Letrozole suppresses plasma oestradiol (E2) levels more completely than anastrozole in postmenopausal women with breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 552-552 ◽  
Author(s):  
J. M. Dixon ◽  
L. Renshaw ◽  
O. Young ◽  
J. Murray ◽  
E. J. Macaskill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Complete Inhibition ◽  
Whole Body ◽  
Adjuvant Hormone Therapy ◽  
Case Methods ◽  
Highly Sensitive ◽  
Before And After ◽  
Estrogen Receptor Positive

552 Background: Letrozole (L) is a more potent aromatase inhibitor in vitro than anastrozole (A). One study in 12 patients showed that in patients L provides more complete inhibition of whole body aromatase and suppression of estrone sulphate levels than A but L did not significantly suppress E2 levels more than A possibly because of the small size of the study and the difficulty of measuring E2 in postmenopausal women (Geisler et al, JCO, 20, 751, 2002). The current aim was to conduct a much larger study to determine whether 2.5mg L suppresses E2 significantly more than 1mg A and if so in what proportion of patients this is the case. Methods: 54 postmenopausal women with invasive estrogen receptor positive breast cancer were randomised as part of their adjuvant hormone therapy to receive either: 12 weeks of L followed by 12 weeks of A (L→A) or 12 weeks of A followed by 12 weeks of L (A→L). Blood for hormones were taken at the same time of the day before and after 12 weeks of each drug. E2 was measured by a highly sensitive radioimmunoassay (Dowsett et al, Cancer Res 1987;47:1957–61) with a formal detection limit of 3pmol/l. In this study we also quantified values by extrapolation below this limit. Results: 27 patients had L→A and 27 A→L. Baseline E2 levels varied from 3 to 91 pmol/l with a median of 26 pmol/l. Only 1of 54 (2%) patients had an E2 value ≥ 3pmol/l after L compared with 20 of 54 (37%) after A(p <0.000005). After extrapolation, mean E2 level after A was 2.91 (SEM 0.18) pmol/l with a median of 2.70 pmol/l and after L was 1.76 (SEM 0.10) pmol/l with a median of 1.70 pmol/l (p<0.0001). Mean residual estradiol was 9.2% of baseline with A and 5.6% with L. Conclusions: This study has demonstrated unequivocally that the more complete inhibition of aromatase achieved by 2.5mg of letrozole than 1mg of anastrozole results in a greater degree of suppression of E2, the most bioactive oestrogen. [Table: see text]

Letrozole Suppresses Plasma Estradiol and Estrone Sulphate More Completely Than Anastrozole in Postmenopausal Women With Breast Cancer

2008 ◽  
Vol 26 (10) ◽  
pp. 1671-1676 ◽  
Author(s):  
J. Michael Dixon ◽  
Lorna Renshaw ◽  
Oliver Young ◽  
Juliette Murray ◽  
E. Jane Macaskill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Postmenopausal Women ◽  
Estrone Sulfate ◽  
Hormone Receptor Positive ◽  
Plasma Estradiol ◽  
Before And After ◽  
Estrogen Receptor Positive ◽  
Opposite Sequence ◽  
Positive Breast Cancer

PurposeTo compare the effects of anastrozole and letrozole on plasma estradiol (E2) and estrone sulfate (E1S) levels.Patients and MethodsFifty-four postmenopausal women with estrogen receptor–positive breast cancer receiving aromatase inhibitors (AIs) as part of their adjuvant therapy were randomly assigned to receive either 3 months of anastrozole (1 mg) followed by 3 months of letrozole (2.5 mg), both given orally once daily, or 3 months of the opposite sequence. Blood was taken at the same time and the same day of the week from each patient, before and after 3 months of each drug, and plasma levels of E2 and E1S were determined using highly sensitive radioimmunoassays.ResultsThere were 27 patients in each group. The mean age of the patients was 63 years (range, 49 to 83 years). Baseline E2 levels ranged from 3 pmol/L to 91 pmol/L with a mean of 25.7pmol/L. Only one of 54 (2%) patients had an E2 value ≥ 3 pmol/L after receiving letrozole, versus 20 of 54 (37%) patients after receiving anastrozole (P < .001). Extrapolation revealed a mean E2 level after anastrozole treatment of 2.71 pmol/L (range, 2.38 to 3.08 pmol/L). Following letrozole, it was 1.56 pmol/L (range, 1.37 to 1.78 pmol/L). Mean residual E2 was 10.1% for anastrozole and 5.9% for letrozole. Residual E1S levels were 4.6% for anastrozole and 2.0% for letrozole (P = .001).ConclusionLetrozole reduces plasma E2 and E1S levels to a significantly greater extent than anastrozole in postmenopausal women taking AIs as part of their adjuvant therapy for hormone receptor–positive breast cancer.

scholarly journals Virtual screening of natural compounds as combinatorial agents from indian medicinal plants against estrogen positive breast cancer

2020 ◽  
Vol 3 (10) ◽  
pp. 266-275
Author(s):  
Shaleen Jain ◽  
Dr. Asmita Das
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Virtual Screening ◽  
Medicinal Plants ◽  
Natural Compounds ◽  
Binding Energies ◽  
Common Amino Acid ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Facing worldwide challenges associated with multifactorial etiology of breast cancer, designing of combinatorial therapies using natural compounds is currently the emergent way of treating several cancers including breast cancer in a synergistic way, which may mitigate several problems associated with multiple receptor targeting. In this research, Estrogen receptor positive breast cancer was taken as prototype and several key receptors associated with this particular disease were targeted by virtual screening of natural compounds found in Indian originated medicinal plants using Computer aided Drug Designing (CADD) strategies. We found the combination of Carpusin, Paulownin Cornigerine, Nororientaline, Oryzalexin B, Romucosine H and Colchicine as effective against six potential receptors i.e. FGFR2, ESR1, PIK3CA, PIK3CB, PIK3CD and AR in Estrogen receptor positive breast cancer with their binding energies in the range of ∆G ≤ -8.0 Kcal/mol as well as significant number of common amino acid binding residues as compared with binding sites of receptors. Thus this research holds significant implications for the designing of combinatorial therapeutic agents against breast cancer which can be further tested in-vitro and in-vivo to prove their synergistic efficiency.

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