Targeted Oncology

, Volume 11, Issue 3, pp 277–292 | Cite as

Systematic Review of the Side Effects Associated With Anti-HER2-Targeted Therapies Used in the Treatment of Breast Cancer, on Behalf of the EORTC Quality of Life Group

  • Samantha C. SodergrenEmail author
  • Ellen Copson
  • Alice White
  • Fabio Efficace
  • Mirjam Sprangers
  • Deborah Fitzsimmons
  • Andrew Bottomley
  • Colin D. Johnson
Review Article



Targeted therapies (TTs), notably trastuzumab, have improved outcomes for breast cancer characterised by overexpression of human epidermal growth factor receptors including HER2. Compared with chemotherapy treatments, TTs are more specific in their targets and are delivered over longer periods of time, thus presenting different side-effect profiles. The objective of this paper is to systematically review and describe the side effects associated with TTs used in the adjuvant and metastatic settings for HER2+ breast cancer.


The MEDLINE, EMBASE, CINAHL, Web of Science and Cochrane Library databases were searched from January 2007 to March 2015 to identify clinical trials and prospective studies reporting toxicities associated with TTs (mainly trastuzumab and lapatinib) used without other therapies in the treatment of HER2-positive breast cancer. Two independent reviewers selected papers based on their titles and abstracts. All papers selected by either reviewer were included. A third reviewer extracted and tabulated the relevant data using a data extraction form.


We identified 5478 papers, of which 299 were reviewed and 18 trials identified involving 6980 patients. A total of 66 side effects were identified, including 46 "patient-based" symptoms and 20 "medically defined" outcomes. Side effects were more common for patients treated with therapies other than trastuzumab or with dual-HER2 regimens and for patients with metastatic disease. Diarrhoea and skin rash were the most prevalent symptoms, experienced by 29 % and 22 % of patients overall, respectively. There were 119 (2 %) cardiac events reported, and these were not exclusive to trastuzumab-treated patients. The majority of side effects (n = 52) were experienced by 1 % or less of patients and were predominantly of grade 1/2 toxicity.


This systematic review provides a detailed analysis of side effects of HER2+ therapies in a large number of patients included in trials, enabling an accurate estimate of prevalence and a complete understanding of the patients' experience. This will help clinicians and patients in treatment planning.


Epidermal Growth Factor Receptor Trastuzumab Human Epidermal Growth Factor Receptor Lapatinib Skin Rash 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards


This research was funded by the European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QOL) Group.

Conflict of Interest

Deborah Fitzsimmons is Principal Investigator on a grant awarded by Pierre Fabre Ltd. to evaluate the costs of treating HER2+ breast cancer. Deborah is also Principal Investigator on two grants made by the National Co-ordinating Centre for Cancer to support the health economic evaluation of guideline development for NICE on familial breast cancer (CG164) and non-Hodgkins lymphoma (work in progress). Deborah was also the recipient of funds as co-author on a manuscript for Bayer HealthCare entitled "Health technology appraisals: a comparison of principles and processes. Guidelines in practice. March 2015".

The other authors (SS, EC, AW, FE, MS, AB & CJ) declare no conflict of interest.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Samantha C. Sodergren
    • 1
    Email author
  • Ellen Copson
    • 1
  • Alice White
    • 1
  • Fabio Efficace
    • 2
  • Mirjam Sprangers
    • 3
  • Deborah Fitzsimmons
    • 4
  • Andrew Bottomley
    • 5
  • Colin D. Johnson
    • 1
  1. 1.Cancer SciencesUniversity of SouthamptonSouthamptonUK
  2. 2.Health Outcomes Research Unit, GimemaItalian Group for Adult Hematologic Diseases (GIMEMA)RomeItaly
  3. 3.Department of Medical PsychologyUniversity of AmsterdamAmsterdamThe Netherlands
  4. 4.Swansea Centre for Health EconomicsSwansea UniversitySwanseaUK
  5. 5.European Organisation for Research and Treatment of Cancer Quality of Life DepartmentBrusselsBelgium

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