Search Results (78)

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Background: Pathological complete response (pCR) serves as a prognostic surrogate endpoint for long-term clinical outcomes in breast cancer patients receiving neoadjuvant systemic therapy (NAST). This study aims to develop and evaluate machine learning-based biomarkers for predicting pCR and recurrence-free survival (RFS). Methods: This retrospective monocentric study included 235 women (mean age 46 ± 11 years) with non-metastatic breast cancer treated with NAST. We developed various machine learning models using clinical features (age, genetic mutations, TNM stage, hormonal receptor expression, HER2 status, and histological grade), along with morphological features (size, T2 signal, and surrounding edema) and radiomics data extracted from pre-treatment MRI. Patients were divided into training and test groups with different MRI models. A customized machine learning pipeline was implemented to handle these diverse data types, consisting of feature selection and classification components. Results: The models demonstrated superior prediction ability using radiomics features, with the best model achieving an AUC of 0.72. Subgroup analysis revealed optimal performance in triple-negative breast cancer (AUC of 0.80) and HER2-positive subgroups (AUC of 0.65). Conclusion: Machine learning models incorporating clinical, qualitative, and radiomics data from pre-treatment MRI can effectively predict pCR in breast cancer patients receiving NAST, particularly among triple-negative and HER2-positive breast cancer subgroups. Full article

Purpose: Neoadjuvant endocrine therapy (NET) represents a valuable treatment option for hormone receptor-positive (HR+)/HER2-negative breast cancer, particularly in postmenopausal women. This study aimed to evaluate the clinical and histopathological efficacy of NET and to explore early and late changes in Ki-67 and progesterone receptor (PgR) expression as indicators of endocrine response. Methods: A prospective cohort of 127 postmenopausal patients with stage cT1–4N0–3M0 HR+/HER2− breast cancer was enrolled between 2019 and 2021. Patients received NET (mostly letrozole) for a mean of 7.7 months. In 80 cases, a second core biopsy was performed after four weeks. Tumor size, histological grade, and biomarkers (Ki-67, PgR) were assessed pre- and post-treatment. Results: NET led to a significant reduction in tumor size, with median shrinkage of 47.0% (from 32.0 mm to 17.0 mm, p < 0.0001). Breast-conserving surgery (BCS) was performed in 52.2% of patients and lymph node negativity (pN0) was observed in 50.4%. Median Ki-67 decreased from 20.0% at baseline to 5.0% after four weeks (p < 0.0001) and remained low in surgical specimens (median 5.0%, p < 0.0001). In 33.3% of patients, Ki-67 dropped below 2.7%, and 67.0% showed a concordant decrease in both Ki-67 and PgR. PgR expression declined significantly during treatment (p < 0.0001). HER2 status conversion was noted in 6.4% of patients during treatment. Pathological complete response (pCR) occurred in 3.5%, while minimal or moderate residual disease (RCB I–II) was identified in 71.3% of cases. Conclusions: NET effectively reduced tumor burden and histological aggressiveness, enabling higher rates of BCS. Early reduction in Ki-67 and PgR may serve as surrogate markers of endocrine responsiveness, supporting their use for treatment stratification and monitoring during NET in HR+/HER2− breast cancer. Full article

Pathological complete response (pCR) following neoadjuvant therapy for IBC has shown a strong correlation with event-free survival and overall survival. Over the past three decades, the five-year net survival rate for breast cancer has generally increased; however, several Eastern European countries exhibit lower survival rates. Data from Romania, specifically regarding Her2-positive breast cancer response to therapy, are notably limited. Background/Objectives: The aim of our study was to evaluate the response to NAT using chemotherapy and Her2-targeted therapy in a cohort of 167 patients diagnosed with invasive breast cancer in our institution. Methods: We retrospectively analyzed 167 consecutive cases diagnosed with IBC in our institution between January 2020 and September 2024 with Stages II and III Her2-positive IBC. The overall pCR rates and several factors cited in the literature as predictors of pCR were analyzed. Results: Overall, the pCR rate was 50.29%, with higher values in 3+ cases (62.28%) compared to 2+ cases/ISH amplified (24.53%). Higher pCR rates were observed in hormone-negative cases, Stage II cases, estrogen receptor-negative cases, and high Ki-67 values. Patient age, ISH group, Her2 copy number, Her2:CEP17 ratio, and clinical lymph node involvement did not seem to influence pCR rates in our study. Conclusions: The data presented in our study represent, to the best of our knowledge, the largest cohort of patients diagnosed with Her2-positive IBC from Romania. The presented results and the pCR predictive factors were comparable to those cited in other studies on Her2-positive IBC cases. Full article

