Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term “low ER-positive breast cancer” for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC.

Background and Objectives: A recent clinical trial has demonstrated that breast cancer with low-HER2 expression levels responds to trastuzumab deruxtecan treatment. This has prompted a re-evaluation of HER2-targeted therapies in the HER2-negative group. Further research is required in the form of more detailed information about HER2-negative breast cancers with HER2-null, HER2-ultralow, and HER2-low subgroups. This study represents a novel approach to this field. Materials and Methods: HER2-negative breast cancer patients were classified into three groups as HER2-null, HER2-ultralow, and HER2-low. A comparison of clinicopathological features was analyzed retrospectively. Results: Of 722 patients, 22.3% were HER2-null, 23.7% were HER2-ultralow, 54.0% were HER2-low. While two-thirds of all the patients were evaluated as having T2 tumors, T4 tumors constituted 2.4%. Among HER2-negative cases, 11.8% were triple-negative and 88.2% were hormone-positive. The mean tumor diameter was 0.57 cm larger in the HER2-ultralow group than in the HER2-null group and 0.34 cm larger in the HER2-low group than in the HER2-null group. HER2-null tumors tend to be smaller. The HER2-low group was more likely to relapse than the HER2-null group. There were no significant differences in the distribution of hormone positivity or negativity (TNBC) among the groups; they accounted for 89.2% and 10.8% of all cases, respectively. Conclusions: HER2-negative breast cancer is a heterogeneous disease and deserves a detailed review in terms of diagnosis and treatment. HER2-ultralow tumors are larger in size and have a prognosis comparable to HER2-null tumors. HER2-low tumors tend to recur much more frequently and with poorer outcomes. In this field, new therapeutic approaches may result in better outcomes.

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: Non-obstructive azoospermia (NOA) represents a severe form of male infertility characterized by impaired spermatogenesis and heterogeneous histopathological findings. Identifying candidate non-invasive biomarkers associated with underlying testicular histopathology before surgical sperm retrieval may provide additional information during preoperative evaluation and patient counseling. Introduction: This study aimed to investigate the association of serum inhibin B (INHB), follicle-stimulating hormone (FSH), and their ratio (INHB/FSH) with histopathological groups in men undergoing microdissection testicular sperm extraction (micro-TESE). Materials and Methods: A total of 73 men with NOA who underwent micro-TESE were retrospectively analyzed. Patients with obstructive azoospermia, endocrine disorders, or incomplete data were excluded. Serum FSH, luteinizing hormone (LH), testosterone, and INHB levels were measured within 2 months before surgery. Based on histopathological evaluation, patients were classified into five histopathological groups: Sertoli cell-only syndrome (SCOS), early maturation arrest (EMA), late maturation arrest (LMA), hypospermatogenesis (HSG), and normospermatogenesis (NS). The association between hormonal parameters and histopathological groups was evaluated using receiver operating characteristic (ROC) analysis and binary logistic regression. Results: The INHB/FSH ratio differed significantly among the histopathological groups ( p < 0.001). Receiver operating characteristic analysis demonstrated moderate-to-high discriminative performance, with area under the curve values ranging from 0.77 to 0.91. In this exploratory cohort, provisional thresholds were observed across the histopathological groups, with lower values generally associated with SCOS, EMA, and LMA and higher values associated with HSG and NS. These findings should be considered hypothesis-generating and require internal and external validation before clinical application. Binary logistic regression demonstrated that higher INHB/FSH ratios were significantly associated with favorable sperm retrieval outcomes, with an odds ratio of 2.36 per 10-unit increase. Conclusions: The serum INHB/FSH ratio was associated with histopathological groups and sperm retrieval outcomes in men with NOA undergoing micro-TESE. These findings suggest that the INHB/FSH ratio may warrant further investigation as a candidate non-invasive biomarker associated with histopathological groups in men with NOA.