Chemotherapy-induced ovarian failure in young women with early breast cancer: Prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials

Furlanetto, Jenny; Marmé, Frederik; Seiler, Sabine; Thode, Christian; Untch, Michael; Schmatloch, Sabine; Schneeweiß, Andreas; Bassy, M; Fasching, Peter A.; Strik, D.; Stickeler, Elmar; Schem, Christian; Karn, Thomas; Grischke, Eva‐Maria; Denkert, Carsten; Mackelenbergh, Marion van; Müller, Volkmar; Nekljudova, Valentina; Loibl, Sibylle

doi:10.1016/j.ejca.2021.04.038

Cited by 21 publications

(14 citation statements)

References 35 publications

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“…The changes in estradiol, FSH, and LH levels in premenopausal patients observed in our study are consistent with published studies reporting that the majority of young women receiving (neo)adjuvant chemotherapy rendered postmenopausal after chemotherapy ( 8 , 14 ), although these studies focus on menstrual status or ovarian function rather than hormones. In postmenopausal patients, a slightly significant decrease in FSH levels and no significant changes in LH levels were observed in our study, as previously reported ( 7 ).…”

Section: Discussionsupporting

confidence: 92%

“…Our previous works ( 11 ) and other studies ( 12 , 13 ) found an association between pre-treatment hormones and prognosis in patients who received NAC treatment. A recent study has described the association of chemotherapy-induced ovarian failure with the improved outcome regardless of hormone receptor status ( 14 ), highlighting the vital role of ovarian function suppression after neoadjuvant/adjuvant chemotherapy in inhibiting disease progression. Although this study reveals the potential role of reproductive hormones in cancer progression, it is not clear the exact effect of hormone changes after neoadjuvant/adjuvant chemotherapy on survival outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Association of serum reproductive hormones changes after neoadjuvant chemotherapy with hormone receptors expression alterations and survival outcomes in breast cancer

Lan

Jin²,

Wang³

et al. 2022

Front. Surg.

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PurposeThis study aimed to determine the effect of neoadjuvant chemotherapy (NAC) on circulating levels of reproductive hormones and evaluate the correlation of hormone changes after NAC with hormone receptors expression alterations and relapse-free survival (RFS) outcomes in breast cancer.MethodsInformation from 181 breast cancer patients who received NAC was retrospectively analyzed. For hormones parameters, the median and interquartile range (IQR) were provided at baseline and the end of NAC then was compared by Wilcoxon signed-rank test. Categorical variables were represented as numbers and percentages and were compared via two-sided chi-square and Fisher's tests. The RFS outcomes were compared between patients according to hormone changes using the log-rank test. Univariate and multivariate survival analyses with hazard ratios (HR) and 95% confidence intervals (95% CI) were carried out using Cox regression.ResultsSex steroids including estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels decreased significantly after NAC among both premenopausal and postmenopausal patients (all P < 0.05). Decreased estradiol levels were associated with reduced progesterone receptor (PR) expression (P = 0.030). In multivariate survival analysis, the non-decreased progesterone level was strongly associated with worse RFS (non-decreased vs. decreased, HR = 7.178, 95% CI 2.340–22.019, P = 0.001). Patients with decreased progesterone levels exhibited better 3-year RFS compared with those with non-decreased (87.6% vs. 58.3%, log-rank, P = 0.001).ConclusionMultiple reproductive hormone levels were influenced by NAC. The change in estradiol level had a positive connection with PR expression alteration. Furthermore, an inverse association between the change in progesterone level and RFS outcomes was found. These findings may provide a theoretical basis for pre-operative endocrine therapy combined with NAC in breast cancer patients.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Association of serum reproductive hormones changes after neoadjuvant chemotherapy with hormone receptors expression alterations and survival outcomes in breast cancer

Lan

Jin²,

Wang³

et al. 2022

Front. Surg.