Triple-negative breast cancer (TNBC) is a heterogenous group of breast tumors. This type of breast tumor is relatively difficult to manage, due to the lack of expression of Hormone Receptors (HR) and human epidermal growth factor receptor (HER2). Efforts have been made to understand the factors involved in determining how a triple-negative breast tumor responds to therapy. The standard of treatment in most cases today is a combined modality of immune checkpoint inhibitors (ICIs) and chemotherapy with agents such as anti-mitotic (taxanes) or DNA-damaging agents (alkylating agents, cyclophosphamides, platin salts). In this study, we investigated the predictive and prognostic factors for TNBC, in the neoadjuvant setting; understanding each patient’s response before treatment initiation is crucial to guiding the subsequent approach and finally improving patient outcomes. We focused on tumor-infiltrating lymphocytes at the site of the primary tumor (TILs), circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), the mutational status of protein 53 (p53), and Ki-67, investigating the potential roles of these factors in predicting responses to anti-cancer agents. Full article

Background and Objectives: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological complete response (pCR) rates and disease-free survival (DFS) among early-stage breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: We retrospectively analyzed 134 early BC patients treated with NAC between 2017 and 2023. Patients were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or 2+/ISH–). The primary endpoint was total pCR (tpCR); secondary endpoints included breast (bpCR), nodal (npCR), and radiologic complete response (rCR), alongside DFS analysis stratified by hormone receptor (HR) status. Results: Of the cohort, 91 patients (67.9%) were HER2-zero and 43 (32.1%) were HER2-low. There was no statistically significant difference in tpCR (26.4% vs. 27.9%, p = 0.852), bpCR (28.6% vs. 30.2%, p = 0.843), npCR (37.4% vs. 32.6%, p = 0.588), and rCR (23.1% vs. 30.2%, p = 0.374) between HER2-zero and HER2-low groups. DFS did not significantly differ between HER2-zero and HER2-low groups overall (p = 0.714), nor within HR-positive (p = 0.540) or TNBC (p = 0.523) subgroups. Conclusions: HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies. Full article

Background: The role of neoadjuvant endocrine therapy (NET) in patients with luminal tumors is still not well defined in everyday clinical practice. To assess the efficacy of combination NET, we analyzed the outcomes of fulvestrant and aromatase inhibitors (AI) in combination in a real-world population. Methods: This was a single-arm, retrospective longitudinal study of the total population of patients diagnosed with locoregionally advanced, clinical stage II-III, HR+ HER2-, luminal-type eBC, who were treated with the neoadjuvant combination of fulvestrant and AI between 2019 and 2024 at the Clinical University Hospital of Split, Croatia. Results: We enrolled 44 patients in the intention-to-treat (ITT) population, while 34 completed NET and surgery (per-protocol population; PPP). The median duration of NET was 11 months (interquartile range [IQR] of 9–16 months). The best radiological objective response rate (partial or complete response) was achieved by 30 (68.2%) in ITT, and 26 (76.5%) in PPP, defined by radiological examination, breast ultrasound, or MR. In the PPP, the minimal or moderate pathological response according to residual cancer burden (I or II) was observed in 29 (85.3%) patients. The median of absolute changes in Ki-67 was −5 (95% CI: −9 to 0), and the median of relative Ki67 changes was −40% (95% CI: −72% to 0%). Post-surgical Ki-67 was significantly predicted by initial Ki-67, positive lymph nodes, and time from diagnosis to the initiation of NET. Treatment was well tolerated, with no therapy discontinuation or dose reductions needed due to toxicity. The most commonly reported side effects included musculoskeletal pain (45.5%), asthenia (34.1%), and hot flashes (29.5%). Conclusions: Dual hormonal therapy with fulvestrant and AI is an active, easily given, non-toxic, promising neoadjuvant treatment in real-world patients with locally advanced luminal-type eBC who are not candidates for chemotherapy. Full article

Objectives: In this study, the effect of positive surgical margin (PSM) length on predicting postoperative biochemical recurrence (BCR) after radical prostatectomy was evaluated, and based on the findings, an additional R subclassification to the TNM-R system was proposed. Methods: We retrospectively analyzed patients who underwent robot-assisted radical prostatectomy between 30 July 2008 and 31 December 2019. Only patients with PSM were included. Those with negative margins, those receiving neoadjuvant/adjuvant hormone therapy, or those with prior pelvic radiotherapy were excluded. A total of 353 pathology specimens were re-evaluated by a uropathologist, and the PSM length was quantitatively measured. BCR was defined as a PSA level of ≥0.2 ng/mL in two consecutive measurements. Results: The median follow-up time of the patients was 49.5 ± 33.4 months. BCR occurred in 27.1% (n = 96) of patients. A PSM cut-off length of 3.5 mm was identified for predicting BCR (p < 0.001). Among patients with PSM < 3.5 mm, 9.8% experienced BCR, while 54.3% of those with PSM ≥ 3.5 mm did. A PSM length ≥ 3.5 mm was associated with a higher risk of recurrence (OR: 1.249, 95% CI: 1.160–1.345, p < 0.001). In multivariate logistic regression analysis, PSM length remained an independent prognostic factor for BCR (p < 0.001). Conclusions: Quantitative measurement of PSM length serves as an independent predictor of BCR following radical prostatectomy. We propose subclassifying R1 margins into R1a (<3.5 mm) and R1b (≥3.5 mm), which may enhance prognostic accuracy in pathological reporting. Full article

