Dataset Information

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer.

ABSTRACT:

Objective

To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer.

Design

Genome-wide association study.

Setting

Not applicable.

Patient(s)

Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded.

Intervention(s)

None.

Main outcome measure(s)

The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status.

Result(s)

The median age of the 1,168 women was 41 years (range 19-45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5' upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation.

Conclusion(s)

Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.

SUBMITTER: Ruddy KJ

PROVIDER: S-EPMC6765404 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer.

Ruddy Kathryn J KJ Schaid Daniel J DJ Partridge Ann H AH Larson Nicholas B NB Batzler Anthony A Häberle Lothar L Dittrich Ralf R Widschwendter Peter P Fink Visnja V Bauer Emanuel E Schwitulla Judith J Rübner Matthias M Ekici Arif B AB Aivazova-Fuchs Viktoria V Stewart Elizabeth A EA Beckmann Matthias W MW Ginsburg Elizabeth E Wang Liewei L Weinshilboum Richard M RM Couch Fergus J FJ Janni Wolfgang W Rack Brigitte B Vachon Celine C Fasching Peter A PA

Fertility and sterility 20190729 4

<h4>Objective</h4>To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer.<h4>Design</h4>Genome-wide association study.<h4>Setting</h4>Not applicable.<h4>Patient(s)</h4>Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of ...[more]

PMID: 31371054

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Project description:Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition. To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL). The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis. The current study reports outcomes up to 4 years after diagnosis for participants enrolled from 2012 to 2017. Participants included premenopausal women younger than 50 years treated with chemotherapy and not receiving adjuvant ovarian function suppression. Data analysis was performed from September 2021 to June 2023. Clinical, socioeconomic, tumor, and treatment characteristics assessed at diagnosis (for the analysis of factors associated with CRA) and persistent CRA (for the QOL analysis). The main outcome of interest was CRA at year 1 (Y1), year 2 (Y2), and year 4 (Y4) after diagnosis. Generalized estimating equations assessed associations of exposure variables with CRA. In the QOL analysis, QOL at Y4 (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23) was the outcome of interest. Multivariable random-effect mixed models assessed the association of persistent CRA (ie, never recovering menses after treatment) with QOL. Among 1636 women, the mean (SD) age at diagnosis was 42.2 (5.6) years. Overall, 1242 of 1497 women (83.0%) reported CRA at Y1, 959 of 1323 women (72.5%) reported it at Y2, and 599 of 906 women (66.1%) reported it at Y4. Older age vs 18 to 34 years (adjusted odds ratio [OR] for 35 to 39 years, 1.84 [95% CI, 1.32 to 2.56]; adjusted OR for 40 to 44 years, 5.90 [95% CI, 4.23 to 8.24]; and adjusted OR for ≥45 years, 21.29 [95% CI, 14.34 to 31.61]) and receipt of adjuvant tamoxifen (adjusted OR, 1.97 [95% CI, 1.53 to 2.53]) were associated with higher likelihood of CRA. In the QOL analysis, 416 of 729 women (57.1%) had persistent CRA. However, late menses recovery among women aged 18 to 34 years with no menses at Y2 were reported by 11 of 21 women (52.4%) between Y2 and Y4. Persistent CRA was associated with worse insomnia (mean difference vs recovery at any time, 9.9 points [95% CI, 3.2 to 16.5 points]; P = .004), systemic therapy-related adverse effects (mean difference, 3.0 points [95% CI, 0.2 to 5.8 points]; P = .04), and sexual functioning (mean difference, -9.2 points [95% CI, -14.3 to -4.1 points]; P < .001) at Y4. In this cohort study of premenopausal women with breast cancer, persistent CRA was common, although some women recovered menses late, and was associated with worse long-term QOL. This study can help inform risk communication, personalized counseling, and early supportive care referrals for such patients.

Project description: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.

