Study of SAR439859 Versus Letrozole in ER Positive, HER2 Negative Pre-operative Post-menopausal Primary Breast Cancer

2019 ◽  
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Er Positive ◽  
Post Menopausal

Different prediction of distant recurrence risk in primary breast cancer patients stratified by ER and ERBB2 status

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20120-20120
Author(s):  
P. Urban ◽  
V. Vuaroqueaux ◽  
M. Labuhn ◽  
M. Delorenzi ◽  
P. Wirapati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Scoring Systems ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Good Prognosis ◽  
Breast Cancer Patients ◽  
Expression Levels ◽  
Cancer Subtypes ◽  
Er Positive

20120 Background: Molecular profiling recently defined biological characteristics of several long-recognized breast cancer subtypes including ER-positive (luminal subtype), ER-negative/ERBB2-positive (ERBB2 subtype) and ER-negative/ErBB2-negative (basal-like subtype). Each of these particular subtypes has different impact on patient outcome and should be therefore taken in consideration for individual scoring calculations. Methods: The quantitative RNA expression levels of 70 relevant genes were simultaneously determined in fresh frozen samples of 317 primary breast cancer (BC) patients comprehending ER-positive (70%), ER-negative/ERBB2-positive (15%) and ERBB2-negative/ER-negative (15%) and with known follow-up data. Five years distant recurrence scoring systems were calculated by means of Cox-hazard regression models. Results: Two main prognostic scoring systems were developed: one based on genes relative to proliferation representing tumor growth and its velocity, the other based on proteases. A low proliferation score identified 30% of patients at very good prognosis (probability of distant recurrence 12%, CI: 1.5–22%) all belonging to the ER-positive subcategory as compared to cases with higher proliferation (probability of distant recurrence 31%, 32–38%). The probability to develop distant recurrence within 5 years for 30% of ERBB2-positive patients was of only 12% (CI 0–25%) when accompanied by low levels of proteases as compared to the remaining ERBB2-positive patients with a probability of recurrence of 40% (CI 22–54%). Conclusions: ER, ERBB2 and the expression levels of the few identified genes involved in tumor proliferation and invasion can be easily and precisely detected by means of QRT-PCR. This robust method allows fine tuned prognosis and gives predictive information for the treatment of individual breast cancer. [Table: see text]

Is incomplete estradiol suppression during aromatase inhibitor treatment in post-menopausal patients with breast cancer due to insufficient systemic drug concentrations?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1063-1063
Author(s):  
Daniel Louis Hertz ◽  
Kelley M. Kidwell ◽  
Kelly A Speth ◽  
Christina L Gersch ◽  
Zeruesenay Desta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Limit Of Quantification ◽  
Drug Concentrations ◽  
Menopausal Women ◽  
Er Positive ◽  
Post Menopausal ◽  
Positive Breast Cancer

1063 Background: Aromatase inhibitors (AI) suppress estrogen biosynthesis and are effective treatments for estrogen receptor (ER)-positive breast cancer. In a prospectively enrolled cohort we observed a subset of post-menopausal women who exhibit high plasma estradiol (E2) concentrations during AI treatment, which could potentially contribute to treatment failure. We tested the hypothesis that incomplete E2 suppression is due to insufficient systemic AI concentrations. Methods: Five hundred post-menopausal women with ER-positive breast cancer were randomized to daily exemestane (Exe) 25 mg or letrozole (Let) 2.5 mg. Plasma E2 was measured using GC/MS/MS (lower limit of quantification (LLOQ) = 1.25 pg/mL) at baseline and after 3 months. Let and Exe plasma concentrations measured after 1 or 3 months were compared with the magnitude of E2 depletion using four complementary statistical procedures to assess associations of drug concentrations with: 1) a binary outcome of E2 suppression below LLOQ (logistic regression), 2) 3-month E2 concentrations (linear regression), 3) absolute change from baseline in E2 concentrations (Spearman correlation), and 4) an ordinal outcome defined by E2: decreased to below LLOQ, decreased but not to LLOQ, stayed the same, or increased from baseline (cumulative logistic regression). Results: 397 patients with E2 and AI concentration measurements were evaluable (Exe n = 199, Let n = 198). Thirty (7.6%) patients (Exe n = 13, Let n = 17) had E2 concentrations above the LLOQ at 3 months (range: 1.42-63.8 pg/mL). Exe and Let concentrations were not associated with achievement of unmeasurable E2 concentrations, on-treatment E2 concentrations, E2 change from baseline, or ordinal groupings of E2 change (all p > 0.05). In a parallel analysis there was no association of estrone-sulfate and drug concentrations (data not shown). Conclusions: Our results suggest that circulating drug concentrations do not explain incomplete E2 suppression in women receiving AI therapy. Additional studies are underway to determine whether age, body mass and genetic variation in the aromatase enzyme influence AI treatment response.

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