Introduction: Tumor-infiltrating lymphocytes (TIL) are linked to responses to chemotherapy and immunotherapy and clinical outcomes, especially in high-risk breast carcinomas. MammaPrint® (MP) and BluePrint® (BP) are genomic tests designed to provide risk stratification and molecular classification for early-stage hormone receptor (HR)-positive breast carcinomas, which could include tumors with HER2-low expression. We investigated correlations between TIL measurements, HER2 status, and MP/BP assays in early-stage HR-positive breast carcinomas. Materials and Methods: 167 early-stage HR-positive breast carcinomas with known MP/BP risk categorization were evaluated for TIL using whole slide scanned images according to the International TILs Working Group 2014 guidelines. HER2-low breast cancers were identified by IHC scores of 1+ and 2+ without HER2 amplification. A subset of high-TIL, high-risk cases underwent TSO500 (Illumina) next-generation sequencing (NGS). Results: The patients had a mean age of 51 years, ranging from 26 to 75 years. Among the profiled cases, 97% were either luminal A (96/167) or luminal B (66/167) breast carcinomas, with only five cases classified as HER2-enriched (n = 2) or basal-like (n = 3) carcinomas. Tumor grade was strongly associated with recurrence risk (p<0.001). The prevalence of the HER2-low phenotype was 65%, including 46/69 (67%) high-risk cases. TIL levels ranged from 0 to 70% and were low (≤10%) in the majority (75%) of cases in the cohort. However, high TIL levels were more frequently observed in cases with high recurrence risk (56% vs. 39%, p = 0.03). Additionally, TIL-enriched high-recurrence risk carcinomas contained targetable genomic alterations, including PIK3CA, BRCA1, BRCA2, and HER2 mutations. Conclusions: TIL levels are higher in early-stage HR-positive breast carcinomas with a high recurrence risk. These tumors also harbor targetable genomic alterations, suggesting that TIL measurement and genomic profiling could enhance risk stratification and identify patients who might benefit from targeted therapies. Her-2 low expression in high-risk patients provides a consideration for including novel ADC therapies in this subset of patients. Citation Format: Zoran Gatalica, Inga Rose, Faruk Skenderi, Nataliya Kuzmova, Semir Beslija, Timur Ceric, Inga Marijanovic, Ilir Kurtishi, Semir Vranic. High Tumor-Infiltrating Lymphocyte Levels Correlate with High MammaPrint® Recurrence Risk in Early-Stage Breast Carcinomas [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-11-17.

In the current study, we assessed the prevalence and molecular features of HER2-low phenotype in the apocrine carcinomas of the breast (ApoCa) and its relationship with tumor-infiltrating lymphocytes (TILs). A cohort of 64 well-characterized therapy-naïve ApoCa was used. The TIL distribution was assessed using the hematoxylin and eosin whole slide/scanned images following the international TILs working group recommendations. Next-generation sequencing (NGS) was performed in a subset of HER2-low ApoCa. All patients were women, with a mean age of 62 years. Forty-three carcinomas were pure apocrine carcinoma (PAC; ER−/AR+), and the remaining 21 were classified as apocrine-like carcinomas (ALCs; ER+/−, AR+/−). HER2/neu was positive (score 3+ by IHC and/or amplified by FISH) in 20/43 (47%) PAC and 4/21 (19%) ALC. The prevalence of HER2-low expression (scores 1+ or 2+ without HER2 amplification) in ApoCa was 39% without significant differences between PAC and ALC (P ═ 0.14); however, the HER2-low phenotype was more prevalent in triple-negative PAC than in ALC (P < 0.001). Levels of TILs were low (≤10%) in 74% of ApoCa (median: 5%, range 0%–50%). TIL levels were significantly higher in ALC than in PAC (P ═ 0.02). HER2 status had no impact on TIL distribution (P ═ 0.45). The genomic profile of HER2-low ApoCa was similar to other subtypes of ApoCa. ApoCa has predominantly low TIL, particularly PAC. The prevalence of the HER2-low phenotype in ApoCa is high, which should have therapeutic and clinical implications given the recently approved therapies with antibody–drug conjugates (ADCs) for HER2-low breast cancers.

From February 2023 (Volume 23, Issue 1), the title of the Bosnian Journal of Basic Medical Sciences will be changed to Biomolecules and Biomedicine. The new title reflects the increasing number of published research done on subcellular/molecular level as well as translational and clinical research contained in the term Biomedicine. Biomolecules and Biomedicine will continue to be published by the Association of Basic Medical Sciences of the Federation of Bosnia and Herzegovina. Read more in the PDF.

SUMMARY In prostate adenocarcinoma, both tumorous stroma and epithelium have important role in tumor progression. Transforming growth factor beta (TGF- β) is a promotor in advanced stages of prostate cancer. Matrix Metalloproteinase 2 (MMP2), the endopeptidase that degrades extracellular matrix is considered to be overexpressed in prostatic carcinoma related to its growth and aggressiveness. Therefore, the aim was to analyze the expression of proteins TGF- β and MMP2 between both epithelium and stroma of prostatic adenocarcinoma and adjacent unaffected parenchyma. The intensity of TGF- β and MMP2 expression in epithelium, tumorous stroma and adjacent unaffected parenchyma was analyzed in 62 specimens of prostatic adenocarcinoma by microarray-based immunohistochemistry. TGF- β was more expressed in tumorous than in prostate stroma (p =0.000), while no statistical significance in case of MMP2 (p = 0.097) was found. MMP2 was more expressed in tumorous than in prostate epithelium (p =0.000), while no statistical significance in case of TGF- β (p = 0.096) was observed. The study results indicate that both tumorous stroma and epithelium have a role in tumor progression and support potential role of TGF- β and MMP2 in prostatic adenocarcinoma progression.

Purpose Apocrine carcinoma of the breast (APO) expresses HER2 in 30–50% of cases. This study explored the clinicopathological features and outcome of HER2+/APO and matched HER2+/NST cohort. Methods We used the SEER database to explore the cohorts. Univariate and multivariate analyses were used to assess the survival. Based on ER and PR [steroid receptors/SR/] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons. Results We retrieved 259 cases of HER2+/APO. Most HER2+/APO were SR negative (65%). HER2+/APO were more prevalent in the 80+ age group (24.7% vs. 15.7%, p  < 0.001). HER2+/SR−/APO had a significantly lower histological grade than the HER2+/SR−/NST ( p  < 0.001). Breast cancer-related deaths were more prevalent in HER2+/NST (7.8% vs. 3.9%, p  = 0.019). This was particularly evident between SR− subgroups (10.4% in HER2+/SR−/NST vs. 4.2% in HER2+/SR−/APO, p  = 0.008) and was reaffirmed in breast cancer-specific survival in univariate analysis ( p  = 0.03). Other than race and SR status, HER2+/APO subgroups did not differ in clinicopathological parameters. Conclusions Our study confirms the rarity of the APO and reveals that SR status in APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity.