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Discoidin Domain Receptor 2 Expression as Worse Prognostic Marker in Invasive Breast Cancer
Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcinoma (BC). The ability of DDR2 to bind to collagen promotes protumoral responses in cancer cells that influence the tumor microenvironment (TME). Nonetheless, the interrelation between DDR2 expression and TME modulation during BC progression remains poorly known. For this reason, we aim to evaluate the correlation between intratumoral expression of DDR2 and the infiltration of the main TME cell populations, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs). First, collagen and DDR2 expression levels were analyzed in human invasive BC samples. Then, DDR2 status correlation with tumor aggressiveness and patient survival were retrieved from different databases. Subsequently, the main pathways, cell types, and tissues correlated with DDR2 expression in BC were obtained through bioinformatics approach. Finally, we studied the association of DDR2 expression with the recruitment of CAFs and TAMs. Our findings showed that, together with the expected overexpression of TME markers, DDR2 was upregulated in tumor samples. Besides, we uncovered that altered TME markers were linked to DDR2 expression in invasive BC patients. Consequently, DDR2 modulates the stromal reaction through CAFs and TAMs infiltration and could be used as a potential worse prognostic factor in the treatment response of invasive BC.
Altered Expression of RB and pRB in Tissue Arrays of Primary Breast Cancers and Matched Axillary Lymph Node Metastases
Objectives. The retinoblastoma (RB) pathway is crucial in the development and progression of many cancers. To better understand the biology of progressive breast cancer (BC), we examined protein expression of the RB pathway in primary BCs and matched axillary lymph node metastases (LM). Methods. Immunohistochemistry was used to evaluate cyclin D1, CDK4/6, RB, phosphorylated RB (pRB), and E2F1 expression in tissue arrays containing cores of 50 primary BCs and matched LM. The number of positive tumor cells and staining intensity were scored. Results. The proteins were localized in the nucleus, while CDK6 was detected in the cytoplasm and CDK4 was found in both. pRB and E2F1 showed higher expression in matched LM than in primary tumors. Expression of these proteins differed significantly by the percentage of positive tumor cells, while proteins in the proximal portion of the RB pathway showed no significant differences. The main path of alteration consisted of high pRB in primary BC, remaining pRB high in the majority of LM, variations occurring in fewer cases. All matched LM of the few primary tumors that had unaltered RB and pRB expression showed changes in RB or pRB expression. Conclusion. Expression of pRB and E2F1 was significantly higher in LM than in primary BC. A majority of cancers with LM showed altered RB or pRB expression, suggesting that proteins downstream in the RB pathway play a critical role in metastatic BC and disease progression. So looking at the RB pathway could be an option for chemotherapy decisions in patients with only few LM.
Minimally Invasive Excision of Breast Masses under Ultrasound Guidance: A Single Center’s Five-Year Experience on the Breast Lesion Excision System
Background. The purpose of this study was to investigate the feasibility of the percutaneous radiofrequency (RF) excision system (BLES) as a primary method of diagnosis and removal of small breast masses. Methods. Ninety-six lesions in 95 patients with 50.5 ± 8.4 years of age were treated in a five-year period by a single operator. Inclusion criteria were as follows: size (<20 mm), depth (>10 mm), and indeterminate or suspicious radiological features (74 BI-RADS 3 and 22 BI-RADS 4). The procedure was performed under ultrasound (US) guidance using 6 G retriever probes with 12-, 15-, and 20-mm baskets. Results. Lesions were between 5 and 20 (12.3 ± 3.8) mm in length. They were removed at the first attempt in all but one case. The technical success rate was 98.95%, and the diagnostic success rate was 100%. Ninety-one lesions were histologically benign and five were neoplastic. Two lesions that were previously classified as BI-RADS 3 were diagnosed as neoplasia (atypical lobular hyperplasia), and nineteen lesions that were previously classified as BI-RADS 4a were diagnosed as benign. The complete excision rate (presence of tumor-free negative surgical margin) was 40% in neoplastic lesions. There were no major complications. The minor complication rate was 1.58%. No recurrence was observed during 18 months of follow-up. Conclusion. BLES delivers surgical quality specimens for confident histopathological examination and is a safe alternative to surgical resection in lesions with suitable size.
