What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis

Abstract

To evaluate the incidence of chemotherapy-induced amenorrhea (CIA) and its therapeutic impact in premenopausal breast cancer patients. A systematic search was performed to identify clinical studies that compared the incidence of CIA with different chemotherapy regimens and oncological outcomes with and without CIA. The fixed-effects and random-effects models were used to assess the pooled estimates. Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. A total of 15,916 premenopausal breast cancer patients from 46 studies were included. The cyclophosphamide-based regimens, taxane-based regimens, and anthracycline/epirubicin-based regimens all increased the incidence of CIA with pooled odds ratios of 2.25 (95 % CI 1.26-4.03, P = 0.006), 1.26 (95 % CI 1.11-1.43, P = 0.0003) and 1.39 (95 % CI 1.15-1.70, P = 0.0008), respectively. The three-drug combination regimens of cyclophosphamide,anthracycline/epirubicin, and taxanes (CAT/CET) caused the highest rate of CIA compared with the other three drug combinations (OR 1.41, 95 % CI 1.16-1.73, P = 0.0008). Tamoxifen therapy was also correlated with a higher incidence of CIA, with an OR of 1.48. Patients with CIA were found to exhibit better disease-free survival (DFS) and overall survival (OS) compared with patients without CIA. With respect to molecular subtype, this DFS advantage remained significant in hormone-sensitive patients (HR 0.61, 95 % CI 0.52-0.72, P < 0.00001). The current meta-analysis has demonstrated that anthracycline/epirubicin, taxanes, cyclophosphamide, and tamoxifen all contributed to elevated rates of CIA, and CIA was not merely a side effect of chemotherapy but was a better prognostic marker, particularly for ER-positive premenopausal early-stage breast cancer patients. However, this topic merits further randomized control studies to detect the associations between CIA and patient prognosis after adjusting for age, ER status, and other influential factors.

Elevated risks of subsequent endometrial cancer development among breast cancer survivors with different hormone receptor status: a SEER analysis

“…Based on the current study’s finding that endometrial cancer risks are increased for ER+PR+, ER+PR−, ER−PR+ breast cancers in the 40–49 age group, it is possible that the shared risk factors such as obesity, hormone replacement therapy, and reproductive factors may contribute to the elevated risk of endometrial cancer in these patients [20–24]. Additionally, several studies have reported higher incidence of chemotherapy-induced amenorrhea (CIA) in premenopausal ER-positive breast cancer patients [27–29]. The low estrogenic environment caused by chemotherapy along with tamoxifen treatment may lead to the activation and increased synthesis of endometrial estrogen and progesterone receptors, which may also contribute to increased risk of endometrial cancer [30, 31].…”

Predicting Ovarian Activity in Women Affected by Early Breast Cancer: A Meta-Analysis-Based Nomogram

“…Although in the majority of studies recovery of menses occurs within 1 year, some patients may recover their menses within 3 years from EoC. Notably, whether taxanes increase CRA rates when added to anthracycline and cyclophosphamide-based regimens is still uncertain [56][57][58]. In terms of fertility, 1-year CRA and return of menses unreliably predict post-CT residual fertility potential [59]; however, pretreatment estimation of individual risk of residual ovarian reserve at the EoC could help tailor fertility preservation options for patients who require them.…”

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

“…This is reflected by the use of various definitions (that included amenorrhea in almost all cases) and timepoints of its evaluation in the different trials. However, amenorrhea is not an optimal surrogate marker for defining the gonadotoxicity of anticancer treatments [124,125]; the use of this endpoint is of particular concern when tamoxifen is given as adjuvant endocrine therapy considering the perturbation of menstrual function induced by the use of this treatment [126,127]. In the absence of a clear-cut definition, experts recommend to empirically define chemotherapy-induced POI with a composite definition of amenorrhea for ≥2 years and post-menopausal hormonal profile [6,128].…”