Up to 15-20% of patients with early breast cancer have tumors that exhibit overexpression, amplification, or both, of the HER2 receptor or oncogene[2]. Trastuzumab has a major effect in reducing recurrence and death in patients with this type of early breast cancer[3]. Although there are other targeting HER2 agents currently available for patients of HER2-positive breast cancer, such as pertuzumab, trastuzumab remains the gold standard for treatment of this disease subtypes. Accumulating evidences have shown that trastuzumab played a critical role in immune regulation to achieve an anti-tumor efficacy. It can either induce immune-mediated anti-tumor effect, or increase the possibility of synergistic regulation of the immune system. In addition, trastuzumab combined with chemotherapy can enhance chemotherapy-induced cytotoxicity by decreasing DNA repair activity and increasing apoptosis[4]. It has been reported that when trastuzumab was applied in conjunction with adjuvant chemotherapy, the advantage of 1-year treatment was even more significant[4].
Nonetheless, trastuzumab also exhibited some side effects, mainly manifested as heart damage. Peripheral edema and lymphedema are commonly observed, but mainly exhibit as local edema. To our knowledge, no cases of diffuse edema in multiple parts of the body have been reported previously. We considered that the severe edema in the reported patient might be related to the trastuzumab-induced allergic reaction, which resulted in endothelial cell damage and inflammatory cytokines production. Subsequently, it could cause decreased vascular wall integrity, increased vascular permeability, aberrant hemorheology, so that blood flow into peripheral tissues leading to edema[5]. Since allergies could induce increased energy consumption, insufficient protein intake will further aggravate the edema. Another possibility is that due to protein exudation into the infarct area combined with membrane rupture that resulting in increased permeability. It leads to regional blood flow suppression, and irreversible tissue damage is occurred[6]. In addition, allergic reaction can further aggravate oxidative stress, leading to angiotensin II upregulation, which in turn results in more inhibitory signals and enhanced oxidative stress[1]. Furthermore, it can activate NADPH oxidase, which lead to mitochondrial dysfunction and cell death. In this case report, after 5 days of treatment with methylprednisone, the edema in neck, face and both upper limbs of the patient were mildly reduced. These suggested that if hormone therapy is given at the early stage, the patient may not experience severe edema later on.
Our report suggests that trastuzumab administration in breast cancers may cause severe allergic reactions, which should be concerned in clinical application. Individual patient may have different sensitivities to drugs, and the occurrence of adverse reactions are various. In clinical application, the early-stage adverse reactions induced by drug administration should be paid great attention, so as to avoid the possibility of subsequent serious adverse reactions.