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Drug-induced Interstitial Lung Disease in Breast Cancer Patients: A Lesson We Should Learn From Multi-Disciplinary Integration

Systemic therapy is an indispensable part of the treatment for breast cancer, including chemotherapy, endocrine therapy, and targeted therapy [1]. Systemic therapy is commonly used in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer, which is one of the four subtypes of breast cancer. This subtype accounts for about 20% of all types of breast carcinoma [2]. And it is characterized by a high mortality rate in early stage, a short interval to relapse, and a predisposition to metastasis until HER-2-targeted therapies were invented [3, 4]. As a representative of targeted therapy, trastuzumab (Herceptin®) is a monoclonal antibody that targets the HER-2 molecule, inhibits HER-2 expression, and blocks ligand-independent HER-2 signaling [5, 6]. Paclitaxel, a chemotherapy drug belonging to the group of taxanes is a regular treatment for HER-2-positive patients [7]. The combination of paclitaxel and trastuzumab can reduce the relapse rate and drastically improve pathological complete response rate and prognosis of early-stage or advanced HER-2-positive breast cancer [8–11]. Nevertheless, we cannot neglect their toxicity and interstitial lung diseases (ILD) is one of them. ILDs include a class of non-malignant respiratory diseases [12]. ILDs are marked by pathologic changes such as inflammation and fibrosis in the lung parenchyma [13]. According to the latest classification, interstitial pneumonia is a major form of ILDs [14, 15]. Drug toxicity is one of the causes of interstitial pneumonia (IP) [15] and this condition is usually named as a drug-induced interstitial lung disease (DILD). Medications disposed to cause DILD include chemotherapy agents such as taxanes (docetaxel and paclitaxel) [16–19], or monoclonal antibodies such as trastuzumab, adalimumab, bevacizumab, etc. [19, 20]. The frequency of paclitaxel-induced ILDs was 0.73–12% while the incidence of trastuzumab was estimated to be 0.4%–0.6% [21, 22]. This complication is perilous and difficult to be firmly diagnosed due to its atypical clinical presentation. Also, the medical imaging of ILD are indistinguishable from other common pulmonary diseases [15, 23, 24]. In this article, we discuss a case that was encountered on a ward and review previous studies with similar drug-induced pulmonary injury. We 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, P.R. China