Treatment Break Prolongs Sensitivity to Letrozole

research highlights

Hormonal tHerapies Treatment break prolongs sensitivity to letrozole he use of aromatase inhibitors is associated with considerably timproved outcomes in postmenopausal women with hormone- responsive breast cancer. many patients, however, do not respond or experience relapse after treatment. sabnis and colleagues previously developed a mouse model using human estrogen- receptor-α (erα) breast cancer cells that were transfected with human placental aromatase gene and grown in group were given trastuzumab, and the mice treated with letrozole had doubled ovariectomized female nude mice, in third discontinued treatment. every week in volume, whereby they were assigned to order to simulate postmenopausal breast tumors were collected to assess changes the three treatment groups. there were no cancer. using this model, the researchers in tumor protein expression and activity, differences in tumor growth between the had established that aromatase inhibitors and uteri were also weighed. sabnis and three groups at 26 weeks. the group that were more effective than tamoxifen for coauthors noticed that tumors in mice who did not receive treatment was then split treating hormone-responsive breast received 6 weeks of letrozole treatment into two: continuation without letrozole or cancer; however, these responsive followed by 6 weeks off treatment acquired treatment with letrozole; between weeks tumors eventually developed resistance. resistance quicker than those who received 26 and 33 the tumor growth rates between therefore, this group carried out another continuous letrozole. the two groups were not significantly study to investigate the mechanisms of the mice receiving continuous letrozole different. Compared with the mice treated resistance to aromatase inhibitors and had significantly lower mean tumor with continuous letrozole, the mice that possible ways to reverse resistance so that weights than those receiving intermittent were switched back to letrozole had the use of chemotherapy could be delayed. letrozole (P <0.01). Cyclic treatment significantly lower growth rate (P = 0.02). in this study, the researchers compared consisting of 22 weeks of letrozole the mice receiving trastuzumab were the effects of intermittent letrozole treatment, followed by withdrawal for split into three groups: trastuzumab, treatment with switching treatment 6 weeks and 6 weeks further treatment trastuzumab plus letrozole or letrozole. between letrozole and trastuzumab on did not reduce the tumor volume. mice the growth rates across these groups were the outcomes on tumor growth. “we who continued to receive letrozole similar over 32 weeks suggesting that concluded that resistance to letrozole did not experience a change in mean single-agent trastuzumab does not provide was a result of adaptation of tumor cells uterine weight, whereas mice who were any benefit in letrozole-resistant tumors. to a low-estrogen environment through taken off treatment had increased mean additionally, the tumors continued to upregulation of Her-2 and downregulation uterine weights. moreover, the uterine grow when treatment was switched from of erα.” comment the authors. weight of mice treated with trastuzumab letrozole to trasuzumab and back to the investigators used a novel was significantly increased, and this letrozole or letrozole plus trastuzumab. hormone-dependent model to identify the finding correlated with an increase in However, when the mice were given mechanism of resistance to letrozole. they aromatase activity. upregulation of the a 4-week break in treatment and then found that lack of response to letrozole Her-2/maPK pathway was observed in switched back to letrozole, tumor growth was accompanied by upregulation of the letrozole-resistant tumors accompanied by was inhibited for 18 weeks. Her-2/mitogen-activated protein kinase downregulation of erα and aromatase. the results of this study suggest that (maPK) pathway and downregulation of Fluorescence in situ hybridization was a period of time off treatment reverses erα and aromatase activity. in addition, used to assess Her-2 upregulation. the resistance; the intermittent treatment they found that use of trastuzumab to Her-2 gene was not amplified in tumors strategy presented in this study could inhibit Her-2 could reverse resistance that were resistant to letrozole. the effect result in prolonged response and disease to letrozole, as could discontinuation of of intermittent treatment was assessed stabilization in patients. letrozole treatment. in a mCF-7Ca xenograft model. over Mandy Aujla mice were treated with letrozole until the first 9 weeks of the study, the growth they developed resistance and were then rate of tumors treated with letrozole was Original article Sabnis, G. et al. Sensitivity to the randomized into three groups: one group significantly lower than control tumors aromatase inhibitor letrozole is prolonged after a “break” continued letrozole treatment, the second (P <0.0001). By week 22, the tumors of in treatment. Mol. Cancer Ther. 9, 46–56 (2010)