Aromatase Inhibitors in Breast Cancer: An Update

2002 ◽  
Vol 9 (6) ◽  
pp. 490-498 ◽  
Author(s):  
Diana E. Lake ◽  
Clifford Hudis
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Metastatic Disease ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Management Approach ◽  
Free Survival ◽  
Early Results ◽  
Disease Free

Background Tamoxifen has been the endocrine treatment of choice for patients with breast cancer. The development of selective aromatase inhibitors has offered an alternative management approach for patients in whom a hormonal approach is indicated. Methods The authors reviewed reports in which aromatase inhibitors were compared with tamoxifen for the treatment of metastatic disease, as well as information pertinent to their use as adjuvant therapy. Results Both nonsteroidal (anastrozole and letrozole) and steroidal (exemestane) aromatase inhibitors for metastatic disease appear to provide superior efficacy and a better toxicity profile in first- and second-line treatment of metastatic disease than tamoxifen. Early results from the ATAC trial suggest anastrozole is superior to tamoxifen for disease-free survival, particularly in receptor-positive patients, and in reducing the incidence of contralateral breast cancer. Conclusions Aromatase inhibitors have important roles in optimal management of postmenopausal patients with hormone-responsive metastases in both the adjuvant and advanced-disease settings.

Could treatment with tamoxifen be superior to aromatase inhibitors in early-stage breast cancer after pharmacogenomic testing? A modeling analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
R. S. Punglia ◽  
E. P. Winer ◽  
J. C. Weeks ◽  
H. J. Burstein
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Treatment Strategy ◽  
Early Stage ◽  
Disease Free Survival ◽  
Optimal Treatment ◽  
Endocrine Treatment ◽  
Free Survival ◽  
Disease Free ◽  
Optimal Treatment Strategy

502 Background: Adjuvant endocrine treatment with upfront aromatase inhibitors yields improved disease-free survival compared to tamoxifen in unselected women with estrogen receptor-positive breast cancer. However, levels of endoxifen, the active tamoxifen metabolite, are known to vary with the number of mutant alleles of the cytochrome P450 CYP2D6 enzyme. We created a Markov model to examine whether the optimal treatment strategy for patients with wild type genetics (wt/wt) might differ from that for patients with homozygous (*4/*4) or heterozygous (wt/*4) mutations. Methods: Annual recurrence risks with aromatase inhibitors and tamoxifen in unselected women were taken from the BIG 1–98 trial. Based on data from Goetz et al., we assumed that the percent of patients who are homozygous and heterozygous for mutations are 6.8% and 21.1%, respectively, and that the hazard ratio (HR) for increased cancer recurrence on tamoxifen among *4/*4 carriers is 1.86 relative to patients with wt/wt or wt/*4 genotypes. Because the efficacy of tamoxifen among wt/*4 patients is not known, we tested the full possible range, from efficacy same as wt/wt patients (Ehet=0) to that of *4/*4 mutation carriers (Ehet=1). Results: In the unselected group, 5-year disease-free survival (5-DFS) with aromatase inhibitors and tamoxifen was 0.840 and 0.813, respectively. Under baseline assumptions, tamoxifen is more effective than aromatase inhibitors among wt/wt patients as long as the effect in heterozygotes is at least 54% (Ehet=0.54) of that in *4/*4 patients. With increasing HR for *4/*4 patients, tamoxifen estimates exceed those of aromatase inhibitors in the wt/wt cohort even at lower assumed Ehet ratios (see table ). Conclusion: In patients without CYP2D6 mutations, modeling suggests that initial treatment with tamoxifen could be superior to treatment with aromatase inhibitors, supporting the use of genetic testing to determine the optimal treatment strategy. [Table: see text] No significant financial relationships to disclose.

scholarly journals Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Luminal Breast Cancer ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

Clinical experience in the use of the antioestrogen tamoxifen in the treatment of breast cancer

1989 ◽  
Vol 95 ◽  
pp. 231-237
Author(s):  
Helen J. Stewart
Keyword(s):  
Breast Cancer ◽  
Total Dose ◽  
Metastatic Disease ◽  
Systemic Therapy ◽  
Primary Breast Cancer ◽  
Oestrogen Receptor ◽  
Disease Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Disease Free

SynopsisThe use of tamoxifen in the treatment of both metastatic and primary breast cancer is reviewed. In metastatic disease, tamoxifen slows progression in at least one-third of patients and is now the preferred first systemic therapy. Results from the larger trials of adjuvant tamoxifen are reviewed in relation to total dose and receptor status. It is suggested that variations in total dose may account for the variable results reported. Although benefit is not confined to those with tumours which are oestrogen-receptor (ER)-positive, the greatest chance of increasing disease-free survival would seem to be in those with high ER levels. Duration of tamoxifen and its effect within defined ER categories, with and without chemotherapy, are areas requiring further study by direct comparison.

