. J Nucl Med 2013; 54(3): 333-340.

Kuji I, Ueda S, Shimano Y, et al. Change of hypoxic status during neoadjuvant chemotherapy for breast cancer by using PET/CT imaging. J Nucl Med 2014; 55 (supplement 1): 568.

Kostakoglu L, Duan F, Idowu MO, et al. A Phase II study of 3’-Deoxy-3’-18F-Fluorothymidine PET in the assessment of early response of breast cancer to neoadjuvant chemotherapy: Results from ACRIN 6688. J Nucl Med 2015; 56(11): 1681-1689.

Woolf DK, Beresford M, Li SP, et al. Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast cancer. Br J Cancer 2014; 110(12): 2847-2854.

Falou O, Soliman H, Sadeghi-Naini A, et al. Diffuse optical spectroscopy evaluation of treatment response in women with locally advanced breast cancer receiving neoadjuvant chemotherapy. Transl Oncol 2012; 5(4): 238-246.

Roblyer D, Ueda S, Cerussi A, et al. Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment. Proc Natl Acad Sci USA 2011; 108(35): 14626-14631.



  • There are currently no refbacks.