Radiological complete remission in HER2-positive metastatic breast cancer patients: what to do with trastuzumab?
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.
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.
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.
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.
KeywordsHER2-positive Metastatic breast cancer Long-term survival Radiological complete remission Trastuzumab
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.
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.
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.
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.
No formal consent was required.
- 9.Andersson M, Lidbrink E, Bjerre K et al (2011) Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol 29:264–271. https://doi.org/10.1200/JCO.2010.30.8213 CrossRefGoogle Scholar
- 10.Valero V, Forbes J, Pegram MD et al (2011) Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeu. J Clin Oncol 29:149–156. https://doi.org/10.1200/JCO.2010.28.6450 CrossRefGoogle Scholar
- 29.(2018) https://www.oncoline.nl/
- 33.Harano K, Lei X, Gonzalez-Angulo AM, Murthy RK, Valero V, Mittendorf EA, Ueno NT, Hortobagyi GN, Chavez-MacGregor M (2016) Clinicopathological and surgical factors associated with long-term survival in patients with HER2-positive metastatic breast cancer. Breast Cancer Res Treat 159:367–374CrossRefGoogle Scholar