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Radiological complete remission in HER2-positive metastatic breast cancer patients: what to do with trastuzumab?

  • T. G. Steenbruggen
  • N. I. Bouwer
  • C. H. Smorenburg
  • H. N. Rier
  • A. Jager
  • K. Beelen
  • A. J. ten Tije
  • P. C. de Jong
  • J. C. Drooger
  • C. Holterhues
  • J. J. E. M. Kitzen
  • M. -D. Levin
  • G. S. SonkeEmail author
Clinical trial

Abstract

Purpose

Patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab may experience durable tumor response for many years. It is unknown if patients with durable radiological complete remission (rCR) can discontinue trastuzumab. We analyzed clinical characteristics associated with rCR and overall survival (OS) in a historic cohort of patients with HER2-positive MBC and studied the effect of stopping trastuzumab in case of rCR.

Methods

We included patients with HER2-positive MBC treated with first or second-line trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Data were collected from medical records. We used multivariable regression models to identify independent prognostic factors for rCR and OS. Time-to-progression after achieving rCR for patients who continued and stopped trastuzumab, and breast cancer-specific survival were also evaluated.

Results

We identified 717 patients with a median age of 53 years at MBC diagnosis. The median follow-up was 109 months (IQR 72-148). The strongest factor associated with OS was achievement of rCR, adjusted hazard ratio 0.27 (95% CI 0.18–0.40). RCR was observed in 72 patients (10%). The ten-year OS estimate for patients who achieved rCR was 52 versus 7% for patients who did not achieve rCR. Thirty patients with rCR discontinued trastuzumab, of whom 20 (67%) are alive in ongoing remission after 78 months of median follow-up since rCR. Of forty patients (58%) who continued trastuzumab since rCR, 13 (33%) are in ongoing remission after 68 months of median follow-up. Median time-to-progression in the latter group was 14 months.

Conclusions

Achieving rCR is the strongest predictor for improved survival in patients with HER2-positive MBC. Trastuzumab may be discontinued in selected patients with ongoing rCR. Further research is required to identify patients who have achieved rCR and in whom trastuzumab may safely be discontinued.

Keywords

HER2-positive Metastatic breast cancer Long-term survival Radiological complete remission Trastuzumab 

Notes

Acknowledgements

We thank Dr. Ritse Mann and Dr. Claudette E. Loo for their valuable comments on radiological imaging. We thank Caroline Pauwels-Heemskerk for her assistance with identifying patients in the Netherlands Cancer Institute’s tumor registry, and Jorine Rigterink for her assistance with collecting data in the Netherlands Cancer Institute.

Author contributions

Study concepts and design: TGS, CHS, GSS. Data acquisition: all authors. Quality control of data and algorithms: TGS. Data analysis and interpretation: TGS, NIB, CHS, AJ, ML, GSS. Statistical analyses: TGS. Manuscript preparation: TGS. Manuscript editing: TGS, NIB, CHS, AJ, ML, GSS. Manuscript review and approval: all authors.

Funding

This project was funded by Stichting A Sister’s Hope and Stichting [Z]aan de Wandel.

Compliance with ethical standards

Conflict of interest

TGS received funding from Memidis Pharma outside the current project. GSS has received institutional research funding from AstraZeneca, Merck, Novartis, and Roche. NIB, CHS, HNvR, AJ, KB, AJtT, PCdJ, JCD, CH, JK, and MDL have no disclosures. All authors have declared no conflict of interest.

Ethical approval

The Review Board of each participating center approved this study. 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.

Informed consent

No formal consent was required.

Supplementary material

10549_2019_5427_MOESM1_ESM.docx (40 kb)
Supplementary material 1 (DOCX 41 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • T. G. Steenbruggen
    • 1
  • N. I. Bouwer
    • 2
  • C. H. Smorenburg
    • 1
  • H. N. Rier
    • 2
  • A. Jager
    • 3
  • K. Beelen
    • 4
  • A. J. ten Tije
    • 5
  • P. C. de Jong
    • 6
  • J. C. Drooger
    • 7
  • C. Holterhues
    • 8
  • J. J. E. M. Kitzen
    • 2
  • M. -D. Levin
    • 2
  • G. S. Sonke
    • 1
    Email author
  1. 1.Department of Medical OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Internal MedicineAlbert Schweitzer HospitalDordrechtThe Netherlands
  3. 3.Department of Medical OncologyErasmus MC Cancer InstituteRotterdamThe Netherlands
  4. 4.Department of Internal MedicineReinier de Graaf HospitalDelftThe Netherlands
  5. 5.Department of Internal MedicineAmphia HospitalBredaThe Netherlands
  6. 6.Department of Medical OncologySint Antonius HospitalUtrechtThe Netherlands
  7. 7.Department of Medical OncologyIkazia HospitalRotterdamThe Netherlands
  8. 8.Department of Internal MedicineHaga HospitalThe HagueThe Netherlands

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