Breast Cancer : Basic and Clinical Research最新文献

Background: Zeste White 10 (ZW10) is a key component of the spindle assembly checkpoint (SAC) that maintains chromosomal stability during mitosis. Dysregulation of ZW10 can cause chromosomal instability and aneuploidy-hallmarks of many cancers, including breast cancer, particularly triple-negative breast cancer (TNBC). However, its prognostic and therapeutic relevance in breast cancer remains unclear.

Objectives: This study aimed to systematically investigate the expression pattern, prognostic significance, mutational profile, and immune associations of ZW10 in breast cancer using integrated omics data.

Design: A computational, cross-cohort bioinformatics analysis combining transcriptomic, proteomic, mutational, and clinical data from publicly available databases.

Methods: The ZW10 expression levels were assessed across normal and cancerous tissues using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and the Human Protein Atlas data sets. Immune infiltration correlations were analyzed using TIMER2.0, Gene Set Cancer Analysis (GSCA), and TNMplot. Survival analyses were performed using Kaplan-Meier Plotter and TCGA clinical data sets. Protein-protein interaction (PPI) and functional enrichment analyses were conducted using STRING and EnrichR, and mutation data were retrieved from COSMIC and cBioPortal.

Results: The ZW10 expression was markedly upregulated across multiple cancers, with the highest expression in TNBC. Elevated ZW10 levels correlated with immune cell infiltration and adverse overall survival, while lower ZW10 expression predicted improved relapse-free survival. Protein-protein interaction and enrichment analyses revealed ZW10's close interaction with key mitotic regulators and its involvement in spindle checkpoint and vesicular trafficking pathways. Mutation analysis identified predominant A > G and A > T substitutions and frequent gene amplifications across malignancies.

Conclusion: The ZW10 acts as a potential prognostic biomarker and therapeutic target in breast cancer, particularly TNBC, through its dual roles in mitotic regulation and immune modulation. Further experimental validation is warranted to confirm its mechanistic role and therapeutic potential.

Background: Breast cancer remains a major global health challenge, as it is the most commonly diagnosed malignancy worldwide, particularly among women. Germline variants in cancer-predisposing genes play a critical role in breast cancers with familial origin.

Objectives: To identify genetic variants in cancer-predisposing genes among breast cancer patients and individuals at risk in a selected cohort from two imaging facilities in the Central Province of Sri Lanka.

Design: A genetic association study involving breast cancer confirmed patients, at-risk individuals, and healthy controls.

Methods: Blood samples were collected from consenting patients, and genomic DNA was extracted from the samples and subjected to Next Generation Sequencing and Sanger sequencing. The inherited predisposition to breast cancer was evaluated to find genes associated with breast cancer using the Ion Torrent PGM platform followed by bioinformatics analysis.

Results: Variants were detected in several high- and moderate-penetrance genes, including BRCA1 [c.3113A>G; p.Glu1038Gly], BRCA2 [c.6509A>G; p.Lys2170Arg; c.7879A>T; p.Ile2627Phe; c.5574_5577delAATT; p.Ile1859LysfsTer3], PALB2 [c.1592delT; p.Leu531fs], BRIP1 [c.2400C>T;], and in MRE11A [c.508C>A; p.Gln170Lys] genes. Among these, BRCA2 mutations and the PALB2 frameshift deletion were classified as pathogenic germline variants. The benign BRCA1 variant [c.3113A>G; p.Glu1038Gly] was the most frequent variant observed. Common missense variants included BRCA1 [c.3113A>G; p.Glu1038Gly; c.3548A>G; p.Lys1183Arg; c.2612C>T; p.Pro871Leu], BRCA2 [c.7397T>C; p.Val2466Ala], and ATM [c.5948A>G; p.Asn1983Ser], while frequently detected intronic variants were found in MUTYH [c.1468-40C>G;], PALB2 [c.3114-51T>A;], and NF1 [c.288+41G>A; c.328+37C>G;]. Pathogenic variants occurred in fewer than 10% of individuals in any group, and other variants were identified in different frequencies. Conclusion: Evaluation of germline variants in this cohort revealed the presence of pathogenic mutations and other variants with benign or uncertain significance. Three pathogenic variants, BRCA2 [c.6509A>G; c.7879A>T; c.5574_5577delAATT] and PALB2 [c.1592delT], were identified in high-risk genes important for breast cancer prediction. Identification of population-based variants may improve breast cancer screening and management in Sri Lanka.

