Chemotherapy-Induced Amenorrhea and Its Prognostic Significance in Premenopausal Women With Breast Cancer: An Updated Meta-Analysis

Abstract

ObjectiveChemotherapy-induced amenorrhea (CIA) is one of the most common side effects in premenopausal patients with breast cancer, and several factors may contribute to the incidence of CIA. In this meta-analysis, we aimed to summarize clinical risk factors associated with CIA incidence and to evaluate their prognostic effects in patients with breast cancer.MethodsThree electronic databases (Cochrane Library, EMBASE, and MEDLINE) were systematically searched for articles published up to October 2021. The articles included clinical trials that evaluated risk factors associated with CIA and their prognostic value in treatment. For the meta-analysis, pooled odds ratio estimates (ORs) and 95% confidence intervals (CIs) were calculated using the inverse variance-weighted approach, in addition to publication bias and the chi-square test.ResultsA total of 68 studies involving 26,585 patients with breast cancer were included in this meta-analysis, and 16,927 patients developed CIA. From the 68 studies, 7 risk factors were included such as age group, hormone receptor (HR) status, estrogen receptor (ER) status, progesterone receptor (PR) status, tamoxifen administration, chemotherapeutic regimen, and tumor stage. Based on our results, patients with age of ≤40, HR-negative status, ER-negative status, PR-negative status, no use of tamoxifen, and use of anthracycline-based regimen (A) compared with anthracycline-taxane-based regimen (A+T) were associated with less incidence of CIA in patients with breast cancer. Moreover, CIA was associated with favorable disease-free survival (OR = 0.595, 95% CI = 0.537 to 0.658, p < 0.001) and overall survival (OR = 0.547, 95% CI = 0.454–0.660, p < 0.001) in premenopausal patients with breast cancer.ConclusionAge, HR status, ER status, PR status, tamoxifen administration, and chemotherapeutic regimen can be considered independent factors to predict the occurrence of CIA. CIA is a favorable prognostic factor in premenopausal patients with breast cancer. CIA should be a trade-off in the clinical management of premenopausal patients with breast cancer, and further large cohort studies are necessary to confirm these results.

Análise da qualidade de vida em pacientes diagnosticadas com câncer de mama e submetidas ao tratamento quimioterápico

“…Como dito anteriormente, a amenorreia induzida por quimioterapia, é um sintoma comum nas pacientes prémenopausa e pode estar associada a disfunções geniturinárias, infertilidade e sintomas da perimenopausa, como ondas de calor e suores, sendo um importante tópico, visto que esse aspecto foi um dos mais importantes de acordo com os resultados do presente estudo. Além disso, a preocupação com o potencial futuro de engravidar, tanto relacionado a falência ovariana, quanto a recorrência da doença, é um importante fator psicológico que afeta diretamente a vida das pacientes (Wang;, essa importância está no fato de que a pontuação no questionamento sobre "perspectivas futuras" foi a menor atingida pelas pacientes entrevistadas, na escala funcional, o que significa que há um prejuízo importante.…”

The effects and mechanism of taxanes on chemotherapy-associated ovarian damage: A review of current evidence

“…Another meta-analysis described that when anthracycline-based chemotherapy combined with taxanes was not related to a higher risk of CIA, but the level of evidence was weak (45). In the latest meta-analysis, Wang et al reported that the addition of taxanes to anthracycline-based regimens would significantly increase the CIA rates with no heterogeneity and publication bias (46).…”

“…However, these differences were not statistically significant in women older than 40 (40). Fourth, many patients were treated with tamoxifen for a long time, and the use of tamoxifen appears to be associated with higher rates of CIA (46). Consequently, the reported CIA rates may be overestimated.…”

A prospective longitudinal analysis of the predictors of amenorrhea after breast cancer chemotherapy: Impact of BRCA pathogenic variants

“…Alkylating agents and topoisomerase inhibitors, which form the backbone for most breast cancer regimens cause DNA double strand breaks in ovarian follicles and induce their apoptotic death 3 . Whereas taxanes do not induce DNA damage in primordial follicles, and therefore, the addition of a taxane to an AC‐based regimen is not expected to compromise ovarian egg reserve, 4,5 and there have been claims to the contrary based on shorter‐term amenorrhea rates 6 . The topoisomerase inhibitors can also induce microvascular and stromal damage in the ovary 7,8 .…”