Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women with breast cancer participating in E5103
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This study aimed to investigate whether pre-chemotherapy anti-mullerian hormone (AMH) is a biomarker for chemotherapy-related amenorrhea (CRA) in breast cancer patients. A multicenter randomized controlled trial, ECOG5103, assigned patients with early stage breast cancer to standard doxorubicin-cyclophosphamide followed by paclitaxel with either placebo or one of two durations of bevacizumab therapy. Five hundred ninety-one patients were part of the decision-making/quality of life substudy, in which there were surveys from baseline through 18-month follow-up. One hundred twenty-four women were included in this analysis of menses data because they were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy. One hundred of the 124 also responded to the 18-month survey. Median age was 45 years (range 25–55), and median serum AMH level was 0.11 ng/mL (range 0.01–8.63) prior to treatment. Eighty-two percent had CRA at 12 months, and 81 % at 18 months. In multivariate analyses, older age (p = 0.0003) was the only statistically significant predictor of 12-month CRA, but at 18-months, lower pre-chemotherapy AMH (p = 0.04) and older age (p = 0.008) were both statistically significant predictors of CRA. Race, bevacizumab therapy, and tamoxifen use were not statistically significantly associated with CRA after adjustment for AMH and age. Pre-chemotherapy AMH level is a potential novel biomarker for CRA in premenopausal women with early stage breast cancer. Further research to evaluate the clinical utility of AMH testing is warranted.
KeywordsBreast neoplasms Fertility Biomarkers Chemotherapy Adjuvant
This study was supported by Public Health Service Grants CA23318, CA66636, CA21115, CA49883, CA14958, CA77651, CA25224, CA32291, as well as a Komen Promise Grant (PI: Schneider) and funds from the Breast Cancer Research Foundation. Chau Dang receives research funding from Roche/Genentech and GlaxoSmithKline and also serves as a consultant/advisor for Pfizer. Kathy Miller, Bryan Schneider, and Joseph Sparano have consultant/advisory roles Genentech, and Dr. Schneider is on the Genentech Speaker’s Bureau. George Sledge receives remuneration from Genentech.
- 5.Wunder DM, Guibourdenche J, Birkhauser MH, Bersinger NA (2008) Anti-Mullerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril 90(6):2203–2210. doi: 10.1016/j.fertnstert.2007.10.078 PubMedCrossRefGoogle Scholar
- 11.Anders C, Marcom PK, Peterson B, Gu L, Unruhe S, Welch R, Lyons P, Behera M, Copland S, Kimmick G, Shaw H, Snyder S, Antenos M, Woodruff T, Blackwell K (2008) A pilot study of predictive markers of chemotherapy-related amenorrhea among premenopausal women with early stage breast cancer. Cancer Invest 26(3):286–295. doi: 10.1080/07357900701829777 PubMedCentralPubMedCrossRefGoogle Scholar
- 14.Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N (2010) Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 362(22):2053–2065. doi: 10.1056/NEJMoa0909638 PubMedCentralPubMedCrossRefGoogle Scholar
- 19.Zhou WB, Yin H, Liu XA, Zha XM, Chen L, Dai JC, Tao AD, Ma JJ, Ling LJ, Wang S (2010) Incidence of chemotherapy-induced amenorrhea associated with epirubicin, docetaxel and navelbine in younger breast cancer patients. BMC Cancer 10:281. doi: 10.1186/1471-2407-10-281 PubMedCentralPubMedCrossRefGoogle Scholar
- 20.Swain SM, Land SR, Ritter MW, Costantino JP, Cecchini RS, Mamounas EP, Wolmark N, Ganz PA (2009) Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial. Breast Cancer Res Treat 113(2):315–320. doi: 10.1007/s10549-008-9937-0 PubMedCrossRefGoogle Scholar
- 21.Han HS, Ro J, Lee KS, Nam BH, Seo JA, Lee DH, Lee H, Lee ES, Kang HS, Kim SW (2009) Analysis of chemotherapy-induced amenorrhea rates by three different anthracycline and taxane containing regimens for early breast cancer. Breast Cancer Res Treat 115(2):335–342. doi: 10.1007/s10549-008-0071-9 PubMedCrossRefGoogle Scholar
- 24.Administration USFaD (2011). http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm274394.htm. Accessed 30 July 2013
- 26.Armed Forces Health Surveillance Center (2013) Female infertility, active component service women, U.S. Armed Forces, 2000–2012. MSMR 20(9):8–12. http://www.afhsc.mil/msmrHowTo