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The Importance of the Pathological Perspective in the Management of the Invasive Lobular Carcinoma
Background. Invasive lobular carcinomas (ILC) account for 10–15% of all breast cancers and are the second most common histological form of breast cancer. They usually show a discohesive pattern of single cell infiltration, tend to be multifocal, and the tumor may not be accompanied by a stromal reaction. Because of these histological features, which are not common in other breast tumors, radiological detection of the tumor may be difficult, and its pathological evaluation in terms of size and spread is often problematic. The SSO-ASTRO guideline defines the negative surgical margin in breast-conserving surgeries as the absence of tumor detection on the ink. However, surgical margin assessment in invasive lobular carcinomas has not been much discussed from the pathological perspective. Methods. The study included 79 cases diagnosed with invasive lobular carcinoma by a Tru-cut biopsy where operated in our center between 2014 and 2021. Clinicopathological characteristics of the cases, results of an intraoperative frozen evaluation in cases that underwent conservative surgery, the necessity of re-excision and complementary mastectomy, and consistency in radiological and pathological response evaluation in cases receiving neoadjuvant treatment were questioned. Results. The tumor was multifocal in 37 (46.8%) cases and single tumor focus in 42 (53.2%) cases. When the entire patient population was evaluated, regardless of focality, mastectomy was performed in 27 patients (34.2%) and breast-conserving surgery (BCS) was performed in 52 patients (65.8%). Of the 52 patients who underwent BCS, 26 (50%) required an additional surgical procedure (cavity revision or completion mastectomy). There is a statistical relationship between tumor size and additional surgical intervention (). BCS was performed in 7 of 12 patients who were operated on after neoadjuvant treatment, but all of them were reoperated with the same or a second session and turned to mastectomy. Neoadjuvant treatment and the need for reoperation were statistically significant (). Additional surgical procedures were performed in 20 (44.4%) of 45 patients in BCS cases who did not receive neoadjuvant therapy. Conclusions. Diagnostic difficulties in the intraoperative frozen evaluation of invasive lobular carcinoma are due to the different histopathological patterns of the ILC. In our study, it was determined that large tumor size and neoadjuvant therapy increased the need for additional surgical procedures. It is thought that the pathological perspective is the determining factor in order to minimize the negative effects such as unsuccessful cosmesis, an additional surgical burden on the patient, and cost increase that may occur with additional surgical procedures; for this reason, new approaches should be discussed in the treatment planning of invasive lobular carcinoma cases.
Bacitracin for Injection Recall: Impact on Immediate Breast Implant Surgical Outcomes
Background. Triple-antibiotic irrigation of breast implant pockets is a mainstay of infection prophylaxis in breast reconstruction and augmentation. The recall of bacitracin for injection due to risk of anaphylaxis and nephrotoxicity in January 2020, a staple component of the irrigation solution, has raised concern for worsened postoperative sequelae. This study aimed to investigate pre- and post-recall implant-based breast surgery to analyze the impact of bacitracin in irrigation solutions on infection rates. Methods. All implant-based breast reconstruction or augmentation surgeries from January 2019 to February 2021 were retrospectively reviewed. In a regression discontinuity study design, patients were divided into pre- and post-recall groups. Patient demographics, surgical details, and outcomes including infection rates were collected. Differences in complication rates were compared between groups and with surgical and patient factors. Results. 254 implants in 143 patients met inclusion criteria for this study, with 172 implants placed before recall and 82 placed after recall. Patients in each cohort did not differ in age, BMI, smoking status, or history of breast radiation or capsular contracture (). All breast pockets were irrigated with antibiotic solution, most commonly bacitracin, cefazolin, gentamycin, and povidone-iodine before recall (116,67.4%) and cefazolin, gentamycin, and povidone-iodine after recall (59,72.0%). There was no difference in incidence of infection (6.4% vs. 8.5%, ) or cellulitis (3.5% vs. 3.7%, ) before and after recall. Implant infection was associated with smoking history () and increased surgical time (). Conclusions. Despite the recent recall of bacitracin from inclusion in breast pocket irrigation solutions, our study demonstrated no detrimental impact on immediate complication rates. This shift in irrigation protocols calls for additional investigations into optimizing antibiotic combinations in solution, as bacitracin is no longer a viable option, to improve surgical outcomes and long-term benefits.
Hospital Rurality and Gene Expression Profiling for Early-Stage Breast Cancer among Iowa Residents (2010–2018)
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 (), 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.
Nontherapeutic Risk Factors of Different Grouped Stage IIIC Breast Cancer Patients’ Mortality: A Study of the US Surveillance, Epidemiology, and End Results Database
Objectives. Stage IIIC breast cancer, as a local advanced breast cancer, has a poor prognosis compared with that of early breast cancer. We further investigated the risk factors of mortality in stage IIIC primary breast cancer patients and their predictive value. Methods. We extracted data from the US Surveillance, Epidemiology, and End Results (SEER) database of female patients with stage IIIC primary breast cancer (n = 1673) from January 2011 to December 2015. Results. Hormone receptor negativity ( and , respectively), aggressive molecular typing ( and , respectively), high T stage ( and , respectively), a high number of positive lymph nodes (≥14) ( and , respectively), and lymph node ratio (≥0.8148) ( and , respectively) were associated with poor disease-specific survival. The indicators of disease-specific survival included estrogen receptor status, progesterone receptor status, molecular typing, T stage, number of positive lymph nodes, and lymph node ratio (,,,, , and , respectively). Conclusion. Hormone receptor negativity, aggressive molecular typing, high T stage, high number of positive lymph nodes, and lymph node ratio are poor prognostic factors patients with stage IIIC primary breast cancer. The efficient indicators of disease-specific survival include estrogen receptor status, progesterone receptor status, molecular typing, T stage, number of positive lymph nodes, and lymph node ratio.
RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway
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.
Survival Outcomes of Breast-Conserving Therapy versus Mastectomy in Early-Stage Breast Cancer, Including Centrally Located Breast Cancer: A SEER-Based Study
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.