FGFR1 Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer.

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News and updates in the treatment of localized stage triple-negative breast cancer

Compared to other breast cancer subtypes, triple-negative breast cancer presents a worse prognosis and higher mortality. Even in localized stages, the risk of relapse is high, especially in patients with ≥ cT2 and/or ≥ cN1. We know that those patients who achieve a complete pathologic response after neoadjuvant treatment have better disease-free survival. Therefore, many research efforts have been made to try to optimize neoadjuvant chemo/immunotherapy to increase pathologic complete response rates. The available evidence related to that subject matter is summarized in this article. In the field of adjuvant therapy, the challenge of improving disease-free survival in those patients who do not achieve pathologic complete response after neoadjuvant therapy stands out. The second part of this article will deal with the challenges inherent to this issue

Two-center experience comparing the use of the FLOT4 and CROSS schemes for patients with gastric, esophageal, and gastroesophageal junction adenocarcinoma

Introduction. Gastric (GAD), gastroesophageal junction (GEJA), and esophageal adenocarcinoma (EAD) share pathophysiological features. At localized stages, FLOT is used perioperatively for the treatment of GAD and GEJA and CROSS for EAD and some GEJA. Although both therapies have been compared with MAGIC, comparative randomized data on FLOT and CROSS are not yet available. Material andmethods. We retrospectively analyzed and compared 40 patients treated with FLOT and 16 patients treated with CROSS in terms of clinical features and neoadjuvant, surgical, adjuvant, and survival outcomes. Results. At the time of analysis, 65% of patients treated with FLOT4 and 56.3% with CROSS remained in complete remission. Those who progressed after FLOT4 did so mainly at the peritoneal level (25%) and after CROSS at the bone, lymph node, and peritoneal levels (12.5% respectively). Six patients (37.5%) died after CROSS (median OS of 17.5 months; 95% CI 2–41) and 10 (25%) after FLOT4 (median OS 16.5 months; 95% CI 11–22). For the living patients, the median numbers of months from diagnosis to the follow-up cutoff date were 47.5 (95% CI 11–67) and 27 (95% CI 14–44) for CROSS and FLOT4, respectively. There were no significant differences in median OS estimated by Kaplan Meier analysis [FLOT4: 50 ± 4.6 months (95% CI 40.9–59.2); CROSS: 51.2 ± 7 months (95% CI 37.4–65.0; p = 0.79)].  Conclusions. Although we obtained lower pCR rates; TNM downstaging after neoadjuvant therapy, R0 rates, tolerance, PFS, and OS were similar in both groups and comparable with trial results. The adjuvant compliance rate was high with FLOT4. CROSS allows sequencing with nivolumab in PD-L1+ tumors

HER2 and BARD1 Polymorphisms in Early HER2-Positive Breast Cancer Patients: Relationship with Response to Neoadjuvant Anti-HER2 Treatment

The addition to chemotherapy of anti-HER2 drugs such as trastuzumab or pertuzumab has improved outcomes in HER2-positive breast cancer patients. However, resistance to these drugs in some patients remains a major concern. This study examines the possible association between the response to neoadjuvant anti-HER2 treatment in breast cancer patients and the presence of 28 SNPs in 17 genes involved in different cell processes (PON1, CAT, GSTP1, FCGR3, ATM, PIK3CA, HER3, BARD1, LDB2, BRINP1, chr6 intergenic region, RAB22A, TRPC6, LINC01060, EGFR, ABCB1, and HER2). Tumor samples from 50 women with early breast cancer were genotyped using the iPlex®Gold chemistry and MassARRAY platform, and patients were classified as good responders (Miller–Payne tumor grades 4–5) and poor responders (Miller–Payne tumor grades 1–3), as assessed upon surgery after 6 months of treatment. Proportions of patients with the HER2Ala1170Pro (rs1058808) SNP double mutation were higher in good (58.62%) than poor (20%) responders (p = 0.025). Similarly, proportions of patients carrying the synonymous SNP rs2070096 (BARD1Thr351=) (wv + vv) were higher in patients showing a pathological complete response (46.67%) than in those not showing this response (15.15%) (p = 0.031). The SNPs rs1058808 (HER2Ala1170Pro) and rs2070096 (BARD1Thr351=) were identified here as potential biomarkers of a good response to anti-HER2 treatment.Universidad Europea de Madrid (2020/UEM15)Foundation of the Universidad Europea, (FGUE001804 and FGUE0018056.575 Q1 JCR 20211.349 Q1 SJR 2021No data IDR 2021UE

Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer

Angiogenesis pathway genes show substantial genetic variability causing inter-individual differences in responses to anti-angiogenic drugs. We examined 20 single nucleotide polymorphisms (SNPs) in 13 of these genes to predict tumour response and clinical outcome measured as progression free survival (PFS) and overall survival (OS) in 57 patients with metastatic colorectal cancer (mCRC) given bevacizumab plus chemotherapy. SNPs were detected (iPLEX®Assay) in genomic DNA extracted from formalin-fixed paraffin-embedded tumour specimens. The variant allele CD39 rs11188513 was associated with a good tumour response (p = 0.024). Patients homozygous for the wild-type allele FGF2 rs1960669 showed a median PFS of 10.95 months versus 5.44 months for those with at least one variant allele-A (HR 3.30; 95% CI: 1.52–7.14; p = 0.001). Patients homozygous for wild-type MMP9 rs2236416 and rs2274755 showed a median PFS of 9.48 months versus 6 and 6.62 months, respectively, for those with at least one variant allele (p = 0.022, p = 0.043, respectively). OS was also lengthened to 30.92 months (p = 0.034) in carriers of wild-type ANGPT1 rs2445365 versus 22.07 months for those carrying at least one variant allele-A. These gene variants were able to predict clinical outcome and tumour response in mCRC patients given bevacizumab-based therapyUniversity Hospital of Fuenlabrada, Universidad Europea de Madrid (project 2018/UEM25 and 2017/UEM04)Foundation of the European University (project numbers FGUE001804 and FGUE001805)5.924 JCR (2020) Q1, 67/295 Biochemistry & Molecular Biology1.455 SJR (2020) Q1, 62/2196 Computer Science ApplicationsNo data IDR 2020UE

Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and CXCL5 expression: Six case reports

BACKGROUND In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment. CASE SUMMARY We report six cases of stage IV KRAS-mutated mCRC. Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada. The six patients differed in terms of primary tumor location (right/left side), tumor burden (mostly hepatic and peritoneal disease) and clinical disease course. Before treatment onset, total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures. Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival (under 6 mo) from the start of treatment. CONCLUSION A higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment.Fundación UEM FGUE001804, FGUE0018052015/UEM12, 2016/UEM135.742 JCR (2020) Q2, 28/92 Gastroenterology & Hepatology1.427 SJR (2020) Q1, 26/144 GastroenterologyNo data IDR 2020UE

Objective evaluation of physical activity in Spanish breast cancer survivor

Obesity and physical inactivity are poor prognostic indicators for breast cancer. Cardiorespiratory fitness (CRF) is a good predictor of survival for general population and for breast cancer survivors (BCS). CRF depends on genetic factors and on the PA performed by the individual. International organizations recommend at least 150 minutes per week of moderate-vigorous physical activity (MVPA). A limitation of physical activity (PA) research has been the use of self-reported measures. Some studies show that a minority of BCS are meeting the PA recommendations.Sin financiación20.982 JCR (2015) Q1, 5/213 OncologyUE

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible. A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p 6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p  Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET