Search Results (552)

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods: We retrospectively analyzed MBC patients diagnosed between 1991 and 2024 at the Institute for Oncology and Radiology of Serbia. Data included demographics, tumor characteristics, and stage, treatment, hormone receptor and HER2 status, Ki-67 index, genetic testing, and survival. Results: A total of 191 patients were identified (median age 66). Family history was negative in 91% and positive in 5.8%. T2 tumors were most frequent (36%), and 96% presented without metastasis. Mastectomy with axillary or sentinel lymph node dissection was performed in 78.5%. Neoadjuvant chemotherapy and radiotherapy were administered in 5.8% and 8.4%. Estrogen receptor positivity was 72%, progesterone receptor 88%, HER2 overexpression 11.0%, and triple-negative tumors 2.6% (40% with axillary involvement). High Ki-67 (≥15%) was recorded in 28.8%. Adjuvant chemotherapy, radiotherapy, and hormone therapy were given in 36%, 58%, and 68%. Among 37 genetically tested patients, seven had pathogenic variants (BRCA1, BRCA2, CHEK2, PALB2). Disease recurrence occurred in 30%. Median follow-up was 53 months. Median disease-free survival (DFS) was 82 months (1-, 2-, 5-, 10-year DFS: 87%, 73%, 57%, 39%). Median overall survival (OS) 131 months (1-, 2-, 5-, 10-year OS: 95%, 93%, 73%, 53%). Conclusions: This long-term cohort highlights the predominance of hormone-receptor positivity, the infrequency of germline mutations, and moderate survival rates, informing patient management and guiding future studies. Full article

Background and Clinical Significance: Breast cancer is the most frequent malignancy in women. Metastatic breast cancer is considered a treatable but incurable condition, with a median overall survival of only 2–3 years. Among its subtypes, triple-negative breast cancer (TNBC) accounts for a high proportion of breast cancer-related deaths. It is characterized by an aggressive clinical course, early recurrence, and a strong propensity for visceral and brain metastases. Case Presentation: We report the case of a Caucasian woman who developed systemic disease recurrence with lung and mediastinal lymph node metastases, occurring two years after her primary diagnosis and treatment for TNBC. The patient received three months of chemotherapy combined with an adjuvant integrative protocol consisting of melatonin, cannabidiol, and oxygen–ozone therapy. This combined approach led to the complete disappearance of the lung nodules. Subsequently, stereotactic radiotherapy was performed and, in association with the ongoing integrative treatment, resulted in a significant reduction in mediastinal adenopathy. Introduction of immunotherapy, supported continuously by the same adjuvant strategy, achieved a complete and durable remission. Strikingly, the patient remained disease-free five years after the diagnosis of lung and mediastinal metastases. Conclusions: This clinical case highlights the potential benefit of using melatonin, cannabidiol, and oxygen–ozone therapy as part of an integrative approach in patients with aggressive metastatic TNBC. While it is not possible to establish causality from a single case, the sustained remission observed suggests that such unconventional adjuvant strategies could play a supportive role in enhancing the efficacy of standard oncologic therapies. Full article

