Low-dose tamoxifen for pre-cancer and early disease: A pooled analysis by menopausal status.

Abstract

10515 Background: Adjuvant endocrine prevention reduces the risk of subsequent breast cancer events after ductal carcinoma in situ (DCIS) and precursor lesions, but the toxicity of standard-dose tamoxifen or aromatase inhibitors limits its use. Low-dose tamoxifen (Babytam) has demonstrated a favorable balance of efficacy and tolerability. Whether the magnitude and pattern of benefit vary by menopausal status remains undefined. We performed a pooled analysis of three studies to evaluate Babytam according to menopausal status and type of breast cancer event. Methods: Individual patient data from two randomized trials (Trial 007, JCO 2009; 27:3749; Trial Tam-01, JCO 2023; 41:3116) and one observational study (Int J Cancer 2016; 139:2127) were pooled. Babytam was administered at 5 mg/day (RCTs) or 10 mg every other day (observational). The primary endpoint was recurrence of any breast cancer event, defined as ipsilateral recurrence or new ipsilateral breast cancer, contralateral breast cancer (CBC), distant metastases, or death. Competing risk models were applied for CBC. Multivariable Cox proportional hazards models with study-level random effects were used. Analyses were stratified by menopausal status. Results: A total of 1,772 women were included, 1,568 with DCIS, 101 with ADH, 81 with LCIS, and 21 with pT1a. Babytam significantly reduced overall breast cancer events, with differential effects by menopausal status and event type (table). Reduction in any breast cancer event was driven by a marked decrease in ipsilateral events among postmenopausal women, whereas the preventive effect on CBC was confined to premenopausal women. Few distant metastases or deaths occurred. Conclusions: In this pooled analysis, Babytam significantly reduced breast cancer events following in situ and microinvasive disease, confirming and extending the preventive efficacy observed in TAM-01. Menopausal status was a key modifier of benefit, with ipsilateral risk reduction predominating in postmenopausal women and CBC prevention in premenopausal women. These findings underscore the biological heterogeneity of early breast neoplasia and support Babytam as a risk-adapted, de-escalated endocrine prevention strategy that enables individualized decision-making balancing efficacy, toxicity, and patient characteristics. Clinical trial information: NCT06982313 . Effect of low-dose tamoxifen (babytam) on overall recurrence and contralateral breast cancer by menopausal status. Population Menopausal status Babytam events/N Control events/N HR (95% CI) p-value ER+ Overall 152/678 192/629 0.68 (0.55-0.84) <0.001 Pre 109/366 98/269 0.83 (0.63-1.09) 0.17 Post 40/292 91/354 0.52 (0.36-0.76) <0.001 ER- Overall 7/19 57/225 1.20 (0.54-2.65) 0.65 Considering CBC only All patients Overall 39/812 68/960 0.66 (0.44–1.00) 0.05 Pre 22/457 40/387 0.46 (0.27–0.77) 0.003 Post 16/335 27/560 1.04 (0.55–1.96) 0.89 ER+ Overall 35/678 51/629 0.65 (0.42-0.99) 0.046