Breast Cancer Research and Treatment

, Volume 164, Issue 1, pp 99–106 | Cite as

MRI predicts pathologic complete response in HER2-positive breast cancer after neoadjuvant chemotherapy

  • Mette S. van Ramshorst
  • Claudette E. Loo
  • Emilie J. Groen
  • Gonneke H. Winter-Warnars
  • Jelle Wesseling
  • Frederieke van Duijnhoven
  • Marie-Jeanne T. Vrancken Peeters
  • Gabe S. SonkeEmail author
Clinical trial



Neoadjuvant treatment of HER2-positive breast cancer frequently leads to a pathologic complete response (pCR), which is associated with favourable long-term outcome. Treatment regimens typically consist of 6–9 cycles of trastuzumab-based chemotherapy, although many patients achieve early radiologic complete response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles can possibly be reduced.


We performed a diagnostic accuracy study to determine the association between rCR and pCR in patients with stage II–III HER2-positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at the Netherlands Cancer Institute. RCR was defined as the disappearance of pathologic contrast enhancement in the original tumour region on repeated magnetic resonance imaging (MRI). PCR was defined as the absence of invasive tumour cells in the resected breast specimen (ypT0/is). Diagnostic accuracy was estimated in the overall population and in subgroups based on hormone receptor (HR) status. The prognostic value of rCR for recurrence-free interval was evaluated as an exploratory analysis.


We identified 296 eligible patients with 297 HER2-positive tumours (154 HR-negative and 143 HR-positive) treated with neoadjuvant trastuzumab-based chemotherapy between 2004 and 2016. Overall, the rCR rate was 69% (206/297) and the pCR rate was 61% (181/297). Among 206 patients with rCR, 150 also had pCR (negative predictive value [NPV] = 150/206 = 73%). Among 91 patients without rCR, 60 had residual tumour at pathology (positive predictive value [PPV] = 60/91 = 66%). The NPV was better in HR-negative compared to HR-positive tumours (88 vs. 57%), while the PPV was better in HR-positive tumours (50 vs. 78%). Achieving rCR was associated with a 5-year recurrence-free interval of 88% compared to 68% without rCR (hazard ratio 0.34, 95% confidence interval 0.17–0.65, P = 0.001).


Achieving rCR corresponds well with pCR in HER2-positive breast cancer, particularly in the HR-negative subgroup. RCR is also associated with improved long-term outcome.


HER2-positive breast cancer Neoadjuvant therapy Response monitoring Magnetic resonance imaging 



The authors thank M. van Loveren for her contributions to the manuscript.


No financial research support has been received for this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. Relevant financial activities outside the submitted work and other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing: GSS received institutional research support funding from Roche, AstraZeneca, Merck and Novartis.

Informed consent

For this retrospective study formal consent was not required.

Supplementary material

10549_2017_4254_MOESM1_ESM.pdf (104 kb)
Supplementary material 1 (PDF 104 kb)
10549_2017_4254_MOESM2_ESM.pdf (108 kb)
Supplementary material 2 (PDF 108 kb)
10549_2017_4254_MOESM3_ESM.pdf (91 kb)
Supplementary material 3 (PDF 90 kb)
10549_2017_4254_MOESM4_ESM.pdf (124 kb)
Supplementary material 4 (PDF 123 kb)


