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



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


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


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).


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.

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Data availability

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


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Correspondence to Yoon Sim Yap.

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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.

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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).

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  • Neoadjuvant chemotherapy
  • Breast cancer
  • Recurrence
  • Surveillance