scholarly journals Novel aromatase inhibitors selection using induced fit docking and extra precision methods: Potential clinical use in ER-alpha-positive breast cancer

2016 ◽  
Vol 12 (06) ◽  
pp. 324-331 ◽  
Author(s):  
Ranjith Kumavath ◽  
◽  
Manan Azad ◽  
Pratap Devarapalli ◽  
Sandeep Tiwari ◽  
...  
Author(s):  
Stephen R. Johnston

Overview: Adjuvant endocrine therapy for early-stage breast cancer has had the single biggest impact on improving survival from the disease—with tamoxifen alone contributing to saving many thousands of lives. In postmenopausal women, additional progress has been made by the incorporation of aromatase inhibitors into the treatment of early-stage, estrogen receptor (ER)–positive breast cancer, as several large well-conducted trials have established either “up-front” or “switch” strategies that are now widely used. To date, both have been shown to be beneficial when compared with tamoxifen alone, although controversy exists as to which approach is superior. Increasingly, extended adjuvant therapy is being considered, as “longer may be better” for some women who have an ongoing risk of recurrence beyond 5 years. However, controversy remains as to how long adjuvant endocrine therapy should be given for; in clinical practice, clinicians balance the level of risk for individual patients versus any ongoing toxicity concerns. For premenopausal women, with ER-positive breast cancer, tamoxifen remains the gold standard with uncertainty in the added overall benefit of ovarian suppression. Important clinical trials have recently been completed that may help answers this question, including whether complete estrogen deprivation using a luteinizing hormone releasing hormone (LHRH) agonist plus aromatase inhibitors (AIs) is of added benefit. In recent years, molecular profiling of ER-positive breast cancer has started to distinguish those women with a low risk of recurrence on endocrine therapy who may not need chemotherapy. Thus, with more therapy options and greater tumour stratification, modern, adjuvant endocrine therapy is becoming increasingly personalised to suit each individual patient's risk.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19627-e19627
Author(s):  
Abdullah Ladha ◽  
Josy Mathew

e19627 Background: Hormonal therapy with aromatase inhibitors (AI) or tamoxifen (TAM) is standard of care for hormone receptor positive breast cancer and DCIS. Fractures are a complication of treatment with AI due to accelerated bone loss. Risk factors for fracture in patients on hormonal therapy (HT) for breast cancer and DCIS are poorly defined. Methods: All 71 patients with breast cancer or DCIS seen in the bone and mineral clinic of our institution from 2000 to 2010 were analyzed. Data on demographics, pathology, type and duration of HT, bone mineral density studies (BMD), number and site of fractures were collected. Statistical analysis: t test, chi square test and Fisher’s exact test for categorical data. Results: The age of the patients ranged 40 to 97 years. 65 patients had ER positive breast cancer, 6 patients had DCIS. 9 patients had fractures.41 patients were on an AI alone, 8 were on TAM alone and 14 were on both sequentially. Fractures involved: vertebral compression, femur, hip, distal radioulnar, rib, hand and feet bones. Patients who had osteoporosis at the femur, osteoporosis or osteopenia in the lumbar spine or forearm in the initial BMD study were found to have an increased risk of fracture (P<0.05). Patients who were on TAM and AI sequentially had an increased risk of fracture (P<0.05) compared AI alone. The use of bisphosphonates and the duration of use were significantly associated with fracture (P<0.05) as these patients already had osteoporosis. The age, race, duration of AI use and the use of calcium and vitamin D were not found to be significantly different in patients who had fractures compared to those who did not. In the 24 patients who had two BMD studies, there was no significant change in the BMD overall. Conclusions: Patients with osteoporosis or osteopenia at baseline have an increased risk of fracture with the use of hormonal therapies for breast cancer and DCIS. This risk was not eliminated by the use of bisphosphonates. Sequential use of tamoxifen and aromatase inhibitors increase the risk of fractures. Bone mineral density studies done prior to the initiation of hormonal therapy for breast cancer maybe useful estimating the risk of fracture while on treatment.


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