scholarly journals Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study

2020 ◽  
Vol 184 (2) ◽  
pp. 421-431
Author(s):  
Francesco Schettini ◽  
Navid Sobhani ◽  
Anna Ianza ◽  
Tiziana Triulzi ◽  
Alfredo Molteni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Hormone Receptor Positive ◽  
Phase Iiib ◽  
Circulating Lymphocytes ◽  
Tumor Neoangiogenesis

Abstract Purpose mTOR inhibitor everolimus is used for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). No reliable predictive biomarker of response is available. Following evidences from other solid tumors, we aimed to assess the association between treatment-associated immune system features and everolimus activity. Methods We retrospectively explored a correlation with the therapeutic activity of everolimus and tumor-associated immune pathways with ingenuity pathway analysis (IPA), neutrophil-to-lymphocyte ratio (NLR), circulating lymphocytes, and endothelial cells (CECs) in 3 different HR+ mBC studies, including the BALLET phase IIIb study. Results The circulating levels of CD3+/CD8+, CD3+/CD4+, and overall T lymphocytes were higher in responders versus non-responders at baseline (p = 0.017, p < 0.001, p = 0.034) and after treatment (p = 0.01, p = 0.003, p = 0.023). Reduced CECs, a tumor neoangiogenesis marker, were observed in responders after treatment (p < 0.001). Patients with low NLR (≤ 4.4) showed a better progression-free survival compared to patients with high NLR (> 4.4) (p = 0.01). IPA showed that the majority of immunity-related genes were found upregulated in responders compared to non-responders before treatment, but not after. Conclusions Lymphocytes subpopulations, CECs and NLR could be interesting biomarkers predictive of response to everolimus-based regimens, potentially useful in daily clinical practice to select/monitor everolimus-based treatment in mBC. Further studies to confirm such hypotheses are warranted.

scholarly journals Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Raffaella Palumbo ◽  
Rosalba Torrisi ◽  
Federico Sottotetti ◽  
Daniele Presti ◽  
Anna Rita Gambaro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Receptor ◽  
Treatment Line ◽  
Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

2020 ◽  
Vol 20 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Jonathan Wilkie ◽  
M. Alexandra Schickli ◽  
Michael J. Berger ◽  
Maryam Lustberg ◽  
Raquel Reinbolt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hormone Receptor Positive

Phase II randomized trial of toremifene 120 mg compared with exemestane 25 mg after prior nonsteroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive breast cancer.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 105-105 ◽  
Author(s):  
Hirotaka Iwase ◽  
Yutaka Yamamoto ◽  
Takashi Ishikawa ◽  
Yasuo Hozumi ◽  
Masahiko Ikeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Postmenopausal Breast Cancer ◽  
Comparative Trial ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
High Dose ◽  
Hormone Receptor Positive

105 Background: The non-steroidal aromatase inhibitors (nsAIs) have been mainly employed as adjuvant therapy or as early recurrent treatment for postmenopausal breast cancer with hormone receptor-positive tumor. When its treatment fails, it is unclear which endocrine therapy including selective estrogen receptor modulator (SERM), steroidal AI (sAI), or fulvestrant is the most appropriate. Methods: Open labeled multicenter randomized comparative trial of high-dose toremifene for nsAI resistant breast cancer compared to exmestane (Hi-FAIR ex; registry number UMIN000001841) was performed from Nov 2008 to Oct 2011. Toremifene 120 mg (TOR120) or exemestane 25mg (EXE) was administered once daily. The primary end point was clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Results: A total of 91 women were randomly assigned to TOR120 (n=46) or EXE (n=45). Two of 46 cases allocated for TOR120 refused this trial before the administration. There was no difference of patients’ characteristics between both groups. In the analysis as of median 16.9 months for an observation period, TOR120 were superior to EXE in CBR (47.5% vs. 26.7%; p=0.046) and in PFS (Hazard ratio; 0.62, 95% CI; 0.38-0.99, p=0.047). There was, however, no statistical differences in ORR (11.6% vs. 2.2%; p=0.065) and in OS (hazard ratio; 0.57, 95% CI; 0.24-1.34, p=0.19). Both treatments were well-tolerated, with no severe adverse events, although 3 of 44 women treated by TOR120 were stopped in a couple of weeks because of nausea and general fatigue which were thought to be early endocrine-related symptoms. Conclusions: Our data suggested that toremifene 120mg, as a following therapy for postmenopausal metastatic breast cancer who have failed non-steroidal AI treatment, could be potentially useful than steroidal AI.

