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This retrospective cohort study aimed to determine whether adjuvant radiation therapy increases the risk of cardiac toxicity in Asian women with breast cancer, with a focus on patient-specific factors.
Preoperative partial breast irradiation (PBI) has the potential to induce tumor regression. We evaluated the differences in the numbers of preirradiation tumor infiltrating lymphocytes (TILs) between responders and nonresponders after preoperative PBI in low-risk patients with breast cancer. Furthermore, we evaluated the change in number of TILs before and after irradiation.
Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials’ cost-effectiveness analyses and key areas for future research.
To investigate whether the dose planned for cardiac structures is associated with the risk of heart disease (HD) in patients with breast cancer treated with radiation therapy, and whether this association is modified by the presence of coronary artery calcification (CAC).
Highlights: • Targeted therapy can be a useful therapeutic method along with traditional methods for breast cancer treatment. • Decreasing Akt/Nf-Kβ signaling pathway is crucial target in order to decreasing angiogenesis in TNBC. • The recombinant antibody can have inhibitory effects on production IL6,8, MMP2, and MMP9. Tumor progression and metastasis, especially in invasive cancers (such as triple-negative breast cancer [TNBC]), depend on angiogenesis, in which vascular epithelial growth factor (VEGF)/vascular epithelial growth factor receptor [1] has a decisive role, followed by the metastatic spread of cancer cells. Although some studies have shown that anti-VEGFR2/VEGF monoclonal antibodies demonstrated favorable results in the clinic, this approach is not efficient, and further investigations are needed to improve the quality of cancer treatment. Besides, the increased expression of epithelial cell adhesion molecule (EpCAM) in various cancers, for instance, invasive breast cancer, contributes to angiogenesis, facilitating the migration of tumor cells to other parts of the body. Thus, the main goal of our study was to target either VEGFR2 or EpCAM as pivotal players in the progression of angiogenesis in breast cancer. Regarding cancer therapy, the production of bispecific antibodies is easier and more cost-effective compared to monoclonal antibodies, targeting more than one antigen or receptor; for this reason, we produced a recombinant antibody to target cells expressing EpCAM and VEGFR2 via a bispecific antibody to decrease the proliferation and metastasis of tumor cells. Following the cloning and expression of our desired anti-VEGFR2/EPCAM sequence in E. coli, the accuracy of the expression was confirmed by Western blot analysis, and its binding activities to VEGFR2 and EPCAM on MDA-MB-231 and MCF-7 cell lines were respectively indicated by flow cytometry. Then, its anti-proliferative potential was indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assay to evaluate inhibitory effects of the antibody on tumor cells. Subsequently, the data indicated that migration, invasion, and angiogenesis were inhibited in breast cancer cell lines via the bispecific antibody. Furthermore, cytokine analysis indicated that the bispecific antibody could moderate interleukin 8 (IL-8) and IL-6 as key mediators in angiogenesis progression in breast cancer. Thus, our bispecific antibody could be considered as a promising candidate tool to decrease angiogenesis in TNBC.
To compare the risk of subclinical breast cancer–related lymphedema (sBCRL) using bioimpedance spectroscopy (BIS) or tape measure (TM) by the extent of axillary surgery and regional nodal irradiation (RNI).
Breast cancer has been identified as the most common malignant tumors among women and the morbidity of breast cancer is still increasing rapidly. MEX3A possesses important functions in the regulation of mRNAs and may be involved in a variety of human diseases including cancer, whose relationship with breast cancer is still not clear. In this study, MEX3A was identified as a potential promotor in breast cancer, whose expression was strongly higher in breast cancer tissues than normal tissues. The in vitro experiments showed that MEX3A is capable of promoting the development of breast cancer through stimulating cell proliferation, inhibiting cell apoptosis, arresting cell cycle and promoting cell migration. The functions of MEX3A were also verified in vivo. Furthermore, a combination of genechip analysis and Ingenuity pathway analysis (IPA) identified PIK3CA as a potential downstream target of MEX3A, knockdown of which executes similar inhibitory effects on breast cancer and could alleviate MEX3A-induced progression of breast cancer. In conclusion, our study unveiled, as the first time, MEX3A as a tumor promotor for breast cancer, whose function was carried out probably through the regulation of PIK3CA.
To characterize the early changes in echocardiographically derived measures of cardiac function with contemporary radiation therapy (RT) in breast cancer and to determine the associations with radiation dose-volume metrics, including mean heart dose (MHD).
Simple intensity modulation of radiation therapy reduces acute toxicity compared with 2-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiation therapy (IMRT) offers an advantage over forward-planned, 3-dimensional conformal radiation therapy (3DCRT).