Background and Objectives: This study aimed to identify clinicopathological factors associated with axillary pathological complete response (ApCR) in patients with HER2-positive breast cancer presenting with clinically node-positive disease (cN+) confirmed by biopsy who received neoadjuvant therapy (NAT), and to assess the prognostic significance of ApCR on survival outcomes. Materials and Methods: A total of 221 patients with clinically node-positive (cN+) HER2-positive invasive breast cancer, with nodal involvement confirmed by fine-needle aspiration or core needle biopsy, who received neoadjuvant therapy (NAT) and subsequently underwent surgery at three centers between January 2015 and January 2025 were retrospectively reviewed. The association between clinicopathological factors and axillary pathological complete response (ApCR) was analyzed using logistic regression. Survival analyses were performed using the Kaplan–Meier method. Results: The median follow-up duration was 34.3 months. Axillary pathological complete response (ApCR) was achieved in 67.9% of patients. The ApCR rate was higher in stage II disease compared with stage III (76.9% vs. 62.9%). Patients with HER2 3+ tumors demonstrated a higher ApCR rate (70.8%) than those with HER2 2+/FISH+ tumors (46.2%). In multivariable logistic regression, HER2 3+ status (OR = 2.745; 95% CI: 1.138–6.619; p = 0.025) and lower clinical stage (OR = 2.251; 95% CI: 1.182–4.287; p = 0.014) were independently associated with a higher likelihood of achieving ApCR. In survival analyses, the 3-year event-free survival rate was 92% (95% CI: 86–98%) in the ApCR group, compared with 75% (95% CI: 63–87%) in the non-ApCR group. Kaplan–Meier analysis demonstrated that ApCR was a significant prognostic factor for EFS (p = 0.001). Median overall survival (OS) was not reached in either group due to the limited number of death events. Conclusions: ApCR was frequent in node-positive HER2-positive breast cancer after neoadjuvant therapy. HER2 3+ status and lower clinical stage independently predicted ApCR, which in turn was associated with improved event-free survival. These findings underscore the prognostic relevance of ApCR in this setting. Full article

This study aimed to develop machine learning models based on conventional MRI features to classify HER2 expression levels in invasive breast cancer and explore their association with disease-free survival (DFS). A total of 678 patients from two centers were included, with Center 1 divided into training and internal test sets and Center 2 serving as an external test set. Random Forest models were trained to distinguish HER2-positive vs. HER2-negative (Task 1) and HER2-low vs. HER2-zero tumors (Task 2) using BI-RADS–based MRI features. SHapley Additive exPlanations were applied to rank feature importance, assist feature selection, and enhance model interpretability. DFS was analyzed using Kaplan–Meier curves and log-rank tests. In Task 1, key features included tumor size, axillary lymph nodes, fibroglandular tissue, peritumoral edema, and multifocal, achieving AUCs of 0.75 and 0.73 in the internal and external test sets, respectively. In Task 2, tumor size, peritumoral edema, and multifocal yielded AUCs of 0.73 and 0.72, respectively. Higher task-specific model scores were associated with shorter DFS in Task 1 (p = 0.037) and longer DFS in Task 2 (p = 0.046). MRI-based machine learning models can noninvasively stratify HER2 expression levels, with potential for prognostic stratification and clinical application. Full article

Background: The clinical and oncologic significance of residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remains poorly defined. While traditionally regarded as radiologic indicators of residual malignancy warranting complete surgical excision, accumulating evidence suggests that many post-treatment calcifications represent benign or in situ changes with limited prognostic relevance. This systematic review synthesizes current evidence to clarify the diagnostic, pathologic, and oncologic implications of persistent calcifications after NAC. Methods: Following PRISMA 2020 guidelines, we conducted a comprehensive search of PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between January 2000 and May 2025. Eligible studies included adult breast cancer patients treated with NAC who demonstrated residual calcifications on mammography or MRI with corresponding histopathologic or survival data. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle–Ottawa Scale and AMSTAR-2. Results: Twenty-four studies involving over 3000 patients were included. Across cohorts, 35–55% of residual calcifications were benign, and many others corresponded to ductal carcinoma in situ rather than invasive carcinoma. Calcifications frequently persisted despite pathologic complete response (pCR), particularly in HER2-positive and triple-negative subtypes. MRI demonstrated superior concordance with pathology compared with mammography. Persistent calcifications did not consistently correlate with worse disease-free or overall survival when pCR was achieved. Radiologic–pathologic discordance contributed to overtreatment in some cohorts, including unnecessary mastectomy or extensive resections. Conclusions: Residual calcifications after NAC should not be regarded as a definitive surrogate of residual invasive disease nor as an obligatory indication for complete surgical removal. Their frequent benign or in situ pathology and limited prognostic value support a more individualized approach to surgical planning, prioritizing pathologic response and margin status over radiographic calcifications alone. Full article

