21-Gene Recurrence Score Assay and Outcomes of Adjuvant Radiotherapy in Elderly Women With Early-Stage Breast Cancer After Breast-Conserving Surgery

Abstract

Introduction: To assess the role of the 21-gene recurrence score (RS) assay on decision-making of postoperative radiotherapy (RT) following breast-conserving surgery (BCS) in elderly women with early-stage breast cancer.Methods: The 21-gene RS for elderly (≥65 years) women with stage T1–2N0M0 estrogen receptor-positive breast cancer who underwent BCS from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results program. We estimated the association of 21-gene RS and adjuvant RT related to breast cancer-specific survival (BCSS) using propensity score matching (PSM).Results: We identified 18,456 patients, of which 15,326 (83.0%) received postoperative RT. Of identified patients, 58.9, 34.0, and 7.1% of patients had a low-, intermediate-, and high-risk RS, respectively. Receipt of postoperative RT was not related to the year of diagnosis according to the 21-gene RS groups. Multivariate analysis suggested that receipt of postoperative RT was an independent predictor of better BCSS before (hazard ratio [HR] 0.587, 95% confidence interval [CI] 0.426–0.809, P = 0.001) and after (HR 0.613, 95%CI 0.390–0.963, P = 0.034) PSM. However, subgroups analyses indicated that receipt of postoperative RT was related to better BCSS in women with intermediate-risk RS before (HR 0.467, 95%CI 0.283–0.772, P = 0.003) and after (HR 0.389, 95%CI 0.179–0.846, P = 0.017) PSM, but not in women with low- and high-risk RS groups before and after PSM.Conclusions: Although causation cannot be implied, adjuvant RT in elderly women was associated with a greater effect size in patients with an intermediate-risk RS.

Diagnostic Value of VEGF-A, VEGFR-1 and VEGFR-2 in Feline Mammary Carcinoma

“…Furthermore, results demonstrated that cats with strong positive VEGF-A expression in TILs showed higher serum VEGF-A levels than cats with a weak positive or negative VEGF-A expression, suggesting an effective endocrine mechanism for the release of serum VEGF-A from stromal cells to the bloodstream. Accordingly, as part of tumor microenvironment, TILs are able to release VEGF-A and inflammatory cytokines, showing immunosuppressive effects [ 41 ], including the formation of new blood vessels by acting on endothelial cells [ 42 ] and enhancing the inflammatory processes by increasing hypoxia inducible factor 1-alpha (HIF-1α) and VEGF-A synthesis [ 13 ]. Moreover, high serum VEGF-A levels were also associated with an intense VEGFR-2 reactivity, suggesting that serum VEGF-A also contributes to the activation of VEGFR-2 [ 18 ].…”

Radiotherapy after breast‐conserving surgery for elderly patients with early‐stage breast cancer: A national registry‐based study

“…Several previous studies outside of clinical trials have reported that adjuvant RT not only decreased the risk of ipsilateral breast cancer recurrence and secondary mastectomy, [20][21][22] but also improved breast cancer-specific survival among patients aged ≥70 and with Stage I/ER+ disease. [23][24][25] However, information on endocrine therapy, surgical margin status and comorbidity status was unavailable for these studies. In our study, with these factors and other prognosticrelated factors taken into account, elderly breast cancer patients who did not receive RT, including NCCN guideline eligible patients, were found to have higher mortality, even among those age ≥90.…”

“…Furthermore, the effect size associated with RT omission in our study is consistent in magnitude with findings from studies that evaluated breast cancer-specific survival. 23,25 Although thorough stratified analyses were conducted, and extensive covariates were adjusted for, we cannot completely rule out selection bias and residual confounding due to the observational design.…”

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

“…The clinical success of immunotherapy with checkpoint inhibitors relies significantly on effective processing and cross-presentation of tumor-specific antigens captured by DCs [ 158 ]. The blockade of inhibitory receptors on the cell surface of T cells by monoclonal antibodies, can intensify antitumor responses initially primed by DCs [ 166 ]. Tumor-bearing mice with impaired cross-presentation pathways showed resistance to therapy with antibodies targeting ICs [ 167 , 168 ].…”

“…There is extensive published literature that correlates high mutation burden and neoantigen frequency with durable survival and regression benefit from/after ICI therapy in several types of tumors. Neoantigens have been proposed to be good predictive and prognostic markers of better clinical outcomes, although tumors with low mutational load can still respond to checkpoint blockade, indicating a non-linear correlation and the involvement of additional factors [ 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 ].…”