Abstract P6-09-27: The EA2clin test significantly predicts response and survival in both pre and post-menopausal women with ER-positive breast cancers

2017 ◽  
Author(s):  
AK Turnbull ◽  
DA Pearce ◽  
LM Arthur ◽  
C Martinez-Perez ◽  
JS Thomas ◽  
...  
Keyword(s):  
Breast Cancers ◽  
Menopausal Women ◽  
Er Positive ◽  
Post Menopausal

Responses to concurrent radiotherapy and hormone-therapy and outcome for large breast cancers in post-menopausal women

2007 ◽  
Vol 85 (3) ◽  
pp. 336-345 ◽  
Author(s):  
Marc A. Bollet ◽  
Youlia M. Kirova ◽  
Guillemette Antoni ◽  
Jean-Yues Pierga ◽  
Brigitte Sigal-Zafrani ◽  
...  
Keyword(s):  
Hormone Therapy ◽  
Breast Cancers ◽  
Concurrent Radiotherapy ◽  
Large Breast ◽  
Menopausal Women ◽  
Post Menopausal

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.

Modulation of breast cancer development in MMTV-PyVT mice by adiponectin: A perspective on tumor microenvironment.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 34-34
Author(s):  
Yu Wang
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Tumor Development ◽  
Mammary Tumors ◽  
Breast Cancers ◽  
Adipose Tissues ◽  
Flow Cytometric ◽  
Menopausal Women ◽  
Post Menopausal

34 Background: The survival and growth of epithelial carcinoma cells are critically dependent on the interactions with the neighboring stromal cells. Adiponectin, a molecule exclusively produced by adipose tissue, possesses potent anti-inflammatory and anti-tumorigenic activities. Its expression and production are inversely associated with breast cancer risks in pre- and post-menopausal women. Reduced or completely loss of adiponectin expression enhances the development of mammary tumors in MMTV-PyVT mice. Despite these evidences, the mechanisms underlying the anti-breast cancer activity of adiponectin remain poorly understood. Methods: Adiponectin-deficient MMTV-PyVT mice that show distinct basal epithelial-like features of mammary tumors are used for analyzing the stromal vascular fractions (SVF) of the adipose tissues in tumor microenvironment. Results: Flow cytometric analyses demonstrate that adiponectin deficiency significantly alters the composition of cells in SVF isolated from the mammary adipose tissues. Adiponectin-deficient SVF contribute to the metaplastic features of the basal epithelial-like breast cancers. Co-implantation of SVF derived from adiponectin-deficient mice accelerates mammary tumor development and metastasis in NOD/SCID mice engrafted with MDA-MB-231 human breast cancer cells. Fluorescence Activated Cell Sorting isolates a population of CD44+CD25-CD100+ cells that are enriched in both thymus and SVF of mice lacking the expression of adiponectin. Upregulated CD100 expression interrupts early T-cell development and maturation. In mammary tissues, CD44+CD25-CD100+ cells facilitate the development of metaplastic basal epithelial-like breast cancers. Adiponectin treatment down-regulates CD100 expression, in turn enhancing Notch signaling and T-cell maturation in the thymus, and reduces the accumulation of CD44+CD25-CD100+ cells in the tumor microenvironment. Conclusions: These results support a pivotal role of adiponectin in mediating the epithelial-stroma crosstalk to prevent mammary carcinogenesis and shed new lights on the development of immuno-therapeutics for breast cancer diseases.

Biological heterogeneity of er-positive breast cancers in the post-menopausal population

1994 ◽  
Vol 59 (1) ◽  
pp. 17-19 ◽  
Author(s):  
Sylvie Romain ◽  
Olivier Chinot ◽  
Olivier Guirou ◽  
Marc Soullière ◽  
Pierre-Marie Martin
Keyword(s):  
Breast Cancers ◽  
Er Positive ◽  
Biological Heterogeneity ◽  
Post Menopausal

scholarly journals Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women

2009 ◽  
Vol 1 ◽  
pp. CMT.S9 ◽  
Author(s):  
Monica Milani ◽  
Gautam Jha ◽  
David A. Potter
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Estrogen Receptor ◽  
Hormone Receptor ◽  
Early Stage ◽  
Breast Cancers ◽  
Adjuvant Setting ◽  
Hormone Receptor Positive ◽  
Menopausal Women ◽  
Post Menopausal

