Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

TY - JOUR

T1 - Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

AU - Kümler, Iben

AU - Knoop, Ann S

AU - Jessing, Christina A R

AU - Ejlertsen, Bent

AU - Nielsen, Dorte L

PY - 2016/7

Y1 - 2016/7

N2 - BACKGROUND: Endocrine therapy constitutes a central modality in the treatment of oestrogen receptor (ER)-positive advanced breast cancer.PURPOSE: To evaluate the evidence for endocrine treatment in postmenopausal patients with advanced breast cancer focusing on the aromatase inhibitors, letrozole, anastrozole, exemestane and fulvestrant.METHODS: A review was carried out using PubMed. Randomised phase II and III trials reporting on ≥100 patients were included.RESULTS: 35 trials met the inclusion criteria. If not used in the adjuvant setting, a non-steroid aromatase inhibitor was the optimal first-line option. In general, the efficacy of the different aromatase inhibitors and fulvestrant was similar in tamoxifen-refractory patients. A randomised phase II trial of palbociclib plus letrozole versus letrozole alone showed significantly increased progression-free survival (PFS) when compared with endocrine therapy alone in the first-line setting (20.2 vs 10.2 months). Furthermore, the addition of everolimus to exemestane in the Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) study resulted in an extension of median PFS by 4.5 months after recurrence/progression on a non-steroid aromatase inhibitor. However, overall survival was not significantly increased.CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin-dependent kinase 4/6 (CDK4/6) inhibition might represent substantial advances for selected patients in some specific settings. However, there is an urgent need for prospective biomarker-driven trials to identify patients for whom these treatments are cost-effective.

AB - BACKGROUND: Endocrine therapy constitutes a central modality in the treatment of oestrogen receptor (ER)-positive advanced breast cancer.PURPOSE: To evaluate the evidence for endocrine treatment in postmenopausal patients with advanced breast cancer focusing on the aromatase inhibitors, letrozole, anastrozole, exemestane and fulvestrant.METHODS: A review was carried out using PubMed. Randomised phase II and III trials reporting on ≥100 patients were included.RESULTS: 35 trials met the inclusion criteria. If not used in the adjuvant setting, a non-steroid aromatase inhibitor was the optimal first-line option. In general, the efficacy of the different aromatase inhibitors and fulvestrant was similar in tamoxifen-refractory patients. A randomised phase II trial of palbociclib plus letrozole versus letrozole alone showed significantly increased progression-free survival (PFS) when compared with endocrine therapy alone in the first-line setting (20.2 vs 10.2 months). Furthermore, the addition of everolimus to exemestane in the Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) study resulted in an extension of median PFS by 4.5 months after recurrence/progression on a non-steroid aromatase inhibitor. However, overall survival was not significantly increased.CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin-dependent kinase 4/6 (CDK4/6) inhibition might represent substantial advances for selected patients in some specific settings. However, there is an urgent need for prospective biomarker-driven trials to identify patients for whom these treatments are cost-effective.

KW - Review

KW - Journal Article

U2 - 10.1136/esmoopen-2016-000062

DO - 10.1136/esmoopen-2016-000062

M3 - Review

C2 - 27843622

SN - 2059-7029

VL - 1

JO - ESMO Open

JF - ESMO Open

IS - 4

M1 - e000062

ER -