  1. 1.
    Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284. doi: 10.1093/annonc/mdt182 CrossRefPubMedGoogle Scholar
  2. 2.
    Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, Boileau JF, Brezden-Masley C, Chia S, Dent S, Gelmon K, Paterson A, Rayson D, Berry DA (2016) Association of pathologic complete response to neoadjuvant therapy in HER2-positive breast cancer with long-term outcomes: a meta-analysis. JAMA Oncol 2:751–760. doi: 10.1001/jamaoncol.2015.6113 CrossRefPubMedGoogle Scholar
  3. 3.
    Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172. doi: 10.1016/S0140-6736(13)62422-8 CrossRefPubMedGoogle Scholar
  4. 4.
    von Minckwitz G, Untch M, Nuesch E, Loibl S, Kaufmann M, Kummel S, Fasching PA, Eiermann W, Blohmer JU, Costa SD, Mehta K, Hilfrich J, Jackisch C, Gerber B, du Bois A, Huober J, Hanusch C, Konecny G, Fett W, Stickeler E, Harbeck N, Muller V, Juni P (2011) Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 125:145–156. doi: 10.1007/s10549-010-1228-x CrossRefGoogle Scholar
  5. 5.
    Ribeiro J, Cardoso MJ (2016) Highlights from the Tenth European Breast Cancer Conference (EBCC10), Amsterdam, 9–11 March 2016. Ecancermedicalscience 10:644. doi: 10.3332/ecancer.2016.644 PubMedPubMedCentralGoogle Scholar
  6. 6.
    Chen JH, Feig B, Agrawal G, Yu H, Carpenter PM, Mehta RS, Nalcioglu O, Su MY (2008) MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy. Cancer 112:17–26. doi: 10.1002/cncr.23130 CrossRefPubMedGoogle Scholar
  7. 7.
    Chen JH, Bahri S, Mehta RS, Carpenter PM, McLaren CE, Chen WP, Fwu PT, Hsiang DJ, Lane KT, Butler JA, Su MY (2014) Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology. J Surg Oncol 109:158–167. doi: 10.1002/jso.23470 CrossRefPubMedGoogle Scholar
  8. 8.
    Bufi E, Belli P, Di Matteo M, Terribile D, Franceschini G, Nardone L, Petrone G, Bonomo L (2014) Effect of breast cancer phenotype on diagnostic performance of MRI in the prediction to response to neoadjuvant treatment. Eur J Radiol 83:1631–1638. doi: 10.1016/j.ejrad.2014.05.002 CrossRefPubMedGoogle Scholar
  9. 9.
    Schaefgen B, Mati M, Sinn HP, Golatta M, Stieber A, Rauch G, Hennigs A, Richter H, Domschke C, Schuetz F, Sohn C, Schneeweiss A, Heil J (2016) Can routine imaging after neoadjuvant chemotherapy in breast cancer predict pathologic complete response? Ann Surg Oncol 23:789–795. doi: 10.1245/s10434-015-4918-0 CrossRefPubMedGoogle Scholar
  10. 10.
    Fukuda T, Horii R, Gomi N, Miyagi Y, Takahashi S, Ito Y, Akiyama F, Ohno S, Iwase T (2016) Accuracy of magnetic resonance imaging for predicting pathological complete response of breast cancer after neoadjuvant chemotherapy: association with breast cancer subtype. SpringerPlus 5:152. doi: 10.1186/s40064-016-1800-x CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bouzon A, Acea B, Soler R, Iglesias A, Santiago P, Mosquera J, Calvo L, Seoane-Pillado T, Garcia A (2016) Diagnostic accuracy of MRI to evaluate tumour response and residual tumour size after neoadjuvant chemotherapy in breast cancer patients. Radiol Oncol 50:73–79. doi: 10.1515/raon-2016-0007 PubMedPubMedCentralGoogle Scholar
  12. 12.
    Marinovich ML, Houssami N, Macaskill P, Sardanelli F, Irwig L, Mamounas EP, von Minckwitz G, Brennan ME, Ciatto S (2013) Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst 105:321–333. doi: 10.1093/jnci/djs528 CrossRefPubMedGoogle Scholar
  13. 13.
    McGuire KP, Toro-Burguete J, Dang H, Young J, Soran A, Zuley M, Bhargava R, Bonaventura M, Johnson R, Ahrendt G (2011) MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol 18:3149–3154. doi: 10.1245/s10434-011-1912-z CrossRefPubMedGoogle Scholar
  14. 14.
