## 3 Results
### TILs and Clinicopathological Features  
Of the 47 cases of HER-2 positive BC considered here, six were treated with treated with adjuvant chemotherapy plus trastuzumab but underwent progression of disease (local recurrence): the average time to progression for these patients was 10 months; five of the six cases that progressed showed low TILs (0-10%) at the time of the histological diagnosis, in addition to an absent or mild peritumoral lymphocytic infiltrate; the remaining relapsed case TILs levels were intermediate, equal to about 25%, with a moderate peritumoral  
Figure 1: Hematoxylin and eosin (H&E) stained sections illustrating different TILs distribution in our series. (**A**) Invasive breast carcinoma with low TILs (0–10%) in stromal tissue within the tumor (H&E, \(\times\)10). (**B**) Another case in our series demonstrating increased TILs in tumor stroma, categorized as intermediate (11–40%) (H&E, \(\times\)10). (**C**) High TILs (>40%) in tumor stroma are depicted in this invasive breast cancer case (H&E, \(\times\)20).  
Figure 2: Hematoxylin and eosin (H&E) stained sections illustrating different TILs distribution in our series. (**A**) Invasive breast carcinoma demonstrating low TILs (H&E, \(\times\)10). (**B**) Higher magnification of the same case (H&E, \(\times\)20) illustrating the TILs distribution in tumor stroma. (**C**) Another invasive breast cancer case categorized as intermediate TILs (H&E, \(\times\)10). (**D**) Higher magnification of the same case (H&E, \(\times\)20) demonstrating the increased TILs distribution in tumor stroma.  
lymphocyte infiltrate; notably, none of the 6 relapsed cases exhibited high TILs (40-90%). Considering the surgical management of these patients, two patients underwent mastectomy, while in four patients a more conservative approach was preferred (quadrantectomy). In all patients, clear margins were reported.  
Taking into consideration tumor stage, according to The American Joint Committee on Cancer (AJCC) staging, 12/47 patients showed a prognostically unfavorable stage of III and IV (Table 1); this subgroup of patients showed low levels of TILs, while intermediate and high TILs were never observed (Table 2). No other significant correlation has emerged between TILs distribution and clinicopathological variables.  
Considering nodal status, 19/47 patients showed metastatic nodes (Table 1); this subgroup of patients showed low levels of TILs in 12 cases, while intermediate-high TILs were observed in 7 cases (Table 3). A positive nodal status was significantly related to low TILs (\(p\)-value: 0.006)  
In regard to the correlation between TILs and tumor response to neoadjuvant chemotherapy, our series included only six cases of locally advanced HER-2 positive BC, preoperatively treated with a combination of anthracyclines, taxanes and trastuzumab. All cases examined showed low TILs and none of them underwent tumor pathological complete response (pCR). In addition, 1/6 cases exhibited local disease progression. From an immunohistochemical point of view, in two patients, the neoplasms were luminal HER2 (HR+/HER2+) BCs; in four patients, the neoplasms were pure HER2 (HR-/HER2+, one of which also exhibited immunopositivity for basal CKs--CK14, CK5/6 and focally for CK17, as a basal HER2: HR-/HER2+/basal CKs+).  
No statistically significant associations have been observed between TIL status, histotype and pathological grade.