ABSTRACT
PURPOSE: We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression. METHODS: We prospectively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during treatments, and along the follow-up. We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis, its prognosis value, and its utility during the monitoring of a neoadjuvant treatment and the follow-up. RESULTS: Elevated HER2/ECD at diagnosis correlated positively with parameters associated with tumor aggressiveness. Disease-free survival of non-metastatic patients was significantly shorter in patients with high HER2/ECD at diagnosis (HR = 13.6, 95 % CI 1.6-113.6, P < 0.0001). Progression-free survival of metastatic patients was better for patients with low HER2/ECD (HR = 2.6, 95 % CI 1.2-5.3, P = 0.033). A multivariate analysis revealed that HER2/ECD level at diagnosis was an independent prognosis factor. During neoadjuvant therapy, a significant decrease in HER2/ECD was reported only for the complete histological response group (P = 0.031). During the follow-up, HER2/ECD helped predict relapse, disease progression, and metastases before imaging in 18.6 % cases of the studied cohort. CONCLUSIONS: HER2/ECD is a prognosis factor that is valuable in evaluating the neoadjuvant treatment efficiency. HER2/ECD also appears to be a helpful surveillance biomarker for the early diagnosis of relapses and to predict the fate of metastases. This study brings evidences to support the use of HER2/ECD in the management of HER2-positive breast cancer.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms/blood , Breast Neoplasms/genetics , Gene Expression , Protein Domains , Receptor, ErbB-2/blood , Receptor, ErbB-2/genetics , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnosis , Breast Neoplasms/mortality , Female , Humans , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Prospective Studies , Receptor, ErbB-2/chemistryABSTRACT
On April 27th 2011, the French Supreme Administrative Court (Conseil d'État) granted the Recommendations for Good Practice set out by the French National Authority for Health (Haute Autorité de santé--[HAS]) a legal status, considering that they "must be regarded as ( ) decisions which may be subject to an action for annulment". The judge came to this conclusion through a quasi-syllogistic reasoning. Firstly, the French Code of Medical Ethics requires physicians to care for their patients in accordance with established scientific knowledge. Secondly, the HAS recommendations recall in particular this established scientific knowledge. Treating patients according to established scientific knowledge requires then that physicians follow the HAS recommendations. While the case at bar does not directly involve liability for medical malpractice-since the applicant only sought to have an HAS recommendation declared void-it is nonetheless necessary to examine the impact of this ruling for health professionals. Indeed, this decision raises a number of concerns for everyday medical practice. Guidelines concerning the endocrine treatment of hormonodependant breast cancers are plentiful. In January 2010, the HAS and the French National Institute for Cancer (Institut national du cancer) issued a "Guide for long-term illnesses-Breast cancer" (Guide ALD - Cancer du sein). In addition to these nation-wide guidelines, the Regional Networks for Cancer (réseaux régionaux de cancérologie) issued their own recommendations. Other guidelines are also set out in the framework of consensus conferences, such as the Nice Saint-Paul-de-Vence (France) and St. Gallen (Switzerland) conferences. In the United States, the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), and in Europe, the European Society of Medical Oncology (ESMO) make recommendations as well. Therefore, the HAS recommendations are hardly the sole source of information for physicians and these documents sometimes contradict each other. Besides, these can quickly become obsolete, what still limits their relevance. Nevertheless, in the judge's mind, there is no place for conflicting interpretations; scientific knowledge must be consistent, homogeneous and objective. However, the reality is quite the opposite. This simplistic vision shared by judges does not seem to grasp the complexity of everyday medical practice. After a critical reading of the Conseil d'État judgment, we shall consider the potential issues and concerns raised by this ruling in medical practice using the example of hormone therapy for breast cancer patients.
