Measuring Estradiol During Ovarian Function Suppression

Hannah Linden, MD, FACP

Measuring estradiol levels during ovarian function suppression (OFS) remains debatable. It can be argued that the assessment of estradiol levels is clinically irrelevant since general OFS can be achieved with the currently available approaches, and the outcomes of OFS trials are not based on estradiol levels. However, a variety of factors may lead to ovarian escape (OE). For instance, aromatase inhibitor (AI) therapy could increase the risk of OE via the pituitary axis.¹ Additionally, achieving OFS in younger patients and those who are obese can be difficult.²

In the SOFT-EST Substudy, which assessed estradiol levels over 12 months, most patients on exemestane plus triptorelin had estradiol levels below the defined threshold of 2.72 pg/mL, consistent with levels reported in postmenopausal patients on AI therapy. At each time point, however, at least 17% of patients had levels greater than the threshold.³ The 27 patients who had estradiol levels exceeding the threshold had lower baseline follicle-stimulating hormone (P=.002) and luteinizing hormone (P=.004), higher body mass index (P=.05), and were less likely to have received prior chemotherapy (P=.06) than patients whose estradiol levels remained below 2.72 pg/mL.³ OE was found to be more frequent in chemotherapy-naïve patients (46%) and in patients aged <35 years.

A retrospective, real-world study of 46 women receiving leuprolide or goserelin demonstrated that older age was associated with a lower chance of OE compared with younger patients; however, factors such as body mass index, prior chemotherapy, and drug used (tamoxifen vs AI) did not correlate with the likelihood of OE in this patient cohort.⁴

Collectively, outcomes from OFS trials are not based on estradiol levels, and the treatment, if adhered to, is sufficient. Early Breast Cancer Trialists’ Collaborative Group meta-analysis confirmed the benefit of ovarian ablation or suppression in preventing breast cancer recurrence.⁵ In addition, the measurement of estradiol levels could create unnecessary anxiety for patients with breast cancer.

References

1. Gupta A, Bandaru S, Manthri S. Goserelin ovarian ablation failure in premenopausal women with breast cancer. Cureus. 2021;13:e19608.
2. Henry NL, Xia R, Banerjee M, et al. Predictors of recovery of ovarian function during aromatase inhibitor therapy. Ann Oncol. 2013;24:2011-2016.
3. Bellet M, Gray K, Francis P, et al. Twelve-month estrogen levels in premenopausal women with hormone receptor-positive breast cancer receiving adjuvant triptorelin plus exemestane or tamoxifen in the Suppression of Ovarian Function Trial (SOFT): the SOFT-EST Substudy. J Clin Oncol. 2016;34:1584-1593.
4. Burns E, Koca E, Xu J, et al. Measuring ovarian escape in premenopausal estrogen receptor-positive breast cancer patients on ovarian suppression therapy. Oncologist. 2021;26:e936-e942.
5. Gray RG, Bradley R, Braybrooke J, et al. Effects of ovarian ablation or suppression on breast cancer recurrence and survival: patient-level meta-analysis of 14,993 pre-menopausal women in 25 randomized trials. J Clin Oncol. 2023;41(16_suppl):503.