Tamoxifen pause safe for pregnancy without boosting breast cancer risk

Tamoxifen pause safe for pregnancy without boosting breast cancer risk | Image Credit: © leszekglasner - © leszekglasner - stock.adobe.com.

Temporary tamoxifen interruption can lead to successful pregnancy without an increase in short-term breast cancer (BC) recurrence, according to a recent study published in the International Journal of Molecular Sciences.¹

BC and fertility challenges

BC is one of the most common conditions in reproductive-aged women, with a yearly age-adjusted rate of 129.4 per 100,000 individuals. Treatment advances have decreased the rate of mortality by 1.2% per year between 2013 and 2022, increasing survival rates. However, women receiving these treatments may struggle to achieve pregnancy.²

“The gonadotoxic effects of systemic therapies can lead to premature ovarian insufficiency (POI) and impaired fertility, and it is important to note that tamoxifen’s teratogenicity requires strict contraception during treatment and appropriate washout periods after its conclusion,” wrote investigators.¹

Women planning pregnancy may consider halting treatment temporarily, but strong data is needed to determine the safety of this approach. Therefore, investigators conducted a systematic review to evaluate data about the impact of tamoxifen in treating premenopausal BC.

Studying temporary tamoxifen interruption

Participants included women receiving adjuvant tamoxifen therapy for hormone-receptor-positive (HR+) BC. Exposures included standard adjuvant endocrine treatment with tamoxifen therapy, successful pregnancy after tamoxifen therapy, and temporary cessation of tamoxifen to achieve pregnancy.

Women with uninterrupted tamoxifen therapy, no pregnancy after tamoxifen, and not receiving tamoxifen therapy were included as references. Reproductive events were reported as primary outcomes, including pregnancy rates, live birth rates, and ovarian reserve evaluation. Oncological safety parameters were reported as secondary outcomes.

Study selection and data extraction

Randomized controlled trials (RCTs), prospective or retrospective cohort studies, and observational studies were eligible for inclusion. These articles were identified through comprehensive searches of the PubMed, EMBASE, and Cochrane Library databases.

Data was extracted by 2 independent reviewers and included study characteristics, population demographics, intervention details, comparator information, and outcomes. A third reviewer was consulted when disagreements could not be solved through consensus.

Benefits of pausing tamoxifen treatment

There were 974 women across 1 RCT and 2 observational studies included in the final analysis. The RCT was named the POSITIVE trial and included 516 premenopausal women with prior stage 1 to 3 HR + BC receiving 18 to 30 months of tamoxifen.

Temporary treatment suspension during follow-up was reported in 263 of these patients, 74% of whom achieved pregnancy, and 63.8% live birth. These patients had no significant variations in 3-year BC recurrence rates compared to those continuing treatment, with rates of 8.9% and 9.2%, respectively.

A 3-year incidence of direct recurrence of 4.5% was reported in the tamoxifen group and 5.8% in the control group, indicating an absolute difference of -1.4% and a hazard ratio (HR) of 0.70.

Odds of live birth and BC recurrence

In one of the observational studies, tamoxifen users had an HR of 0.25 for live birth, indicating significantly reduced odds. However, ovarian reserve markers were higher in this population, including anti-Müllerian hormone levels of 2.3 ng/mL vs non-users with levels of 1.8 ng/mL.

In the other observational study, a median 7-month duration was reported between tamoxifen cessation and conception. BC recurrence did not significantly differ between women with pregnancy in the 5 months following their initial diagnosis and those without pregnancy.

Implications for fertility preservation

These results highlighted high pregnancy success and low short-term recurrence from temporarily halting tamoxifen treatment. Investigators concluded tamoxifen’s potential ovarian protective effects highlight possible fertility preservation options.

“Long-term follow-up data and larger-scale studies are necessary to ensure the safety and efficacy of tamoxifen interruption over extended periods,” concluded investigators.

References

1. Maiorano MFP, Cormio G, Loizzi V, Maiorano BA, D'Oronzo S, Silvestris E. Tamoxifen and fertility in women with breast cancer: a systematic review on reproductive outcomes and oncological safety of treatment interruption. Int J Mol Sci. 2025;26(8):3787. doi:10.3390/ijms26083787
2. Shandley LM, Spencer JB, Fothergill A, et al. Impact of tamoxifen therapy on fertility in breast cancer survivors. Fertil Steril. 2017;107(1):243-252.e5. doi:10.1016/j.fertnstert.2016.10.020