Optimal duration of endocrine therapy with extended aromatase inhibitors for postmenopausal patients with hormone receptor-positive breast cancer: a meta-analysis.
BACKGROUND
The optimal duration of endocrine therapy for patients with hormone receptor-positive (HR-positive) breast cancer is still unclear. This meta-analysis aims to determine the optimal duration of endocrine therapy with extended aromatase inhibitors (AI) for postmenopausal patients with HR-positive early breast cancer who have finished 5 years of endocrine therapy.


METHODS
Eligible randomized controlled trials were classified into three categories according to the whole duration of endocrine therapy (10 years versus 5 years, 7-8 years versus 5 years, and 10 years versus 7-8 years). For each category, hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS), and risk ratio (RR) for the incidence of adverse events were pooled.


RESULTS
Altogether 9 RCTs enrolling a total of 22,313 postmenopausal women with HR-positive breast cancer were included. Pooled data showed an improvement in DFS when extending endocrine therapy from 5 to 7-8 years (HR = 0.79 [0.69, 0.91]), specifically among those who had been treated with only tamoxifen (HR = 0.40 [0.22, 0.73]) or sequential tamoxifen followed by AI (HR = 0.82 [0.71, 0.95]), with tumors that were node-positive (HR = 0.72 [0.56, 0.93]), estrogen receptor (ER) and progesterone receptor (PR) positive (HR = 0.61 [0.47, 0.78]), or ≥ 2 cm in size (HR = 0.72 [0.51, 0.98]). However, no improvement in DFS was obtained when extending from 7-8 to 10 years (HR = 0.98 [0.87, 1.11]). In addition, the extension of endocrine therapy was not associated with an improvement in OS, but was associated with an increased risk of bone fracture and osteopenia/osteoporosis.


CONCLUSION
Patients who have been treated with AI for 5 years, with tumors that are node-negative, ER+/PR- or ER-/PR+, and < 2 cm in size do not need to receive extended AI therapy. For those who have been treated with only tamoxifen or sequential tamoxifen followed by an AI for a total of 5 years, with tumors that are node-positive, ER+/PR+ or ≥ 2 cm in size, 2-3 years of extended AI is necessary and maybe enough.
['Chen|Juan|J|', 'Zhang|Xiaohui|X|', 'Lu|Yan|Y|', 'Zhang|Ting|T|', 'Ouyang|Zhaolian|Z|http://orcid.org/0000-0002-2220-3007', 'Sun|Qiang|Q|']
D018931:Antineoplastic Agents, Hormonal D000971:Antineoplastic Combined Chemotherapy Protocols D047072:Aromatase Inhibitors D001943:Breast Neoplasms D018572:Disease-Free Survival D005260:Female D006801:Humans D017698:Postmenopause D000077982:Progression-Free Survival D016032:Randomized Controlled Trials as Topic D013629:Tamoxifen D013997:Time Factors
Aromatase inhibitors Postmenopausal patients Hormone receptor-positive breast cancer Extended endocrine therapy Treatment duration