## 4 Discussion  
In recent years, the immunogenicity of breast cancer has become subject of great scientific attention, with the aim of better understanding whether it can influence the biological behavior of BC, acquiring prognostic and/or predictive significance of therapeutic response [9; 12; 14; 15; 16]. The presence of TILs is an expression of the antitumor immune response. Many studies have therefore focused on the predictive and/or prognostic impact of TILs in patients with different types of cancers, including BC [9; 10; 11]. TILs are classified into stromal and intratumoral TILs, depending on whether we consider the lymphocytes dispersed in the tumor stroma, or the lymphocytes located within the tumor nests [9; 14; 15]. Due to the absence of a standardized method for evaluating TILs, many studies have evaluated both the sTILs and the iTILs; however, the evaluation of the former was easier to \begin{table}
\begin{tabular}{c c c c} \hline \hline  & \multicolumn{3}{c}{**TILs**} \\ \hline  & **LOW** & **INTERMEDIATE** & **HIGH** \\ \hline CNB & 19 & 21 & 7 \\ \hline SURGICAL & 17 & 23 & 7 \\ SAMPLES & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 6: TILs distribution in CNB vs. surgical samples. \begin{table}
\begin{tabular}{c c c} \hline \hline  & **Ki-67 \textgreater{} 20\%** & **Ki-67 \textless{} 20\%** & **Total** \\ \hline LOW TILs & 9 (19.15\%) & 8 (17.02\%) & 17 \\ \hline I-HIGH TILs & 27 (57.45\%) & 3 (6.38\%) & 30 \\ \hline Total & 36 & 11 & 47 \\ \hline \(p\)-value & & 0.0094 \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Relation between TILs and proliferative index (Ki-67). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**TILs** & **LOW** & **INTERMEDIATE-** & **Total** \\ \hline HR+/HER2+ & 6 (12.77\%) & 22 (46.81\%) & 28 \\ \hline HR-/HER2+ & 11 (23.4\%) & 8 (17.02\%) & 19 \\ \hline Total & 17 & 30 & 47 \\ \hline \(p\)-value & & 0.0150 \\ \hline \hline \end{tabular}
\end{table} 
Table 5: Relation between TILs and hormone receptors. detect and more reproducible [9; 14; 15; 16]. In 2014 a series of recommendations for a standardized assessment of TILs in breast cancer was proposed by an international TILs working group [14]; in addition, several studies demonstrated the prognostic and predictive value of TILs in various cohorts of patients; particularly, among triple negative BCs (TNBCs), TILs can be used as a prognostic marker because they positively correlated with the response to adjuvant chemotherapy, in terms of overall survival [9; 12; 16; 17; 18]. Recent studies aimed to investigate the potential prognostic role of TILs in patients affected by HER-2 positive BC treated with chemotherapy plus trastuzumab. In this regard, the FIN-HER study [18] demonstrated that patients affected by BC exhibiting high TILs levels showed a better response to adjuvant chemotherapy with trastuzumab and, consequently, longer overall survival than those affected by BC showing low TILs. On the other hand, [PERSON] et al. [19] reported that HER2-positive lymphocytic-dominant BCs, defined by the presence of at least 60% STILs, had a slightly worse response when combining trastuzumab with chemotherapy than those treated with chemotherapy alone in terms of relapse-free survival times (80% and 90.9% at 10 years, respectively). Therefore, based on these data, the potential role of TILs in mediating the response to adjuvant chemotherapy plus trastuzumab still remains controversial. Further data from neoadjuvant therapy-based studies [20; 21] showed that high rates of TILs were significantly associated with higher rates of pCR; accordingly, TILs appeared as predictive biomarkers of positive response/resistance to neoadjuvant chemotherapy. Post-neoadjuvant treatment TILs have also been found to be associated with breast cancer prognosis [22; 23]. The aim of the present study was to demonstrate that the evaluation of TILs was capable of identifying, among 47 patients with HER-2 positive BC, specific subgroups of patients characterized by different prognostic and clinical features.