Does Breast Cancer Subtype Impact Margin Status in Patients Undergoing Partial Mastectomy?

Background Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy. Methods Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. Patients were classified as luminal if they were ER and/or PR positive; HER2 enriched if they were ER and PR negative but HER2 positive; and TN if they were negative for all 3 receptors. The impact of subtype on the margin status was evaluated at completion of standard PM, prior to randomization to CSM versus no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. Results Molecular subtype was significantly correlated with race ( P = .011), palpability ( P = .007), and grade ( P < .001). Subtype did not correlate with Hispanic ethnicity ( P = .760) or lymphovascular invasion ( P = .756). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate 33.7% for patients with luminal tumors vs 36.4% for those with TN tumors, P = .425). Discussion Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.

Dihydroartemisinin-Transferrin Adducts Enhance TRAIL-Induced Apoptosis in Triple-Negative Breast Cancer in a P53-Independent and ROS-Dependent Manner

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype independent of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. It has a poor prognosis and high recurrence. Due to its limited treatment options in the clinic, novel therapies are urgently needed. Single treatment with the death receptor ligand TRAIL was shown to be poorly effective. Recently, we have shown that artemisinin derivatives enhance TRAIL-induced apoptosis in colon cancer cells. Here, we utilized transferrin (TF) to enhance the effectiveness of dihydroartemisinin (DHA) in inducing cell death in TNBC cell lines (MDA-MB-231, MDA-MB-436, MDA-MB-468 and BT549). We found that the combination of DHA-TF and the death receptor 5-specific TRAIL variant DHER leads to an increase in DR5 expression in all four TNBC cell lines, while higher cytotoxicity was observed in MDA-MB-231, and MDA-MB-436. All the data point to the finding that DHA-TF stimulates cell death in TNBC cells, while the combination of DHA-TF with TRAIL variants will trigger more cell death in TRAIL-sensitive cells. Overall, DHA-TF in combination with TRAIL variants represents a potential novel combination therapy for triple-negative breast cancer.

Mapping Intellectual Structures and Research Hotspots of Triple Negative Breast Cancer: A Bibliometric Analysis

BackgroundTriple negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with a poor prognosis due to its extremely aggressive nature and lack of effective treatment options. This study aims to summarize the current hotspots of TNBC research and evaluate the TNBC research trends, both qualitatively and quantitatively.MethodsScientific publications of TNBC-related studies from January 1, 2010 to October 17, 2020 were obtained from the Web of Science database. The BICOMB software was used to obtain the high-frequency keywords layout. The gCLUTO was used to produce a biclustering analysis on the binary matrix of word-paper. The co-occurrence and collaboration analysis between authors, countries, institutions, and keywords were performed by VOSviewer software. Keyword burst detection was performed by CiteSpace.ResultsA total of 12,429 articles related to TNBC were identified. During 2010-2020, the most productive country/region and institution in TNBC field was the USA and The University of Texas MD Anderson Cancer Center, respectively. Cancer Research, Journal of Clinical Oncology, and Annals of Oncology were the first three periodicals with maximum publications in TNBC research. Eight research hotspots of TNBC were identified by co-word analysis. In the core hotspots, research on neoadjuvant chemotherapy, paclitaxel therapy, and molecular typing of TNBC is relatively mature. Research on immunotherapy and PARP inhibitor for TNBC is not yet mature but is the current focus of this field. Burst detection of keywords showed that studies on TNBC proteins and receptors, immunotherapy, target, and tumor cell migration showed bursts in recent three years.ConclusionThe current study revealed that TNBC studies are growing. Attention should be paid to the latest hotspots, such as immunotherapy, PARP inhibitors, target, and TNBC proteins and receptors.

Survival outcomes in elderly Taiwanese women according to breast cancer subtype and lymph node status: A single-center retrospective study

This study aimed to determine the rates of overall survival and recurrence-free survival among elderly Taiwanese women (>65 years old) according to breast cancer subtype and lymph node status. We identified 554 eligible patients who were >65 years old and had been treated based on international recommendations at our center between June 2005 and June 2015. Patients with the luminal A subtype had the highest rates of overall survival (90.6%) and recurrence-free survival (97.0%), while the lowest overall survival rate was observed in those with the triple-negative subtype (81.3%) and the lowest recurrence-free survival rate was observed in those with the luminal B subtype (84.0%). Multivariate Cox proportional hazard analysis, using the luminal A subtype as the reference, revealed significant differences in recurrence-free survival among luminal B patients according to lymph node status. Among elderly Taiwanese women with breast cancer, the breast cancer subtype might help predict survival outcomes. The luminal B subtype was associated with poor recurrence-free survival, and lymph node status was useful for predicting recurrence-free survival in this subset of patients.

Cannabinoids in Breast Cancer: Differential Susceptibility According to Subtype

Although cannabinoids have been used for centuries for diverse pathological conditions, recently, their clinical interest and application have emerged due to their diverse pharmacological properties. Indeed, it is well established that cannabinoids exert important actions on multiple sclerosis, epilepsy and pain relief. Regarding cancer, cannabinoids were first introduced to manage chemotherapy-related side effects, though several studies demonstrated that they could modulate the proliferation and death of different cancer cells, as well as angiogenesis, making them attractive agents for cancer treatment. In relation to breast cancer, it has been suggested that estrogen receptor-negative (ER−) cells are more sensitive to cannabinoids than estrogen receptor-positive (ER+) cells. In fact, most of the studies regarding their effects on breast tumors have been conducted on triple-negative breast cancer (TNBC). Nonetheless, the number of studies on human epidermal growth factor receptor 2-positive (HER2+) and ER+ breast tumors has been rising in recent years. However, besides the optimistic results obtained thus far, there is still a long way to go to fully understand the role of these molecules. This review intends to help clarify the clinical potential of cannabinoids for each breast cancer subtype.

