Breast Journal最新文献

Objective. Given the challenges rural cancer patients face in accessing cancer care as well as the slower diffusion and adoption of new medical technologies among rural providers, the aim of our study was to examine trends in gene expression profiling (GEP) testing and evaluate the association between hospital rurality and receipt of GEP testing. Methods. Data from the Iowa Cancer Registry (ICR) were used to identify women with newly diagnosed, histologically confirmed breast cancer from 2010 through 2018 who met eligibility criteria for GEP testing. Patients were allocated to the hospitals where their most definitive surgical treatment was received, and Rural-Urban Commuting Area codes were used to categorize hospitals into urban (N = 43), large rural (N = 16), and small rural (N = 48). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression to evaluate the association between hospital rurality and GEP test use, adjusting for demographic and clinical characteristics. The association between test result and treatment received was assessed among patients who received Oncotype DX (ODX) testing. Results. Of 6,726 patients eligible for GEP test use, 46% (N = 3,069) underwent testing with 95% receiving ODX. While overall GEP testing rates increased over time from 42% between 2010 and 2012 to 51% between 2016 and 2018 (P_trend < 0.0001), use continued to be the lowest among patients treated at hospitals in small rural areas. The odds of GEP testing remained significantly lower among patients treated at hospitals located in small rural areas (aOR 0.55; 95% CI 0.43–0.71), after adjusting for demographic and clinical characteristics. ODX recurrence scores were highly correlated with chemotherapy use across all strata of hospital rurality. Conclusions. GEP testing continues to be underutilized, especially among those treated at small rural hospitals. Targeted interventions aimed at increasing rates of GEP testing to ensure the appropriate use of adjuvant chemotherapy may improve health outcomes and lower treatment-related costs.

Background. Breast cancer (BC) is the most prevalent malignancy in women. This study is aimed to explore the role and regulatory mechanism of RNA-binding motif protein 8A (RBM8A) in BC. Methods. We detected the expression of RBM8A in BC tissues and cell lines (MCF-7, MDA-MB-231, and MDA-MB-436), and explored the correlation of RBM8A expression with clinicopathological features in patients. The function of RBM8A deficiency in MCF-7 and MDA-MB-231 cells was determined using MTT, wound healing, and transwell assay. The effect of RBM8A suppression on the cisplatin (DDP) resistance in MCF-7 and MDA-MB-231 cells was also evaluated. Besides, western blotting was used to examine AKT/mTOR pathway-related proteins. The mouse model was constructed to confirm the effect of RBM8A on tumor growth. Results. The expression of RBM8A was elevated in BC tissues and cell lines. RBM8A silencing restrained the malignant behaviors of MCF-7 and MDA-MB-231 cells, including viability, migration, and invasion, while promoting apoptosis. Silencing of RBM8A overcame resistance to DDP in MCF-7 and MDA-MB-231 cells. Furthermore, RBM8A suppression restrained the activation of the AKT/mTOR pathway in both MCF-7 and MDA-MB-231 cells. Feedback experiments revealed that SC79 treatment reversed the reduction effects of RBM8A knockdown on viability, DDP resistance, migration, and invasion of MDA-MB-231 cells. Moreover, the silencing of RBM8A inhibited the growth of tumor xenograft in vivo. Conclusions. RBM8A knockdown may reduce DDP resistance in BC to repress the development of BC via the AKT/mTOR pathway, suggesting that RBM8A may serve as a new therapeutic target in BC.

Purpose. This study aims to analyze the survival outcomes of breast cancer (BC) patients, especially centrally located breast cancer (CLBC) patients undergoing breast-conserving therapy (BCT) or mastectomy. Methods. Surveillance, epidemiology, and end results (SEER) data of patients with T1-T2 invasive ductal or lobular breast cancer receiving BCT or mastectomy were reviewed. We used X-tile software to convert continuous variables to categorical variables. Chi-square tests were utilized to compare baseline information. The multivariate logistic regression model was performed to evaluate the relationship between predictive variables and treatment choice. Survival outcomes were visualized by Kaplan–Meier curves and cumulative incidence function curves and compared using multivariate analyses, including the Cox proportional hazards model and competing risks model. Propensity score matching was performed to alleviate the effects of baseline differences on survival outcomes. Result. A total of 180,495 patients were enrolled in this study. The breast preservation rates fluctuated around 60% from 2000 to 2015. Clinical features including invasive ductal carcinoma (IDC), lower histologic grade, smaller tumor size, fewer lymph node metastases, positive ER and PR status, and chemotherapy use were independently correlated with BCT in both BC and CLBC cohorts. In all the classic Cox models and competing risks models, BCT was an independent favorable prognostic factor for BC, including CLBC patients in most subgroups. In addition, despite the low breast-conserving rate compared with tumors located in the other areas, CLBC did not impair the prognosis of BCT patients. Conclusion. BCT is optional and preferable for most early-stage BC, including CLBC patients.