The majority of breast cancers express the estrogen receptor and depend on estradiol (E2) for their growth. Hormonal therapy aims at depriving estrogen signaling either by using selective estrogen receptor modulators (SERM)–-that interfere with the binding of E2 to its receptor (ER)–-or aromatase inhibitors (AI)–-that block the aromatase-dependent synthesis of E2. While SERMs are recommended for both pre- and post-menopausal patients, AIs are indicated only for post-menopausal patients. For the past 20 years, the SERM tamoxifen has been considered the “gold standard” for the treatment of hormone receptor positive breast cancers. However, tamoxifen's role is now challenged by third generation AIs, such as anastrozole, which exhibit greater efficacy in the adjuvant setting in several recently reported trials. This review will focus on anastrozole's mechanism of action, dosing, pharmacology, pharmacokinetics, and clinical applications. It will briefly discuss the clinical trials that determined anastrozole's efficacy in the treatment of advanced breast cancer (ABC) and in the neo-adjuvant setting. Finally, it will present the clinical trials that established anastrozole as a frontline agent in the treatment of post-menopausal women with hormone receptor positive early breast cancer.

scholarly journals Pre-Menopausal Women With Breast Cancers Having High AR/ER Ratios in the Context of Higher Circulating Testosterone Tend to Have Poorer Outcomes

2021 ◽  
Vol 12 ◽  
Author(s):  
Savitha Rajarajan ◽  
Aruna Korlimarla ◽  
Annie Alexander ◽  
C. E. Anupama ◽  
Rakesh Ramesh ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Disease Free Survival ◽  
High Ratio ◽  
Total Testosterone ◽  
Breast Cancers ◽  
Serum Samples ◽  
Transcript Levels ◽  
Menopausal Women ◽  
Er Positive ◽  
Hormonal Milieu

PurposeWomen with breast tumors with higher expression of AR are in general known to have better survival outcomes while a high AR/ER ratio is associated with poor outcomes in hormone receptor positive breast cancers mostly in post menopausal women. We have evaluated the AR/ER ratio in the context of circulating androgens specifically in patients younger than 50 years most of whom are pre-menopausal and hence have a high estrogenic hormonal milieu.MethodsTumor samples from patients 50 years or younger at first diagnosis were chosen from a larger cohort of 270 patients with median follow-up of 72 months. Expression levels of ER and AR proteins were detected by immunohistochemistry (IHC) and the transcript levels by quantitative PCR. Ciculating levels of total testosterone were estimated from serum samples. A ratio of AR/ER was derived using the transcript levels, and tumors were dichotomized into high and low ratio groups based on the third quartile value. Survival and the prognostic significance of the ratio was compared between the low and high ratio groups in all tumors and also within ER positive tumors. Results were further validated in external datasets (TCGA and METABRIC).ResultsEighty-eight (32%) patients were ≤50 years, with 22 having high AR/ER ratio calculated using the transcript levels. Circulating levels of total testosterone were higher in women whose tumors had a high AR/ER ratio (p = 0.02). Tumors with high AR/ER ratio had significantly poorer disease-free survival than those with low AR/ER ratio [HR-2.6 (95% CI-1.02–6.59) p = 0.04]. Evaluation of tumors with high AR/ER ratio within ER positive tumors alone reconfirmed the prognostic relevance of the high AR/ER ratio with a significant hazard ratio of 4.6 (95% CI-1.35–15.37, p = 0.01). Similar trends were observed in the TCGA and METABRIC dataset.ConclusionOur data in pre-menopausal women with breast cancer suggest that it is not merely the presence or absence of AR expression but the relative activity of ER, as well as the hormonal milieu of the patient that determine clinical outcomes, indicating that both context and interactions ultimately influence tumor behavior.

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