Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2019

Open Access 01-12-2019 | Fertility | Research

Adverse reproductive health outcomes in a cohort of young women with breast cancer exposed to systemic treatments

Authors: Cristina Silva, Ana Cristina Ribeiro Rama, Sérgio Reis Soares, Mariana Moura-Ramos, Teresa Almeida-Santos

Published in: Journal of Ovarian Research | Issue 1/2019

Login to get access

Abstract

Background

Breast cancer is the most common cancer in young women. Fortunately current survival rates of BC are significant which makes future fertility very important for quality of life of BC survivors. Chemotherapy carries a significant risk of infertility in BC patients so it is important to support fertility preservation decisions in premenopausal women. Amenorrhea has long been used as a surrogate marker of infertility in cancer patients but more reliable ovarian reserve (OR) markers are available. This study aimed to prospectively measure levels of OR in a cohort of young women with breast cancer exposed to chemotherapy, to identify adverse reproductive health outcomes in this population and to assess the influence of patient and treatment-related factors in those outcomes.

Methods

This prospective observational study included premenopausal women with breast cancer aged 18–40 years at diagnosis and proposed for (neo) adjuvant chemotherapy. Patients were evaluated before, during and a minimum of 9 months after the end of chemotherapy. Reproductive health outcomes: menses, hormonal and ultrasound OR markers, recovery of ovarian function and Premature Ovarian Insufficiency (POI).

Results

A total of 38 patients were included (mean age 32.9 ± 3.5 years). Levels of OR significantly decreased during the study. At the last follow up, 35 patients had AMH below the expected values for age; eight presented postmenopausal FSH; ten had not recovered their ovarian function and five met the defined criteria for POI. Age and baseline AMH were positively correlated with AMH at the last follow-up. AMH levels were higher in the group of patients treated with trastuzumab and lower in those under hormonal therapy, at the last follow-up.