Curing Metastatic Breast Cancer

2016 ◽  
Vol 12 (1) ◽  
pp. 6-10 ◽  
Author(s):  
George W. Sledge
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Disease ◽  
Research Agenda ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Free Survival ◽  
Patient Interactions ◽  
Disease Free

Metastatic breast cancer is generally considered incurable, and this colors doctor-patient interactions for patients with metastatic disease. Although true for most patients, there appear to be important exceptions, instances where long-term disease-free survival occurs. Although these instances are few in number, they suggest the possibility of cure. How will we move toward cure for a much larger population of patients with metastatic disease? This article outlines a potential research agenda that might move us toward that distant goal.

scholarly journals The Place of Extensive Surgery in Locoregional Recurrence and Limited Metastatic Disease of Breast Cancer: Preliminary Results

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
M. Berlière ◽  
F. P. Duhoux ◽  
L. Taburiaux ◽  
V. Lacroix ◽  
C. Galant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Locoregional Recurrence ◽  
Primary Tumour ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Free Survival ◽  
Disease Free ◽  
Extensive Surgery ◽  
Limited Metastatic Disease

The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence.Material and Methods. Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable.Results. The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival.Conclusion. Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent.

Use of microarray analysis of differentially expressed genes in luminal B subtype of breast cancers to evaluate NHERF1 as a marker of endocrine resistance

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11015-11015
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
E. Ruckhaeberle ◽  
L. Hanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Biology ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Free Survival ◽  
Luminal B ◽  
Disease Free

11015 Background: In vitro and in vivo data demonstrate that the expression of estrogen receptor (ER) in breast cancer is mainly associated with low proliferation. Gene expression profiling has recently been used to identify a group of high proliferating estrogen receptor positive breast cancers (the luminal B subtype), which are associated with a prognosis that is even worse than that of high proliferating estrogen receptor negative tumors. The analysis of those tumors might provide valuable information about breast cancer biology and could be helpful for adjuvant or neoadjuvant treatment decisions.Methods and Results: We analyzed microarray data from breast cancer specimens to gain insight into genes which play a role in estrogen receptor signalling. Genes were identified showing strong expression in high proliferating ER-positive tumors but no expression in either Ki67-/ER+ or Ki67+/ER- samples. Among these genes the Na+/H+ exchanger regulatory factor NHERF1 was found. We assessed the clinical relevance of NHERF1 transcript levels using a total of 2469 breast cancers. Analysis indicates that enhanced NHERF1 expression is associated with metastatic progression and poor prognosis of breast cancer patients. We found no correlation between NHERF1 and the nodal status as well as age, but positive correlations for tumor size (P<0.001), grade (P<0.001) and erbb2 (P=0.033). Weak NHERF1 expression correlated with longer disease free survival (DFS) in grade 1 and 2 tumors, but not in grade 3 breast cancers. Since NHERF1 expression is strongly linked to the presence of ER, the predictive value for endocrine treatment was analyzed. For samples with weak or none NHERF1 expression a treatment benefit was observed (P=0.007). While untreated patients display a 10 yr DFS rate of 67.2 ± 3.8%, endocrine treatment resulted in 80.1 ± 4.0%. In contrast no differences in disease free survival were found for corresponding NHERF1 expressing breast cancers. Conclusions: Our data indicate that expression of NHERF1 defines a state of differentiation, where breast cancer cells are refractory to endocrine treatment. No significant financial relationships to disclose.

scholarly journals A Novel Automated Immunoassay Platform to Evaluate the Association of Adiponectin and Leptin Levels with Breast Cancer Risk

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3303
Author(s):  
Debora Macis ◽  
Valentina Aristarco ◽  
Harriet Johansson ◽  
Aliana Guerrieri-Gonzaga ◽  
Sara Raimondi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cox Model ◽  
Disease Free Survival ◽  
Postmenopausal Breast Cancer ◽  
Enzyme Linked Immunosorbent Assay ◽  
Baseline Serum ◽  
Free Survival ◽  
Disease Free

Adiponectin and leptin are adipokines secreted by the adipose tissue that are associated with several chronic diseases including cancer. We aimed to compare the immunoassay platform ELLA with an enzyme-linked immunosorbent assay (ELISA) kit and to assess whether the results of the association analyses with breast cancer risk were dependent on the assay used. We measured adiponectin and leptin with ELLA and ELISA on baseline serum samples of 116 Italian postmenopausal women enrolled in two international breast cancer prevention trials. Results were compared with Deming, Passing–Bablok regression and Bland–Altman plots. Disease-free survival was analyzed with the Cox model. There was a good correlation between the methods for adiponectin and leptin (r > 0.96). We found an increased breast cancer risk for very low adiponectin levels (HR for ELLA = 3.75; 95% CI: 1.37;10.25, p = 0.01), whereas no significant association was found for leptin levels. The disease-free survival curves were almost identical for values obtained with the two methods, for both biomarkers. The ELLA platform showed a good concordance with ELISA for adiponectin and leptin measurements. Our results support the association of very low adiponectin levels with postmenopausal breast cancer risk, irrespective of the method used. The ELLA platform is a time-saving system with high reproducibility, therefore we recommend its use for biomarker assessment.

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