Chemotherapy-induced ovarian failure in young women with early breast cancer: prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials
Background - Young women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by asse...
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
8 June 2021
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| In: |
European journal of cancer
Year: 2021, Volume: 152, Pages: 193-203 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2021.04.038 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejca.2021.04.038 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804921002902 
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| Author Notes: | Jenny Furlanetto, Frederik Marmé, Sabine Seiler, Christian Thode, Michael Untch, Sabine Schmatloch, Andreas Schneeweiss, Martina Bassy, Peter A. Fasching, Dominika Strik, Elmar Stickeler, Christian Schem, Thomas Karn, Eva-Maria Grischke, Carsten Denkert, Marion van Mackelenbergh, Volkmar Müller, Valentina Nekljudova, Sibylle Loibl |
| Summary: | Background - Young women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by assessing hormone parameters, CIA, and antral follicle count (AFC). - Methods - Blood samples of women aged ≤45 years treated with anthracycline/taxane-based chemotherapy for EBC from four neoadjuvant/adjuvant trials were collected at baseline, at the end of treatment (EOT), and at 6, 12, 18, and 24 months after EOT. Centrally assessed oestradiol (cutoff <52.2 ng/L) and follicle-stimulating hormone (cutoff >12.4IU/L) were used to define CIOF for patients with baseline premenopausal hormone levels, anti-Müllerian hormone (AMH), and AFC to assess ovarian reserve. Further analyses included CIA, regain of premenopausal hormone levels, and disease-free survival (DFS) also in subgroups. - Results - Six hundred ninety-six patients aged ≤45 years had premenopausal hormone levels at baseline. Overall, 85.1% (592/696) experienced CIOF at EOT, and 147 of 592 had further hormone measurements after EOT. Of those, 32.7% (48/147) regained premenopausal hormone levels after 6 months, 57.9% (66/114) regained premenopausal hormone levels after 12 months, 83.0% (73/88) regained premenopausal hormone levels after 18 months, and 89.2% (74/83) regained premenopausal hormone levels after 24 months. After 24 months, 72.4% (21/29) of patients without CIOF and 100% (14/14) with CIOF had low AMH levels. Four-year DFS without CIOF versus CIOF was 65.9% versus 84.6% (hazard ratio [HR] = 2.09, 95% confidence interval [CI]: 1.37-3.19; P < 0.001); in hormone receptor positive 61.8% versus 87.5% (HR = 2.69, 95% CI: 1.57-4.60; P < 0.001); in <30 years 68.3% versus 92.6% (HR = 4.87, 95% CI: 1.05-22.63; P = 0.026). - Conclusion - Most premenopausal women experienced CIOF after chemotherapy for EBC. After 2 years, nearly all regain premenopausal hormone levels. CIOF was associated with better DFS, especially in patients with hormone receptor-positive EBC or aged <30 years. |
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| Item Description: | Gesehen am 14.10.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2021.04.038 |