Incidence and predictors of ovarian function recovery (OFR) in breast cancer (BC) patients with chemotherapy-induced amenorrhea (CIA) who switched from tamoxifen to exemestane

Guerrero, Ángel; Gavilá, J.; Folkerd, Elizabeth; Murillo-Ortíz, Blanca; Martínez, F.; García, Agustin A.; Climent, Miguel Ángel; Guillém, Vicente; Ruiz, A.

doi:10.1093/annonc/mds464

Cited by 35 publications

(31 citation statements)

References 18 publications

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“…Our reported findings of an ∼25% incidence of ovarian function recovery during AI therapy are similar to the retrospective results from Smith et al [4] as well as a prospective Spanish study by Guerrero et al [9]. Our study differs substantially from the latter study, however, since the majority of our patients were incidentally found to have increased estradiol levels during monitoring, whereas most of the patients on the Spanish study reported recurrent menses.…”

Section: Discussionsupporting

confidence: 88%

Predictors of recovery of ovarian function during aromatase inhibitor therapy

Henry

Xia²,

Banerjee³

et al. 2013

Annals of Oncology

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15. Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000; 92: 205-216. 16 Background: Aromatase inhibitors (AIs) may cause a rise in estrogen levels due to ovarian function recovery in women with clinical chemotherapy-induced ovarian failure (CIOF). We carried out a prospective registry trial to identify predictors of ovarian function recovery during AI therapy. Patients and methods:Women with hormone receptor (HR)-positive breast cancer who remained amenorrheic and had hormonal levels consistent with ovarian failure after adjuvant chemotherapy were enrolled in a multi-institutional clinical trial of anastrozole. Subjects underwent frequent assessment using an ultrasensitive estradiol assay. Multivariable analysis was used to evaluate clinical and biochemical predictors of ovarian function recovery within 48 weeks.Results: Recovery of ovarian function during AI therapy was observed in 13 of 45 (28.9%) assessable subjects after a median 2.1 months (range 0.6-11.9). Median age at chemotherapy initiation was statistically significantly different between those who regained ovarian function (43 years, range 40-51) and those who remained postmenopausal (49 years, range 44-52; P < 0.0001).Conclusions: A significant proportion of women with CIOF recover ovarian function during AI therapy, including a woman over age 50 at initiation of chemotherapy. Tamoxifen remains the standard of care for women with CIOF. If an AI is used, patients should be monitored frequently with high-quality estradiol assays. Clinicaltrials.gov: NCT00555477.

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Section: Discussionsupporting

confidence: 88%

Predictors of recovery of ovarian function during aromatase inhibitor therapy

Henry

Xia²,

Banerjee³

et al. 2013

Annals of Oncology

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“…So far, only one other study reported on the impact of OFR in women using AIs . In that study, 17 out of 53 (32%) patients with chemotherapy‐induced amenorrhea developed OFR during exemestane therapy after prior tamoxifen.…”

Section: Discussionmentioning

confidence: 99%

“…In premenopausal women, AIs stimulate the gonadotropin secretion by inducing feedback stimulation of the hypothalamus–pituitary–ovary axis, resulting in a strong rise of the E2 level . Consequently, AI‐monotherapy is contraindicated in premenopausal breast cancer patients . However, in postmenopausal women, AIs have been shown to be more efficient than tamoxifen in preventing disease recurrence and improving survival…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

Hellemond

Vriens

Peer³

et al. 2019

Intl Journal of Cancer

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The DATA study (NCT00301457) compared 6 and 3 years of anastrozole in postmenopausal women with hormone receptor‐positive early breast cancer after 2–3 years of tamoxifen. Patients with chemotherapy‐induced ovarian function failure (CIOFF) were also eligible, but could be at risk of ovarian function recovery (OFR). The current analysis compared the survival of women with CIOFF with definitely postmenopausal women and examined the influence of OFR on survival. Therefore, we selected patients from the DATA study aged 45–57 years at randomization who had received (neo)adjuvant chemotherapy. They were classified by reversibility of postmenopausal status: possibly reversible in case of CIOFF ( n = 395) versus definitely postmenopausal ( n = 261). The former were monitored by E2 measurements for OFR. The occurrence of OFR was incorporated as a time‐dependent covariate in a Cox‐regression model for calculating the hazard ratio (HR). We used the landmark method to calculate residual 5‐year survival rates. When comparing CIOFF women with definitely postmenopausal women, the survival was not different. Among CIOFF women with available E2 follow‐up values ( n = 329), experiencing OFR ( n = 39) had an unfavorable impact on distant recurrence‐free survival (HR 2.27 [95% confidence interval [CI] 0.98–5.25; p = 0.05] and overall survival (HR 2.61 [95% CI 1.11–6.13; p = 0.03]). After adjusting for tumor features, the HRs became 2.11 (95% CI 0.89–5.02; p = 0.09) and 2.24 (95% CI 0.92–5.45; p = 0.07), respectively. The residual 5‐year rate for distant recurrence‐free survival was 76.9% for women with OFR and 92.1% for women without OFR, and for 5‐year overall survival 80.8% and 94.4%, respectively. Women with CIOFF receiving anastrozole may be at increased risk of disease recurrence if experiencing OFR.

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“…As previously stated, determination of menopausal status in patients who have received chemotherapy is a pathophysiologic and clinical cornerstone especially important in choosing hormonal treatment, for example in switching from tamoxifene to an aromatase inhibitor (Guerrero et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Anti-Müllerian hormone: determination of ovarian reserve in early breast cancer patients

Bozza¹,

Puglisi²,

Lambertini³

et al. 2013

Endocrine-Related Cancer

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Breast cancer is the most common invasive cancer in women of reproductive age. In young women, chemotherapy may induce amenorrhea: it is still uncertain how to assess menopausal status in these patients despite the importance of its definition for choosing appropriate endocrine treatment. In the development of sensitive biomarkers for fertility and ovarian reserve, anti-Mü llerian hormone (AMH) is considered a promising marker of ovarian reserve. The clearest data regarding a clinical use of AMH are related to the measurement of the ovarian pool in women who undergo IVF: the available data, also in breast cancer patients, seem to suggest that AMH measurement, before gonadotropin administration, can be a useful marker for the prediction of women at risk for poor-response or no response to ovarian stimulation. The utility of AMH as a potential marker of chemotherapy-induced ovarian follicular depletion and an early plasma marker of chemotherapy-induced gonadal damage has been evaluated both in young women after treatment for cancer in childhood and in young survivors of hematological malignancies and solid tumors. Several studies have demonstrated a potential utility of AMH, inhibin, or follicle-stimulating factor as biomarkers predicting infertility risk in breast cancer patients, but the studies conducted so far are not conclusive. Further studies are needed in order to define the regimen-specific action of chemotherapy on AMH levels, the percentage of post-treatment recovery of plasma levels of the hormone, and the relationship between menopausal status and AMH.

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Incidence and predictors of ovarian function recovery (OFR) in breast cancer (BC) patients with chemotherapy-induced amenorrhea (CIA) who switched from tamoxifen to exemestane

Abstract: Even with a clinical and biochemical profile compatible with menopause, switching from tamoxifen to an AI should be avoided in patients <48 with CIA.

Cited by 35 publications

References 18 publications

Predictors of recovery of ovarian function during aromatase inhibitor therapy

Predictors of recovery of ovarian function during aromatase inhibitor therapy

Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

Anti-Müllerian hormone: determination of ovarian reserve in early breast cancer patients

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