Conclusions

Significant effects of systemic treatments on several reproductive outcomes and a strong relation of those outcomes with patient’s age and baseline level of AMH were observed. Our results point to a possible lower gonadotoxicity when treatment includes targeted therapy with trastuzumab. Also, this investigation highlights the lack of reliable OR markers in women under hormonal therapy.
Literature
1.
2.
Ribnikar D, Ribeiro JM, Pinto D, Sousa B, Pinto AC, Gomes E, et al. Breast cancer under age 40: a different approach. Curr Treat Options in Oncol. 2015;16(4):16.CrossRef
3.
Assi HA, Khoury KE, Dbouk H, Khalil LE, Mouhieddine TH, El Saghir NS. Epidemiology and prognosis of breast cancer in young women. J Thorac Dis. 2013;5(Suppl 1):S2–8.PubMedPubMedCentral
4.
Anders CK, Johnson R, Litton J, Phillips M, Bleyer A. Breast cancer before age 40 years. Sem Oncol. 2009;36(3):237–49.CrossRef
5.
6.
Freour T, Barriere P, Masson D. Anti-mullerian hormone levels and evolution in women of reproductive age with breast cancer treated with chemotherapy. Eur J Cancer. 2017;74:1–8.PubMedCrossRef
7.
Abusief ME, Missmer SA, Ginsburg ES, Weeks JC, Partridge AH. The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer. 2010;116(4):791–8.PubMedCrossRef
8.
Ben-Aharon I, Granot T, Meizner I, Hasky N, Tobar A, Rizel S, et al. Long-term follow-up of chemotherapy-induced ovarian failure in young breast Cancer patients: the role of vascular toxicity. Oncol. 2015;20(9):985–91.
9.
Ruddy KJ, Partridge AH. Fertility (male and female) and menopause. J Clin Oncol. 2012;30(30):3705–11.PubMedCrossRef
10.
Nelson SM. Biomarkers of ovarian response: current and future applications. Fertil Steril. 2013;99(4):963–9.PubMedCrossRef
11.
Partridge AH, Ruddy KJ, Gelber S, Schapira L, Abusief M, Meyer M, et al. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril. 2010;94(2):638–44.PubMedCrossRef
12.
Su HI, Chung K, Sammel MD, Gracia CR, DeMichele A. Antral follicle count provides additive information to hormone measures for determining ovarian function in breast cancer survivors. Fertil Steril. 2011;95(5):1857–9.PubMedCrossRef
13.
Broekmans FJ, de Ziegler D, Howles CM, Gougeon A, Trew G, Olivennes F. The antral follicle count: practical recommendations for better standardization. Fertil Steril. 2010;94(3):1044–51.PubMedCrossRef
14.
Seifer DB, Baker VL, Leader B. Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril. 2011;95(2):747–50.PubMedCrossRef
15.
Almog B, Shehata F, Shalom-Paz E, Tan SL, Tulandi T. Age-related normogram for antral follicle count: McGill reference guide. Fertil Steril. 2011;95(2):663–6.PubMedCrossRef
16.
Su HI. Measuring ovarian function in young cancer survivors. Min Endocrin. 2010;35(4):259–70.
17.
Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, et al. Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol. 2009;27(19):3192–7.PubMedCrossRef
18.
19.
Dezellus A, Barriere P, Campone M, Lemanski C, Vanlemmens L, Mignot L, et al. Prospective evaluation of serum anti-Mullerian hormone dynamics in 250 women of reproductive age treated with chemotherapy for breast cancer. Eur J Cancer. 2017;79:72–80.PubMedCrossRef
20.
Trapp E, Steidl J, Rack B, Kupka MS, Andergassen U, Juckstock J, et al. Anti-Mullerian hormone (AMH) levels in premenopausal breast cancer patients treated with taxane-based adjuvant chemotherapy - a translational research project of the SUCCESS a study. Breast. 2017;35:130–5.PubMedCrossRef
21.
Shandley LM, Spencer JB, Fothergill A, Mertens AC, Manatunga A, Paplomata E, et al. Impact of tamoxifen therapy on fertility in breast cancer survivors. Fertil Steril. 2017;107(1):243–52 e5.PubMedCrossRef
22.
Su HI, Maas K, Sluss PM, Chang RJ, Hall JE, Joffe H. The impact of depot GnRH agonist on AMH levels in healthy reproductive-aged women. J Clin Endocrin Metab. 2013;98(12):E1961–6.CrossRef
23.
Hagen CP, Sorensen K, Anderson RA, Juul A. Serum levels of antimullerian hormone in early maturing girls before, during, and after suppression with GnRH agonist. Fertil Steril. 2012;98(5):1326–30.PubMedCrossRef
24.
Anderson RA, Themmen AP, Al-Qahtani A, Groome NP, Cameron DA. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod. 2006;21(10):2583–92.PubMedCrossRef
25.
Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–37.PubMedCrossRef
26.
Hamy AS, Porcher R, Cuvier C, Giacchetti S, Schlageter MH, Coussieu C, et al. Ovarian reserve in breast cancer: assessment with anti-Mullerian hormone. Reprod BioMed Online. 2014;29(5):573–80.PubMedCrossRef
27.
Jacobson MH, Mertens AC, Spencer JB, Manatunga AK, Howards PP. Menses resumption after cancer treatment-induced amenorrhea occurs early or not at all. Fertil Steril. 2016;105(3):765–72 e4.PubMedCrossRef
28.
Sukumvanich P, Case LD, Van Zee K, Singletary SE, Paskett ED, Petrek JA, et al. Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study. Cancer. 2010;116(13):3102–11.PubMedCrossRef
29.
Leonard RCF, Adamson DJA, Bertelli G, Mansi J, Yellowlees A, Dunlop J, et al. GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic group OPTION trial. Ann Oncol. 2017;28(8):1811–6.PubMedCrossRef
30.