Purpose: Marker placement in a pathological node improves extirpation rates in breast cancer cases with limited axillary involvement. Our goal was to assess the current indications for seed-marked axillary lymph node dissection (SMALND). Methods: We conducted a descriptive observational study, including 93 patients with cN1 breast cancer treated between January 2019 and December 2023. Seed placement was performed under ultrasound guidance, days before the procedure. Intraoperative detection was achieved using a probe, and resection was confirmed radiologically. Results: The primary indication was post-neoadjuvant therapy (72 patients: 60 for chemotherapy and 12 for hormone therapy), followed by initial surgery (14) and a single axillary recurrence (8). The extirpation rate of the marked axillary lymph node was 100%. In targeted axillary dissection (TAD), the concordance rate between the sentinel node and the marked axillary node was 85%. In the 12 cases of initial surgery, axillary lymphadenectomy was avoided because the marked node matched the sentinel node and was the only one involved. Conclusions: The use of seeds was proven to be highly useful in axillary surgery, both in cases of negativization following neoadjuvant therapy and in those with low axillary involvement or a single axillary recurrence. Full article

The systemic treatment of breast cancer has evolved remarkably over the past decades. With the introduction of immune checkpoint inhibitors (ICIs), clinical outcomes for solid tumor malignancies have significantly improved. However, in breast cancer, the indication for ICIs is currently limited to triple-negative breast cancer (TNBC) only. In high-risk luminal B hormone receptor-positive (HR+) breast cancer (BC) and HER2-positive (HER2+) BC, modest efficacy of ICI and chemotherapy combinations were identified in the neoadjuvant setting. To address the unmet need, several novel immunotherapy strategies are being tested in ongoing clinical trials as summarized in the current review: bispecific antibodies, chimeric antigen receptor T-cell therapy (CAR-T), T-cell receptors (TCRs), tumor-infiltrating lymphocytes (TILs), tumor vaccines, and oncolytic virus therapy. Full article

The association between breast cancer and non-Hodgkin lymphoma of the spleen is extremely rare, with very few cases documented in the medical literature. We present the case of a 39-year-old woman in good health but with a family history of breast cancer, who, in 2017, developed invasive lobular carcinoma in her right breast, which was treated with mastectomy followed by hormonal therapy. In 2024, she presented with a suspicious right axillary mass, suspected of recurrence, which was confirmed by fine-needle aspiration biopsy. The patient received neoadjuvant chemotherapy, followed by axillary lymph node dissection and bilateral adnexectomy. CT and PET scans showed suspicious splenic lesions suggestive of metastases. Infectious and hematological tests were negative, leading to the decision to perform laparoscopic splenectomy. Histological examination revealed follicular B-cell non-Hodgkin lymphoma. The patient is now in good general condition and is on a biannual follow-up. The case highlights the diagnostic complexity of tumor recurrences and the need to consider alternative diagnoses other than metastasis in oncological patients. Full article

Background/Objectives: Breast cancer is the most prevalent cancer in adult women. Currently, new therapies and protein determinations with prognostic value are under development. Fascin (encoded by the FSCN1 gene) is an actin-binding protein that is critical for the development of cytoplasmic projections that are essential for tumor invasion. DNA topoisomerase 2-alpha (TOP2A) is a nuclear protein crucial for ATP-dependent breakage, passage, and rejoining of double-stranded DNA and cell division. Both proteins are associated with higher proliferation rates and worse prognosis in breast cancer and together can provide comprehensive information on prognosis and treatment response. Methods: We simultaneously assessed fascin expression and TOP2A/CEP17 DNA copy number ratios in various histological and molecular subtypes. Additionally, these markers were analyzed along with previously established diagnostic markers and other relevant clinical data. Results: Our series included 265 patients, four of whom were male, and all of which were diagnosed with breast carcinoma. Of the 265 patients initially included, sufficient material for analysis was available for 175 cases, as some samples were excluded because of insufficient tissue quantity, poor preservation, or lack of hybridization in certain assays. Immunohistochemical (IHC) expression of fascin, both in its aggregated form and by category, showed no association with the TOP2A gene alteration ratio. Fascin expression was significantly associated with histological subtype (p < 0.001), molecular subtype (p < 0.001), hormone receptor (HR) (p < 0.001), BCL2 (p = 0.003), Ki67 (p = 0.002), and histological grade (p < 0.001). TOP2A was significantly associated with molecular subtype (p = 0.041), Ki67 (p = 0.048), and histological grade (p = 0.033). In our study, molecular subtype (p = 0.037) emerged as an independent variable for the complete histological response to neoadjuvant treatment. Multivariate analysis linked pathological stage (p = 0.002) and estrogen receptor (ER) expression (p = 0.004) to overall survival (OS) and disease-free survival (DFS). Conclusions: No statistical relationship was evident between fascin expression (IHC) and the TOP2A copy ratio. The results of this study suggested that the mechanisms of increased cell proliferation associated with alterations in fascin and TOP2A are independent. Full article

