According to research reported in JAMA Oncology, based on findings from a phase IIb trial, 25 mg exemestane thrice weekly is noninferior to the standard dosing of 25 mg once daily pertaining to reduction of serum estradiol among postmenopausal patients with stage 0 to II estrogen receptor (ER)-positive breast cancer.
Minimal effective dose is an important consideration in Successful therapeutic cancer prevention. According to previous research, Aromatase inhibitors decrease the incidence of breast cancer among high-risk women, but their usage is hampered due to adverse events.

A team of researchers compared the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor–positive breast cancer given exemestane, 25 mg, three times weekly or once weekly vs a standard daily dose with a noninferiority margin of −6%.
Solid-phase extraction, liquid chromatography–tandem mass spectrometry detection, National Cancer Institute terminology criteria, and immunohistochemistry were used in the study.
The study results are:
Researchers randomized 180 women into 1 of the three arms. The study centre was two hospitals in Italy and 3 in US.
The median age in the once-daily, 3-times-weekly, and once-weekly arms was 66, 63 and 65 years respectively.
In the intention-to-treat population, including 171 women, the least square mean percentage change of serum estradiol was −89% (once daily, 55 women), −85% (three times weekly, 56 women) and −60% (once weekly, 60 women) respectively.
The difference in estradiol percentage change was -3.6 % between the once-daily and 3-times-weekly arms, whereas, in compliant participants with 153 women, it was 2.0%.
Considering secondary endpoints, Ki-67 and progesterone receptors were reduced in all arms.
The 3-times-weekly arm had a better profile of Sex hormone–binding globulin and high-density lipoprotein cholesterol
There were similar adverse events in all arms.
Concluding further, they said that giving 25 mg of exemestane thrice weekly in compliant patients was noninferior based on the findings of our study compared to the once-daily dosage in reducing serum estradiol.
The study results should be further investigated in prevention studies and in those women who are intolerant to daily dosing in the adjuvant setting.
Further reading:
Serrano D, Gandini S, Thomas P, et al. Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor–Positive Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. Published online March 23, 2023. doi:10.1001/jamaoncol.2023.0089