Background: Pregnancy-associated breast cancer (PABC), defined as breast cancer diagnosed during pregnancy or within one year postpartum, is a unique and clinically challenging entity. Evidence suggests that tumors diagnosed during pregnancy (PrBC) and postpartum (PPBC) may differ in biology and prognosis. This study compares clinical features, treatment patterns and outcomes between PrBC and PPBC. Methods: We performed a retrospective analysis of 76 women diagnosed with PABC from January 2000 to June 2023 across two tertiary centers. Patients were classified according to ESMO guidelines as PrBC (n = 41) or PPBC (n = 35). Clinical presentation, tumor characteristics, treatment approaches and survival outcomes were evaluated. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan–Meier analysis and compared with log-rank tests. Results: A total of 76 patients with PABC were included (41 PrBC, 35 PPBC; median age 37 years). Most tumors were high-grade invasive ductal carcinomas, with Luminal B predominant in PrBC and triple-negative breast cancer (TNBC) in PPBC. Locally advanced disease was common (axillary involvement 52%; de novo metastases 9%). Surgery was performed in most cases, with breast conservative surgery (BCS) more frequent in PrBC and mastectomy in PPBC; 46% received neoadjuvant chemotherapy. At median follow-up of 68 months, 7.9% of patients had died and 29% experienced recurrence. Oncologic outcomes were similar between subgroups, with a trend in favor of PrBC. Pregnancy continuation did not adversely affect outcomes. Conclusions: PrBC and PPBC display heterogeneous clinical presentations with a trend toward more favorable outcomes in PrBC. These findings support the need for tailored counseling, individualized management and research designs that differentiate between PrBC and PPBC. Full article

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis and a high risk of early relapse. The incorporation of platinum-based agents into neoadjuvant chemotherapy (NACT) regimens has been linked to improved pathological complete response (pCR) rates. However, the clinical benefit of carboplatin (CBDCA) remains debated due to variable long-term survival outcomes and concerns over cumulative toxicity. This meta-analysis evaluates the efficacy of adding CBDCA to NACT in early-stage TNBC (eTNBC). Methods: A systematic review and meta-analysis were conducted by searching MEDLINE, PubMed, and major oncology conference proceedings (2014–2024), with no language restrictions. Randomized phase II–III trials assessing the addition of CBDCA to standard NACT in eTNBC and reporting pCR and survival outcomes were included. The systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol has not been registered. The primary endpoint was pCR; the secondary endpoint was disease-free survival (DFS). For pCR, a random-effects model was used, and odds ratios (OR) were log-transformed. For DFS, a mixed-effects model was applied, extracting hazard ratios (HR) and converting them into logHR values. Heterogeneity was assessed using I² statistics, and publication bias was evaluated through the Fail-Safe N method and Egger’s regression test. Statistical analyses were performed using Jamovi v2.4.11. Results: Of 30 studies identified, 9 randomized clinical trials were eligible; 6 (BrighTNess, GeparSixto, GS5-01, BR-15-1 PEARLY, NACATRINE, CALGB 40603) met all inclusion criteria, totaling 3402 patients. The addition of CBDCA to NACT significantly improved pCR (OR 1.63; 95% CI: 1.38–1.92; p < 0.001), with low heterogeneity (I² = 0.81%) and no publication bias. DFS was also significantly improved (SHR 0.81; 95% CI: 0.63–0.91; p = 0.003), with moderate heterogeneity (I² = 27.95%) and no bias detected. Conclusions: Adding carboplatin to NACT significantly improves pCR and DFS in patients with early-stage TNBC. Full article

Background/Objectives: To identify preoperative MRI features using computer-assisted diagnosis (CAD) that are associated with invasive disease-free survival (IDFS) and distant metastasis-free survival (DDFS) in patients with primarily operable triple-negative breast cancer (TNBC). Methods: This retrospective study was approved by the institutional review board with informed consent was waived. Between January 2012 and December 2014, 74 consecutive women with primary TNBC (mean age, 51 years; range, 29–77 years) who underwent preoperative MRI were included and followed until August 2021. Dynamic contrast-enhanced and T2-weighted images were obtained using 3T scanners. Peritumoral edema and central necrosis were evaluated retrospectively. CAD was used to extract 3D diameters, angiovolume, and kinetic parameters, and kinetic heterogeneity was calculated. Cox proportional hazards models were used to assess associations between MRI features and IDFS and DDFS, adjusting for clinicopathologic factors. Results: During a median follow-up of 80.9 months, 12 patients developed invasive disease, and 8 developed distant metastasis. In multivariable analysis, peak enhancement (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06–1.84; p = 0.019) and angiovolume (HR, 2.86; 95% CI, 1.26–6.47; p = 0.012) were independently associated with IDFS, whereas angiovolume (HR, 2.47; 95% CI: 1.28–4.78; p = 0.007) was independently associated with DDFS. Conclusions: Preoperative CAD-derived MRI features, particularly peak enhancement and angiovolume, were associated with IDFS in TNBC patients whereas angiovolume alone was associated with DDFS. Full article

Objectives: This single-center retrospective study evaluates the clinical efficacy and safety of percutaneous ablation using microwave ablation (MWA) and irreversible electroporation (IRE) in patients with breast cancer liver metastases (BCLM). Methods: Between August 2018 and December 2023, 32 patients underwent 40 image-guided ablations for 57 BCLM. Mean age was 61.3 years (range: 32–85), and mean tumor size was 2.9 cm (range: 0.9–7.0 cm). Fifty lesions were treated with MWA and seven with IRE. Clinical efficacy was assessed by m-RECIST response at first follow-up imaging (after ≥1 month) and by monitoring local tumor progression (LTP), local tumor progression-free survival (LTPFS), and overall survival (OS). Safety was evaluated by adverse events according to CTCAE. Kaplan–Meier statistics were used for LTPFS and OS. Results: Median follow-up was 32.4 months (95% CI 16.6–48.0). Complete response was observed in 34 tumors (59.6%), partial response in 14 (24.6%), and progressive disease in 9 (15.8%). LTP occurred in 37 tumors (64.9%), with a median time to progression of 11.1 months (95% CI 1.4–20.8). One- and two-year LTPFS rates were 43.6% and 34.1%. Sixteen patients died during follow-up, with median OS of 27.8 months (95% CI 19.0–36.6) and 1- and 2-year OS rates of 90.1% and 55.9%. No major complications occurred. Complications included eight Grade 1 and two Grade 2 complications. Conclusions: Percutaneous ablation demonstrates clinical efficacy and a favorable safety profile in selected BCLM patients, achieving OS comparable to the current literature. Further studies should clarify its additive role within multimodality treatment. Full article

Background: Radioactive colloids are considered the standard of care for sentinel lymph node (SLN) detection. An alternative detection method using superparamagnetic iron oxide (SPIO) nanoparticles is well documented in breast cancer but poorly studied for gynecological tumors, including vulvar cancer (VC). Objective: Our aim was to evaluate the feasibility, accuracy, and safety of SPIO nanoparticles for SLN mapping in patients with VC as a stand-alone technique compared with the combination of two methods: the standard of care using a radioactive isotope (technetium-99; Tc-99) and SPIO as a new tracer. Methods: We conducted a prospective and observational study of SLN mapping in patients with stage IB VC and tumor size ≤ 4 cm. We calculated detection and malignancy rates per patient and per groin in both study groups. During the 36-month follow-up, the groin recurrence rate was estimated for positive and negative SLNs. Kaplan–Meyer curves were used to analyze the probability of survival, depending on disease-free survival. Results: A total of 110 groins assessed by SLN in 60 patients included in this study were analyzed (70 groins from 40 patients in the group with a single tracer and 40 groins from 20 patients in the group of combined tracers). At least one sentinel lymph node was detected in every patient while the bilateral detection rate was 92.3% for the SPIO group and 88.2% for the Tc-99 and SPIO group. The groin detection rate was 94.3% and 90%, respectively. SLN mapping failure was similar in both groups (2.8% and 2.5%, respectively). During a 3-year follow-up, the isolated groin recurrence rate was 2.1% for negative groins and for disease-free survival it was 28.9 months in the combined tracer group versus 32.8 months in the SPIO group. The Kaplan–Meyer curves showed the increased probability of survival for the SPIO group (87.5%); however, it was insignificant. Conclusions: SLN mapping using the SPIO technique in patients with VC is non-inferior to the combined SPIO and Tc-99 method. Full article

