Randomised phase II trial evaluating the safety of peripherally inserted catheters versus implanted port catheters during adjuvant chemotherapy in patients with early breast cancer.

BACKGROUND: Both peripherally inserted central catheters (PICCs) and implanted port catheters (PORTs) are used for adjuvant chemotherapy (ACT) administration in patients with early breast cancer (EBC). We aimed to compare the safety between PICCs and PORTs in this setting. PATIENTS AND METHODS: This monocentric phase II randomised trial (NCT02095743) included patients with EBC who were eligible for ACT. Patients with curative anticoagulation therapy were excluded. The primary objective was to identify which device has a lower probability of catheter-related significant adverse events (CR-SAEs) within the 35 weeks after device implantation. The secondary objective was to evaluate quality of life (QoL) and patient satisfaction. RESULTS: From February 2014 to May 2018, 256 patients were included, and 253 (99%) were analysed. Overall, 31 patients (12.2%) experienced CR-SAEs, which mainly included thromboembolic events. In an intention-to-treat analysis, the probability that a CR-SAE would occur was 7.8% (10 events) with PORTs versus 16.6% (21 events) with PICCs (hazard ratio [HR] = 2.2 [1.03-4.62], P = 0.036). In a per-protocol analysis, PICCs were also associated with a higher risk of CR-SAEs than PORTs (HR = 2.82 [1.26-6.25], P = 0.007). Regarding the secondary objectives, if there was no difference in QoL between the arms, then significantly more discomfort was reported among patients with PICCs than among patients with PORTs (P = 0.002 after implantation and P < 0.001 at mid-treatment or at the end of treatment). CONCLUSIONS: CR-SAEs in patients with EBC are frequent but rarely impact the ACT process. Compared with PORTs, PICCs are associated with a significantly higher risk of CR-SAEs and more discomfort. PORTs should be preferred for ACT administration in patients with EBC.

Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor.

PURPOSE: To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. PATIENTS AND METHODS: ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. RESULTS: Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. CONCLUSION: ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.

Reliability of Prognostic and Predictive Factors Evaluated by Needle Core Biopsies of Large Breast Invasive Tumors.

OBJECTIVES: Preoperative biopsy of breast cancer allows for prognostic/predictive marker assessment. However, large tumors, which are the main candidates for preoperative chemotherapy, are potentially more heterogeneous than smaller ones, which questions the reliability of histologic analyses of needle core biopsy (NCB) specimens compared with whole surgical specimens (WSS). We studied the histologic concordance between NCB specimens and WSS in tumors larger than 2 cm. METHODS: Early pT2 or higher breast cancers diagnosed between 2008 and 2011 in our center, with no preoperative treatments, were retrospectively screened. We assessed the main prognostic and predictive validated parameters. Comparisons were performed using the κ test. RESULTS: In total, 163 matched NCB specimens and WSS were analyzed. The correlation was excellent for ER and HER2 (κ = 0.94 and 0.91, respectively), moderate for PR (κ = 0.79) and histologic type (κ = 0.74), weak for Ki-67 (κ = 0.55), and minimal for SBR grade (κ = 0.29). Three of the 21 HER2-positive cases (14% of HER2-positive patients or 1.8% of all patients), by WSS analysis, were initially negative on NCB specimens even after chromogenic in situ hybridization. CONCLUSIONS: NCB for large breast tumors allowed reliable determination of ER/PR expression. However, the SBR grade may be deeply underestimated, and false-negative evaluation of the HER2 status would have led to a detrimental lack of trastuzumab administration.

CD70: A Potential Target in Breast Cancer?

CD70 is a co-stimulatory molecule involved in the immune response and also in cancer development and progression. Recent studies show that high CD70 expression in cancer cells may inhibit the anti-tumor response. Furthermore, CD70 expression has been reported as a predictive marker of resistance to chemotherapy in ovarian cancers. Some in vitro studies have shown that CD70 expression is epigenetically down-regulated through hypermethylation of its promoter during tumoral progression. This study evaluated the level of CD70 expression in surgical samples of breast invasive tumors and determined its correlation with CD70 promoter methylation. Twenty "luminal A" and 20 "basal-like" frozen samples from early breast tumors were retrospectively selected. CD70 expression was evaluated by quantitative real-time PCR. Total DNA was bisulfite-treated, and methylation levels of 5 consecutive CG sites present in the proximal region (-464, -421) of the promoter were assessed by pyrosequencing analysis. Statistical analyses were performed using the Mann-Whitney test. The median relative CD70 expression level was 0.37 and was significantly higher in the basal-like group (0.78 [0.24-31.7]) compared to the luminal A group (0.25 [0.03-1.83], p=0.0001). The median methylation level was 61%, with no significant difference between the basal-like (63%) and luminal A (58%) groups. No correlation was found between CD70 expression and CD70 methylation level. In this study, higher CD70 expression was observed in the basal-like group, but this expression was not related to promoter methylation. The higher expression in the poor-prognosis subgroup of patients makes CD70 a potential target for emerging anti-CD70 therapies.