Letrozole As A Neoadjuvant Treatment In Postmenopausal And Premenopausal Patients With Highly Endocrine-responsive Operable Breast Cancer

Purpose:Neoadjuvant endocrine therapy(NET)is effective in postmenopausal and premenopausal patients with estrogen receptor-expressing breast cancer(BC).However,there is currently no consensus on the optimal duration of NET before surgery,especially for the premenopausal population.The therapeutic benefit of NET in the premenopausal population has not been fully characterized.We aimed to assess the efficacy and safety of six months of neoadjuvant letrozole between postmenopausal and premenopausal(combined with triptorelin)patients with highly endocrine-responsive operable BC.Patients and Methods:A total of 46 untreated patients with operable and highly endocrine-responsive breast cancer(ER≥50%,PR≥50%and Her2-)were recruited.Patients were assigned to receive 2.5 mg letrozole daily(combined with triptorelin in the premenopausal patients)for a period of 6 months.The primary end point of the study was the objective response rate(ORR)measured by breast ultrasound monthly.The secondary end points included safety and rate of pathological complete response(pCR),breast-conserving surgery(BCS)and time to response.Results:The total ORR of this study was 72%(33 out of 46).Clinical benefit rates were comparable between the two groups 76%for the premenopausal and 65%for the postmenopausal(P=0.505).The pCR rate was 7%(2 of 27)for the premenopausal and 0%(0 of 14)for the postmenopausal patients(P=0.450).The BCS rate was 41%(11 of 27)for the premenopausal and 50%(7 of 14)for the postmenopausal patients(P=0.571).No treatment-related adverse events of grade 3/4 were recorded in either group.However,The adverse effects occurred more frequently in the premenopausal group reflected in hot flashes,agrypnia,arthralgia,and headache.46 patients had both 3 month and>3 month ultrasound measurements.The median time to objective response was 4 months(95%CI,2.9-5.1),the postmenopausal was 5 months(95%CI,3.0-7.0)compared to 4 months(95%CI,2.5-5.5)for the premenopausal(P=0.210).Conclusions:Letrozole displays high activity and excellent tolerability as a neoadjuvant therapy in both post and premenopausal patients with highly endocrine-responsive operable breast cancer.It should be noticed that letrozole plus triptorelin for the premenopausal resulted in more adverse effects than letrozole alone for the postmenpausal.6 months of NET helps reduce mean tumor size futher compared to 3 months.Four or more months of letrozole as NET should be considered in both postmenopausal and premenopausal group.