Background: Breast cancer is the most common malignancy among Saudi women, and early detection remains a critical factor for improving survival outcomes. Despite ongoing awareness initiatives, screening uptake remains low, suggesting that perceptions and beliefs may influence women's engagement in preventive behaviors.

Objectives: To assess perceptions of breast cancer among women attending Johns Hopkins Aramco Healthcare (JHAH) facilities using the Breast Cancer Perception Scale (BPS) and to examine associations between perception domains and sociodemographic as well as screening-related factors.

Design: A cross-sectional, questionnaire-based study was conducted between October 2024 and March 2025.

Methods: Eligible female patients aged 20 years or older with active MyChart accounts were invited to participate electronically. Perception was measured using the validated 24-item BPS, which comprises 6 subscales. Due to non-normal data distribution, non-parametric tests (Kruskal-Wallis and Mann-Whitney U) were employed, with a Bonferroni correction for multiple comparisons.

Results: Participants had a mean age of 37.5 ± 8.3 years, and 61.4% held a university degree. Postgraduate education was significantly associated with higher scores for Perceived Knowledge, Treatment Belief, Health Check, and Risk, as well as lower stigma (P < .001). Employed women demonstrated greater Perceived Knowledge (P < .001). Those with a family history of breast cancer reported higher Fear and Risk perceptions (P < .001). Prior screening experience (clinical breast examination or Mammography) correlated with higher Knowledge and Health Check perceptions and lower stigma (P < .001). Overall, 51.7% of participants reported adequate knowledge, while 64% to 70% expressed moderate to high levels of fear.

Conclusion: Perceptions of breast cancer among Saudi women are shaped by educational level, employment status, family history, and screening experience. Targeted educational interventions that address knowledge gaps and cultural stigmas are essential for enhancing participation in screening and early detection practices.

Background: Human epidermal growth factor receptor 2 (HER2) is an important predictive and prognostic biomarker in breast cancer. Immunohistochemistry (IHC) is the preferred initial test due to its cost-effectiveness and simplicity. While fluorescence in situ hybridization (FISH) is the traditional gold standard test for HER2 gene amplification, DISH has emerged as an accepted alternative that allows evaluation under a standard light microscope.

Objectives: To evaluate agreement between HER2 IHC (2+/3+) and DISH in node-positive primary breast cancers and compare findings with published IHC and FISH data.

Design: Retrospective single-center cohort study using nationwide referral specimens.

Methods: Cases of pathologically confirmed lymph node metastasized invasive breast carcinoma with HER2 IHC scores of 2+ and 3+ were retrieved. Interpretation of HER2 IHC was performed using the 2023 ASCO/CAP guideline. HER2 DISH was conducted and evaluated by the HER2/CEP17 signal ratio on primary tumors first, and on metastasized lymph nodes in cases of persistent technical failure.

Results: Among 1,307 breast cancers, DISH detected HER2 amplification in 933 cases, including 92% (760) of IHC 3+ cases and 36% (173) of IHC 2+ cases. Seven cases with persistent technical failure on primary tumors were resolved when switching to lymph node specimens. Comparison with the meta-analysis data of IHC and FISH showed no significant differences, indicating that DISH is a reliable alternative to FISH.

Conclusion: Our study demonstrates a high concordant rate between HER2 IHC and DISH in the IHC 3+ group and a low positive rate in the IHC 2+ group. We found no significant difference in the positive rates of HER2 IHC to DISH when compared with prior data of IHC to FISH, reaffirming the use of HER2 DISH as an effective and more accessible alternative to FISH in HER2 2+/3+ breast cancer.

Background: Although BRCA1 and BRCA2 mutations are known to be associated with different breast cancer (BC) subtypes, real-world evidence on how these genetic differences influence tumor behavior and treatment decisions remains limited, particularly in Japanese patients. With the recent expansion of PARP inhibitor indications in Japan, BRCA testing has become increasingly routine, highlighting the need for clinical data tailored to local populations.