Expression of CD4, CD8 Biomarkers in Invasive Carcinoma of Breast with Clinicopathological Correlation

Introduction: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in various cancers, including invasive breast cancer (IBC). Aim and Objectives: To correlate the expression of CD4, CD8 T-lymphocytes in invasive carcinoma breast with established markers of prognosis like tumour size, grade, lymph node status and molecular subtypes mainly ER, PR, Her 2Neu, Ki67 status, mainly the triple negative breast cancers(TNBC). Methodology: 58 Invasive breast carcinoma proven tissue blocks were subjected to immunohistochemistry and morphometric analysis for positive CD4, CD8 T-lymphocytes were done. Results: Triple negative breast cancer subtype shows high TILs than other pathologic subtypes. Tumor interface CD8+ cells very well correlated with the pathological higher nodal stage. Majority CD4, CD8 positive cells were populated more towards the stromal and interface of the tumor microenvironment rather thatintratumoral. Conclusion: CD4+ and CD8+ counts may be a valuable independent prognostic tool in predicting the outcome in invasive breast cancer.

Quantitative single-cell analysis of immunofluorescence protein multiplex images illustrates biomarker spatial heterogeneity within breast cancer subtypes

Background The extent of cellular heterogeneity in breast cancer could have potential impact on diagnosis and long-term outcome. However, pathology evaluation is limited to biomarker immunohistochemical staining and morphology of the bulk cancer. Inter-cellular heterogeneity of biomarkers is not usually assessed. As an initial evaluation of the extent of breast cancer cellular heterogeneity, we conducted quantitative and spatial imaging of Estrogen Receptor (ER), Progesterone Receptor (PR), Epidermal Growth Factor Receptor-2 (HER2), Ki67, TP53, CDKN1A (P21/WAF1), CDKN2A (P16INK4A), CD8 and CD20 of a tissue microarray (TMA) representing subtypes defined by St. Gallen surrogate classification. Methods Quantitative, single cell-based imaging was conducted using an Immunofluorescence protein multiplexing platform (MxIF) to study protein co-expression signatures and their spatial localization patterns. The range of MxIF intensity values of each protein marker was compared to the respective IHC score for the TMA core. Extent of heterogeneity in spatial neighborhoods was analyzed using co-occurrence matrix and Diversity Index measures. Results On the 101 cores from 59 cases studied, diverse expression levels and distributions were observed in MxIF measures of ER and PR among the hormonal receptor-positive tumor cores. As expected, Luminal A-like cancers exhibit higher proportions of cell groups that co-express ER and PR, while Luminal B-like (HER2-negative) cancers were composed of ER+, PR- groups. Proliferating cells defined by Ki67 positivity were mainly found in groups with PR-negative cells. Triple-Negative Breast Cancer (TNBC) exhibited the highest proliferative fraction and incidence of abnormal P53 and P16 expression. Among the tumors exhibiting P53 overexpression by immunohistochemistry, a group of TNBC was found with much higher MxIF-measured P53 signal intensity compared to HER2+, Luminal B-like and other TNBC cases. Densities of CD8 and CD20 cells were highest in HER2+ cancers. Spatial analysis demonstrated variability in heterogeneity in cellular neighborhoods in the cancer and the tumor microenvironment. Conclusions Protein marker multiplexing and quantitative image analysis demonstrated marked heterogeneity in protein co-expression signatures and cellular arrangement within each breast cancer subtype. These refined descriptors of biomarker expressions and spatial patterns could be valuable in the development of more informative tools to guide diagnosis and treatment.

Value of 18F-FDG PET/CT for predicting axillary pathologic complete response following neoadjuvant systemic therapy in breast cancer patients: emphasis on breast cancer subtype

Background Neoadjuvant systemic therapy (NST) is a widely accepted initial treatment modality that can lead to pathologic downstaging of the axillary disease burden in breast cancer patients. Axillary response as well as baseline 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography with computed tomography (PET/CT) differ between breast cancer subtypes. The value of baseline 18F-FDG PET/CT in predicting axillary response to NST is not yet established, possibly since breast cancer subtype was not taken into account. The purpose of this study was to investigate the value of baseline 18F-FDG PET/CT in predicting axillary response to NST with a specific emphasis on subtype. Methods PET-parameters derived from the primary tumor as well as the most FDG-avid axillary lymph node were measured on baseline 18F-FDG PET/CT. Overall imaging findings were compared with the gold standard of histopathology of the axillary surgery specimen. Analyses for ER-positive/HER2-negative were performed separately from HER2-positive and TN patients. In addition, separate analyses for clinically node-positive patients were performed. Results Sixty-six patients with 69 primary tumors were included in this study. Thirty-three axillae contained ER-positive/HER2-negative, 16 HER2-positive, and 20 TN breast cancer. No significant difference in PET-parameters between patients with axillary residual disease and axillary pathologic complete response were found for ER-positive/HER2-negative breast cancer. In the combined HER2-positive/TN subgroup, the SUVmax was significantly lower in patients without residual axillary disease in both the entire cohort and in patients with clinically node-positive disease. In this combined subgroup, a cut-off of 4.89 SUVmax measured on the most FDG-avid axillary lymph node could predict residual axillary disease with a sensitivity, specificity, PPV, and NPV of 90%, 69%, 53%, and 95%, respectively. Conclusions Predicting axillary response following NST with baseline 18F-FDG PET/CT can be performed when focusing on breast cancer subtypes. The easily computed PET-parameter SUVmax can predict axillary response in HER2-positive and TN breast cancer. This study adds to the accumulating evidence that studies investigating the value of 18F-FDG PET/CT in breast cancer should always take subtypes into account.