Adjuvant endocrine therapy for postmenopausal breast cancer in the era of aromatase inhibitors: an update

Ramia Mokbel,Kefah Mokbel,Isabella Karat

doi:10.1186/1477-7800-3-31

Ramia Mokbel, Kefah Mokbel + Show 1 more

Open Access

https://doi.org/10.1186/1477-7800-3-31

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Abstract

There is overwhelming evidence that optimal adjuvant endocrine therapy for hormone sensitive breast cancer in postmenopausal women should include a third generation aromatase inhibitor (AI). On current evidence, adjuvant anstrozole or letrozole should be used upfront in such patients especially in those with high risk disease (node positive and/or tumours > 2 cm). The sequential approach of tamoxifen for 2–3 years followed by exemestane or anastrozole for 2–3 years is a reasonable alternative to 5 years of AI monotherapy in patients with low risk disease (node negative and tumour smaller than 2 cm) especially if the tumour is positive for estrogen and progesterone receptors.Node-positive patients completing 5 years of adjuvant tamoxifen should be offered letrozole for up 48 months. Further research is required to establish the long-term cardiovascular safety of AIs especially that of letrozole and exmestane, the optimal AI to use, duration of AI therapy and whether monotherapy with an AI for 5 years is superior to sequencing an AI after 2–3 years of tamoxifen.The bone mineral density (BMD) should be measured at baseline and monitored during therapy in women being treated with AIs. Anti-osteoporosis agents should such as bisphosphonates should be considered in patients at high risk of bone fractures.

Highlights

Anti-aromatase drugs inhibit the cytochrome p-450 component of the aromatase enzyme complex responsible for the final step of estrogen biosynthesis in peripheral tissues
Several studies have shown that aromatase inhibitors (AIs) are superior to tamoxifen in the adjuvant setting for postmenopausal women with estrogen receptor (ER) positive breast cancer during the first 5 years
There was no significant difference between the two groups in relation to the incidence of cardiac mortality, myocardial infarction (MI) or ischaemic heart disease (IHD) suggesting no adverse cardiac effect for anastrozole compared with tamoxifen which is considered cardio-protective

Summary

Background

Anti-aromatase drugs inhibit the cytochrome p-450 component of the aromatase enzyme complex responsible for the final step of estrogen biosynthesis in peripheral tissues. Unlike the ATAC study, subgroup analyses of BIG1-98 showed a significant DFS benefit in favour of letrozole among high risk groups such as patients with node positive breast cancer and/or tumours larger than 2 cm. Postmenopausal women completing 5 years of adjuvant tamoxifen, letrozole has been shown to be of value in reducing breast cancer recurrence (p < 0.0001) when given in the extended adjuvant therapy (up to 48 months of treatment) setting in the MA. study [10]. The latter is a double-blind placebo-controlled trial involving 5187 postmenopausal women who had completed 5 years of tamoxifen. The additional http://www.issoonline.com/content/3/1/31 benefits achieved by administering an AI subsequent to 5 years of tamoxifen seem to provide unacceptable costs [11]

Conclusion

Findings

Mokbel K