Introduction. Uncertainty still remains regarding the survival improvement derived from immediate surgery or subsequent surgery in addition to systemic therapy for patients with de novo metastatic breast cancer. The current study aimed to examine the effect of combined treatment administered in different sequences on the survival of these patients. Materials and Methods. We conducted a retrospective cohort study of patients with de novo stage IV breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019. Patients were categorized into 3 groups: (1) systemic therapy without primary surgery, (2) systemic therapy after primary surgery, and (3) systemic therapy before primary surgery. Cumulative incidence curves with Gray’s test were used to compare breast cancer-specific death (BCSD) between groups. Kaplan–Meier curves with the log-rank test were applied to compare overall survival (OS) between groups. A competing risk model and a proportional hazards model were generated to adjust for important prognostic factors. Propensity score matching (PSM) was performed in the primary survival analysis. Stratified analysis was also performed. Results. Patients who underwent systemic therapy after primary surgery and who underwent systemic therapy before primary surgery both showed a significantly reduced risk of BCSD compared to patients who received systemic therapy without primary surgery [subdistribution hazard ratio (SHR): 0.74; 95% confidence interval (CI): 0.69–0.79; and P < 0.001, and SHR: 0.62; 95% CI: 0.56–0.67; and P < 0.001, respectively]. A statistically significant disparity was also noted in OS. In the setting of single-organ metastasis, including the bone, lung, and liver, patients receiving the combination therapy showed an improved prognosis compared with patients receiving systemic therapy without primary surgery. Conclusions. Additional primary tumour excision, whether before or after systemic therapy, may provide survival benefits for patients presenting with de novo metastatic breast cancer, especially for patients with single-organ disease involving the bone, lung, and liver but not the brain. Further investigations mainly focused on these carefully selected candidates are required to improve personalized treatment for metastatic breast cancer.

Introduction. Metaplastic breast carcinoma is a rare special type of breast cancer, which has distinguished clinical characteristics. We aimed to evaluate the clinicopathological features of metaplastic breast carcinoma compared with nonspecific invasive breast carcinoma and study the prognosis of metaplastic breast carcinoma. Methods. We reviewed metaplastic breast carcinoma cases (n = 37) from January 2000 to December 2021 and nonspecific invasive breast carcinoma cases (n = 433) from January 2019 to December 2020 extracted from our institution retrospectively. The following variables were recorded, including the patients’ general information, complications, T stage, expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, molecular subtyping, lymph node status, skin or chest wall involvement, vessel carcinoma embolus, therapy modality (surgical treatments, chemotherapy, and radiotherapy), and survival. Results. Patients with metaplastic breast carcinoma had more advanced disease than patients with nonspecific invasive breast carcinoma (T stage: P = 0.0011). A greater proportion of metaplastic breast carcinoma presented with triple-negative breast cancer than nonspecific invasive breast carcinoma (79.41% vs. 12.47%, P ≤ 0.001). Our study showed that the skin or chest wall invasion was more frequent in metaplastic breast carcinoma patients (11.76% vs. 1.62%, P = 0.005). The 5-year survival rate for metaplastic breast carcinoma patients was 57.66% (95% CI: 0.3195∼0.7667). No local recurrence was observed while distant metastasis occurred in 33.33% of patients with metaplastic breast carcinoma. Death due to disease occurred in 24.24% of patients with metaplastic breast carcinoma. Conclusion. The majority of metaplastic breast carcinoma patients had more advanced disease and triple-negative disease than nonspecific invasive breast carcinoma patients. Also, metaplastic breast carcinoma patients had frequent skin or chest wall invasion and a high rate of distant metastasis and mortality.

