Journal of Breast Cancer最新文献

Phyllodes tumors (PTs) represent an uncommon category of fibroepithelial neoplasms found in the breast tissue and are classified as benign, borderline, or malignant based on their histopathological features. Histological assessment remains the cornerstone of a PT diagnosis. However, recent genomic advancements have revealed the biological mechanisms underlying PTs, particularly malignant phyllodes tumors (MPTs). This comprehensive review integrates current genomic and molecular investigations that have elucidated the distinguishing features of PTs. Mutations in the MED12 gene represent early tumorigenic phenomena that are often observed in benign lesions, whereas modifications in the TERT promoter, alterations in TP53, and amplification of EGFR are associated with malignant transformation. Moreover, novel transcriptomic investigations have characterized discrete molecular subtypes exhibiting epithelial and fibrous attributes, thereby enriching our understanding of MPT heterogeneity. Actionable genomic modifications, including dysregulation of the PI3K/Akt/mTOR, MET, and IGF1R signaling cascades, represent promising directions for targeted therapeutic strategies; however, clinical validation is still insufficient. Advances in patient-derived models have created functional platforms conducive to drug screening and preclinical evaluation. Molecular examination has expanded our understanding of PTs, revealing the genomic components linked to malignant progression and identifying prospective therapeutic targets. Nevertheless, obstacles remain in the practical application of these discoveries, primarily owing to the intratumoral heterogeneity and rarity of MPTs. Future investigations should prioritize the integration of diverse omics methodologies, enhancement of preclinical testing frameworks, and establishment of global data-sharing initiatives to promote biomarker-driven treatment strategies.

Purpose: Patients undergoing breast surgery may experience chronic postoperative pain in the breasts, upper extremities, and axillary regions, and no established methods for preventing this pain are available at present. This study aimed to investigate whether coaptation of the transected intercostal nerve can prevent the development of neuropathic and chronic breast pain after mastectomy in implant-based breast reconstruction.

Methods: A prospective, double-blind, randomized controlled trial was conducted by dividing patients who underwent implant-based breast reconstruction after mastectomy into a control group without nerve coaptation and an experimental group with nerve coaptation. Patient clinical information was collected, and a survey using the pain and quality of life scale was conducted at 6 and 12 months after surgery.

Results: Fifteen patients completed the study, including seven in the control group and eight in the experimental group. The two groups showed no significant differences in terms of clinical factors. The experimental group exhibited lower Short-Form McGill Pain Questionnaire scores than the control group at 6 and 12 months postoperatively, with a statistically significant difference at 6 months. Numerical Rating Scale and Present Pain Intensity scores for both groups were in the "no to mild" range throughout the study period, with no statistically significant differences between the groups. Although the difference in the BREAST-Q™ results did not reach statistical significance, the experimental group showed an improvement in the quality of life.

Conclusion: Intercostal nerve coaptation after mastectomy in implant-based breast reconstruction may facilitate initial nerve recovery. Although trial results are needed to fully determine the clinical impact, our findings support the ongoing scientific and clinical efforts to use this technique.

Angiosarcoma associated with lymphedema is a rare soft tissue malignancy that occurs owing to chronic lymphedema, primarily following breast cancer surgery. We present a case of an 83-year-old female who developed angiosarcoma 14 years after undergoing breast cancer surgery. Diagnosis was confirmed through excisional biopsy, histopathological evaluation, and imaging. Computed tomography and magnetic resonance imaging revealed diffuse dermal thickening with an enhanced subcutaneous nodular lesion on the right arm. This unusual case emphasizes the importance of vigilant monitoring in patients with chronic lymphedema post-breast cancer surgery, as early radiologic and clinical detection can facilitate timely intervention and improve outcomes.

Purpose: The incidence of breast cancer in older females is increasing with increased life expectancy. This study analyzed tumor characteristics and oncological outcomes in patients aged ≥ 70 years compared to patients in a younger postmenopausal group, in conjunction with their adherence to treatment guidelines.

Methods: Patients aged ≥ 50 years, newly diagnosed with breast cancer, were divided into two age categories: ≥ 70 years and 50-69 years. All patients underwent curative surgery at Korea University Guro Hospital between January 2009 and December 2019. Clinical data on tumor subtype, histopathological grade, and clinical stage, along with treatment details were collected. Disease-free survival, distant recurrence-free survival, and breast cancer-specific survival rates were determined.

Results: Of 1,199 patients, 166 (13.8%) were ≥ 70 years at the time of surgery. The disease-free, distant recurrence-free, and breast cancer-specific survival rates were significantly lower in patients aged ≥ 70 years (p < 0.05). In a subgroup analysis, human epidermal growth factor receptor 2-positive tumors were the only subtype with a statistically significant difference in survival outcomes, and adherence to the guidelines was strongly linked to a better prognosis.

Conclusion: Patients aged ≥ 70 years had lower disease-free, distant recurrence-free, and breast cancer-specific survival rates compared to younger postmenopausal patients aged 50-69 years. With the continuous increase in life expectancy and advances in healthcare, it is critical to optimize treatment strategies for older patients with breast cancer to improve survival outcomes and enhance their quality of life.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized.

Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays. Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.

Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14-0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16-1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20.

Conclusion: Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer.

Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses.

Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036). Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway.

Conclusion: This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

Purpose: Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years. We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM.

Methods: Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study. Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated.

Results: In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers. Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations.

Conclusion: The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.

Purpose: This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment.

Methods: This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed.

Results: Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups. The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001). Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953).

Conclusion: Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors. Further investigation into biological differences is warranted.