    De Los Santos JF, Cantor A, Amos KD, Forero A, Golshan M, Horton JK, Hudis CA, Hylton NM, McGuire K, Meric-Bernstam F, Meszoely IM, Nanda R, Hwang ES (2013) 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 119:1776–1783. doi: 10.1002/cncr.27995 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997–4013. doi: 10.1200/JCO.2013.50.9984 CrossRefPubMedGoogle Scholar
  16. 16.
    Loo CE, Rigter LS, Pengel KE, Wesseling J, Rodenhuis S, Peeters MJ, Sikorska K, Gilhuijs KG (2016) Survival is associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer. Breast Cancer Res 18:82. doi: 10.1186/s13058-016-0742-0 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hayashi Y, Takei H, Nozu S, Tochigi Y, Ichikawa A, Kobayashi N, Kurosumi M, Inoue K, Yoshida T, Nagai SE, Oba H, Tabei T, Horiguchi J, Takeyoshi I (2013) Analysis of complete response by MRI following neoadjuvant chemotherapy predicts pathological tumor responses differently for molecular subtypes of breast cancer. Oncol Lett 5:83–89. doi: 10.3892/ol.2012.1004 PubMedGoogle Scholar
  18. 18.
    Ko ES, Han H, Han BK, Kim SM, Kim RB, Lee GW, Park YH, Nam SJ (2015) Prognostic significance of a complete response on breast MRI in patients who received neoadjuvant chemotherapy according to the molecular subtype. Korean J Radiol 16:986–995. doi: 10.3348/kjr.2015.16.5.986 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Price ER, Wong J, Mukhtar R, Hylton N, Esserman LJ (2015) How to use magnetic resonance imaging following neoadjuvant chemotherapy in locally advanced breast cancer. World J Clin Cases 3:607–613. doi: 10.12998/wjcc.v3.i7.607 PubMedPubMedCentralGoogle Scholar
  20. 20.
    Mukhtar RA, Yau C, Rosen M, Tandon VJ, Hylton N, Esserman LJ (2013) 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 20:3823–3830. doi: 10.1245/s10434-013-3038-y CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Santamaria G, Bargallo X, Fernandez PL, Farrus B, Caparros X, Velasco M (2016) Neoadjuvant systemic therapy in breast cancer: association of contrast-enhanced MR imaging findings, diffusion-weighted imaging findings, and tumor subtype with tumor response. Radiology. doi: 10.1148/radiol.2016160176 PubMedGoogle Scholar
  22. 22.
    Ko ES, Han BK, Kim RB, Ko EY, Shin JH, Hahn SY, Nam SJ, Lee JE, Lee SK, Im YH, Park YH (2013) 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 20:2562–2568. doi: 10.1245/s10434-013-2925-6 CrossRefPubMedGoogle Scholar
  23. 23.
    Hylton NM, Gatsonis CA, Rosen MA, Lehman CD, Newitt DC, Partridge SC, Bernreuter WK, Pisano ED, Morris EA, Weatherall PT, Polin SM, Newstead GM, Marques HS, Esserman LJ, Schnall MD (2016) Neoadjuvant chemotherapy for breast cancer: functional tumor volume by MR imaging predicts recurrence-free survival-results from the ACRIN 6657/CALGB 150007 I-SPY 1 trial. Radiology 279:44–55. doi: 10.1148/radiol.2015150013 CrossRefPubMedGoogle Scholar
  24. 24.
    Schipper RJ, Moossdorff M, Beets-Tan RG, Smidt ML, Lobbes MB (2015) Noninvasive nodal restaging in clinically node positive breast cancer patients after neoadjuvant systemic therapy: a systematic review. Eur J Radiol 84:41–47. doi: 10.1016/j.ejrad.2014.09.020 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Mette S. van Ramshorst
    • 1
  • Claudette E. Loo
    • 2
  • Emilie J. Groen
    • 3
  • Gonneke H. Winter-Warnars
    • 2
  • Jelle Wesseling
    • 3
  • Frederieke van Duijnhoven
    • 4
  • Marie-Jeanne T. Vrancken Peeters
    • 4
  • Gabe S. Sonke
    • 1
    Email author
  1. 1.Department of Medical OncologyNetherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of RadiologyNetherlands Cancer InstituteAmsterdamThe Netherlands
  3. 3.Department of PathologyNetherlands Cancer InstituteAmsterdamThe Netherlands
  4. 4.Department of Surgical OncologyNetherlands Cancer InstituteAmsterdamThe Netherlands

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