Project description:Young women with breast cancer experience unique treatment and survivorship issues centering on treatment-related amenorrhea (TRA), including fertility preservation and management of ovarian function as endocrine therapy. The Young Women's Breast Cancer Study (YWS) is a multi-center, prospective cohort study of women diagnosed at age ≤40, enrolled from 2006 to 2016. Menstrual outcomes were self-reported on serial surveys. We evaluated factors associated with TRA using logistic regression. One year post-diagnosis, 286/789 (36.2%) experienced TRA, yet most resumed menses (2-year TRA: 120/699; 17.2%). Features associated with 1-year TRA included older age (OR≤30vs36-40 = 0.29 (0.17-0.48), OR31-35vs36-40 = 0.67 (0.46-0.94), p = 0.02); normal body mass index (BMI) (OR≥25vs18.5-24. =0.59 (0.41-0.83), p < 0.01); chemotherapy (ORchemo vs no chemo = 5.55 (3.60-8.82), p < 0.01); and tamoxifen (OR = 1.55 (1.11-2.16), p = 0.01). TRA rates were similar across most standard regimens (docetaxel/carboplatin/trastuzumab +/- pertuzumab: 55.6%; docetaxel/cyclophosphamide +/- trastuzumab/pertuzumab: 41.8%; doxorubicin/cyclophosphamide/paclitaxel +/- trastuzumab/pertuzumab: 44.1%; but numerically lower with AC alone (25%) or paclitaxel/trastuzumab (11.1%). Among young women with breast cancer, lower BMI appears to be an independent predictor of TRA. This finding has important implications for interpretation of prior studies, future research, and patient care in our increasingly obese population. Additionally, these data describe TRA associated with use of docetaxel/cyclophosphamide, which is increasingly being used in lieu of anthracycline-containing regimens. Collectively, these data can be used to inform use of fertility preservation strategies for women who need to undergo treatment as well as the potential need for ovarian suppression following modern chemotherapy for young women with estrogen-receptor-positive breast cancer.Clinical trial registration: www.clinicaltrials.gov, NCT01468246.

Project description:BACKGROUND: Chemotherapy-induced amenorrhea (CIA) is common in young breast cancer patients. The incidence of CIA associated with regimens involving epirubicin and taxane was not well known. Furthermore, previous studies suggested leucopenia and amenorrhea may reflect inter-individual variations in pharmacokinetics. The purpose of this study was to investigate the association between leucopenia after first cycle of chemotherapy and CIA in young breast cancer patients receiving epirubicin and taxane based chemotherapy. Furthermore, the incidence of CIA was also assessed. METHODOLOGY AND PRINCIPAL FINDINGS: Between October 2008 and March 2010, 186 consecutive premenopausal patients, treated with epirubicin and taxane based chemotherapy, were recruited. Information about CIA was collected by telephone and out-patient clinic. Of these 186 patients, data from 165 patients were included and analyzed. Of all 165 patients, CIA occurred in 72 patients (43.64%). In multivariate analysis, age older than 40 y (OR: 16.10, 95% CI: 6.34-40.88, P<0.001) and previous childbearing (OR: 3.17, 95% CI: 1.06-9.47, P = 0.038) were significantly associated with probability of CIA. Compared to patients treated without taxane, patients treated with taxane-contained regimens did not have a significantly higher rate of CIA (P>0.05). The rate of CIA in leucopenia group (52.56%) was significantly higher than that in normal leukocyte group (34.62%) (P = 0.024). In patients treated with a FEC regimen (cyclophosphamide, epirubicin and 5-fluorouracil), the rate of CIA in leucopenia group (59.57%) was significantly higher than that in normal leukocyte group (36.84%) (P = 0.037). CONCLUSIONS: Age at diagnosis and previous childbearing were both found to significantly increase the risk of CIA, whereas additional taxane was not associated with increased rate of CIA. Importantly, leucopenia after first cycle of chemotherapy was associated with increased risk of CIA, which suggested that leucopenia may be an early predictor of chemotherapy-induced infertility.

Dataset Information

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer.

Objective

Design

Setting

Patient(s)

Intervention(s)

Main outcome measure(s)

Result(s)

Conclusion(s)

Publications

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer.

Similar Datasets

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