Comparative profiling by data-independent acquisition mass spectrometry reveals featured plasma proteins in breast cancer: a pilot study.

Purpose: Breast cancer is known to be influenced by genetic and environmental factors, and several susceptibility genes have been discovered. Still, the majority of genetic contributors remain unknown. We aimed to analyze the plasma proteome of breast cancer patients in comparison to healthy individuals to identify differences in protein expression profiles and discover novel biomarkers. Methods: This pilot study was conducted using bioresources from Seoul National University Bundang Hospital's Human Bioresource Center. Serum samples from 10 breast cancer patients and 10 healthy controls were obtained. Liquid chromatography-mass spectrometry analysis was performed to identify differentially expressed proteins. Results: We identified 891 proteins; 805 were expressed in the breast cancer group and 882 in the control group. Gene set enrichment and differential expression analysis identified 30 upregulated and 100 downregulated proteins in breast cancer. Among these, 10 proteins were selected as potential biomarkers. Three proteins were upregulated in breast cancer patients, including cluster of differentiation 44, eukaryotic translation initiation factor 2-α kinase 3, and fibronectin 1. Seven proteins downregulated in breast cancer patients were also selected: glyceraldehyde-3-phosphate dehydrogenase, α-enolase, heat shock protein member 8, integrin-linked kinase, tissue inhibitor of metalloproteinases-1, vasodilator-stimulated phosphoprotein, and 14-3-3 protein gamma. All proteins had been previously reported to be related to tumor development and progression. Conclusion: The findings suggest that plasma proteome profiling can reveal potential diagnostic biomarkers for breast cancer and may contribute to early detection and personalized treatment strategies. A further validation study with a larger sample cohort of breast cancer patients is planned.

Recurrence is Not Associated with Margin Status in Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial neoplasm of the breast. The proper extent of resection is still under debate. This study aimed to investigate the optimal surgical margin to prevent recurrence after surgery for PT and to evaluate risk factors for local recurrence (LR). METHODS: Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for PT at Seoul National University Bundang Hospital between July 2003 and February 2022 were reviewed. RESULTS: Of the 439 patients included, 285 were benign, 129 were borderline, and 25 were malignant. There was no statistically significant difference in 5-year disease-free survival (DFS) between margin-negative and margin-involved patients (87.3% vs. 85.1%, p = 0.081). When patients were classified into groups, according to margin status, as conventional (≥ 1 cm from tumor), close (< 1 cm from tumor), or involved, 5-year DFS rates were also similar (100% vs. 86.9% vs. 85.1%, p = 0.170). In subgroup analysis for different histologic grades, 5-year DFS was not affected by margin involvement. In univariate analysis, large tumor size (> 5 cm; hazard ratio [HR] 2.857, p = 0.028) and infiltrative tumor border (HR 3.096, p = 0.012) were independent risk factors for LR. Further multivariate analysis found both factors to be prognostic. CONCLUSIONS: Recurrence was not significantly influenced by margin status in all histological grades. In benign and borderline tumors, local excision without wide surgical margins could be sufficient, and watchful waiting could be an option for patients with positive margins after initial surgery.

Conventional versus modified nipple sparing mastectomy in immediate breast reconstruction: Complications, aesthetic, and patient-reported outcomes.

Background: Nipple-sparing mastectomy (NSM) followed by immediate breast reconstruction (IBR) is the optimal surgical treatment for breast cancer. However, investigations are ongoing to improve the surgical technique to achieve better results. This study aimed to evaluate the outcomes of modified NSM (m-NSM), which preserves the anterior lamellar fat layer, in patients who underwent IBR. Methods: All patients who underwent modified NSM (m-NSM) or conventional NSM (c-NSM) followed by IBR using autologous tissue or implants were retrospectively reviewed between January 2014 and January 2021. Two mastectomy types were compared in terms of postoperative complications and aesthetic outcomes using panel assessment scores by physicians and reported outcomes using Breast-Q. In addition, postoperative evaluations of the thickness of mastectomy flap was performed using CT scan images. Results: A total of 516 patients (580 breasts) with NSM (143 breasts with c-NSM and 437 breasts with m-NSM) followed by IBR were reviewed. The mean ± SD flap thickness was 8.48 ± 1.81 mm in patients who underwent m-NSM, while it was 6.32 ± 1.15 mm in the c-NSM cohort (p = 0.02). The overall major complications rate was lower in the m-NSM group (3.0% vs. 9.0%, p < 0.013). Ischemic complications of the mastectomy flap and nipple-areolar complex (NAC) were more in c-NSM, although the difference was not statistically significant. The mean panel assessment scores were higher in the m-NSM group (3.14 (good) and 2.38 (fair) in the m-NSM and c-NSM groups, respectively; p < 0.001). Moreover, m-NSM was associated with greater improvements in psychosocial (p < 0.001) and sexual (p = 0.007) well-being. Conclusion: Preserving the anterior lamellar fat in NSM was associated with thicker mastectomy flap, overall lower rates of complications, including ischemia of the mastectomy flap and nipple-areolar complex, and was associated with better aesthetic outcomes and improved quality of life.

Effect of Estrogen Receptor Expression Level and Hormonal Therapy on Prognosis of Early Breast Cancer.

PURPOSE: Estrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1%-10%) of ER expression have been separately defined as ER low positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh). MATERIALS AND METHODS: Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative [ER-]). RESULTS: A total of 2,162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1,654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER- patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2, negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER- tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (p=0.418). CONCLUSION: ERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.

Contralateral Breast Cancer and Ipsilateral Breast Tumor Recurrence in BRCA1/2 Carriers and Non-Carriers at High-Risk of Hereditary Breast Cancer.

PURPOSE: We evaluated the risk of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) and investigated the predictive factors for CBC and IBTR in breast cancer patients with BRCA mutations and non-carriers at high-risk of hereditary breast and ovarian cancer (HBOC). METHODS: We analyzed prospectively collected clinical data of patients with unilateral breast cancer who were at high-risk for HBOC and were tested for the BRCA mutation between 2003 and 2013. RESULTS: The cohort comprised 540 patients with 45 BRCA1 carriers, 50 BRCA2 carriers, and 445 non-carriers. The median follow-up was 84.5 months. Overall, 61 patients (11.3%) developed CBC (24.4% for BRCA1 carriers, 20% for BRCA2 carriers, and 9% for non-carriers). The 10-year cumulative risk for CBC was 23.8% for BRCA1 carriers, 19.1% for BRCA2 carriers, and 9.8% for non-carriers (p = 0.174). Among the 277 patients who underwent breast-conserving surgery, 29 (10.5%) developed IBTR (9.1% for BRCA1 carriers, 16.7% for BRCA2 carriers, and 10.2% for non-carriers). The 10-year cumulative risk for IBTR for BRCA1 carriers, BRCA2 carriers, and non-carriers was 8.7%, 14.1%, and 20%, respectively (p = 0.577). BRCA1 (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.20-7.20; p = 0.019) and BRCA2 (HR, 2.88; 95% CI, 1.13-7.35; p = 0.027) mutations and negative estrogen receptor status (HR, 4.02; 95% CI, 1.60-10.08; p = 0.003) were the significant predictive factors for CBC, while tumor size ≥ 2 cm was predictive of IBTR (HR, 6.11; 95% CI, 2.03-18.33; p = 0.001). CONCLUSION: While BRCA1/2 mutation carriers had a higher risk of developing CBC compared to non-carriers at high-risk of HBOC, the risk of IBTR was similarly high across breast cancer patients irrespective of the BRCA mutation. Further preventive strategies to reduce CBC and IBTR for all patients at high-risk of HBOC should be investigated.