Search results for " Breast Cancer"
showing 10 items of 427 documents
Abstract 1855: Role of mTOR inhibition in triple-negative breast cancer
2016
Abstract BACKGROUND: Triple-negative breast cancers (TNBC) represent the 10-17% of all diagnosed breast cancers (BC) and are characterized by the absence of ER/PgR expression, HER2 amplification and often show a basal-like phenotype. TNBC are often diagnosed in patients with BRCA1 germline mutation and unfortunately treatment options are still limited. The mTOR (Mammalian Target Of Rapamycin) pathway seems to play an important role in BC pathogenesis and it is possible to target this pathway by inhibitors such as rapamycin. In human BC cross talk between ER/PgR receptors signaling and the mTOR pathway is believed to be responsible for resistance to hormone therapy probably due to a down reg…
Abstract PD1-02: A phase I/Ib study evaluating GDC-0077 + palbociclib (palbo) + fulvestrant in patients (pts) with PIK3CA-mutant (mut), hormone recep…
2021
Abstract Background GDC-0077 is a PI3Kα-selective inhibitor and mutant PI3Kα degrader that demonstrates antitumor activity in PIK3CAmut BC xenograft models. A phase I/Ib study of GDC-0077 alone and combined with endocrine therapy ± the CDK4/6 inhibitor (i) palbo is ongoing (NCT03006172). Data from GDC-0077 + palbo + fulvestrant in pts with PIK3CAmut, HR+/HER2- mBC are presented herein. Methods Safety (NCI-CTCAE v4), pharmacokinetics (PK), and preliminary antitumor activity (clinical benefit rate [CBR]: RECIST v1.1 stable disease for ≥ 24 weeks, partial response [PR], or complete response) of 9 mg oral once daily GDC-0077 + 125 mg palbo 21/28 days + 500 mg intramuscular fulvestrant on day 1 …
Abstract PS11-11: Targeted safety events from a phase I/Ib study evaluating GDC-0077 alone and in combination with endocrine therapy (ET) ± palbocicl…
2021
Abstract Background Activating mutations in PIK3CA, encoding the p110α subunit of phosphatidylinositol 3-kinase (PI3K) occur in ~40% of HR+/HER2- BCs. GDC-0077, a PI3Kα-selective inhibitor and mutant PI3Kα degrader, is being developed as an anticancer agent. A phase I/Ib study of GDC-0077 alone and combined with other therapies is ongoing in pts with locally advanced or metastatic PIK3CAmut, HR+/HER2- mBC (NCT03006172). Targeted safety events are presented here. Methods Safety was assessed via NCI-CTCAE v4 for GDC-0077 administered alone (Arm A), with letrozole and palbo (Arm B), with letrozole (Arm C), with fulvestrant (Arm D), or with fulvestrant and palbo (Arm E, plus metformin in Arm F …
Current Role of Intraoperative Frozen Section Examination of Sentinel Lymph Node in Early Breast Cancer.
2020
Background/Aim: The aim of this study was to evaluate the current role of frozen section in identifying patients who could benefit from an immediate axillary lymph node dissection (ALND), following the criteria of the ASOCOG Z0011 and IBCSG 23-10 trials. Patients and Methods: A retrospective review was performed involving 2,079 patients with early breast cancer who underwent conservative surgery or total mastectomy with sentinel lymph node biopsy. Results: Sensitivity and diagnostic accuracy were 63.8% and 90.3%, respectively. Sensitivity was significantly higher (p<0.001) in finding macrometastases (81.8%) compared to micrometastases (11.9%). Frozen section was useful only in 7.7% of th…
Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients
2019
One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statis…
A French prospective pilot study for identifying dihydropyrimidine dehydrogenase (DPD) deficiency in breast cancer patients (pts) receiving capecitab…
2013
e13519 Background: For fluoropyrimidines, and especially cap, Health Authorities point out that DPD deficiency confers a significant risk of major toxicity (tox). Identification of at-risk pts is thus relevant. This multicentric prospective study of the French GPCO group (Groupe de Pharmacologie Clinique Oncologique, Unicancer) evaluated the sensitivity, specificity and predictive values of DPD phenotyping and genotyping for predicting severe cap-related tox in metastatic breast cancer pts. Methods: 303 pts were included (15 institutions), 88% received cap as monotherapy, 28% were treated as first line (mean dose at 1st cycle 1957 mg/m2/d). Pre-treatment dihydrouracil (UH2) and uracil (U) …
Parthenolide induces superoxide anion production by stimulating EGF receptor in MDA-MB-231 breast cancer cells
2013
The sesquiterpene lactone parthenolide (PN) has recently attracted considerable attention because of its anti-microbial, anti-inflammatory and anticancer effects. However, the mechanism of its cytotoxic action on tumor cells remains scarcely defined. We recently provided evidence that the effect exerted by PN in MDA-MB-231 breast cancer cells was mediated by the production of reactive oxygen species (ROS). The present study shows that PN promoted the phosphorylation of EGF receptor (phospho-EGFR) at Tyr1173, an event which was observed already at 1 h of incubation with 25 µM PN and reached a peak at 8-16 h. This effect seemed to be a consequence of ROS production, because N-acetylcystein…
The oxygen radicals involved in the toxicity induced by parthenolide in MDA-MB-231 cells
2014
It has been shown that the sesquiterpene lactone parthenolide lowers the viability of MDA-MB-231 breast cancer cells, in correlation with oxidative stress. The present report examined the different radical species produced during parthenolide treatment and their possible role in the toxicity caused by the drug. Time course experiments showed that in the first phase of treatment (0-8 h), and in particular in the first 3 h, parthenolide induced dichlorofluorescein (DCF) signal in a large percentage of cells, while dihydroethidium (DHE) signal was not stimulated. Since the effect on DCF signal was suppressed by apocynin and diphenyleneiodonium (DPI), two inhibitors of NADPH oxidase (NOX), we s…
Comparison of relaxation techniques in virtual reality for breast cancer patients
2019
A number of studies demonstrated that virtual reality (VR) featuring pleasant scenarios and relaxing narratives is effective in promoting relaxation in users, both in healthy and pathological contexts. One important field for application of relaxing VR is breast cancer, because of therapy-related distress and changes in body imagine experienced by patients during the care process. However, comparisons between different relaxation techniques adapted to virtual reality are rare. In the present study, the same virtual environment has been integrated with audio narratives designed according to two different relaxation techniques (respiration control and body scan). As initial exploration, 16 br…
Type V collagen and protein kinase C η down-regulation in 8701-BC breast cancer cells.
2011
We previously reported that ductal infiltrating carcinomas (d.i.c.) of the human breast display profound modifications of the stromal architecture, associated with anomalous collagen composition. Among the major alterations observed in the interstitial collagen, the relative increase of type V collagen content was detected. When type V collagen was used as an ‘‘in vitro’’ substrate for 8701-BC d.i.c. cells, it appeared able to restrain cell growth, inhibit cell motility and invasion ‘‘in vitro’’, and modify the expression levels of genes coding for apoptosis factors, caspases and stress response proteins. In the present paper we demonstrate that type V collagen induces the down-regulation o…