Changes in bone metabolism after 2 years’ treatment with exemestane (E) in postmenopausal women with early breast cancer (EBC) at low risk: Follow-up (FU) results of a randomized placebo-controlled study

Lønning, PE; Geisler, Jürgen; Krag, L. E.; Ottestad, Lars; Risberg, Terje; Hagen, Anne Irene; Schlichting, Ellen; Salle, E. Di; Polli, Anna; Paolini, Jolanda

doi:10.1200/jco.2005.23.16_suppl.531

Cited by 9 publications

(3 citation statements)

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“…Interestingly, we observed an increase not only in biomarkers of bone degradation but in markers of bone synthesis as well. Most importantly, this effect on BMD as well as bone markers was partial reversible upon termination of treatment (11) . Our findings are consistent with preliminary data from a subprotocol of the IES study (2) , comparing BMD during treatment with exemestane to tamoxifen (12) .…”

Section: Effects Of Aromatase Inhibitors On Bone Metabolismmentioning

confidence: 92%

Bone safety of aromatase inhibitors versus tamoxifen

Lønning

2006

Int J Gynecol Cancer

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Bone loss may be a potential side effect of implementing aromatase inhibitors in the adjuvant setting. Current evidence suggests a minor bone loss during treatment with the steroidal aromatase inhibitor exemestane compared to placebo and a nonsignificant increase in fracture rate during treatment with exemestane when compared to tamoxifen. Such a difference could be due to the bone-sparing effects of tamoxifen. For the nonsteroidal inhibitors letrozole and anastrozole, the MA17 study revealed a nonsignificant increase in fracture rate for letrozole compared to placebo. In contrast, both anastrozole and letrozole were found to significantly increase fracture rate compared to tamoxifen when administered as monotherapy or given sequentially. While an increased fracture rate may have detrimental effects, evidence suggests that enhanced bone loss may be preventable through careful bone mineral density (BMD) assessment and treatment with bisphosphonates.

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Section: Effects Of Aromatase Inhibitors On Bone Metabolismmentioning

confidence: 92%

Bone safety of aromatase inhibitors versus tamoxifen

Lønning

2006

Int J Gynecol Cancer

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“…38 The prospective longitudinal substudy of the Arimidex, Tamoxifen, Alone or in Combination trial showed that BMD was reduced at the lumbar spine (6.1%) and total hip (7.2%) at 5 years of therapy. 39 Data beyond 5 years are currently limited. Patients treated with AIs will continue to lose bone at a higher rate or will return to the lower rate noted in healthy postmenopausal women once AIs have been suspended; for example, 3-6 months after withdrawal in patients who received 2 years of adjuvant exemestane, lumbar spine BMD loss tended to return to normal rates and hip BMD stabilized.…”

Section: Cancer Treatment-induced Bone Loss Pathophysiologymentioning

confidence: 99%

Pharmacotherapy Options in Cancer Treatment-induced Bone Loss: Focus on Bisphosphonates

Ito

2009

Clinical Medicine. Therapeutics

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Bone loss and its associated risk of fracture is a serious long-term health issue for breast cancer and prostate cancer survivors. Hormone ablation therapy, in particular aromatase inhibitors (AIs) for breast cancer and androgen deprivation therapy (ADT) for prostate cancer, causes marked reduction in circulating estrogen or testosterone levels, resulting in increased bone resorption, decreased bone mineral density (BMD), and an increased risk of fragility fracture. In several clinical trials with small sample sizes and short follow-up periods, oral and intravenous bisphosphonates have been shown to improve BMD, but not actual fracture rates, in cancer patients on hormone ablation therapy. A number of professional organizations and expert panels recommend the use of bisphosphonates for selected patients at risk. Although bisphosphonates are generally well tolerated, physicians should be aware of safety concerns, including the risk of osteonecrosis of the jaw. With the growing number of older breast and prostate cancer survivors, additional research is needed to characterize patients who would benefit from pharmacotherapy and optimize strategies to prevent cancer treatment-induced bone loss.

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“…One year of treatment with EXE resulted in a 2%-3% loss in BMD, while TAM had no significant effect on BMD [50,51]. After discontinuation of 2 years of EXE therapy, the significant loss in BMD normalized (lumbar spine) or stabilized (femoral neck) but still remained significantly higher than BMD loss in the placebo group [52]. In a planned comparison of 1,618 patients in the Tamoxifen and Exemestane Adjuvant Multicenter (TEAM) trial, EXE was also associated with significantly more bone and muscle aches [53].…”

Section: Ais and Bone Diseasementioning

confidence: 99%

Appraising Adjuvant Aromatase Inhibitor Therapy

Perez

2006

The Oncologist

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Tamoxifen, once the gold standard adjuvant endocrine therapy for early breast cancer, is being challenged by third-generation aromatase inhibitors (AIs) that have demonstrated improved disease-free survival in a variety of adjuvant settings for early breast cancer. Tamoxifen and AIs have different safety profiles, which should allow physicians to begin to individualize treatment based on a patient's comorbidities and risk factors. Because of its properties as a partial estrogen agonist, tamoxifen has a positive effect on serum lipids and may confer a cardioprotective benefit, as well as a beneficial effect on bone health. However, tamoxifen increases the risk for endometrial cancer and cerebrovascular/thromboembolic events. In comparison, the major side effect of AIs is increased bone loss, which may heighten the risk for osteoporotic fractures and bone pain. Because of their superior efficacy and manageable side effects, AIs are a cost-effective alternative to tamoxifen, and clinical guidelines now embrace AIs as appropriate adjuvant therapy for hormone-sensitive early breast cancer. The anticipated results of ongoing trials will provide further insights into the long-term safety and application of AI therapy in the adjuvant setting.

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Changes in bone metabolism after 2 years’ treatment with exemestane (E) in postmenopausal women with early breast cancer (EBC) at low risk: Follow-up (FU) results of a randomized placebo-controlled study

Cited by 9 publications

References 0 publications

Bone safety of aromatase inhibitors versus tamoxifen

Bone safety of aromatase inhibitors versus tamoxifen

Pharmacotherapy Options in Cancer Treatment-induced Bone Loss: Focus on Bisphosphonates

Appraising Adjuvant Aromatase Inhibitor Therapy

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