Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2019

01-12-2019 | Metastasis | Clinical trial

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

Authors: 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. Sonke

Published in: Breast Cancer Research and Treatment | Issue 3/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
7.
go back to reference Gullo G, Zuradelli M, Sclafani F et al (2012) Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer. Ann Oncol 23:2204–2208CrossRef Gullo G, Zuradelli M, Sclafani F et al (2012) Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer. Ann Oncol 23:2204–2208CrossRef
9.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
10.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
15.
go back to reference Yardley D, Tripathy D, Brufsky AM et al (2014) Long-term survivor characteristics in HER2 positive MBC from registHER. Br J Cancer 110:2756–2764CrossRef Yardley D, Tripathy D, Brufsky AM et al (2014) Long-term survivor characteristics in HER2 positive MBC from registHER. Br J Cancer 110:2756–2764CrossRef
16.
go back to reference Spano J-P, Beuzeboc P, Coeffic D et al (2015) Long term HER2+ metastatic breast cancer survivors treated by trastuzumab: results from the French cohort study LHORA. Breast 24:376–383CrossRef Spano J-P, Beuzeboc P, Coeffic D et al (2015) Long term HER2+ metastatic breast cancer survivors treated by trastuzumab: results from the French cohort study LHORA. Breast 24:376–383CrossRef
18.
go back to reference Bishop A, Ensor J, Moulder S et al (2015) Prognosis for patients with metastatic breast cancer who achieve NED after systemic or local therapy. Cancer 121:4324–4332CrossRef Bishop A, Ensor J, Moulder S et al (2015) Prognosis for patients with metastatic breast cancer who achieve NED after systemic or local therapy. Cancer 121:4324–4332CrossRef
33.
go back to reference 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 159:367–374CrossRef 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 159:367–374CrossRef
35.
go back to reference Palma DA, Salama JK, Lo SS et al (2014) The oligometastatic state—separating truth from wishful thinking. Nat Rev Clin Oncol 11:549–557CrossRef Palma DA, Salama JK, Lo SS et al (2014) The oligometastatic state—separating truth from wishful thinking. Nat Rev Clin Oncol 11:549–557CrossRef
Metadata
Title
Radiological complete remission in HER2-positive metastatic breast cancer patients: what to do with trastuzumab?
Authors
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. Sonke
Publication date
01-12-2019
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05427-1

Other articles of this Issue 3/2019

Breast Cancer Research and Treatment 3/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine