The Breast Journal[JOURNAL]
Sun
200 papers
Systematic Review and Meta-Analysis: Association Between Circulating and Tissue Levels of Selenium and Zinc and Breast Cancer Risk.
Lucarelli AP, Martins MM, Teruya MM … +2 more , Yauti TT, Hayashi DR
Breast J · 2026 · PMID 42390038 · Full text
BACKGROUND: Selenium (Se) and zinc (Zn) are essential micronutrients that play roles in antioxidant defense and the regulation of cell proliferation. Increasing evidence suggests that disturbances in trace element balanc...
BACKGROUND: Selenium (Se) and zinc (Zn) are essential micronutrients that play roles in antioxidant defense and the regulation of cell proliferation. Increasing evidence suggests that disturbances in trace element balance may contribute to breast carcinogenesis; however, findings across studies remain inconsistent. OBJECTIVE: To evaluate the association between circulating and tissue Se and Zn levels and breast cancer. METHODS: A systematic review and meta-analysis were conducted according to PRISMA 2020 and MOOSE recommendations. Searches were performed in MedLine, EMBASE, and LILACS from database inception until April 15, 2026. Case-control studies comparing selenium and zinc levels between women with breast cancer and control groups were eligible. Two independent reviewers performed study selection, data extraction, risk-of-bias assessment, and publication bias analysis using Egger's regression test. RESULTS: Thirty case-control studies were included. Most studies (83.3%) were classified as high methodological quality according to the Newcastle-Ottawa Scale. Meta-analyses revealed significantly lower selenium levels in plasma (MD = -12.10 μg/L; 95% CI: -17.54 to -6.65; p < 0.0001), selenium in nails (MD = -0.02 μg/g; 95% CI: -0.04 to -0.01; p = 0.006), and zinc in plasma (MD = -0.33; 95% CI: -0.47 to -0.19; p < 0.00001) in breast cancer patients compared with controls. CONCLUSIONS: The pooled findings indicate an inverse association between breast cancer and selenium levels measured in plasma and nails, as well as plasma zinc concentrations. Nevertheless, interpretation should remain cautious because all included studies had observational designs, with marked heterogeneity and potential residual confounding. Lower circulating selenium and zinc levels, together with reduced selenium concentrations in nails, were associated with breast cancer occurrence. Additional prospective studies are required to clarify causality and determine the clinical significance of these associations.
Real-World Practice Patterns in Diagnosis and First-Line Treatment in Metastatic Breast Cancer.
Manohar PM, Shankaran V, Davidson NE … +10 more , Hunter N, Gwin WR, Yung RL, Specht JM, Federenko C, Qin S, Wu QV, Voustinas JM, Roth JA, Linden HM
Breast J · 2026 · PMID 42365454 · Full text
INTRO: Divergence from national guidelines and variations in practice patterns impact care and outcomes in patients with metastatic breast cancer (MBC). We sought to assess the quality of care in the diagnosis and treatm...
INTRO: Divergence from national guidelines and variations in practice patterns impact care and outcomes in patients with metastatic breast cancer (MBC). We sought to assess the quality of care in the diagnosis and treatment of real-world patients with MBC in Washington State. METHODS: Data were retrospectively analyzed using a linked cancer registry and insurance claims platform for patients with recurrent or de novo MBC diagnosed between 2008 and 2019. RESULTS: We identified 1101 patients with MBC (median age: 66), 715 recurrent and 386 de novo. Most patients were White (89%), all were insured (Commercial [47%], Medicaid [4%], Medicare [35%], or multiple [13%]), and 15% lived in areas of high deprivation (Area Deprivation Index [ADI]: 8-10). Of the patients with recurrent MBC, less than half received a biopsy (49.5%) or biomarker reassessment (48.7%) to confirm the diagnosis of MBC. Patients treated at high- and medium-volume centers had higher rates of biopsy than low-volume clinics (51.9%, 54.3%, and 40.7%, respectively, p = 0.03). ET alone was more common in patients who did not undergo biopsy (62.3% vs. 37.7%, p < 0.001) or biomarker reassessment (62.7% vs. 37.3%, p < 0.001). Among the 677 patients with estrogen receptor (ER)+/HER2- MBC (de novo and recurrent), most received ET alone (69%), followed by CT (22%) and CDKi + ET (9%). Importantly, 40% of patients were treated before CDK4/6i approval. Most patients who received CDKi + ET were < 65 years old (65.2%, p < 0.02). Patients with commercial insurance were more likely to receive CDKi + ET compared to those with Medicare/Medicaid. (60.9% vs. 26.1%, p = 0.10). CONCLUSION: Our findings highlight key gaps in MBC management and serve as a launch point for patient-centered and quality-promoting initiatives.
Factors Associated With Preoperative Radiological Tumor Size Underestimation in Clinical T1-2 Breast Cancer Patients.
Kim J, Lee Y, Yoon SY … +6 more , Cho H, Seo YY, Kim JY, Shin YJ, Park K, Gwak G
Breast J · 2026 · PMID 42363571 · Full text
BACKGROUND: Accurate preoperative tumor size measurement is essential for determining optimal surgical margins in breast cancer patients. Thus, this study aimed to evaluate the factors associated with preoperative radiol...
BACKGROUND: Accurate preoperative tumor size measurement is essential for determining optimal surgical margins in breast cancer patients. Thus, this study aimed to evaluate the factors associated with preoperative radiological tumor underestimation in clinical T (cT) Stage 1-2 breast cancer patients. METHODS: We retrospectively reviewed the data of 365 cT1-2 breast cancer patients. Radiological tumor size was defined as the larger dimension on ultrasonography or magnetic resonance imaging. A pathological-to-radiological tumor size ratio > 1.2 or a tumor size discrepancy (pathology minus radiology) ≥ 5 mm was considered indicative of radiological underestimation. Preoperative variables, including age, body mass index (BMI), cT stage, maximum standardized uptake value of tumor, molecular subtype, and histologic subtype and grade, were analyzed to identify associated factors. Tumor size discrepancy (pathology minus radiology) was compared across subgroups, and the difference between pathological and radiological tumor size measurements was evaluated in each subgroup. RESULTS: A BMI ≥ 25 kg/m (p = 0.006) and invasive lobular carcinoma (ILC) histology (p = 0.030) were associated with a pathological-to-radiological tumor size ratio > 1.2. A BMI ≥ 25 kg/m (p = 0.015), ILC histology (p = 0.022), and cT stage (p = 0.027) were associated with a tumor size discrepancy (pathology minus radiology) ≥ 5 mm. Significant differences in tumor size discrepancy between patients with a BMI ≥ 25 kg/m and those with a BMI < 25 kg/m (p = 0.003) and between patients with an ILC and those with non-ILC (p = 0.041) were observed. Bland-Altman analysis showed radiological underestimation in ILCs (4.3 mm). CONCLUSION: In cT1-2 breast cancer patients, a BMI ≥ 25 kg/m and/or an ILC are predictive of radiological tumor underestimation, warranting supplemental imaging and intraoperative margin assessment.
Long-Term Side Effects of Breast Cancer Treatments: A Systematic Review.
Babaee E, Soheyli M, Nafissi N
Breast J · 2026 · PMID 42345555 · Full text
BACKGROUND: Breast cancer treatments, including chemotherapy, radiotherapy, endocrine therapy, targeted therapy, and surgical interventions, have significantly improved survival rates. However, these treatments are assoc...
BACKGROUND: Breast cancer treatments, including chemotherapy, radiotherapy, endocrine therapy, targeted therapy, and surgical interventions, have significantly improved survival rates. However, these treatments are associated with long-term side effects that can impact the quality of life of survivors. Understanding these adverse effects is crucial for optimizing survivorship care. METHODS: This systematic review was conducted following PRISMA guidelines to assess the long-term side effects of breast cancer treatments. A comprehensive literature search was performed for studies published between 2005 and 2024. Studies examining long-term (≥ 12 months posttreatment) adverse effects in breast cancer survivors were included, with data extraction and risk of bias assessments conducted by independent reviewers. RESULTS: The review identified a broad spectrum of long-term side effects, including cardiovascular complications, cognitive impairment, persistent fatigue, lymphedema, menopausal symptoms, and psychological distress. Chemotherapy was frequently associated with peripheral neuropathy and cognitive decline, while radiotherapy increased the risk of fibrosis, secondary malignancies, and ischemic heart disease. Endocrine therapy contributed to osteoporosis, joint pain, and metabolic disturbances, whereas HER2-targeted therapies were linked to cardiotoxicity. In addition, surgical interventions, particularly axillary lymph node dissection, were a primary cause of lymphedema. Psychological distress, including anxiety, depression, and posttraumatic stress disorder, was also prevalent among survivors. CONCLUSION: The long-term side effects of breast cancer treatments highlight the need for comprehensive survivorship care, including routine monitoring, personalized rehabilitation programs, lifestyle modifications, and psychosocial support. Future research should focus on identifying risk factors, developing targeted interventions, and optimizing treatment strategies to minimize adverse effects and improve the quality of life for breast cancer survivors.
Exploratory Clinical Trial of Honghua Xiaoyao Pills for the Treatment of Liver Depression and Haemostasis-Type Hyperplasia of Mammary Glands: A Single-Centre, Single-Arm Study.
Zheng L, Liu W, Qiu JY … +6 more , Zhao Y, Li XF, Zhou ZG, Wang JT, Cui Y, Zhang XJ
Breast J · 2026 · PMID 42340092 · Full text
BACKGROUND: Hyperplasia of mammary glands (HMG) is a common benign disease of the female breast. OBJECTIVE: This study aimed to observe the clinical efficacy and safety of Honghua Xiaoyao pills in the treatment of liver...
BACKGROUND: Hyperplasia of mammary glands (HMG) is a common benign disease of the female breast. OBJECTIVE: This study aimed to observe the clinical efficacy and safety of Honghua Xiaoyao pills in the treatment of liver depression and haemostasis-type HMG, as well as their impact on menstruation. METHODS: Sixty patients diagnosed with liver depression and haemostasis-type HMG in the breast disease department of our hospital were selected as the study participants. The treatment involved oral administration of Honghua Xiaoyao pills: four pills per dose, three times a day, for a duration of 3 months without interruption during menstruation. Hormones, Western painkillers and similar Chinese herbal medicines were prohibited during the trial. Changes in breast pain, breast masses, menstrual volume and safety indicators were observed. RESULTS: Three patients were lost to follow-up after 2 months of treatment, and four patients voluntarily withdrew from the study. The changes in breast pain scores, breast mass size scores and breast mass texture scores relative to baseline and their respective change rates showed statistically significant differences (p < 0.0001). Changes in lower abdominal distension, breast distension, menstrual blood clots, chest tightness/discomfort and emotional scores relative to baseline were also statistically significant (p < 0.0001). CONCLUSION: Honghua Xiaoyao pills are effective in reducing breast pain, shrinking breast masses and improving lower abdominal distension, breast distension, menstrual blood clots, chest tightness/discomfort and emotional symptoms in patients with liver depression and haemostasis-type HMG. TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry: ITMCTR2024000165.
HER2-Ultralow: Prevalence, Characteristics, and Treatment Choices Among Advanced Breast Cancer Patients With Tumors Initially Scored as IHC 0.
Iyengar AR, Downs EP, Mehta S … +14 more , Rangarajan N, Woo MS, Sredni ST, Donato RD, Simsek S, Wilson DM, Krieser K, Patzke EB, Kyek N, Anderson C, Wagner T, Hipp J, Nassar A, Barman H
Breast J · 2026 · PMID 42340017 · Full text
Historically, HER2 status in invasive breast cancer has been categorized as HER2-positive (IHC 3+, IHC 2+/ISH+) or HER2-negative (IHC 0, IHC 1+, IHC 2+/ISH-). Patients meeting IHC 0 with membrane staining (HER2-ultralow)...
Historically, HER2 status in invasive breast cancer has been categorized as HER2-positive (IHC 3+, IHC 2+/ISH+) or HER2-negative (IHC 0, IHC 1+, IHC 2+/ISH-). Patients meeting IHC 0 with membrane staining (HER2-ultralow) criteria may benefit from HER2-targeted therapies such as trastuzumab deruxtecan. This cohort study assessed the prevalence of HER2-ultralow expression by re-scoring HER2 IHC slides using Mayo Clinic electronic health record data. Three hundred patients with advanced breast cancer (Stages III-IV) and documented HER2 IHC 0 status (January 2017-March 2023) were identified. One slide per patient was digitized and independently re-scored by two Mayo Clinic pathologists following the 2023 ASCO-CAP guidelines, including tumor staining percentage to denote HER2-ultralow status. A sensitivity analysis was performed by a third independent pathologist. The re-scored patients had a mean age of 57.7 years (SD = 13.6). Most samples (95%, n = 285) remained scored IHC 0 by at least one pathologist; 60% of these met HER2-ultralow criteria per at least one pathologist. HER2-ultralow prevalence ranged from 43% to 45% per pathologist, with 57% overall interpathologist concordance. Samples with no observable staining comprised most of the concordant cases. Treatment patterns were similar between HER2-ultralow and no-staining groups; however, time to treatment failure (TTF) varied between groups across lines of therapy (LOT). In HR- positive cohorts, median TTF for LOT1 was 7.73 months in patients with HER2-ultralow versus 9.43 months with no observable IHC staining. In HR- negative cohorts, median TTF was 5.00 months for HER2-ultralow versus 3.17 months with no observable IHC staining. Similar TTF trends were observed in LOT2-LOT3. Approximately three in five samples originally classified as IHC 0 met HER2-ultralow criteria, suggesting many patients may benefit from HER2-directed therapy if reclassified. These findings highlight potential challenges of identifying HER2-ultralow expression and suggest the need for enhanced pathologist training, adherence to best practices, and integration of digital pathology and artificial intelligence solutions. Trial Registration: ClinicalTrials.gov_identifier: NCT03734029.
Clinical Characteristics and Prognostic Risk Factors in Breast Cancer With Liver Metastasis.
Yu D, Zhu C, Yang S … +2 more , Wang D, Guan X
Breast J · 2026 · PMID 42322174 · Full text
BACKGROUND: Liver metastasis is a key adverse prognostic factor in breast cancer patients. This research was aimed to assess the development, risk factors, and prognostic determinants of breast cancer liver metastasis (B...
BACKGROUND: Liver metastasis is a key adverse prognostic factor in breast cancer patients. This research was aimed to assess the development, risk factors, and prognostic determinants of breast cancer liver metastasis (BCLM). METHODS: We retrospectively analyzed the data of breast cancer from the Surveillance, Epidemiology, and End Results (SEER) (N = 560,908) and Jiangsu Province Hospital (JSPH) database (N = 294). The risk factors for BCLM were identified via multivariate logistic regression, and overall survival (OS) was assessed with Kaplan-Meier (KM) survival curves and Cox regression models. RESULTS: In the SEER cohort, liver metastasis attacked 1.3% of patients, and the highest incidence was found in the HR-/HER2+ subtype (4.4%). The risk factors for BCLM include young age, high pathological grade, concurrent bone, lung or brain metastasis, and HER2-positive or triple-negative subtype. The median OS of BCLM patients was short (SEER: 22 months; JSPH: 33.5 months). OS was shorter in patients with concomitant metastasis to other organs or with HER2-negative subtype. Hepatic resection remarkably prolonged survival (SEER: 90 vs. 35 months; JSPH: not reached vs. 31.3 months). In the JSPH cohort, molecular subtype changed in 27.5% of patients during metastasis. CONCLUSIONS: The occurrence of BCLM is affected by age, tumor grade, other organ involvement, and molecular subtype. Survival was improved in BCLM patients with liver-only metastasis, HER2-positive subtype, or those who underwent hepatic resection. The number and molecular characteristics of liver metastasis are important prognostic predictors, and receptor conversion highlights the need for reassessment of therapeutic strategies during metastatic progression.
Effectiveness and Safety of Hypofractionated Radiotherapy in Patients With Ductal Carcinoma In Situ (DCIS).
Samiee R, Kharaghani M, Shahsavand A … +6 more , Forghani S, Mozafar M, Dehnavi NS, Ghanbari Z, Nicosia L, Jafari F
Breast J · 2026 · PMID 42253163 · Full text
OBJECTIVE: To synthesize the available evidence on the oncologic outcomes, toxicity, and cosmesis of hypofractionated whole-breast irradiation (HF-WBI) in patients with ductal carcinoma in situ (DCIS) following breast-co...
OBJECTIVE: To synthesize the available evidence on the oncologic outcomes, toxicity, and cosmesis of hypofractionated whole-breast irradiation (HF-WBI) in patients with ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS). METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, Embase, and Web of Science were searched from inception until July 12, 2025. We included studies of DCIS patients treated with BCS followed by HF-WBI (fraction size > 2.0 Gy). Both comparative studies (against conventional fractionation [CF]) and single-arm studies reporting outcomes for HF-WBI alone were included. Pooled incidence rates for outcomes from single-arm studies and pooled hazard ratios (HRs) or odds ratios (ORs) from the limited comparative studies were calculated using random-effects models. RESULTS: Nineteen studies were included. Local control and overall survival were excellent and equivalent between HF-WBI and CF-WBI. The pooled HR for local recurrence comparing ultrahypofractionation to CF was 0.89 (95% CI 0.64-1.24). HF-WBI significantly reduced the odds of acute dermatitis (OR 0.22, 95% CI 0.13-0.35). Late toxicities were infrequent (e.g., telangiectasia: 2%, 95% CI 0%-5%). Good/excellent cosmesis was reported in 90% (95% CI 84%-94%) of patients. CONCLUSION: HF-WBI is a safe and effective treatment for DCIS, achieving oncologic outcomes equivalent to CF while offering improved tolerability, reduced acute skin toxicity, and excellent cosmetic results. These benefits, combined with increased convenience and potential cost savings, support the integration of HF-WBI into standard practice for DCIS.
Expert Opinions on Postoperative Complications in Breast Cancer Surgery After Neoadjuvant Chemotherapy: A Descriptive Study Through Structured Interviews With Surgeons in Austria.
Leser C, Eisl R, Dorffner G … +5 more , Kabashi F, Gschwantler-Kaulich D, Deutschmann C, Danzinger S, Koller R
Breast J · 2026 · PMID 42218781 · Full text
BACKGROUND: Neoadjuvant chemotherapy (NACT) is an important component in preparing breast cancer patients for surgery. Its impact on postoperative complications, such as wound infections and bleeding, remains unclear. Wh...
BACKGROUND: Neoadjuvant chemotherapy (NACT) is an important component in preparing breast cancer patients for surgery. Its impact on postoperative complications, such as wound infections and bleeding, remains unclear. While most studies show no increase in complication rates, factors such as smoking may elevate risk. Understanding surgeons' perspectives on bleeding and related influences is therefore essential. METHODS: This study used a questionnaire on bleeding and wound healing. After ethical approval in Vienna and Burgenland, 33 surgeons were recruited. Data were collected between July and December 2022 through interviews or self-administered questionnaires and analyzed descriptively. RESULTS: Overall, 63.6% of surgeons reported recognizing NACT-treated patients intraoperatively. Perceptions of blood loss varied, with some noting no difference and others reporting increased bleeding. The influence of tumor size and smoking was debated, with no clear consensus. Most surgeons did not observe prolonged operative times. Challenges in axillary dissection and sentinel lymph node identification were reported, particularly after NACT. CONCLUSION: Surgeons' views on the impact of NACT in breast surgery vary considerably. These findings highlight the complexity of integrating NACT into surgical practice and the need for further research to improve training, patient counseling, and evidence-based guidelines.
Development and Validation of a Cuproptosis-Based Risk Score Model for Predicting Neoadjuvant Chemotherapy Response in Breast Cancer: A Transcriptomic Analysis.
Zhang L, Wang J, Tan B … +2 more , Wang X, Luan Z
Breast J · 2026 · PMID 42212700 · Full text
OBJECTIVE: This study developed a cuproptosis-related transcriptomic risk score model to predict neoadjuvant chemotherapy (NAC) response in breast cancer (BC) patients and explored its association with the tumor immune m...
OBJECTIVE: This study developed a cuproptosis-related transcriptomic risk score model to predict neoadjuvant chemotherapy (NAC) response in breast cancer (BC) patients and explored its association with the tumor immune microenvironment. METHODS: Analysis of transcriptomic and clinical data from TCGA and GEO revealed differentially expressed cuproptosis-related genes. LASSO-based Cox regression was used to build the risk score. Model performance was evaluated using Kaplan-Meier survival, ROC curves, and GSEA/GSVA in the training cohort and further validated in an independent external cohort. Drug sensitivity was predicted using the oncoPredict tool, and RT-qPCR was used to validate key gene expression. RESULTS: A 10-gene prognostic model was developed based on the identification of 71 cuproptosis-related genes. The risk score correlated with survival outcomes, PAM50 subtypes, tumor stage, and pathologic response. It showed good predictive performance in both training (AUC = 0.719) and testing (AUC = 0.689) cohorts. Key genes (CIRBP, INPP4B, IL6ST, and CCL20) were validated and linked to NAC response. CONCLUSION: The cuproptosis-based risk score model effectively predicts NAC response and may guide personalized treatment in BC. It also reveals the relevance of cuproptosis-related genes in immune modulation and chemotherapy sensitivity.
Clinical Analysis of Comprehensive Pharmacotherapy Combined With Ultrasound-Guided Precise Lesion Resection Plus Primary Microplasty in the Treatment of Nonpuerperal Mastitis.
Yao BZ, Peng K, Sang SL … +6 more , Lin L, Chen HC, Li HL, Shi DW, Li L, Xiong QR
Breast J · 2026 · PMID 42206629 · Full text
OBJECTIVE: To explore the clinical efficacy, cosmetic outcome, and safety of comprehensive pharmacotherapy (traditional Chinese medicine + hormone + antibiotic) combined with ultrasound-guided precise lesion resection pl...
OBJECTIVE: To explore the clinical efficacy, cosmetic outcome, and safety of comprehensive pharmacotherapy (traditional Chinese medicine + hormone + antibiotic) combined with ultrasound-guided precise lesion resection plus primary microplasty in the treatment of refractory nonpuerperal mastitis (NPM). METHODS: The clinical and pathological data of refractory NPM patients who underwent surgical treatment at our hospital from February 2021 to December 2024 were retrospectively analyzed. The sample size was calculated using a superiority test, and a total of 97 patients were finally included. They were assigned to two groups using a random number table for retrospective stratification assignment (to balance baseline clinical characteristics and reduce selection bias): The control group (45 cases) underwent extended lesion resection combined with fascial flap plasty and nipple-areola correction and the observation group (52 cases) underwent ultrasound-guided precise lesion resection plus primary microplasty. The recurrence rate, breast cosmetic score (Harris score), postoperative psychological status (24-item Hamilton Depression Rating Scale [HAMD-24]), hospital stay, and incidence of complications were compared between the two groups. RESULTS: All surgeries were successfully completed in both groups without serious complications. All patients were followed up for more than 12 months (median follow-up period: 16.8 ± 2.9 months). There were no statistically significant differences in the incidence of postoperative complications [7.7% (4/52) vs. 6.7% (3/45), p = 1], drainage time [(3.5 ± 0.3) d vs. (3.6 ± 0.4) d, t = -1.398, p = 0.166], and hospital stay [(10.7 ± 0.6) d vs. (10.6 ± 0.5) d, t = 0.894, p = 0.373] between the two groups. The recurrence rate of the observation group was lower than that of the control group [0% (0/52) vs. 11.1% (5/45), X = 9.836, p = 0.002], and the cosmetic effect and patient satisfaction of the observation group were superior to those of the control group. The HAMD-24 score of the observation group [(7.8 ± 2.9) points] was lower than that of the control group [(12.5 ± 3.8) points], with a statistically significant difference (t = 11.562, p = 0.001). CONCLUSION: For refractory NPM, the combination of comprehensive pharmacotherapy, ultrasound-guided precise lesion resection, and primary microplasty achieves remarkable therapeutic effects, characterized by reduced complication rates and low short-to-long-term recurrence. This integrated traditional Chinese and Western medicine strategy is not only safe and effective but also provides excellent cosmetic benefits for patients.
Akkermansia muciniphila-Driven ceRNA Networks Regulate Immune Modulation and Breast Cancer Progression.
Chaudhary U, A S A, A M
Breast J · 2026 · PMID 42187123 · Full text
BACKGROUND: Microbiota-derived metabolites are increasingly recognized as modulators of systemic immunity and cancer biology. This study investigates how a structurally distinct lipid from Akkermansia muciniphila influen...
BACKGROUND: Microbiota-derived metabolites are increasingly recognized as modulators of systemic immunity and cancer biology. This study investigates how a structurally distinct lipid from Akkermansia muciniphila influences immune transcriptional programs and their connection to breast cancer (BRCA)-associated pathways. METHODS: Donor-adjusted reanalysis of PBMC RNA-seq data was performed to identify lipid-responsive transcriptional changes while minimizing interindividual variability. Differential expression was assessed across time points, followed by pathway enrichment and immune gene filtering. Immune cell composition was inferred using deconvolution analysis. Integration with The Cancer Genome Atlas (TCGA)-BRCA datasets enabled tumor immune infiltration profiling and network-based identification of hub genes. ceRNA interactions were refined using correlation-supported datasets and prognostic relevance was evaluated in TCGA and METABRIC cohorts. RESULTS: Transcriptional variation was primarily driven by the treatment and exposure duration rather than donor effects. A biphasic immune response (IR) was observed, with early suppression followed by progressive activation. Lipid-responsive genes significantly overlapped with BRCA immune signatures and were enriched in metabolic and stress-related pathways. Immune deconvolution revealed shifts in macrophage polarization and cytotoxic cell populations. Network analysis identified key regulators, including ADIPOR1, KLF4, MYC, CXCL10, and ALDH1A1, linked to distinct immune infiltration patterns. ceRNA networks highlighted oncogenic and tumor-suppressive miRNA interactions. A five-gene signature demonstrated moderate prognostic value across cohorts. CONCLUSION: Microbial lipid signaling induces dynamic immune reprogramming that converges on tumor-relevant pathways, suggesting a systemic immune-mediated link between microbiota and BRCA progression, with potential implications for immune-targeted therapeutic strategies.
Refining Sentinel Lymph Node Biopsy Decisions for Clinically Node-Negative Microinvasive DCIS.
Huang C, Parmar P, Habboosh N … +8 more , Bhimani F, Chen Y, Entenberg D, Oktay M, Gupta A, Pastoriza J, McEvoy M, Feldman S
Breast J · 2026 · PMID 42144978 · Full text
BACKGROUND: Ductal carcinoma in situ with microinvasion (DCISM), defined as invasion ≤ 1 mm, occurs in 5%-10% of DCIS cases. There is ongoing debate on whether DCISM should be managed as DCIS or as small invasive cancer....
BACKGROUND: Ductal carcinoma in situ with microinvasion (DCISM), defined as invasion ≤ 1 mm, occurs in 5%-10% of DCIS cases. There is ongoing debate on whether DCISM should be managed as DCIS or as small invasive cancer. As treatments increasingly emphasize minimizing morbidity, efforts have focused on identifying low-risk patients who may safely forgo axillary surgery, including sentinel lymph node biopsy (SLNB). However, axillary management of DCISM remains unclear due to limited data. This study aims to identify preoperative predictors of upstaging to invasive carcinoma on final pathology to guide SLNB use. METHODS: A retrospective chart review was conducted of women aged ≥ 19 years with confirmed or suspected DCISM on initial biopsy who were clinically node negative and treated at a tertiary center from 2013 to 2023. Fisher's exact test and Student's t-test were used for categorical and continuous variables, respectively. Univariate and multivariate analyses were performed to identify predictors of upstaging. RESULTS: A total of 61 women with DCISM on initial biopsy were identified. Of these, 40.9% (25/61) were upstaged to invasive carcinoma on final pathology. Among upstaged patients, 95% (19/20) underwent SLNB at the time of surgery, and 12.5% (3/24) had positive lymph nodes. Time from biopsy to surgery did not differ significantly between groups (p = 0.12). Preoperative predictors of upstaging included palpable mass (OR 9.0, 95% CI 2.38-44.98, p = 0.003), mass on mammogram (OR 12.86, 95% CI 1.95-255.34, p = 0.02), and mass with calcifications (OR 13.34, 95% CI 1.30-255.08, p = 0.047). CONCLUSION: Clinically node-negative DCISM patients without a palpable or mammographic mass (with or without calcifications) had a low risk of upstaging and lymph node involvement, suggesting that they may safely forgo SLNB. Identifying preoperative variables can guide risk stratifications and de-escalation of axillary surgery. Larger prospective studies are needed to further inform guidelines for DCISM management in diverse populations.
Cancer-Associated Adipocytes in Human Breast Cancer: An Observational Histopathological Study of Dedifferentiation and Stromal Transition.
Xiao J, Zhou X, Wang Y … +3 more , Wu H, Zeng H, Wu Y
Breast J · 2026 · PMID 42053153 · Full text
BACKGROUND: Adipose tissue is a major stromal component of the breast cancer (BC) tumor microenvironment (TME), playing a crucial role in BC progression. Cancer-associated adipocytes (CAAs), located at the invasive tumor...
BACKGROUND: Adipose tissue is a major stromal component of the breast cancer (BC) tumor microenvironment (TME), playing a crucial role in BC progression. Cancer-associated adipocytes (CAAs), located at the invasive tumor front, undergo significant morphological and functional alterations. This observational case-control study investigated the dedifferentiation trajectory of CAAs and its impact on BC progression. METHODS: Paired tumor and distant normal adipose tissues from 20 BC patients were analyzed. Histological and immunohistochemical analyses were performed to assess morphological changes and marker expressions α-SMA, S100A4, and CD36 in CAAs. RESULTS: CAAs exhibited features consistent with dedifferentiation toward a myofibroblast-like phenotype, marked by expressing α-SMA and S100A4, indicators of myofibroblasts and tumor-associated fibroblasts. Metabolically, CAAs showed increased CD36 expression and histological features compatible with augmented lipolysis and were spatially associated with areas of extracellular matrix (ECM) remodeling. Masson's trichrome staining demonstrated augmented pericellular collagen deposition, accompanied by increased tissue stiffness and enhanced angiogenesis at the tumor-adipose boundary. In addition, nuclear translocation of β-catenin in peritumoral adipocytes implicates the Wnt/β-catenin signaling axis as a potential regulator of adipocyte-mesenchymal transition in this context.
Imaging Findings in Patients With Benign Adenomyoepithelioma: A Retrospective Analysis.
Öztekin PS, Özdemir Ö, Yakıştıran S … +3 more , Altıner S, Erel S, Aslan Yay F
Breast J · 2026 · PMID 42030079 · Full text
BACKGROUND AND AIM: Adenomyoepithelioma (AME) is a rare breast tumor characterized by the biphasic proliferation of epithelial and myoepithelial cells. Due to its rarity, data on its imaging characteristics-particularly...
BACKGROUND AND AIM: Adenomyoepithelioma (AME) is a rare breast tumor characterized by the biphasic proliferation of epithelial and myoepithelial cells. Due to its rarity, data on its imaging characteristics-particularly magnetic resonance imaging (MRI) findings-remain limited. This study aimed to evaluate the radiological features of AME and assess the diagnostic contribution of multiparametric imaging. METHODS: This retrospective study included 11 patients pathologically diagnosed with AME between 2013 and 2024 who underwent mammography, ultrasound (US), and MRI prior to diagnosis. Lesions were evaluated according to BI-RADS criteria: mammography (shape, margin, density, and calcifications); US (shape, margin, orientation, echogenicity, posterior features, vascularity, and elastography); and MRI (morphology, T2 signal intensity, ADC values, and enhancement kinetics). RESULTS: The most common mammographic finding was an isodense oval or round mass with partially obscured margins (36.4%). No lesions demonstrated irregular shape or suspicious microcalcifications. On US, 90.9% of lesions were oval/round with circumscribed (45.5%) or indistinct (54.5%) margins. All lesions were hypoechoic and vascular; 71.4% exhibited soft elasticity on strain elastography. On MRI, 54.5% were hyperintense on T2 weighted images (T2WI) with circumscribed margins. ADC values ranged from 1.00 to 1.434 × 10 mm/s (mean 1.273 × 10 mm/s). Enhancement kinetics demonstrated Type I in 3/11, Type II in 3/11, and Type III in 5/11 lesions. CONCLUSION: Although AME often demonstrates benign morphological features, it is frequently categorized as BI-RADS 4 due to vascular and kinetic characteristics that raise suspicion for malignancy. Our findings suggest that relatively low ADC values further contribute to this suspicious imaging profile. However, the absence of suspicious microcalcifications, an oval or round shape, and hyperintensity on T2WI may aid in the differential diagnosis. Given the malignant potential of these lesions, wide local excision with negative margins is essential, and radiological findings play a crucial role in guiding the need for pathological confirmation.
Integrin Beta 4 Protein Expression Bimodally Predicts Sensitivity to CDK4/6 Inhibition and Resistance to Immunotherapy in Breast Cancer.
Zhu ZM, Hu L, Ma YW … +1 more , Zhu QN
Breast J · 2026 · PMID 42018338 · Full text
BACKGROUND: Integrin beta 4 (ITGB4) has been implicated in breast cancer progression, yet its clinical utility as a biomarker remains unclear due to inconsistent findings across studies. This discrepancy may stem from th...
BACKGROUND: Integrin beta 4 (ITGB4) has been implicated in breast cancer progression, yet its clinical utility as a biomarker remains unclear due to inconsistent findings across studies. This discrepancy may stem from the failure to distinguish between RNA and protein levels. METHODS: We performed an integrated multiomics analysis of ITGB4 across breast cancer subtypes using data from TCGA, CPTAC, METABRIC, and GEO cohorts. Key findings were functionally validated using CDK4/6 inhibition in luminal cells and via immunohistochemistry on triple-negative breast cancer (TNBC) tissue microarrays. RESULTS: ITGB4 exhibited significant RNA-protein discordance across breast cancer subtypes. High ITGB4 protein expression predicted a favorable prognosis in ER-positive breast cancer (HR = 0.58, 95% CI: 0.39-0.86, p = 0.007) and enhanced sensitivity to CDK4/6 inhibitors. Conversely, high ITGB4 expression in TNBC correlated with immunotherapy resistance, characterized by elevated PD-L1/PD-L2 expression and reduced cytotoxic lymphocyte infiltration. Mechanistically, we identified the ESR1/miR-342-5p/UBE2E3 axis as a potential regulator of ITGB4 protein stability. CONCLUSION: ITGB4 protein expression serves as a bimodal biomarker in breast cancer, predicting CDK4/6 inhibitor sensitivity in luminal subtypes while indicating immunotherapy resistance in TNBC. ITGB4 protein thus represents a critical biomarker for guiding personalized therapy in precision oncology.
Characterization of Novel MRI Findings in Idiopathic Granulomatous Mastitis: Diagnostic Significance and Clinical Perspectives.
Işık F, Öztürk ME, Alper F
Breast J · 2026 · PMID 42017767 · Full text
OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is an uncommon, benign, chronic inflammatory breast disease that frequently mimics carcinoma both clinically and radiologically, posing diagnostic challenges. While cla...
OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is an uncommon, benign, chronic inflammatory breast disease that frequently mimics carcinoma both clinically and radiologically, posing diagnostic challenges. While classical imaging manifestations have been described, the full spectrum of MRI features remains incompletely characterized. This study aimed to identify and characterize novel MRI descriptors of histopathologically confirmed IGM and assess their reproducibility and potential clinical implications. METHODS: In this retrospective single-center study, 45 consecutive women with biopsy-proven IGM were evaluated using 1.5 T breast MRI. Imaging protocols included T2-weighted fat-suppressed, T1-weighted, diffusion-weighted, and dynamic contrast-enhanced sequences. Two experienced radiologists, blinded to clinical and pathological data, independently reviewed all cases for classical and novel MRI features. Interobserver agreement was assessed using raw agreement and Cohen's κ statistics. Associations between imaging descriptors and clinical-demographic variables were tested with nonparametric methods. RESULTS: The most common MRI pattern was a heterogeneously enhancing mass with concomitant nonmass enhancement (NME) (75.6%), followed by rim-enhancing microabscesses (62.2%) and isolated NME (48.9%). Four novel MRI features were identified: spherical transformation of mammary fat lobules (62.2%), disruption of fibroglandular tissue architecture (73.3%), ring-like enhancement with asymmetric wall morphology (46.6%), and nipple-areolar complex retraction (11.1%). Interobserver reproducibility was high (κ = 0.786-1.000; raw agreement > 90%). Novel descriptors, particularly spherical lobule transformation, fibroglandular disruption, and ring-like enhancement, were strongly associated with NME (all p < 0.001), but not with age or lesion laterality. CONCLUSION: These imaging descriptors may contribute to a better radiologic understanding of the morphological manifestations of IGM and may assist radiologists in recognizing imaging patterns associated with granulomatous inflammation. However, given the retrospective design and absence of a comparative cohort, these findings should be considered exploratory and hypothesis-generating.
A Cohort Study on Cardiovascular Disease Mortality in Breast Cancer Patients With Different Subtypes.
Wang Z, Deng L, Wang P … +2 more , Zhang Y, Shen Z
Breast J · 2026 · PMID 41999242 · Full text
PURPOSE: To investigate cardiovascular disease (CVD) mortality among patients with different breast cancer (BC) subtypes to assess its implications for long-term survival. PATIENTS AND METHODS: In total, 423,758 BC patie...
PURPOSE: To investigate cardiovascular disease (CVD) mortality among patients with different breast cancer (BC) subtypes to assess its implications for long-term survival. PATIENTS AND METHODS: In total, 423,758 BC patients were included in this study utilizing data from the Surveillance, Epidemiology, and End Results 17 Registries Database (2010-2020). Competing risk curves were utilized to assess whether the cumulative CVD mortality surpassed the cumulative BC mortality. Multivariate competing risk models were used to explore potential factors associated with CVD mortality. Standardized mortality ratios (SMRs) were calculated to investigate CVD mortality in comparison to the general population. RESULTS: In total, 5863 BC patients died from CVD during follow-up time, accounting for 10.0% of all deaths (56,856). The number of deaths and the percentage of all deaths among patients died from CVD for luminal A, luminal B, HER-2 enriched, and triple-negative subtype were 4160 (12.2%), 615 (9.7%), 291 (7.7%), and 797 (6.2%), respectively. After 9 years, BC mortality remained over 10% higher than CVD mortality for luminal A and B subtypes, but the difference was under 10% for HER-2-enriched and triple-negative subtypes. HER-2-enriched and triple-negative BC patients aged 55-84 had higher CVD mortality compared to the general population. Triple-negative BC was independently associated with increased CVD mortality compared with luminal A (HR 1.103 [95% CI: 1.016-1.199]). CONCLUSIONS: Patients with the triple-negative subtype have a high risk of CVD mortality. This underscores the need for enhanced surveillance and targeted cardiovascular interventions for these patients to improve their long-term health outcomes.
Selected Pathological Criteria That Predict Low Rates of Axillary Lymph Node Metastases Regardless of Patient Age: A Single Institution Study.
Nathanson SD, Leonard-Murali S, Bui J … +7 more , Chitale DA, Bensenhaver J, Schwartz T, Petersen L, Springer K, Baker P, Susick LL
Breast J · 2026 · PMID 41964933 · Full text
BACKGROUND AND AIMS: Omission of sentinel node biopsy is increasingly offered to selected older women with cN0 low-risk breast cancer (BC). We hypothesized that some younger women might exhibit a low enough incidence of...
BACKGROUND AND AIMS: Omission of sentinel node biopsy is increasingly offered to selected older women with cN0 low-risk breast cancer (BC). We hypothesized that some younger women might exhibit a low enough incidence of lymph node metastases to possibly justify excluding axillary surgery. METHODS: We statistically analyzed, using parametric and nonparametric tests as appropriate, multiple demographic and clinicopathologic variables in cT1-2 N0 M0 BC patients of all ages undergoing axillary LN excisional surgery from a long-term, prospectively maintained database. RESULTS: Patients with (816) and without (3617) LN metastases were compared. Although older patients were significantly (p < 0.0001) less likely to have LN metastases compared to younger patients, 3/61 (4.92%) of those < 50 years old with grade 1 tumors ≤ 1 cm in size (T1a and b) and no lymphovascular invasion had LN metastases compared to 30/504 (5.95%) ≥ 50. Patients aged 50 or older with Grade 2/3, < 1 cm, LVI-negative tumors had only 53/774 (6.85%) LN positive, compared to 19/131 (14.5%) in women < 50 with the same pathology. CONCLUSIONS: Women with grade 1, ≤ 1 cm invasive BCs, and no LVI had < 6% incidence of LN metastases regardless of age. Instead of excluding younger women from axillary node surgery de-escalation strategies, this study suggests that any woman with a tumor size ≤ 1 cm, Grade 1, and no LVI could be evaluated in prospective studies whose objective is to safely avoid axillary LN surgery.
Treatment Regimens and Response Rates in Early TNBC: A Review of Real-World Practice in the Second Decade of the 21st Century.
Hatzipanagiotou ME, Tannert V, Gerken M … +6 more , Pigerl M, Räpple S, Roth J, Klinkhammer-Schalke M, Ortmann O, Seitz S
Breast J · 2026 · PMID 41949336 · Full text
BACKGROUND AND AIMS: Real-world evidence on the treatment of early triple-negative breast cancer (TNBC) remains limited. This study provides an overview of neoadjuvant chemotherapy (NACT) regimens used in the 2010s of th...
BACKGROUND AND AIMS: Real-world evidence on the treatment of early triple-negative breast cancer (TNBC) remains limited. This study provides an overview of neoadjuvant chemotherapy (NACT) regimens used in the 2010s of the 21 century, analyzing patient outcomes and treatment patterns based on real-world data from a large population-based cancer registry. METHODS: In this retrospective, noninterventional, single-center study, we analyzed data from TNBC patients diagnosed between January 1, 2010, and December 31, 2018, registered in the Tumor Centre Regensburg. Data included demographics, pathology, treatment regimen, recurrence, and survival, with follow-up extending to December 2023. Outcomes included pathologic complete response (pCR), overall survival (OS), and recurrence-free survival (RFS). RESULTS: A total of 319 patients were included. Among them, 132 patients (41.4%) received NACT with epirubicin/cyclophosphamide (EC) and paclitaxel (EC-T), 74 patients (23.2%) received NACT with EC-T and platinum (EC-P/T), and 22 patients (6.9%) received NACT with EC-P/nab-paclitaxel (EC-P/nabP). Other NACT protocols were administered in 91 (28.5%) patients. A pCR occurred in 49.8% of NACT patients, with a 37.1% rate in the subgroup without platinum. Addition of platinum significantly increased the pCR rate to 54.1% compared to EC-T (odds ratio [OR] 3.476, 95% confidence interval [CI] 1.655-7.300, p = 0.001). EC-P/nabP led to a significant increase in pCR rate to 77.3% (OR 8.767, 95% CI 2.421-31.744, p < 0.001). CONCLUSION: The evidence from clinical trials was quickly incorporated into clinical practice, leading to higher pCR rates and benefits for patients. In the next step, the implementation of immune checkpoint inhibitors in real-world practice will be analyzed.
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