Comparison of therapy benefit from standard anti-HER2 directed approaches in metastatic breast cancer (MBC) between initially HER2-positive patients and patients initially HER2-negative with switch to HER2-positive.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1040-1040
Author(s):  
Hans-Christian Kolberg ◽  
Özlem Yüksel ◽  
Peter A. Fasching ◽  
Sara Brucker ◽  
Hans Tesch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Observation Time ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Free Survival ◽  
Hormone Receptor Positive

1040 Background: Metaanalyses have demonstrated that 5% of initially HER2 negative breast cancer patients switch to HER2 positive during the course of the disease. Whether there is a difference in benefit from standard HER2 targeted therapies between patients initially HER2 positive and patients switching from negative to positive is unclear. We used data from the PRAEGNANT registry to compare the outcome of those patients. Methods: PRAEGNANT is a prospective advanced breast cancer registry (NCT02338167) focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis compared progression-free survival (PFS) with standard HER2 targeted therapies between patients with tumors initially HER2 negative and switched to HER2 positive and patients with tumors that were initially HER2 positive adjusted for age and hormone receptor status. Results: At the time of this analysis 4061 patients with MBC were included in the PRAEGNANT registry, 49 of which met the requirements for this analysis. Median age was 56 (IQR 48-64) years and 87.8% of the patients were hormone receptor positive. At first diagnosis 15 patients were HER2 negative and 34 patients were HER2 positive. Within a median observation time of 9 months (95%CI: 3.8, 23.7) 35 PFS events occurred. Median observation time was 9 months (95% CI: 3.8, 23.7). Initially HER2 positive patients had a longer progression-free survival (HR = 0.49, 95% CI (0.24, 1.03), p = 0.07) as compared to initially HER2 negative patients switched to HER2 positive. The 1- and 2-year-PFS rates were also higher for patients initially HER2 positive: 1-year-PFS: 52% (95% CI: 36%, 73%) versus 26 % (95% CI: 12%, 52%); 2-year-PFS: 44% (95% CI: 29%, 67%) versus 19% (95% CI: 7%, 50%). Conclusions: Median PFS and 1- and 2-year PFS rate seem to be better in patients HER2 positive at initial diagnosis receiving standard HER2 directed therapies. Although our result has to be interpreted with caution because of the small cohort and the retrospective nature of our analysis, it justifies prospective research including the group of initially HER2 negative patients switched to HER2 positive as a distinct entity. Clinical trial information: NCT02338167 .

Final results of a phase II trial of trabectedin (T) in patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to xeroderma pigmentosum gene (XPG) expression.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 547-547
Author(s):  
Ahmad Awada ◽  
Javier Cortes ◽  
Miguel Martin ◽  
Philippe Aftimos ◽  
Mafalda Oliveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Endpoint ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Stage Design ◽  
Hormone Receptor Positive ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Previously Treated

547 Background: Hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (BC) is currently associated with 3-4 years survival and, after ≥2 relapses, therapeutic approaches are reduced. XPG expression is frequently modified in BC. T forms cytotoxic complexes with XPG inducing apoptosis, thus, the inhibitory effects of T may depend on XPG presence. In fact, a better response to T in BC pts with XPG RNA overexpression has been observed. Methods: Pts withHR positive, HER2 negative advanced BC, pretreated with anthracyclines and/or taxanes, who had progressed after 2-5 chemotherapy lines, were stratified according to their XPG expression from paraffin embedded tumor samples, to stratum A (XPG high [>3]) or to stratum B (XPG low [≤3]) (threshold was selected from median XPG expression values observed in a previous trial) and treated with T (1.3 mg/m2 in 3-hour iv infusion every 3 weeks). Primary endpoint: to evaluate the efficacy of T as progression free survival rate at 4 months (PFS4) according to XPG expression. Secondary endpoints: Comparison of PFS, overall response rate, duration of response, overall survival and safety in XPG high and XPG low pts. Statistical methods: A 2-stage design was chosen: at a 1st stage, 20 pts were enrolled in each stratum. A futility analysis (O’Brien Fleming boundary) based on the primary endpoint was done once 40 evaluable pts were recruited. If ≥ 7 out of 20 pts achieved PFS4, recruitment would continue to a maximum of 50 pts per stratum. Results: 44 pts (21 XPG high and 23 XPG low) were enrolled from three countries and five centers. Efficacy is shown in the Table. Most frequent AEs were nausea (54%) and fatigue (70%). ALT increase G4 occurred in 7% of pts and neutropenia G4 in 28%. Conclusions: Trabectedin showed modest activity in advanced HR-positive, HER2-negative BC previously treated with anthracyclines and taxanes, with an acceptable safety profile. XPG does not seem to be a predictor of outcome to T treatment in this patient population. Clinical trial information: 2010-022968-13. [Table: see text]

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