Journal Article
. 2007 Apr; 30(2):126-32.
doi: 10.1097/01.coc.0000251398.57630.4f.

The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane

Yee-Lu Tham 1 Krystal Sexton  Heidi Weiss  Richard Elledge  Lois C Friedman  Rita Kramer  
  • PMID: 17414460
  •     36 citations


Objective: Adjuvant chemotherapy in premenopausal women with breast cancer may induce amenorrhea, which can affect fertility, choice of hormonal therapy, and increase the risk of late toxicity. The incidence of chemotherapy-induced amenorrhea (CIA) resulting from doxorubicin and cyclophosphamide (AC) followed by a taxane (T) is poorly characterized.

Methods: We retrospectively surveyed women who were premenopausal and less than age 50 at initiation of chemotherapy to determine the rates of CIA in women receiving AC followed by T compared with AC alone.

Results: One hundred ninety-one eligible women completed the survey. The rate of CIA in women who received AC followed by T was 64% (95% confidence interval [CI] = 55-72%) compared with 55% (95% CI = 43-66%) in AC alone. As expected, CIA rates were higher in older than younger women (82% vs. 55%, P = 0.004). Multivariate logistic regression analysis revealed that age >40 was associated with a 4.6-fold increased risk of CIA (95% CI = 1.7-12.1, P = 0.002). It also revealed that receiving T after AC was associated with an odds ratio of 1.9 for CIA as compared with receiving AC alone (95% CI = 1.0-3.5, P = 0.05). Despite > or =6 months of amenorrhea, many women < or =40 resumed menses (40%). CIA was more likely to be irreversible in those >40. The addition of taxanes did not alter the rate of reversibility for the group as a whole (P = 0.36).

Conclusions: Older age and the addition of taxane to AC increased the risk of CIA and the amenorrhea was more likely to be irreversible for women >40. Women < or =40 often resume menstruation even after 6 months of amenorrhea, and the addition of T does not play a role. Subsequent resumption of menstrual function must be considered when initiating appropriate hormonal therapy.

Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel.
Martine Berliere, Florence Dalenc, +7 authors, Jean-Pascal Machiels.
BMC Cancer, 2008 Feb 23; 8. PMID: 18291033    Free PMC article.
Cancer and fertility preservation: fertility preservation in breast cancer patients.
Theodoros Maltaris, Michael Weigel, +5 authors, Ralf Dittrich.
Breast Cancer Res, 2008 May 22; 10(2). PMID: 18492214    Free PMC article.
Endocrine sequelae of cancer and cancer treatments.
Charles J Stava, Camilo Jimenez, Rena Vassilopoulou-Sellin.
J Cancer Surviv, 2008 Jul 24; 1(4). PMID: 18648961
Breast cancer in young women and its impact on reproductive function.
M Hickey, M Peate, C M Saunders, M Friedlander.
Hum Reprod Update, 2009 Jan 29; 15(3). PMID: 19174449    Free PMC article.
Maintaining fertility in young women with breast cancer.
Melissa C Hulvat, Jacqueline S Jeruss.
Curr Treat Options Oncol, 2010 Mar 20; 10(5-6). PMID: 20238254    Free PMC article.
Decrease in breast density in the contralateral normal breast of patients receiving neoadjuvant chemotherapy: MR imaging evaluation.
Jeon-Hor Chen, Ke Nie, +6 authors, Min-Ying Su.
Radiology, 2010 Mar 24; 255(1). PMID: 20308443    Free PMC article.
Recovery of menstruation after long-term chemotherapy and endocrine therapy in pre-menopausal patients with breast cancer.
Kenichi Sakurai, Katsuhisa Enomoto, Sadao Amano.
J Cancer Res Clin Oncol, 2010 Jun 10; 137(4). PMID: 20532911
Incidence of chemotherapy-induced amenorrhea associated with epirubicin, docetaxel and navelbine in younger breast cancer patients.
Wen-Bin Zhou, Hong Yin, +8 authors, Shui Wang.
BMC Cancer, 2010 Jun 15; 10. PMID: 20540745    Free PMC article.
Breast cancer and fertility preservation.
S Samuel Kim, Jennifer Klemp, Carol Fabian.
Fertil Steril, 2011 Jan 29; 95(5). PMID: 21272867    Free PMC article.
Association between low-dose pulsed intravenous cyclophosphamide therapy and amenorrhea in patients with systemic lupus erythematosus: a case-control study.
Sayumi Baba, Yasuhiro Katsumata, +5 authors, Hisashi Yamanaka.
BMC Womens Health, 2011 Jun 15; 11. PMID: 21663683    Free PMC article.
The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause.
Jacquie Chirgwin, Zhuoxin Sun, +8 authors, BIG 1-98 Collaborative and International Breast Cancer Study Groups.
Breast Cancer Res Treat, 2011 Sep 06; 131(1). PMID: 21892704    Free PMC article.
Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer.
Pamela N Munster, Amy P Moore, +6 authors, Susan E Minton.
J Clin Oncol, 2012 Jan 11; 30(5). PMID: 22231041    Free PMC article.
The risk of amenorrhea is related to chemotherapy-induced leucopenia in breast cancer patients receiving epirubicin and taxane based chemotherapy.
Wenbin Zhou, Qiang Ding, +4 authors, Shui Wang.
PLoS One, 2012 May 23; 7(5). PMID: 22615953    Free PMC article.
Fertility preservation in breast cancer patients.
Tadahiko Shien, Mikiya Nakatsuka, Hiroyoshi Doihara.
Breast Cancer, 2013 Mar 26; 21(6). PMID: 23526260    Free PMC article.
Impact of chemotherapy-induced amenorrhea in breast cancer patients: the evaluation of ovarian function by menstrual history and hormonal levels.
Kexin Meng, Wei Tian, +2 authors, Yongchuan Deng.
World J Surg Oncol, 2013 May 22; 11. PMID: 23688389    Free PMC article.
Clinical application of magnetic resonance imaging in management of breast cancer patients receiving neoadjuvant chemotherapy.
Jeon-Hor Chen, Min-Ying Su.
Biomed Res Int, 2013 Jul 19; 2013. PMID: 23862143    Free PMC article.
Background parenchymal enhancement in the contralateral normal breast of patients undergoing neoadjuvant chemotherapy measured by DCE-MRI.
Jeon-Hor Chen, Hon Yu, +2 authors, Min-Ying Su.
Magn Reson Imaging, 2013 Sep 03; 31(9). PMID: 23992630    Free PMC article.
Incidence of chemotherapy-induced amenorrhea after adjuvant chemotherapy with taxane and anthracyclines in young patients with breast cancer.
Leila Pourali, Ali Taghizadeh Kermani, +4 authors, Kazem Anvari.
Iran J Cancer Prev, 2013 Jul 01; 6(3). PMID: 25250125    Free PMC article.
Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer.
