Background: The role of the HER2-enriched (HER2E) subtype determined by the Prosigna Assay in the neoadjuvant setting has remained largely uncharacterized. In this study, we examine whether Prosigna can identify a subgroup of HER2+ patients for whom combination neoadjuvant therapy that includes trastuzumab (Herceptin) is associated with a greater likelihood of pathological complete response (pCR). Methods: In this single-arm retrospective analysis, 75 patients determined to be HER2+ by IHC were treated with a neoadjuvant regimen (NAC) consisting of 8-12 cycles of anthracyclines and taxanes as well as Herceptin. The Prosigna Assay was performed on the NanoString nCounter® Dx Analysis System at HU Virgende la Victoria de Málaga/CIMES-UMA. pCR was used as the endpoint for this study and was determined using the Miller & Payne scoring criteria. Results: Mean patient age for this study population was 49 (±11.1yr) and all patients were determined to be HER2+ by IHC. The overall pCR rate in this patient population was 46.2%. Of the 75 patient samples analyzed for this study, 59 (78.6%) were HER2E, 4 (5.3%) were Luminal A and 12 (16.1%) were Luminal B, as identified by the Prosigna Assay. Of the 16 tumors classified as Luminal (A or B) by Prosigna within this HER2+ population, only 2 (12.5%) responders were observed. Categorical analysis revealed that Prosigna subtype predicted response to a NAC regimen combined with Herceptin (Odds ratio [Her2E vs. non-Her2E]=6.4, p=0.023). Further analysis of the Her2E subtype revealed that tumors with profile expression that correlated well with the prototypical Her2E centroid were significantly more likely to respond to combination NAC and Herceptin (Odds ratio [Unit increase of 1 in Her2E correlation]=88.2, p=0.004). Conclusions: The results of this study indicate that HER2+ patients with greater correlations to the HER2E subtype have an increased likelihood of response to combination neoadjuvant regimens that included HER2-targeted therapy. Citation Format: Santonja Á, Ribelles N, Jiménez-Rodríguez B, Sánchez Rovira P, Álvarez M, Vicioso L, Isabel Fernandez A, de Luque V, Fernández de Sousa C, Villar E, Zarcos I, Ramírez C, González-Hermoso C, Jeiranian A, Dowidar N, Schaper C, Buckingham W, Ferree S, Jiménez A, Prat A, Alba E. Prosigna® intrinsic subtyping predicts response to neoadjuvant combination therapy in study that includes herceptin within HER2+ (IHC) patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-14.
Background and purpose: The association of hyperthermia with radiotherapy has been shown to be a valid approach in the treatment of locoregional recurrence of previously irradiated malignant tumors. The purpose of the present study is to describe the initial experience of the Radiation Oncology Department Júlio Teixeira SA (CUF Institute) and the Medical Oncology Service (Hospital CUF Porto) in the treatment of these lesions, reporting the first cases treated in Portugal with this therapeutic approach. Material and methods: The authors performed a retrospective analysis of the 18 patients, 16 females and 2 males, with unresectable tumor recurrences, in previously irradiated areas, treated with radiotherapy associated with hyperthermia between May 2016 and March 2017, totalizing 25 treatments. Breast disease was the most frequent, accounting for 72% of cases. Results: The median follow-up period was 4, 5 months. The complete response rate was 44%. A favorable response was observed in all treatments, with decrease in pain, bleeding and infection, with and no grade 3 toxicities. Conclusions: The results are encouraging, with improved quality of life and patient self-esteem with acceptable toxicity. The combined treatment of hyperthermia and radiotherapy seems to be a valid option in the local control of recurrent unresectable neoplasms at previously irradiated sites, whose therapeutic options are limited.
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