Background: Breast cancer mortality and long-term survival are influenced by the unpredictability of recurrences, which cause significant diagnostic and therapeutic challenges for oncology teams. The risk of local and distant recurrence is higher in advanced stages and in the first two years following initial treatment. Accurate staging and continuous monitoring of recurrence are crucial for effective therapy planning. Indicators of recurrence, such as luminal subtype, disease stage, age, and treatment choice, can provide new knowledge and improve patient disease-free and overall survival rates. Methods: We conducted a retrospective cohort study of patients with stage I-III invasive breast cancer at a regional-based institution. The study population consisted of 98 patients with distant and locoregional recurrences from a large cohort of 744 patients diagnosed and treated at our institution between 2007 and 2024. Data on previous treatment for breast cancer, disease stage, molecular subtype, initial size and location of the tumor in the breast, lymph node status, living environment, and type of recurrence were recorded retrospectively. Results: The recurrence patterns in 98 patients included local recurrence in 25 (25.5%), distant recurrence in 70 (71.4%), and both local and distant recurrence in three (3.1%). Our study showed that patients diagnosed with stage II (40.8%) or stage III (55.1%) breast cancer, as well as those with the luminal B subtype (43.87%), were more likely to experience recurrence. The majority of patients affected by recurrent disease were postmenopausal women aged between 51 and 70 years (32 cases aged 51–60 years and 34 cases aged 61–70 years). Tumors measuring between 2 and 5 cm were more likely to produce distant single-organ recurrence (26 cases). More cases were associated with urban areas (77 cases). Conclusions: In menopausal women, most causes of local breast cancer recurrence are related to advanced stage at diagnosis and luminal B subtype. Patient age, primary tumor location in the CSE, and previous adjuvant treatment with aromatase inhibitors may affect the risk of recurrence. Comprehensive studies on recurrence in postmenopausal women can provide a more precise understanding of the extent of disease in such patients. Full article

Background: Breast cancer is the most prevalent malignancy among women and the leading cause of cancer-related mortality. Sentinel lymph node biopsy (SLNB) has emerged as an alternative to axillary lymph node dissection (ALND), with the ACOSOG Z0011 trial demonstrating that SLNB alone yields equivalent oncologic outcomes to ALND for patients with 1–2 positive sentinel lymph nodes (SLNs). Objective: This study evaluates the adoption of Z0011 recommendations at the American University of Beirut Medical Center (AUBMC) and their impact on oncologic outcomes. Methods: This retrospective cohort study includes female patients with early-stage breast cancer (T1–T2, N0, M0) who underwent breast-conserving surgery with SLNB at AUBMC, between January 2011 and December 2016. Data were extracted from the institutional breast cancer database, including demographics, tumor characteristics, surgical management, and follow-up outcomes. Results: SLNB alone was adopted, following publication of the Z0011 trial, in 93.4% of patients, with 6.6% undergoing ALND. Among patients with 1–2 positive SLNs, 27.1% underwent completion ALND. The median number of lymph nodes retrieved increased from two to four over the study period. The most common molecular subtypes observed were luminal A (54.1%), characterized by a predominant stage T1 presentation and small tumor sizes (median tumor size, 1.4 cm). Among patients with 1–2 positive SLNs who underwent ALND, no recurrences or metastatic events were reported. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 95.9% and 93.4%, respectively. No notable differences in OS and DFS were observed between the SLNB alone and ALND groups. Conclusions: Our study demonstrates that SLNB alone provides comparable oncologic outcomes to ALND, supporting its safety and effectiveness as an alternative for early-stage breast cancer patients with 1–2 positive SLNs. These findings extend the Z0011 trial’s applicability to diverse populations, reinforcing SLNB as a less invasive, safe alternative to ALND. Full article

