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A new study from Mehta and others shows the combination of anastrozole and fulvestrant — which interfere with estrogen signaling by distinct mechanisms — increases progression-free and overall survival as compared with anastrozole alone or anastrozole followed by fulvestrant in women with HR-positive breast cancer. Endocrine therapy plays a central role in the treatment of hormone-receptor (HR)-positive metastatic breast cancer. Fulvestrant (Faslodex, AstraZeneca) is an analogue of estradiol that down-regulates the estrogen receptor by disrupting estrogen-receptor dimerization and accelerating degradation of the unstable fulvestrant-estrogen-receptor complex.
This trial tested the hypothesis that the combination of anastrozole and fulvestrant would delay the development of progressive disease in postmenopausal women with HR-positive metastatic breast cancer. Progression-free survival was significantly longer with the combination therapy than with anastrozole alone.

A: In general, the toxic effects were mild and did not differ significantly between the two groups. Selective aromatase inhibitors, such as anastrozole, letrozole, and exemestane, lower the estrogen level and are used as first-line endocrine treatments of HR-positive metastatic disease, owing to their superiority over tamoxifen. This effect leads to reduced cross-talk between the estrogen receptor and estrogen-independent growth factor signaling, thus delaying resistance to hormone therapy.
The four observed grade 4 toxic effects among patients who received anastrozole alone were thrombosis or embolism, joint pain, thrombocytopenia, and dyspnea.

Two patients receiving the combination therapy had grade 4 toxic effects (thrombosis or embolism in one patient and neutropenia or lymphopenia in one patient).

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