Breast cancer remains one of the most prevalent diseases worldwide, primarily affecting women. Its heterogeneous nature poses a significant challenge in the development of effective and targeted treatments. Molecular characterization has enabled breast cancer to be classified into four main subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer, based on hormone receptor expression and HER2 status. A deeper understanding of these molecular markers and their associated signaling pathways, such as MAPK and PI3K/AKT, is essential for improving prognosis and optimizing treatment strategies. Currently, several therapeutic agents are utilized in neoadjuvant and adjuvant therapies, often in combination with surgical interventions. However, emerging evidence highlights the growing challenge of drug resistance, which significantly limits the efficacy of existing treatments. Addressing this issue may require innovative approaches, including combination therapies and precision medicine strategies, tailored to the molecular profile of each patient. Therefore, a comprehensive understanding of the pathophysiologic mechanisms driving breast cancer progression and resistance is crucial for the development of advanced targeted therapies with greater precision and efficacy. This review aims to explore recent advancements in molecular research related to breast cancer subtypes and provide a critical analysis of current therapeutic approaches within the framework of precision medicine. Full article

Background/Objectives: The effectiveness of robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (ePLND) in improving oncological outcomes for patients with high- or very-high-risk prostate cancer (HR/VHR-PCa) remains a subject of debate. This study aimed to compare the efficacy of neoadjuvant chemohormonal therapy (NCHT) and ePLND in reducing biochemical recurrence (BCR) in patients with HR/VHR-PCa undergoing RARP. Methods: This retrospective, multicenter cohort study included 1182 patients with HR/VHR-PCa who underwent RARP at six Japanese institutions. Patients were stratified into three groups: those who received NCHT followed by RARP without ePLND (Group 1), those who received neoadjuvant hormonal therapy (NHT) followed by RARP with ePLND (Group 2), and those who underwent RARP with ePLND (Group 3). The primary endpoint was the rate of BCR, while the secondary endpoint was biochemical recurrence-free survival (BRFS) following RARP. Results: Of the 1182 patients, 154 patients were included in Group 1, 97 patients were included in Group 2, and 470 patients were included in Group 3. By the end of the follow-up period, 243 patients (33.8%) had experienced BCR, 27 (3.7%) had progressed to castration-resistant prostate cancer, and 5 (0.7%) had died from PCa. Over a median follow-up period of 41.4 months, BCR occurred in 16.5% of patients in Group 1, 36.1% of patients in Group 2, and 38.9% in Group 3 (p < 0.001). The 3-year BRFS rate was 63.6% in Group 1, 53.1% in Group 2, and 63.9% in Group 3. Conclusions: The findings of this study indicate that NCHT in patients with HR/VHR-PCa undergoing RARP without ePLND may reduce the risk of postoperative BCR compared to those undergoing RARP with ePLND. Full article

Background/Objectives: This study evaluates the impact of clinical, pathological, and treatment-related factors on breast cancer recurrence and overall survival following neoadjuvant chemotherapy and surgery. Patients and Method: A total of 298 patients treated at Diakoneo Diak Klinikum, Schwäbisch Hall, Germany (2010–2021) were analyzed. Key variables included hormone receptor status, molecular subtypes, tumor grade, treatment protocols, and metastatic disease at diagnosis. Results: Recurrence was strongly associated with metastatic disease (p < 0.001) but not with hormone receptor status or molecular subtypes. Platinum/taxane-based chemotherapy was linked to a lower recurrence risk (p = 0.05) compared to anthracycline-based regimens. Patients with recurrence had significantly lower overall survival (27.91% vs. 8.24%, p < 0.001). Logistic regression suggested a trend toward increased recurrence in ER-positive and PR-negative patients, though not statistically significant. These findings emphasize the importance of personalized treatment strategies and highlight the need for future studies incorporating genomic data and residual disease analysis to refine recurrence risk prediction and therapy selection. Full article