## 1 Introduction  
Despite extensive improvement in the diagnosis and management of breast cancer, which is the most common cancer type in women with an incidence of around 30/1000 [1; 2], advanced breast cancer is still accompanied by high mortality rates. For instance, in the case of metastatic breast cancer, the 5-year survival rate is around 23% [3]. Given the dismal prognostic of advanced forms of breast cancer, screening continues to be one of the most important strategies of improving the survival of breast cancer patients [4]. To this end, the guidelines issued by the European Society for Medical Oncology (ESMO) recommend biennial screening for all women aged 50 to 69 years using mammography [5]. However, mammography is an unpleasant experience for the patients and the accuracy of the method is affected by the high density of the breast tissue [5]. Therefore, there is ongoing research for simpler, quicker and more accurate strategies of diagnosing breast cancer.  
Raman spectroscopy is a type of vibrational spectroscopy based on the inelastic scattering of laser photons, which can assess the vibrational energy structure and implicitly the molecular structure of samples [6]. However, the use of Raman is often limited by the low sensitivity of the effect. For instance, the concentration of most metabolites in biofluids like serum or urine is below the detection limit of Raman scattering. Thus, analysing biofluids requires Raman amplification methods such as surface-enhanced Raman scattering (SERS).  
SERS is a method of enhancing the Raman signal of molecules [7], using nanometre-sized metal substrates such as metal colloids [8]. SERS has attracted much attention as a method of analysing biofluids in the point-of-care setting, especially for cancer detection [9]. Thus, SERS enables the assessment of the chemical composition of biofluids, which exhibit a wealth of spectral information that can aid diagnosing diseases such as cancer in the point-of-care setting.  
For instance, preliminary results in a murine model showed that Raman spectra of urine samples displayed distinguishable features in the case of rats with breast cancer [10]. Similarly, [PERSON] et al. showed on n = 20 samples that the SERS spectra of urine displayed distinguishable modifications in the case of patients with prostate cancer [11]. Good classification accuracies using SERS spectra of serum were also reported in the case of colorectal, lung, oral, breast or prostate cancer [12; 13; 14; 15; 16; 17].  
Previous reports on SERS spectra acquired from urine showed that the urinary proteins prevent the acquisition of SERS spectra [11]. Therefore, the authors filtered the urine and then acquired the SERS spectra from protein-free urine. On the other hand, the SERS spectra of proteins can be selectively amplified by modifying the nanoparticles with iodide, which facilitate the chemisorption of proteins onto the nanoparticles [18]. The selective amplification of the SERS signal of proteins using iodide-modified nanoparticles suggests that ions can play important roles in promoting the chemisorption of analytes, in line with the chemical mechanism of SERS [19].  
In this study, we aimed to demonstrate the possibility to diagnose breast cancer based on the SERS spectra of urine in the case of n = 53 patients with breast cancer and n = 22 controls. By including in our analysis a larger cohort than in previous reports, the study contributes to the effort of translating SERS in the clinical setting as a novel diagnostic tool for breast cancer.