Objectives: To compare clinicopathological features, recurrence patterns, and surgical choices between BRCA1- and BRCA2-associated BC in Japanese patients, with a focus on ER-positive tumors.

Design: A single-institution retrospective cohort study.

Methods: We retrospectively reviewed 417 patients who underwent BRCA1/2 genetic testing at a single Japanese institution between April 2020 and November 2023. Of these, 38 patients (12 BRCA1, 26 BRCA2) had pathogenic variants. We compared clinicopathological features, recurrence patterns, and choices of risk-reducing surgery between BRCA1 and BRCA2 carriers.

Results: BRCA1-associated cancers were predominantly triple-negative (75%) and diagnosed at earlier stages (T1 in 83.3%), while BRCA2-associated cancers were mainly ER-positive (69.2%) and more likely to present with multiple lymph node metastases (⩾2 nodes in 42.3%). Although Ki-67 levels were higher in BRCA1 tumors, this was largely subtype-dependent. Notably, ER-positive BRCA tumors showed a trend toward higher recurrence. Preferences for prophylactic surgery also varied by mutation type.

Conclusion: This single-institution study highlights clinically meaningful differences between BRCA1- and BRCA2-associated BC in Japanese patients. BRCA2 cancers tended to present with more advanced features, while BRCA1 cancers were more often detected at earlier stage. These findings underscore the value of BRCA testing not only for PARP inhibitor eligibility but also for subtype-specific risk assessment and individualized preventive strategies.

Background: Mammography use and its predictors among older women require further study.

Objectives: Mammography use and its relationship to demographic characteristics, health care access, and breast cancer risk factors in women ages 60 to 85 in the United States were examined.

Design: US Health and Retirement Study 2014 dataset was examined.

Methods: A descriptive study using secondary data was analyzed for use of mammography screening and its predictors in women ages 60 to 85 in United States.

Results: In total, 5177 (73.4%) of respondents reported mammography use. Mammography use was higher among older women who were married, nonsmokers, alcohol drinkers, engaged in vigorous exercise, and had dental visits.

Conclusion: Women ages 60+ in the US HRS dataset revealed continued mammography screening into later years (73.4%), and mammography use was higher among older women who had healthy lifestyles and habits. Insights for health care providers and systems are to recommend mammography use for women age 60 to 85 years are provided. This US study can be used to inform future research and policy regarding breast cancer screening among older women.

Pregnancy-associated breast cancer (PABC) is the most prevalent invasive cancer in pregnant women, notably affecting those aged over 35 years. Postpartum cases exhibit a poorer prognosis than non-PABC women, while the prognosis of PABC is the same as that of non-PABC. Our case report presents a 25-year-old, 20th-week pregnant woman. Abdominal ultrasound revealed hepatic metastases; thus, total body PET/MRI without contrast exhibited two breast masses, bilateral axillary nodules, multiple hepatic metastases and osseous metastases in vertebral column, pelvis, and femoral bones. In conclusion, whole-body MRI (WB/MRI) and PET-MRI are important tools for diagnosing breast cancer in pregnant women and determining the stage of it.

Background: Breast cancer is the most prevalent cancer and second leading cause of cancer-related mortality among Canadian women. Most of cases belong to the HR+/HER2- subtype, representing approximately two-thirds of all instances.

Objectives: This real-world evidence study aims to comprehensively analyze the treatment pattern, and clinical outcomes of Canadian patients diagnosed with early-stage HR+/HER2- breast cancer.

Design: This retrospective, longitudinal cohort study involved 541 patients enrolled in the pan-Canadian cancer patient registry PMT (Personalize My Treatment).

Methods: The cohort included patients with newly diagnosed or recurrent stage II or III HR+/HER2- breast cancer between January 1st, 1992, and May 31st, 2022. Summary statistic to describe treatment pattern and Kaplan Meir analysis for clinical outcome were used.