Drew R Oostra, Maryam B Lustberg, +3 authors, Charles L Shapiro.
Mol Cell Endocrinol, 2015 Jan 13; 402. PMID: 25575458    Free PMC article.
Ovarian stimulation in patients with breast cancer.
Elkin Muñoz, Naira González, +2 authors, Juan A García Velasco.
Ecancermedicalscience, 2015 Mar 03; 9. PMID: 25729417    Free PMC article.
Fertility preservation and breast cancer: a review.
María de Pedro, Borja Otero, Belén Martín.
Ecancermedicalscience, 2015 Mar 03; 9. PMID: 25729416    Free PMC article.
Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial).
Kathryn J Ruddy, Hao Guo, +17 authors, Sara M Tolaney.
Breast Cancer Res Treat, 2015 May 20; 151(3). PMID: 25981899    Free PMC article.
Gonadotropin-Releasing Hormone Agonists for Ovarian Function Preservation in Premenopausal Women Undergoing Chemotherapy for Early-Stage Breast Cancer: A Systematic Review and Meta-analysis.
Rodrigo R Munhoz, Allan A L Pereira, +4 authors, Ricardo J Marques.
JAMA Oncol, 2015 Oct 02; 2(1). PMID: 26426573    Free PMC article.
Systematic Review.
Chemotherapy-Induced Amenorrhea - An Update.
C Liedtke, L Kiesel.
Geburtshilfe Frauenheilkd, 2012 Sep 01; 72(9). PMID: 26640289    Free PMC article.
Fertility Preservation for the Young Breast Cancer Patient.
Shari B Goldfarb, Sabrina A Kamer, +6 authors, Mary L Gemignani.
Ann Surg Oncol, 2016 Jan 23; 23(5). PMID: 26790670    Free PMC article.
Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients.
Se Jeong Jeon, Jae Il Lee, Myung Jae Jeon, Maria Lee.
Medicine (Baltimore), 2016 Apr 09; 95(14). PMID: 27057900    Free PMC article.
Prediction of ovarian function in premenopausal breast cancer patients with amenorrhoea after chemotherapy: a simple clinical score.
Xiao Shi Li, Qing Lv, Zheng Gui Du, Jie Chen.
Springerplus, 2016 Jul 28; 5(1). PMID: 27462500    Free PMC article.
[Chemotherapy-induced amenorrhea in moroccan population: a retrospective cohort study].
Sami Aziz Brahmi, Fatima Zahra Ziani, Seddik Youssef, Said Afqir.
Pan Afr Med J, 2016 Sep 20; 24. PMID: 27642399    Free PMC article.
The correlation of age with chemotherapy-induced ovarian function failure in breast cancer patients.
Ingeborg J H Vriens, Ashley J R De Bie, +6 authors, Vivianne C G Tjan-Heijnen.
Oncotarget, 2017 Jan 12; 8(7). PMID: 28076330    Free PMC article.
Temporal influence of endocrine therapy with tamoxifen and chemotherapy on nutritional risk and obesity in breast cancer patients.
Mariana Tavares Miranda Lima, Kamila Pires de Carvalho, +4 authors, Yara Cristina de Paiva Maia.
BMC Cancer, 2017 Aug 31; 17(1). PMID: 28851304    Free PMC article.
Practical consensus recommendations on fertility preservation in patients with breast cancer.
Jyoti Bajpai, A Majumdar, +8 authors, S Aggarwal.
South Asian J Cancer, 2018 May 04; 7(2). PMID: 29721475    Free PMC article.
Effects of paclitaxel and cisplatin on in vitro ovarian follicle development.
Yoon Young Kim, Woo Oh Kim, +3 authors, Seung-Yup Ku.
Arch Med Sci, 2019 Nov 22; 15(6). PMID: 31749880    Free PMC article.
Menopausal symptoms in relationship to breast cancer-specific quality of life after adjuvant cytotoxic treatment in young breast cancer survivors.
Winnie Yeo, Elizabeth Pang, +6 authors, Frankie K F Mo.
Health Qual Life Outcomes, 2020 Feb 12; 18(1). PMID: 32041627    Free PMC article.
Amenorrhea, fertility preservation, and counseling among young women treated with anthracyclines and taxanes for early-stage breast cancer, a retrospective study.
Hikmat N Abdel-Razeq, Razan A Mansour, +4 authors, Omar A Shahin.
Medicine (Baltimore), 2020 Mar 17; 99(11). PMID: 32176115    Free PMC article.
Cancer Treatment-Related Infertility: A Critical Review of the Evidence.
Philip D Poorvu, A Lindsay Frazier, +6 authors, Ann H Partridge.
JNCI Cancer Spectr, 2019 Jul 31; 3(1). PMID: 31360893    Free PMC article.
Impact of adjuvant chemotherapy or tamoxifen-alone on the ovarian reserve of young women with breast cancer.
Shari B Goldfarb, Volkan Turan, +7 authors, Kutluk H Oktay.
Breast Cancer Res Treat, 2020 Sep 16; 185(1). PMID: 32930927    Free PMC article.