Anderson RA, Mansi J, Coleman RE, Adamson DJA, Leonard RCF. The utility of anti-Mullerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer. Eur J Cancer. 2017;87:58–64.PubMedPubMedCentralCrossRef
31.
Letourneau JM, Ebbel EE, Katz PP, Oktay KH, McCulloch CE, Ai WZ, et al. Acute ovarian failure underestimates age-specific reproductive impairment for young women undergoing chemotherapy for cancer. Cancer. 2012;118(7):1933–9.PubMedCrossRef
32.
Peigne M, Decanter C. Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review. Reprod Biol Endocrin. 2014;12:26.CrossRef
33.
Hamy AS, Porcher R, Eskenazi S, Cuvier C, Giacchetti S, Coussy F, et al. Anti-Mullerian hormone in breast cancer patients treated with chemotherapy: a retrospective evaluation of subsequent pregnancies. Reprod BioMed Online. 2016;32(3):299–307.PubMedCrossRef
34.
Anderson RA, Wallace WH. Antimullerian hormone, the assessment of the ovarian reserve, and the reproductive outcome of the young patient with cancer. Fertil Steril. 2013;99(6):1469–75.PubMedCrossRef
35.
Berliere M, Dalenc F, Malingret N, Vindevogel A, Piette P, Roche H, et al. Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel. BMC Cancer. 2008;8:56.PubMedPubMedCentralCrossRef
36.
Perdrix A, Saint-Ghislain M, Degremont M, David M, Khaznadar Z, Loeb A, et al. Influence of adjuvant chemotherapy on anti-Mullerian hormone in women below 35 years treated for early breast cancer. Reprod BioMed Online. 2017;35(4):468–74.PubMedCrossRef
37.
Zhao J, Liu J, Chen K, Li S, Wang Y, Yang Y, et al. What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis. Breast Cancer Res Treat. 2014;145(1):113–28.PubMedCrossRef
38.
Perez-Fidalgo JA, Rosello S, Garcia-Garre E, Jorda E, Martin-Martorell P, Bermejo B, et al. Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients: the impact of addition of taxanes to anthracycline-based regimens. Breast Cancer Res Treat. 2010;120(1):245–51.PubMedCrossRef
39.
Ruddy KJ, Guo H, Barry W, Dang CT, Yardley DA, Moy B, et al. Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial). Breast Cancer Res Treat. 2015;151(3):589–96.PubMedPubMedCentralCrossRef
40.
Lorenzi E, Simonelli M, Santoro A. Infertility risk and teratogenicity of molecularly targeted anticancer therapy: a challenging issue. Crit Rev Oncol/Hematol. 2016;107:1–13.CrossRef
41.
Meng K, Tian W, Zhou M, Chen H, Deng Y. Impact of chemotherapy-induced amenorrhea in breast cancer patients: the evaluation of ovarian function by menstrual history and hormonal levels. World J Surg Oncol. 2013;11:101.PubMedPubMedCentralCrossRef
42.
Morarji K, McArdle O, Hui K, Gingras-Hill G, Ahmed S, Greenblatt EM, et al. Ovarian function after chemotherapy in young breast cancer survivors. Curr Oncol. 2017;24(6):e494–502.PubMedPubMedCentralCrossRef
43.
Vriens IJ, De Bie AJ, Aarts MJ, de Boer M, van Hellemond IE, Roijen JH, et al. The correlation of age with chemotherapy-induced ovarian function failure in breast cancer patients. Oncotarget. 2017;8(7):11372–9.PubMedPubMedCentralCrossRef
44.
Su HC, Haunschild C, Chung K, Komrokian S, Boles S, Sammel MD, et al. Prechemotherapy antimullerian hormone, age, and body size predict timing of return of ovarian function in young breast cancer patients. Cancer. 2014;120(23):3691–8.PubMedCrossRef
45.
Oktay K, Bedoschi G. Appraising the biological evidence for and against the utility of GnRHa for preservation of fertility in patients with Cancer. J Clin Oncol. 2016;34(22):2563–5.PubMedCrossRef
46.
Lantsberg D, Farhi A, Zaslavsky-Paltiel I, Silverman BG, Lerner-Geva L, Orvieto R. Deliveries following fertility preservation by ovarian tissue cryopreservation without autotransplantation-what should be expected? J Assist Reprod Genet. 2019;36(2):335–40.PubMedCrossRef
47.
Amir E, Freedman O, Allen L, Colgan T, Clemons M. Defining ovarian failure in amenorrheic young breast cancer patients. Breast. 2010;19(6):545–8.PubMedCrossRef
48.
Krekow LK, Hellerstedt BA, Collea RP, Papish S, Diggikar SM, Resta R, et al. Incidence and predictive factors for recovery of ovarian function in Amenorrheic women in their 40s treated with Letrozole. J Clin Oncol. 2016;34(14):1594–600.PubMedCrossRef
Metadata
Title
Adverse reproductive health outcomes in a cohort of young women with breast cancer exposed to systemic treatments
Authors
Cristina Silva
Ana Cristina Ribeiro Rama
Sérgio Reis Soares
Mariana Moura-Ramos
Teresa Almeida-Santos
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2019
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-019-0581-6

Other articles of this Issue 1/2019

Journal of Ovarian Research 1/2019 Go to the issue

Research

Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis

Research

Can complete blood count inflammatory parameters in epithelial ovarian cancer contribute to prognosis? - a survival analysis

Review

Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review

Research

S100A10 silencing suppresses proliferation, migration and invasion of ovarian cancer cells and enhances sensitivity to carboplatin

Research

Pioglitazone suppresses excessive follicular development in murine preantral follicles

Research

Evaluation of the value of preoperative CYFRA21-1 in the diagnosis and prognosis of epithelial ovarian cancer in conjunction with CA125