Appraising Adjuvant Aromatase Inhibitor Therapy

Perez, Edith A.

doi:10.1634/theoncologist.11-10-1058

Cited by 19 publications

(12 citation statements)

References 97 publications

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“…Understanding the risk and benefit profile of tamoxifen therapy is increasingly critical because adjuvant tamoxifen is being replaced by aromatase inhibitors in postmenopausal breast cancer patients (16)(17)(18) and susceptibility to cardiovascular end points may be one consideration in choosing between the therapies (19). The validity of our findings depends ultimately on the quality of the hospital registry data.…”

Section: Discussionmentioning

confidence: 84%

Tamoxifen Treatment in Danish Breast Cancer Patients and 5-Year Risk of Arterial Atherosclerotic Events: A Null Association

Hernandez

Sørensen²,

Jacobsen³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Although the effectiveness of tamoxifen in preventing the recurrence of breast cancer is well established, associations between tamoxifen and the occurrence of atherosclerotic events are not as clear. Breast cancer patients taking tamoxifen have lower serum cholesterol and other lipid levels than those not taking tamoxifen, suggesting that tamoxifen might prevent atherosclerotic events, but the existing studies are conflicting. We examined the relation between tamoxifen and incident hospitalization of angina pectoris, acute myocardial infarction, heart failure, and stroke. The study population of 16,289 women was identified from the Danish Breast Cancer Cooperative Group nationwide clinical database and includes women diagnosed with stage I or II estrogen receptor -positive breast cancer between 1990 and 2004 at ages 45 to 69. Use of a large populationbased sample with complete outcome ascertainment allowed us to calculate precise measures of risks, risk ratios, and adjusted hazard ratios comparing tamoxifen-treated patients with untreated patients. We found strong evidence for null associations for each of the four outcomes of interest during the first year and first 5 years after the start of therapy. These findings are important in risk/benefit analyses as tamoxifen therapy in postmenopausal women is being replaced with aromatase inhibitors. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2509 -11)

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Section: Discussionmentioning

confidence: 84%

Tamoxifen Treatment in Danish Breast Cancer Patients and 5-Year Risk of Arterial Atherosclerotic Events: A Null Association

Hernandez

Sørensen²,

Jacobsen³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…This residue was purified by CC (silica gel 60; PE (60 -808)/AcOEt) to afford 263. 4 (17b)-Androsta-3,5-dien-17-ol (11). To a soln.…”

Section: Experimental Partmentioning

confidence: 99%

Insights into the Synthesis of Steroidal A‐Ring Olefins

Varela

Roleira

Costa

et al. 2014

Helvetica Chimica Acta

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The classical synthesis, followed by purification of the steroidal A‐ring Δ1‐olefin, 5α‐androst‐1‐en‐17‐one (5), from the Δ1‐3‐keto enone, (5α,17β)‐3‐oxo‐5‐androst‐1‐en‐17‐yl acetate (1), through a strategy involving the reaction of Δ1‐3‐hydroxy allylic alcohol, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate (2), with SOCl2, was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast cancer treatment. Surprisingly, the followed strategy also afforded the isomeric Δ2‐olefin 6 as a by‐product, which could only be detected on the basis of NMR analysis. Optimization of the purification and detection procedures allowed us to reach 96% purity required for biological assays of compound 5. The same synthetic strategy was applied, using the Δ4‐3‐keto enone, 3‐oxoandrost‐4‐en‐17β‐yl acetate (8), as starting material, to prepare the potent aromatase inhibitor Δ4‐olefin, androst‐4‐en‐17‐one (15). Unexpectedly, a different aromatase inhibitor, the Δ3,5‐diene, androst‐3,5‐dien‐17‐one (12), was formed. To overcome this drawback, another strategy was developed for the preparation of 15 from 8. The data now presented show the unequal reactivity of the two steroidal A‐ring Δ1‐ and Δ4‐3‐hydroxy allylic alcohol intermediates, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate (2) and 3β‐hydroxyandrost‐4‐en‐17β‐yl acetate (9), towards SOCl2, and provides a new strategy for the preparation of the aromatase inhibitor 12. Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of undesirable by‐products.

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“…Bone metastases from lymphoma, myeloma, or testicular neoplasms respond better than do bone metastases from renal or hepatocellular carcinoma. Hormone therapy is mainly used in hormone-sensitive breast cancer (tamoxifen, letrozole, anastrozole and examesthane) [21] and prostate cancer (antiandrogens and gonadotrophin-releasing hormone analogues), with good palliative effect and disease control [22].…”

Section: Chemotherapy or Hormone Therapymentioning

confidence: 99%

Management of painful bone metastases

Mercadante

Fulfaro

2007

Current Opinion in Oncology

131

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According to new preclinical data, treatment of bone cancer pain requires multidisciplinary therapies such as radiotherapy applied to the painful area along with systemic treatment (hormone therapy or chemotherapy) and supportive care (analgesic therapy and bisphosphonates). In some selected cases use of radioisotopes and other noninvasive or minimally invasive techniques may be useful in the management of metastatic bone pain. The treatment should be individualized according to the patient's clinical condition, life expectancy, and quality of life.

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Appraising Adjuvant Aromatase Inhibitor Therapy

Cited by 19 publications

References 97 publications

Tamoxifen Treatment in Danish Breast Cancer Patients and 5-Year Risk of Arterial Atherosclerotic Events: A Null Association

Tamoxifen Treatment in Danish Breast Cancer Patients and 5-Year Risk of Arterial Atherosclerotic Events: A Null Association

Insights into the Synthesis of Steroidal A‐Ring Olefins

Management of painful bone metastases

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