Table 2.

Systemic hormonal treatments in breast cancer survivors: summary of studies and their outcomes

Ref.	Yr	n 1	Design	Treatment	Conclusion
Holmberg et al[147,149]	2004 2008	221 vs 221	Randomized, non-placebo-controlled noninferiority trial	Oral estradiol hemihydrate and Norethisterone (cyclic or continuous) vs control	In BCSs, an increased risk of new breast cancer events and adverse events were observed after 2 yr of therapy (HR = 2.4)
von Schoultz et al[150]	2005	188 vs 190	Randomized, non-placebo-controlled noninferiority trial	2 mg estradiol for 21 d with addition of 10 mg medroxyprogesterone acetate for last 10 d; or 2 mg estradiol for 84 d with 20 mg medroxyprogesterone acetate for last 10 d; or 2 mg estradiol valerate daily	No increased risk of breast cancer recurrence; trial was closed early. So, HT doses of estrogen and progestogen and treatment regimens for menopausal hormone therapy may be associated with the recurrence of breast cancer
Kenemans et al[153]	2009	1556 vs 1542	Prospective randomized placebo controlled	Tibolone 2.5 mg daily or placebo	Trial was closed early. Tibolone had a significantly increased risk of breast cancer recurrence
Cai et al[168]	2020	1728 vs 3456	Retrospective matched cohort study	Incidence rate in ospemifene users vs untreated patients	No differences were observed in the BC incidence and recurrence rates in ospemifene users compared with matched controls

¹Cases vs control. BC: Breast cancer, BCSs: Breast cancer survivors.