The prognosis of breast cancer patients with brain metastasis is poor. It was aimed to define the clinicopathological features of breast cancer patients with brain metastases and to determine the risk factors and survival outcomes associated with brain metastasis. This is a single-center, retrospective, cross-sectional study. A total number of 127 patients diagnosed with breast cancer and who developed brain metastasis between January 2011 and March 2021 were retrospectively analyzed. The survival and clinicopathological data of these patients according to 4 biological subtypes were evaluated (luminal A, luminal B, HER-2 overexpressing, and triple-negative). The median overall survival for all patients was 45.6 months. The median time from the diagnosis of breast cancer to the occurrence of brain metastasis was 29.7 months, and the median survival time after brain metastasis was 7.2 months. The time from the diagnosis of breast cancer to brain metastasis development was significantly shorter in HER-2 overexpressing and triple-negative subtypes than in luminal A and B subtypes. The median time from breast cancer diagnosis to brain metastasis was 33.5 months in luminal A, 40.6 months in luminal B, 16.8 months in HER-2 overexpressing, and 22.8 months in the triple-negative groups (p = 0.003). We found the worst median survival after brain metastasis in the triple-negative group with 3.5 months. Early and close surveillance of high-risk patients may help early diagnosis of brain metastasis and may provide to perform effective treatments leading to longer overall survival times for this patient population.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal spindle cell tumour with low malignant potential which is extremely rare in breasts. Because of the lack of typical imaging and clinical characteristics of IMT, it is easy to misdiagnose before operation. We now report a case of a 37-year-old woman presenting with a mass in her left breast. Ultrasound showed a well-circumscribed lesion in the lower outer quadrant. The patient underwent lumpectomy, and histopathology revealed a tumor which was composed of fusiform cells and inflammatory cells. Immunohistochemistry (IHC) showed tumor cells are positive for vimentin, ALK, BCL2, and SMA. The FISH test demonstrated ALK (2p23) chromosomal translocation (ALK positive). The final diagnosis of breast IMT was rendered with nonclassical morphology. Postoperative 30-month follow-up no evidence showed residual tumor or recurrence. As a very rare tumor, breast IMT could be easily misdiagnosed clinically and pathologically. Complete surgical resection of the tumor is preferred, and it has the risk of recurrence and metastasis.

Introduction. Critical regulatory genes are functionally silenced by DNA hypermethylation in breast cancer and premalignant lesions. The objective of this study was to examine whether DNA methylation assessed in random fine needle aspirates (rFNA) can be used to inform breast cancer risk. Methods. In 20 women with invasive breast cancer scheduled for surgery at Johns Hopkins Hospital, cumulative methylation status was assessed in a comprehensive manner. rFNA was performed on tumors, adjacent normal tissues, and all remaining quadrants. Pathology review was conducted on blocks from all excised tissue. The cumulative methylation index (CMI) for 12 genes was assessed by a highly sensitive QM-MSP assay in 280 aspirates and tissue from 11 incidental premalignant lesions. Mann–Whitney and Kruskal Wallis tests were used to compare median CMI by patient, location, and tumor characteristics. Results. The median age of participants was 49 years (interquartile range [IQR]: 44–58). DNA methylation was detectable at high levels in all tumor aspirates (median CMI = 252, IQR: 75–111). Methylation was zero or low in aspirates from adjacent tissue (median CMI = 11, IQR: 0–13), and other quadrants (median CMI = 2, IQR: 1–5). Nineteen incidental lesions were identified in 13 women (4 malignant and 15 premalignant). Median CMI levels were not significantly different in aspirates from quadrants (p = 0.43) or adjacent tissue (p = 0.93) in which 11 methylated incidental lesions were identified. Conclusions. The diagnostic accuracy of methylation based on rFNA alone to detect premalignant lesions or at-risk quadrants is poor and therefore should not be used to evaluate cancer risk. A more targeted approach needs to be evaluated.

Background. Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods. A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results. A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions. In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution’s ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).

Introduction. Technetium-labeled sulfur colloid (TSC) is a radiolabeled mapping agent commonly used for sentinel lymph node biopsy (SLNBx). Tilmanocept, a CD206 receptor-targeted mapping agent, has gained recent popularity due to potential advantages of rapid and quick uptake to the SLNs. The objectives of this study were to assess (1) the difference in the number of SLNs harvested using tilmanocept versus TSC and (2) the difference in time to transcutaneous localization when using an intraoperative injection approach. Methods. Patients undergoing breast conservation and SLNBx were consented and randomized to receive either 0.5 mCi of filtered TSC or 0.5 mCi of tilmanocept injected intradermally immediately after induction of anesthesia. Axillary transcutaneous gamma detector probe counts were taken at 1-minute intervals until a hot spot was identified. SLNs were then identified and excised. Additional nodes were excised if their counts per second (cps) were greater than 10% of the cps of the hottest SLN. The number of SLNs was based on both number of nodes collected intraoperatively and the number recorded in the final pathology report. Results. The study population consisted of 86 patients, 48 randomized to tilmanocept and 38 to TSC. There were no significant differences in patient or tumor characteristics between the two groups. Localization rates were 100% for both cohorts. The mean number of SLNs identified and removed was not significantly different (p = 0.34, intraoperatively; p = 0.57, pathology reported). Time to transcutaneous localization was 3.3 ± 2.0 minutes for tilmanocept and 3.9 ± 2.3 minutes for TSC (p = 0.19). The average cps for the hottest node was 2,180.0 ± 2,460.5 in the tilmanocept group compared to 2,679.3 ± 2,687.5 in the TSC group (p = 0.94). Conclusion. There was no significant difference in the number of SLNs harvested or in the time to transcutaneous localization when using tilmanocept versus TSC as the radiolabeled mapping agents for intraoperative injection and mapping. Either agent can be used without any significant difference in performance.