Skip to main content

Advertisement

Log in

Patterns of relapse after neoadjuvant chemotherapy in breast cancer: implications for surveillance in clinical practice

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

This study aimed to identify patterns of relapse after neoadjuvant chemotherapy (NAC) for breast cancer to refine follow-up recommendations.

Methods

Retrospective analysis on 523 breast cancer patients treated with NAC at two public hospitals in Singapore between 2000 and 2014.

Results

Majority of patients (71.9%) had locally advanced disease. Median follow-up was 55 months. 5-year recurrence rate was significantly higher in triple negative breast cancer (TNBC) than non-TNBC subtypes (38.4% vs. 29.5%; p = 0.042); 85% of recurrences involved distant sites. Among TNBC and HR (hormone receptor)-/HER2+ subtypes, 97.0% and 95.0% of relapses occurred within 3 years from diagnosis respectively while 10.6% of relapses among HR+ subgroup occurred beyond 5 years. Recurrence risk in high-grade tumours decreased with time. Stage III at diagnosis (hazard ratio = 2.94; p < 0.001), grade 3 tumours (hazard ratio = 2.87; p = 0.018), not achieving pathologic complete response (pCR) (hazard ratio = 8.77; p = 0.003) and not receiving adjuvant radiotherapy (hazard ratio = 3.19; p < 0.001) were independent predictors of inferior recurrence-free survival. Serum CA 15-3 was raised in 49% of patients upon relapse; it correlated with inferior post-relapse survival (median 11 months vs. 22 months; p = 0.019).

Conclusions

While more intensive follow-up during the first 3 years may be required for patients who do not achieve pCR, especially those with TNBC and HR−/HER2+ tumours, the benefit from blood tests such as CA 15-3 appears limited, and the benefit from intensification of surveillance remains to be addressed in prospective studies on high-risk patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The datasets during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16(8):2672–2685

    Article  CAS  PubMed  Google Scholar 

  2. van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19:4224–4237

    Article  PubMed  Google Scholar 

  3. Mauri D, Pavlidis N, Ioannidis JPA (2005) Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97(3):188–194

    Article  PubMed  Google Scholar 

  4. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2018) Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 19(1):27–39

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172

    Article  PubMed  Google Scholar 

  7. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F et al (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334

    Article  CAS  Google Scholar 

  8. Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281

    Article  PubMed  Google Scholar 

  9. Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K 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

    Article  CAS  PubMed  Google Scholar 

  10. Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B (2001) 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 15212(30):96–102

    Article  Google Scholar 

  11. Chollet P, Amat S, Cure H, De Latour M, Le Bouedec G, Mouret-Reynier MA et al (2002) Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer 86(7):1041–1046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tanioka M, Shimizu C, Yonemori K, Yoshimura K, Tamura K, Kouno T et al (2010) Predictors of recurrence in breast cancer patients with a pathologic complete response after neoadjuvant chemotherapy. Br J Cancer 103(3):297–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Takada M, Ishiguro H, Nagai S, Ohtani S, Kawabata H, Yanagita Y et al (2014) Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab: a multicenter retrospective observational study (JBCRG-C03 study). Breast Cancer Res Treat 145(1):143–153

    Article  CAS  PubMed  Google Scholar 

  14. Hamy-Petit AS, Belin L, Bonsang-Kitzis H, Paquet C, Pierga JY, Lerebours F et al (2016) Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort. Br J Cancer 114(1):44–52

    Article  CAS  Google Scholar 

  15. Hammond ME, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134:48–72

    Google Scholar 

  16. Baulies S, Belin L, Mallon P, Senechal C, Pierga JY, Cottu P et al (2015) Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy. Br J Cancer 113(1):30–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bardia A, Baselga J (2013) Neoadjuvant therapy as a platform for drug development and approval in breast cancer. Clin Cancer Res 19(23):6360–6370

    Article  CAS  PubMed  Google Scholar 

  18. Fei F, Messina C, Slaets L, Chakiba C, Cameron D, Bogaerts J et al (2015) Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase III trial. Eur J Cancer 51(3):301–309

    Article  CAS  PubMed  Google Scholar 

  19. Ghezzi P, Magnanini S, Rinaldini M, Berardi F, Di Biagio G, Testare F et al (1994) Impact of follow-up testing on survival and health-related quality of life in breast cancer patients: a multicenter randomized controlled trial. JAMA 271(20):1587–1592

    Article  Google Scholar 

  20. Rosselli Del Turco M, Palli D, Cariddi A, Ciatto S, Pacini P, Distante V (1994) Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up. JAMA 271(20):1593–1597

    Article  CAS  PubMed  Google Scholar 

  21. Oltra A, Santaballa A, Munárriz B, Pastor M, Montalar J (2007) Cost-benefit analysis of a follow-up program in patients with breast cancer: a randomized prospective study. Breast J 13(6):571–574

    Article  PubMed  Google Scholar 

  22. Pivot X, Asmar L, Hortobagyi GN, Theriault R, Pastorini F, Buzdar A (2000) A retrospective study of first indicators of breast cancer recurrence. Oncology 58:185–190

    Article  CAS  PubMed  Google Scholar 

  23. Viot J, Bachour M, Meurisse A, Pivot X, Fiteni F (2017) Follow-up of patients with localized breast cancer and first indicators of advanced breast cancer recurrence: a retrospective study. Breast 34:53–57

    Article  PubMed  Google Scholar 

  24. Hojo T, Masuda N, Mizutani T, Shibata T, Kinoshita T, Tamura K et al (2015) Intensive vs. standard post-operative surveillance in high-risk breast cancer patients (INSPIRE): Japan clinical oncology group study JCOG1204. Jpn J Clin Oncol 45:983–986

    Article  PubMed  Google Scholar 

  25. Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL et al (2016) American cancer society/American society of clinical oncology breast cancer survivorship care guideline. J Clin Oncol 34:611–635

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No funding was required for this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoon Sim Yap.

Ethics declarations

Conflict of interest

Dr Yap reported consulting for and receiving honoraria, travel support from Novartis, Pfizer, Lilly, Astra Zeneca, Roche, Eisai, and research support from Novartis.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was done under approval of SingHealth Centralised Institutional Review Board (Reference Number: CIRB 2004/422/B) and was conducted according to institutional and ethical rules concerning research on patients, with waiver of consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saw, S., Lim, J., Lim, S.H. et al. Patterns of relapse after neoadjuvant chemotherapy in breast cancer: implications for surveillance in clinical practice. Breast Cancer Res Treat 177, 197–206 (2019). https://doi.org/10.1007/s10549-019-05290-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-019-05290-0

Keywords

Navigation