Results: In the adjuvant setting, our study found that ET was administered to 75.6% of the cohort, with a significant preference for combining ET with cytotoxic agents and, particularly in stage III patients. In addition, neoadjuvant therapy, primarily using cytotoxic agents, was higher in stage III patients, and those receiving neoadjuvant therapy were more likely to either continue with ET as adjuvant treatment. The median duration of adjuvant ET was 4.5 years. In the adjuvant patient population, recurrence rates progressively increased over time from 13.2% after 2 years, 21.4% after 3 years, 30.3% after 5 years, and peaking at 58.4% after 10 years. Median time to recurrence for the patient population on ET was 7.76 years. OS rate for patients on ET was 94.6% at 5 years and 78.3% at 10 years.

Conclusions: This study highlights the high unmet need in stage II and stage III breast cancer, with 1 patient out of 3 recurring after 5 years, and more than half recurring after 10 years despite adjuvant treatment with ET alone. This highlights the need for more effective and tolerable treatment options to address disease recurrence in both the short and long term for eBC HR+/HER2- patients in Canada.

Background: Male breast cancer (MBC) is a rare disease entity globally with poor prognosis compared with female breast cancer; however, studies reporting on MBC are rare especially in resource-limited settings.

Objectives: We aimed to study the expression of Ki67 and its association with clinicopathological factors and intrinsic subtypes among male patients with breast cancer (BC) from a resource-limited setting.

Design: This was a cross-sectional study which included retrospective data.

Methods: The study included data of 54 males with BC who were diagnosed from January 2014 to December 2024. The study was conducted at the Department of Pathology, Uganda Cancer Institute (UCI) in Kampala Uganda from February to June 2025. Data were extracted from the electronic dataset and patients' clinical files and laboratory forms. One-way analysis of variance statistical test was used to assess the association of Ki67 absolute value (mean) with clinical and pathological factors and intrinsic subtypes of BC, followed by performing multivariable linear regression analysis for adjusting for confounding factors.

Results: The mean age of the patients was 56.4 ± 15.1 years, and the youngest patient had 25 years. Majority 68.5% (38/54) of the patients had advanced disease (stage III and IV). Also, majority 68.5% (37/54) of the cases comprised of ER+, PR+, and HER2- intrinsic subtype. Only intrinsic subtypes of BC (95% confidence interval [CI] = 3.397-16.503, P = .032) and PR status (95% CI = 5.693-24.397, P = .042) remained the predictors of Ki67 expression after performing multivariable linear regression analysis.

Conclusion: The findings of this study have shown high expression in cases of MBC which are triple negative and negative PR status. This indicates that high Ki67 expression in MBC may be used in stratification of male patients with BC based on disease aggressiveness.

Background: Breast cancer is the most common cancer among women, and chemotherapy is a key treatment option. Doxorubicin is frequently used for breast cancer but poses a risk of cardiotoxicity. Recently, memantine, an N-Methyl-D-aspartate antagonist, has shown both antitumor and cardioprotective effects.

Objectives: We conducted a study to examine the combined effects of doxorubicin and memantine on the 4T1 cell line in a breast cancer animal model and to assess memantine's potential in reducing doxorubicin-induced cardiotoxicity in breast cancer model mouse.

Design: The 4T1 cell line was cultured and subsequently inoculated into mice. After that animals were randomly divided into four groups: (1) control, (2) memantine, (3) doxorubicin, and (4) memantine + doxorubicin.

Methods: After 30 days, mice were sacrificed, and their lungs, liver, and heart were collected for histological analysis. Myeloperoxidase, Malondialdehyde, and TNF-α levels in cardiac tissues were measured, and the TUNEL test was conducted for breast tumors.

Results: Our results showed that memantine + doxorubicin reduced MDA activity and TNF-α levels in cardiac tissue in comparison to the doxorubicin group. TUNEL test revealed that the memantine + doxorubicin group demonstrated significantly more tumor cell apoptosis than the mice in other groups (P-value < 0.05), although tumor volume reduction was not significantly greater than that in the doxorubicin group.

Conclusion: This study is the first to demonstrate that memantine can enhance the therapeutic efficacy of doxorubicin chemotherapy while also reducing doxorubicin-induced cardiac oxidative stress and inflammation in a breast cancer model.