We conducted a prospective observational study for premenopausal women receiving adjuvant adriamycin and cyclophosphamide-containing regimens to define the pattern of chemotherapy-induced amenorrhea (CIA), the menopause-specific quality of life (MENQOL), and the hormone profiles.
From October 2003 to July 2007, 387 patients with breast cancer who underwent curative surgery were prospectively included. Patient self-assessment by MENQOL questionnaires and blood samples for hormone assays were taken before chemotherapy, and 1, 6, and 12 months after chemotherapy was completed.
Patients were categorized into three groups according to their duration and reversibility of amenorrhea, with 312 eligible patients split into long-term CIA (n = 180, 57.7 %), temporary CIA (n = 113, 36.2 %), and menstrual irregularity (n = 19, 6.1 %) groups. Risk factors for long-term CIA were identified as age ≥40 years (p < 0.001), the addition of taxane (p = 0.01), and tamoxifen use (p = 0.03). MENQOL was worst immediately after the completion of adjuvant chemotherapy, and this was not fully recovered even 12 months after chemotherapy had finished. Age ≥40 years and tamoxifen exposure were inversely associated with MENQOL. In long-term CIA patients, the level of follicle-stimulating hormone increased after chemotherapy; this level, however, was reduced in patients who received tamoxifen, but remained high and stable in those who did not (p < 0.001 at 6 months; p < 0.001 at 12 months).
This study showed that most premenopausal breast cancer patients who received adjuvant chemotherapy experienced clinically significant CIA, followed by impaired MENQOL. Our findings may be relevant in the decision-making processes for premenopausal women with breast cancer.
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Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29
Early, Breast, Cancer, Trialists’, Collaborative, Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717
Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thurlimann B, Senn HJ (2005) Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 16:1569–1583
Walshe JM, Denduluri N, Swain SM (2006) Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 24:5769–5779
Ganz PA, Rowland JH, Desmond K, Meyerowitz BE, Wyatt GE (1998) Life after breast cancer: understanding women’s health-related quality of life and sexual functioning. J Clin Oncol 16:501–514
Couzi RJ, Helzlsouer KJ, Fetting JH (1995) Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy. J Clin Oncol 13:2737–2744
Jung KW, Park S, Kong HJ, Won YJ, Boo YK, Shin HR, Park EC, Lee JS (2010) Cancer statistics in Korea: incidence, mortality and survival in 2006-2007. J Korean Med Sci 25:1113–1121
Parulekar WR, Day AG, Ottaway JA, Shepherd LE, Trudeau ME, Bramwell V, Levine M, Pritchard KI (2005) Incidence and prognostic impact of amenorrhea during adjuvant therapy in high-risk premenopausal breast cancer: analysis of a National Cancer Institute of Canada Clinical Trials Group Study–NCIC CTG MA.5. J Clin Oncol 23:6002–6008
Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E (1996) A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 24:161–175
Zollner YF, Acquadro C, Schaefer M (2005) Literature review of instruments to assess health-related quality of life during and after menopause. Qual Life Res 14:309–327
Park YJ, Koo BS, Kang HC, Chun SH, Yoon JW (2001) The menopausal age and climacteric symptoms, and the related factors of Korean women. Korean J Women Health Nurs 7:473–485
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 115:335–342
Partridge A, Gelber S, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Winer E (2007) Age of menopause among women who remain premenopausal following treatment for early breast cancer: long-term results from International Breast Cancer Study Group Trials V and VI. Eur J Cancer 43:1646–1653
Tham YL, Sexton K, Weiss H, Elledge R, Friedman LC, Kramer R (2007) The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane. Am J Clin Oncol 30:126–132
Kil WJ, Ahn SD, Shin SS, Lee SW, Choi EK, Kim JH, Son BH, Ahn SH, Kim WK, Kim SB (2006) Treatment-induced menstrual changes in very young (<35 years old) breast cancer patients. Breast Cancer Res Treat 96:245–250
Petrek JA, Naughton MJ, Case LD, Paskett ED, Naftalis EZ, Singletary SE, Sukumvanich P (2006) Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol 24:1045–1051
Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C (2005) Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352:2302–2313
Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD (2006) Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol 24:1332–1341
Goodwin PJ, Ennis M, Pritchard KI, Trudeau M, Hood N (1999) Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 17:2365–2370
Ganz PA, Land SR, Geyer CE, Cecchini RS, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff JA, Vogel VG, Erban JK, Livingston RB, Perez EA, Mamounas EP, Wolmark N, Swain SM (2011) Menstrual history and quality-of-life outcomes in women with node-positive breast cancer treated with adjuvant therapy on the NSABP B-30 trial. J Clin Oncol 29:1110–1116
Williams RE, Levine KB, Kalilani L, Lewis J, Clark RV (2009) Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas 62:153–159
Ganz PA, Greendale GA, Petersen L, Zibecchi L, Kahn B, Belin TR (2000) Managing menopausal symptoms in breast cancer survivors: results of a randomized controlled trial. J Natl Cancer Inst 92:1054–1064
Lee MS, Kim JH, Park MS, Yang J, Ko YH, Ko SD, Joe SH (2010) Factors influencing the severity of menopause symptoms in Korean post-menopausal women. J Korean Med Sci 25:758–765
Ganz PA (2001) Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life. J Natl Cancer Inst Monogr 2001:130–134
Day R, Ganz PA, Costantino JP, Cronin WM, Wickerham DL, Fisher B (1999) Health-related quality of life and tamoxifen in breast cancer prevention: a report from the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Clin Oncol 17:2659–2669
Avis NE, Crawford S, Manuel J (2005) Quality of life among younger women with breast cancer. J Clin Oncol 23:3322–3330
Ganz PA, Greendale GA, Petersen L, Kahn B, Bower JE (2003) Breast cancer in younger women: reproductive and late health effects of treatment. J Clin Oncol 21:4184–4193
Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, De Maio E, Di Maio M, Piccirillo MC, De Feo G, D’Aiuto G, Botti G, Chiodini P, Gallo C, Perrone F, de Matteis A (2009) Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol 27:3192–3197
Jordan VC, Fritz NF, Tormey DC (1987) Endocrine effects of adjuvant chemotherapy and long-term tamoxifen administration on node-positive patients with breast cancer. Cancer Res 47:624–630
Conflict of interest
Changhoon Yoo and Mi Ra Yun have equally contributed.
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Yoo, C., Yun, M.R., Ahn, J. et al. Chemotherapy-induced amenorrhea, menopause-specific quality of life, and endocrine profiles in premenopausal women with breast cancer who received adjuvant anthracycline-based chemotherapy: a prospective cohort study. Cancer Chemother Pharmacol 72, 565–575 (2013). https://doi.org/10.1007/s00280-013-2227-5
- Chemotherapy-induced amenorrhea
- Breast cancer
- Quality of life