Outcomes for triple negative breast cancer (TNBC) are poor and may be improved by increasing CD8{sup +} tumor infiltrating lymphocytes (TIL) to augment antitumor immunity. Radiation (RT) can promote immunogenic cell death with increased antitumor T cell activity but also stimulates suppressive regulatory T cells (Tregs). Because metabolic alterations affect immune homeostasis and prior studies show caloric restriction (CR) combined with RT improves preclinical TNBC outcomes, we hypothesized that CR augments RT, in part, by altering intratumoral immunity. Using an in vivo model of TNBC, we treated mice with ad libitum (AL) diet, radiation, a CR diet, or CR + RT, and demonstrated an immune suppressive environment with a significant increase in CD4{sup +} CD25{sup +}Foxp3{sup +} Tregs after RT but not in CR-fed mice. CD8:Treg ratio in CR + RT TIL increased 4-fold compared with AL + RT mice. In vivo CD8 depletion was performed to assess the role of effector T cells in mitigating the effects of CR, and it was found that in mice undergoing CR, depletion of CD8 T cells resulted in increased tumor progression and decreased median survival compared with isotype control–treated mice. In addition, PD-1 expression on CD3{sup +}CD8{sup +} T cells within the tumor microenvironment was significantly increased in CR + RT versus AL + RT treated mice as per immunofluorescence. Serum from breast cancer patients undergoing RT alone or CR and RT was collected pre- and postintervention, and a cytokine array demonstrated that patients treated with CR + RT had notable decreases in immunosuppressive cytokines such as IL-2Rγ, IL-10Rβ, and TGF-β2 and 3 compared with patients receiving RT alone. In conclusion, combining CR with RT decreases intratumoral Tregs, increases CD8:Treg, and increases PD-1 expression via a process dependent on CD8 T cells in a TNBC model. Breast cancer patients undergoing CR concurrently with RT also had significant reduction in immunosuppressive cytokine levels compared with those receiving RT alone.
The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.
Tumor biomarkers are used routinely in oncology to assign risk categorization, screen and assist in diagnosis of malignancy, allow for prognostication and prediction of outcomes and treatment response, and allow for monitoring of patients after treatment completion. Although tissue-based biomarkers have a long history of use, the emergence of liquid-based biomarkers, including circulating tumor cells (CTCs), may soon revolutionize the management of patients with cancer. Here, we review the discovery of CTCs and their role as prognostic and predictive biomarkers, with an emphasis on breast cancer. We discuss the platforms for CTC enumeration and focus on studies using the only US Food and Drug Administration–approved platform for CTC enumeration (CellSearch). In addition, we examine the role of CTCs in women with metastatic, inflammatory, and nonmetastatic breast cancer, as well as the clinical evidence for their use as a surrogate for radiation treatment response as well as surveillance after treatment. Finally, we conclude by investigating ongoing clinical studies assessing CTCs as radiation response predictors and discuss unanswered questions.
Accelerated partial breast irradiation (APBI) represents a validated technique for low-risk breast cancer. Recently, ultra-APBI (uAPBI) using fewer than 5 fractions was described in the literature. We compared clinical outcomes and late toxicity after APBI or uAPBI in older patients.
There is a paucity of data on the rates of ipsilateral breast tumor recurrence (IBTR) in BRCA1/2–associated breast cancer (BC). Scarcer yet are outcomes data in BRCA1/2 mutation carriers in the setting of newer mastectomy techniques, such as skin-sparing mastectomies (SSM) and nipple-sparing mastectomies (NSM).
Patients with triple-negative breast cancer (TNBC) experience higher local-regional recurrence rates than those with luminal or HER2-positive tumors. This prospective, phase 1B trial was designed to assess the safety and to establish the maximum tolerated dose (MTD) of cisplatin with radiation therapy for women with early-stage TNBC.
Use of hypofractionated radiation (HR) as a component of breast-conserving treatment (BCT) in breast cancer is relatively low in the United States despite studies demonstrating its efficacy and guidelines supporting its use from the American Society for Radiation Oncology (ASTRO) in 2011 and 2018. Little is known regarding national trends in uptake and factors associated with uptake of HR in the US since the 2011 ASTRO guidelines.
Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy.
Y-box binding protein 1 (YB-1) overexpression is associated with chemotherapy- and radiation therapy resistance. Ionizing radiation (IR), receptor tyrosine kinase ligands, and mutation in KRAS gene stimulate activation of YB-1. YB-1 accelerates the repair of IR-induced DNA double-strand breaks (DSBs). Ribosomal S6 kinase (RSK) is the main kinase inducing YB-1 phosphorylation. We investigated the impact of RSK targeting on DSB repair and radiosensitivity.