Background and Objective: The clinical success of novel antibody-drug conjugates has led to the identification of a new subgroup within traditionally HER2-negative breast cancers, termed ‘HER2-low.’ The aim of this study was to investigate the clinicopathological differences between HER2-low and HER2-negative groups in neoadjuvant-naive primary breast cancer patients, with a specific focus on stromal tumor-infiltrating lymphocyte (sTIL) density. Materials and Methods: The study included 731 neoadjuvant-naive invasive breast cancer patients. Tumors were classified as HER2-negative (IHC 0) and HER2-low (IHC 1+ or 2+/ISH-negative). sTIL levels were evaluated following the International TILs Working Group guidelines. Results: The HER2-low group (38.7%) demonstrated significantly higher histological grade (p = 0.033) and higher sTIL density (p = 0.006) compared to the HER2-negative group. A stepwise increase in sTIL rates was observed parallel to the HER2 immunohistochemical score (0 → 1+ → 2+) (p = 0.015). The HER2-low/hormone receptor (HR)-negative subgroup exhibited the highest sTIL density (median 35%). No statistically significant difference in overall or disease-free survival was found between the groups. Conclusions: HER2-low breast cancers were associated with a more immunogenic tumor microenvironment compared to HER2-negative tumors. This robust immune infiltration may offset the higher histological grade observed in the HER2-low cohort, potentially explaining the comparable survival outcomes. These findings provide a biological rationale for exploring the synergy between novel antibody–drug conjugates and immune checkpoint inhibitors, particularly in the highly immunogenic HER2-low/HR-negative subgroup.

Background and Objectives: Axillary lymph node metastasis and the number of metastatic lymph nodes are important prognostic factors which are directly related to overall survival in women with breast cancer. Several factors have been identified to predict the likelihood of axillary lymph node metastasis in early-stage breast cancer. High PR expression is often more prevalent in the luminal A subgroup, which is associated with a better prognosis. The aim of this study was to determine the relationship between the percentage of PR expression and the likelihood of axillary metastasis in Her-2-negative, clinical T1-T2N0 luminal type breast cancer. Materials and Methods: A hundred and ninety-nine cases with luminal type, Her-2-negative, clinically and radiologically axilla-negative T1-T2 breast cancer who received radiotherapy were evaluated retrospectively. The pathological specimens were assessed by an experienced pathologist. Results: The statistical evaluation showed that tumor diameter greater than 2 cm, (p = 0.003), presence of lymphovascular invasion (p = 0.001), and PR expression level below 80% (p = 0.037) were identified as significant predictors of lymph node positivity in breast cancer patients. Conclusions: Percentage of progesterone receptor expression along with other molecular biological markers and clinicopathological parameters should be evaluated altogether when predicting axillary metastasis risk before surgery.

Background and Objectives: The aim of this study is to assess the mismatch repair (MMR) status and immunohistochemical changes in cases of recurrent endometrial cancer following primary surgery and to evaluate the impact of these changes on prognosis. Materials and Methods: Thirty-one patients diagnosed with endometrial cancer who underwent surgery and had pathologically confirmed recurrences were evaluated. Changes in MMR protein expression, estrogen receptor (ER)/progesterone receptor (PR), and p53 expression in primary surgery and recurrent tumor tissues were assessed using immunohistochemical methods. Prognostic factors influencing these parameters and survival data were investigated. Results: In the assessment of recurrent materials, there were four cases where the MLH-1&PMS-2 staining status changed from intact to loss and four cases that changed from loss to intact. No changes were observed in regard to MSH-2 &MSH-6 staining. The ratios of pMMR and dMMR following the primary surgery were 55% (n = 17) and 45% (n = 14), respectively. Four cases transitioned from pMMR to dMMR, and four cases transitioned from dMMR to pMMR. After recurrence, changes in the ER, PR, and P53 status were observed in seven, three, and three patients, respectively. Conclusions: Changes in the MMR status, receptors, and P53 were observed. It is necessary to re-evaluate prognostic parameters via biopsies in recurring cases and to adjust rescue treatments accordingly.