Letrozole (Femara) causes potent suppression of breast cancer tissue estrogen levels in the neoadjuvant setting

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10532-10532 ◽  
Author(s):  
J. Geisler ◽  
H. Helle ◽  
D. Ekse ◽  
N. K. Duong ◽  
D. Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Geometric Mean ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Postmenopausal Breast Cancer ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Mean Values ◽  
Tissue Levels

10532 Background: Aromatase inhibitors of the third generation like letrozole, anastrozole and exemestane are known to suppress plasma estrogens by 90–99% in postmenopausal women. However, little is known about their influence on tissue estrogen levels. Methods: We investigated the effect of neoadjuvant treatment with letrozole (2.5 mg o.d.) given for 16 weeks to patients with locally advanced breast cancers on tissue levels of estradiol (E2), estrone (E1) and estrone sulfate (E1S) measured with a previously published, highly sensitive, HPLC-RIA method (J. Steroid. Biochem. Mol. Biol. 72, 259–264, 2000). All patients had either estrogen receptor (ER) and/or progesterone receptor (PGR) positive tumors (at least one of the receptors expressed in > 50% of the tumor cells). Results: Mean tissue levels of E2, E1 and E1S were found to be 475.8, 272.4, and 160.5 fmol/g tissue at baseline (geometric mean values). Following 16 weeks of treatment with letrozole, these levels fell to 11.3, 18.2, and 16.0 fmol/g corresponding to a suppression of tissue levels of E2, E1 and E1S by 97.6%, 90.7%, and 90.1%, respectively. All plasma levels of E2, E1 and E1S were in the normal range expected for postmenopausal women prior to treatment with letrozole. The individual plasma estrogen fractions were found suppressed by 96.6%, 99.1% and 99.5%, respectively, during treatment with letrozole. Conclusions: Treatment with neoadjuvant letrozole 2.5 mg o.d. potently suppressed tissue estrogen levels in postmenopausal breast cancer patients by 90.1 to 97.6%, surpassing the results previously reported for anastrozole in a similar setting (Clin. Cancer Res. 7, 1230–1236, 2001). While a significant superiority of letrozole versus anastrozole concerning total body aromatase inhibition and plasma estrogen suppression has previously been recorded (J. Clin. Oncol. 20 (3), 751–757, 2002), we are now able to extend this observation to tissue estrogen levels as well. Letrozole (2.5 mg o.d.) seems superior to anastrozole 1 mg daily with respect to plasma as well as tissue estrogen suppression, advocating head to head comparison of these compounds in early breast cancer. [Table: see text]

MMTV Prevalence in Breast Cancer Samples in Romania - Do Major Geographical Differences Exist in The World Population?

2021 ◽  
Author(s):  
Zsolt Fekete ◽  
Bristena Octavia Terțan ◽  
Lajos Ráduly ◽  
Dan Tudor Eniu ◽  
Rares Buiga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Sequences ◽  
Mus Musculus ◽  
Breast Tissue ◽  
Neoadjuvant Treatment ◽  
Metastatic Breast ◽  
Radical Mastectomy ◽  
Cancer Tissue ◽  
World Population ◽  
Breast Cancer Patients

Abstract Background Breast cancer, although the most frequently diagnosed malignant tumor in humans, has a less clear etiology compared to other frequent cancer types. Mouse-mammary tumor virus (MMTV) is involved in breast cancer in mice and dogs and might play a role in the etiology of some breast cancers in humans, since it has been identified in 20-40% of breast cancer samples in Western Europe, USA, Australia and some other parts of the world’s population. The purpose of our study was to identify MMTV DNA sequences in breast tissue samples from breast cancer patients who underwent curative surgery in our regional center in Romania, EU. MethodsWe selected 75 patients with non-metastatic breast cancer treated surgically with curative intent, which did not undergo any neoadjuvant treatment. Out of these patients, 50 underwent radical lumpectomy and 25 modified radical mastectomy. We searched using PCR the MMTV-like DNA env sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. ResultsNone of the examined samples was positive for MMTV-like target sequences on PCR.ConclusionsWe could not prove that MMTV plays a role in the etiology of breast cancer in our patient group. This finding is similar to publications of other geographically related research groups and might be due to the fact that only the Mus musculus domesticus mouse species was proven to carry infectious MMTV, but not the Mus musculus musculus species, which is specific to South-Eastern Europe (including Romania) and some parts of Asia.

Hormonal Therapy for the Treatment of Postmenopausal Breast Cancer Patients

2008 ◽  
Vol 21 (1) ◽  
pp. 36-45
Author(s):  
Rebecca E. Greene ◽  
Vivian Tsang
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Postmenopausal Women ◽  
Hormonal Therapy ◽  
Early Stage ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Receptor Modulator

Breast cancer is the most common cancer diagnosed and the second leading cause of cancer-related death in women. The majority of breast cancers diagnosed in postmenopausal women are hormone receptor positive and involve therapy with hormonal agents. Tamoxifen, a selective estrogen-receptor modulator, has been the mainstay of hormonal therapy since the 1970s. The more recent approval and success of aromatase inhibitors, such as anastrozole, letrozole, and exemestane, have seen these agents move to the front line of therapy for postmenopausal women with hormone-positive breast cancer in the adjuvant and metastatic settings. Fulvestrant, a selective estrogen receptor— downregulator, provides an additional hormonal therapy with a novel mechanism of action. This article reviews the current literature available regarding the use of these agents for postmenopausal women with early stage or advanced breast cancer.

Bone turnover markers in postmenopausal breast cancer patients treated with fulvestrant

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 680-680
Author(s):  
A. Agrawal ◽  
R. A. Hannon ◽  
K. L. Cheung ◽  
R. Eastell ◽  
J. F. Robertson
Keyword(s):  
Breast Cancer ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Objective Response ◽  
Locally Advanced ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Patients ◽  
Median Percentage ◽  
Bone Formation Markers ◽  
Turnover Markers

680 Background: Aromatase inhibitor (AI) therapy in patients with breast cancer accelerates bone turnover with increased secretion and excretion of bone turnover markers. Here, we report the effect of fulvestrant, an estrogen receptor (ER) antagonist with no agonist activity, on bone metabolism. Methods: 23 patients with either locally advanced primary [LAPC] or metastatic [MBC] disease who had clinical benefit (objective response/stable disease ≥6 months) during fulvestrant therapy were included in the study. Sequential tumor biopsies and blood samples were taken at baseline and after 3, 6, 9, 12 and 18 months of fulvestrant treatment (disease being stable throughout the study period). Serum was analyzed for bone formation markers (N-terminal propeptide of procollagen Type 1 [PINP] and bone-specific alkaline phosphatase [bone ALP]) and for the resorption marker C-terminal telopeptide (CTX). Data are presented as median percentage change (from baseline) in marker level with 95% confidence intervals (CI). Data were analyzed separately for patients with LAPC and MBC. Results: Changes in bone ALP (reference range: 3.9–46.8 ng/mL), PINP (20.6–82.1 ng/mL) and CTX (0.14–1.35 ng/mL) in patients with LAPC, are shown in the table . In a further 5 patients with LAPC who were already established on fulvestrant, there were no significant changes in markers over a 15-month period. No changes in markers were noted in the 4 patients with MBC. Conclusions: In this study, there was long-term stability of bone turnover markers in postmenopausal women with LAPC treated with fulvestrant over a period of 18 months. This property may be exploited in future with the use of fulvestrant earlier in the sequence of endocrine therapies particularly in the adjuvant setting and/or in patients with pre-existing decreased bone mass. [Table: see text] [Table: see text]

Neoadjuvant Treatment of Postmenopausal Breast Cancer With Anastrozole, Tamoxifen, or Both in Combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) Multicenter Double-Blind Randomized Trial

2005 ◽  
Vol 23 (22) ◽  
pp. 5108-5116 ◽  
Author(s):  
Ian E. Smith ◽  
Mitch Dowsett ◽  
Stephen R. Ebbs ◽  
J. Michael Dixon ◽  
Anthony Skene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Postmenopausal Women ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Operable Breast Cancer ◽  
Her2 Positive ◽  
Long Term Outcome ◽  
Er Positive

Purpose The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor (ER) –positive, invasive, nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen Alone or in Combination (ATAC) adjuvant therapy trial. Patients and Methods Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was assessed by both caliper and ultrasound. Comparisons were also made of clinical response with ultrasound response, actual and feasible surgery with feasible surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2) –positive cancers, and tolerability. Results There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen, anastrozole, or the combination. In patients who were assessed as requiring mastectomy at baseline (n = 124), 44% of patients received breast-conserving surgery (BCS) after anastrozole compared with 31% of patients after tamoxifen (P = .23); this difference became significant for patients who were deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole compared with 22% for tamoxifen (P = .18). All treatments were well tolerated. Conclusion Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled.

Final Results of a Randomized Phase III Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With a Dose-Intensified Epirubicin and Cyclophosphamide + Filgrastim as Neoadjuvant Treatment in Locally Advanced Breast Cancer: An EORTC-NCIC-SAKK Multicenter Study

2003 ◽  
Vol 21 (5) ◽  
pp. 843-850 ◽  
Author(s):  
P. Therasse ◽  
L. Mauriac ◽  
M. Welnicka-Jaskiewicz ◽  
P. Bruning ◽  
T. Cufer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Dose Intensity ◽  
Advanced Breast ◽  
Phase Iii ◽  
Breast Cancer Patients

Purpose: To compare the efficacy of a standard anthracycline-based regimen to a dose-intensified anthracycline regimen in locally advanced breast cancer.Patients and Methods: Locally advanced breast cancer patients were randomly assigned onto a study comparing cyclophosphamide (C; 75 mg/m2orally days 1 to 14), epirubicin (E; 60 mg/m2intravenously [IV] days 1, 8), and fluorouracil (F; 500 mg/m2IV days 1, 8) six cycles every 28 days versus E (120 mg/m2IV day 1), C (830 mg/m2IV day 1), and granulocyte colony-stimulating factor (filgrastim; 5 μg/kg/d subcutaneously days 2 to 13) six cycles every 14 days. The study was designed to detect a 15% improvement; that is, from 50% to 65% in median progression-free survival (PFS) in favor of the dose-intensified regimen.Results: A total of 448 patients were enrolled over a period of 3 years. The median dose intensity delivered for C and E reached, respectively, 85% and 87% of that planned in the CEF arm and 96% and 95% of that planned in the EC arm. The dose-intensified arm was slightly more emetogenic and generated more grade 3 to 4 anemia but less febrile neutropenia episodes. After a median follow-up of 5.5 years, 277 events have been reported. The median PFS was 34 and 33.7 months for CEF and EC, respectively (P = .68), and the 5-year survival rate was 53% and 51% for CEF and EC, respectively (P = .94).Conclusion: Dose-intensified EC does not provide a measurable therapeutic benefit over CEF as neoadjuvant chemotherapy for unselected locally advanced breast cancer patients.

scholarly journals Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ozkan Alan ◽  
Tugba Akin Telli ◽  
Bilge Aktas ◽  
Sinan Koca ◽  
Ilker Nihat Ökten ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Insulin Resistance ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Her 2

Abstract Purpose Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. Methods Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. Results Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7–17.2), p = 0.01]. Conclusion Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.

The effect of folate-related SNPs on clinicopathological features, response to neoadjuvant treatment and survival in pre- and postmenopausal breast cancer patients

Gene ◽  
2013 ◽  
Vol 518 (2) ◽  
pp. 397-404 ◽  
Author(s):  
Nataliya Babyshkina ◽  
Elena Malinovskaya ◽  
Mariya Nazarenko ◽  
Mariya Koval ◽  
Polina Gervas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Neoadjuvant Treatment ◽  
Postmenopausal Breast Cancer ◽  
Clinicopathological Features ◽  
Breast Cancer Patients

scholarly journals Need for Weight Management among Postmenopausal Early Breast Cancer Patients Receiving Adjuvant Endocrine Therapy

2005 ◽  
Vol 1 (2) ◽  
pp. 205-222 ◽  
Author(s):  
Michelle Harvie ◽  
Tony Howell
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Cancer Patients ◽  
Weight Management ◽  
Endocrine Therapy ◽  
Breast Cancer Survivors ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Patients ◽  
Mortality And Morbidity ◽  
The Impact

Increasingly effective adjuvant therapies mean that the prognosis for postmenopausal women with breast cancer has never been better. Weight problems are common among breast cancer patients and worsen due to the impact of diagnosis and treatment. Recent studies have linked excess weight with the risk of recurrence of breast cancer among premenopausal women. While general obesity (body mass index) does not appear to influence the already much improved prognosis for postmenopausal women, there is some evidence that limiting central obesity and improving insulin resistance may improve survival. The focus of attention for postmenopausal breast cancer survivors is also shifting to consider the mortality and morbidity from other weight-related cancers and noncancer causes, such as cardiovascular disease, making weight control a potentially important adjunct to endocrine therapy. This paper outlines the rationale and optimal design for effective weight management strategies among postmenopausal breast cancer patients receiving endocrine therapy.

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