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“…Age is the most relevant factor for the return of menses after chemotherapy, and most women over 45 years of age go through menopause after undergoing chemotherapy [28,32,33]. However, about 70% of premenopausal women under the age of 45 who developed CIA regained their premenopausal hormone levels by 2 years after completing chemotherapy [29].…”

Section: Discussionmentioning

confidence: 99%

Changes in the severity of chemotherapy-induced nausea and vomiting according to the menopausal stage of breast cancer patients during adjuvant chemotherapy: A prospective observational study

Yeom

Lee

et al. 2023

Preprint

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Purpose Breast cancer has been reported to be common in middle-age, but little is known about the relationship between menopausal stage and the severity of chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients. Therefore, we examined the association between menopausal stage and CINV severity.Methods Participants were prospectively enrolled from a tertiary general hospital. We evaluated CINV severity of 187 breast cancer patients receiving adjuvant chemotherapy, using a Likert scale from 1 to 10, before chemotherapy (W0), 4 weeks after the first chemotherapy (W4), and 12 weeks (W12) after the first chemotherapy. Premenopause, perimenopause, and postmenopause period were classified by age 45 and 55 years, respectively. CINV severity at different time-points and change values in CINV severity (cCIN, cCIV) at each time point, relative to W0, were compared using a linear mixed modelResults Significant group-by-time interactions were observed for CIN (p = 0.011), CIV (p = 0.027), and cCIN (p = 0.030). In postmenopausal period women, unlike in premenopausal and perimenopausal period women, the mean change values for CIN and CIV at each time point relative to W0 were not significantly different. In the post-hoc analysis, there was a significant difference (p = 0.007) in cCIN at W4 between perimenopausal and postmenopausal period women.Conclusions Changes in CINV severity in breast cancer patients follow different patterns according to menopausal stage. Perimenopausal period women seem to be particularly susceptible to CINV. During chemotherapy, it is necessary to manage CINV with consideration of menopausal stage.

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“…The mean age of onset of menopause is 51 years in Western countries and by age 55 approximately 85% of women have undergone menopause 7 , 8 . Adjuvant chemotherapy in pre-menopausal women can induce menopause in an age-dependent manner 9 , 10 . The NSABP B-47 clinical trial showed that chemotherapy induced amenorrhea in pre-menopausal women is common but it is often discordant with hormone level measurements.…”

Section: Introductionmentioning

confidence: 99%

“…Adjuvant chemotherapy in pre-menopausal women can induce menopause in an age-dependent manner 9,10 . The NSABP B-47 clinical trial showed that chemotherapy induced amenorrhea in pre-menopausal women is common but it is often discordant with hormone level measurements.…”

Section: Introductionmentioning

confidence: 99%

Molecular differences between younger versus older ER-positive and HER2-negative breast cancers

et al. 2022

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The RxPONDER and TAILORx trials demonstrated benefit from adjuvant chemotherapy in patients age ≤ 50 with node-positive breast cancer and Recurrence Score (RS) 0–26, and in node-negative disease with RS 16–25, respectively, but no benefit in older women with the same clinical features. We analyzed transcriptomic and genomic data of ER+/HER2− breast cancers with in silico RS < 26 from TCGA (n = 530), two microarray cohorts (A: n = 865; B: n = 609), the METABRIC (n = 867), and the SCAN-B (n = 1636) datasets. There was no difference in proliferation-related gene expression between age groups. Older patients had higher mutation burden and more frequent ESR1 copy number gain, but lower frequency of GATA3 mutations. Younger patients had higher rate of ESR1 copy number loss. In all datasets, younger patients had significantly lower mRNA expression of ESR1 and ER-associated genes, and higher expression of immune-related genes. The ER- and immune-related gene signatures showed negative correlation and defined three subpopulations in younger women: immune-high/ER-low, immune-intermediate/ER-intermediate, and immune-low/ER-intermediate. We hypothesize that in immune-high cancers, the cytotoxic effect of chemotherapy may drive the benefit, whereas in immune-low/ER-intermediate cancers chemotherapy induced ovarian suppression may play important role.

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Chemotherapy-induced ovarian failure in young women with early breast cancer: Prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials

Cited by 21 publications

References 35 publications

Association of serum reproductive hormones changes after neoadjuvant chemotherapy with hormone receptors expression alterations and survival outcomes in breast cancer

Association of serum reproductive hormones changes after neoadjuvant chemotherapy with hormone receptors expression alterations and survival outcomes in breast cancer

Changes in the severity of chemotherapy-induced nausea and vomiting according to the menopausal stage of breast cancer patients during adjuvant chemotherapy: A prospective observational study

Molecular differences between younger versus older ER-positive and HER2-negative breast cancers

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