Outcome Analysis Depending on the Different Types of Incision following Immediate Breast Reconstruction
Background. Immediate breast reconstruction following nipple-sparing mastectomy (NSM) is widely used for its cosmetic benefits. Due to the lack of guidelines, the types of incisions in NSM vary and which method is superior remains a debate. In this study, we hypothesized that the periareolar incision has a higher risk of complications, such as nipple-areolar complex (NAC) necrosis, than other incisions. Methods. A retrospective chart review was conducted and divided into three groups: the periareolar, radial, and lateral incision groups. The reconstruction method and complications of NAC necrosis, wound dehiscence, seroma, hematoma, infection, and reconstruction failure were investigated. Results. A total of 103 patients (periareolar incision (33%, n = 34), radial incision (39.8%, n = 41), and lateral incision (27.2%, n = 28)) who underwent NSM and immediate breast reconstruction from 2018 to 2020 were included. The reconstruction methods were direct-to-implant, DIEP flap, LD flap, and PAP flap, and there was all of which had no statistically significant difference between the groups regarding the reconstruction method (). In terms of complications, there was no significant difference in NAC necrosis (29.4%, 19.5%, and 21.4%, in the periareolar, radial, and lateral groups, respectively; ), wound dehiscence, seroma or hematoma, infection, and reconstruction failure. Conclusion. Breast reconstruction following NSM through periareolar incision does not increase the incidence of complications, including NAC necrosis. However, since only Asian patients with low BMI were included, if an appropriate patient group is selected for immediate reconstruction after NSM, reconstruction can be safely performed through the periareolar incision, and good cosmetic results can be obtained.
Survival Estimation, Prognostic Factors Evaluation, and Prognostic Prediction Nomogram Construction of Breast Cancer Patients with Bone Metastasis in the Department of Bone and Soft Tissue Tumor: A Single Center Experience of 8 Years in Tianjin, China
Purpose. Bone metastasis in breast cancer remains globally concerned. Accurate survival estimation would be beneficial for clinical decision-making, especially for the patients with potential indications of surgery. Based on a retrospective cohort from China, the study aimed to construct a prognostic prediction nomogram for breast cancer patients with bone metastasis. Methods. Breast cancer patients with bone metastasis diagnosed between 2009 and 2017 in our department were retrospectively selected. The total cohort was divided into construction and validation cohorts (ratio 7 : 3). A nomogram was constructed to predict the probability of survival, and the performance of model was validated. Results. A total of 343 patients were enrolled with 243 and 100 patients in construction and validation cohorts, respectively. The median overall survival for the total cohort was 63.2 (95% CI: 52.4–74.0) months. Elevated ALP (HR = 1.71, 95% CI: 1.16–2.51; ), no surgery for breast cancer (HR = 2.19, 95% CI: 1.30–3.70; ), synchronous bone metastasis (HR = 1.98, 95% CI: 1.22–3.22; ), and liver metastasis (HR = 1.68, 95% CI: 1.20–2.37; ) were independent prognostic factors for worse survival. The independent predictors and other five factors (including age at diagnosis, ER status, PR status, Her-2 status, and the performance of bisphosphonate) were incorporated to construct the nomogram. The C-index was 0.714 (95% CI: 0.636–0.792) and 0.705 (95% CI: 0.705) in the construction cohort and validation cohort, respectively. All the calibration curves were close to the 45-degree line, which indicated satisfactory calibration. Conclusion. A retrospective study aiming at prognostic estimation of breast cancer patients with bone metastasis was designed. Four independent prognostic factors were identified and a prognostic nomogram was constructed with satisfactory discrimination and calibration. The model could be used in survival estimation and individualized treatment planning.
Under- and Normal-Weight Patients Are More Susceptible to Recurrence of Phyllodes Tumor
Purpose. Phyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms, and factors associated with the recurrence of PTs are poorly understood. This study sought to identify clinicopathological factors associated with the recurrence of PTs. Method. From January 2009 to December 2019, we identified 100 patients who underwent definitive surgery for PT. Clinicopathological risk factors associated with the recurrence of PT were assessed. Results. The median age of the patients was 44 y (range, 19–62 y), and the median tumor size was 4 cm (0.8–30 cm). At a median follow-up of 26.7 mo (0–103 mo), 22 of the 100 patients experienced local recurrence. In the univariate and multivariate analyses, body mass index ≥ 23 kg/m2 ( = 0.042 in the univariate analysis; = 0.039 in the multivariate analysis), tumor size ≥ 5 cm ( = 0.006 in the univariate analysis; = 0.036 in the multivariate analysis), and the presence of stromal overgrowth ( = 0.032 in the univariate analysis; = 0.040 in the multivariate analysis) were associated with an increased risk of local recurrence. Resection margins and grade were not associated with local recurrence. Conclusion. Normal- or underweight patients and those with larger tumor sizes were more prone to local recurrence. Further larger, multicenter studies with a long-term follow-up are required.