Background/Objectives: Breast cancer is a heterogeneous disease, and the role of the transcription factor SPDEF remains controversial. We aimed to clarify the prognostic value of SPDEF, explore demographic and molecular correlates of its expression, and investigate potential regulatory mechanisms underlying its dysregulation. Methods: Genomic and clinical data for 1218 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA). SPDEF mRNA expression was compared across intrinsic subtypes, age, and race, and prognostic significance was evaluated by Kaplan–Meier analysis. Promoter methylation patterns and DNA methyltransferase (DNMT) expression were examined as potential regulatory drivers. Co-expression analysis was performed using gene panels representing luminal differentiation, basal identity, EMT, proliferation, DNA repair, and immune signaling. Results: Low SPDEF expression was significantly associated with worse overall, relapse-free, and metastasis-free survival across all breast cancers. Expression was lowest in Basal tumors, as well as among younger and Black or African American patients. Promoter methylation at six CpG islands correlated with both reduced SPDEF expression and inferior survival, and DNMT1, DNMT3A, and DNMT3B overexpression also aligned with poor prognosis and Basal enrichment. Co-expression analysis revealed that SPDEF downregulation coincided with loss of luminal markers and increased EMT, proliferation, DNA repair, and immune pathways. Conclusions: SPDEF functions as a tumor suppressor in breast cancer, with reduced expression linked to poor outcomes, aggressive molecular features, and epigenetic regulation. These findings highlight SPDEF and DNMT-driven methylation as potential prognostic biomarkers for enhanced risk stratification and targets for novel therapies, particularly in Basal breast cancers. Full article

Background and Objectives: In early-stage HER2-positive breast cancer, ado-trastuzumab emtansine (T-DM1) has been adopted as the preferred adjuvant approach for patients left with residual invasive disease despite neoadjuvant therapy. The influence of different neoadjuvant regimens on subsequent outcomes in real-world settings remains uncertain. Materials and Methods: From 2019 to 2025, 102 patients treated with adjuvant T-DM1 following surgery after neoadjuvant chemotherapy were retrospectively assessed. Neoadjuvant regimens included doxorubicin plus cyclophosphamide followed by trastuzumab-paclitaxel, doxorubicin plus cyclophosphamide with pertuzumab–trastuzumab–docetaxel, or docetaxel–carboplatin–trastuzumab–pertuzumab. Clinical features, treatment response, survival, and toxicity were evaluated. Results: The mean age of the cohort was 49.7 years, and the majority of patients (80.4%) were aged 40 years or older. Hormone receptor positivity was 82.0%, and invasive ductal carcinoma accounted for 97.1% of cases. Regional responses included 39.2% with axillary pCR despite residual breast lesions, and 5.9% with breast pCR accompanied by axillary disease. Kaplan–Meier analysis demonstrated disease-free survival rates of 100%, 95.2%, and 92.2% at 1, 3, and 5 years, respectively. Adverse events were predominantly grade 1–2, while grade 3–4 toxicities occurred in under 5% of the cohort. Baseline characteristics varied across regimens, reflecting real-world treatment preferences, but survival outcomes remained comparable. Conclusions: Adjuvant T-DM1 was associated with high survival rates and manageable toxicity across different neoadjuvant regimens, underscoring its consistent benefit in routine clinical practice. Full article