Abstract
A growing number of young breast cancer survivors consider reproductive health issues, including subsequent fertility and pregnancy, of great importance, but many questions regarding safety remain unanswered. We conducted a comprehensive literature search and review of published articles, control-matched, population-based, and co-operative group reports that addressed various aspects of pregnancy after breast cancer (patients’ expectations, fertility damage, assessment and preservation, maternal and fetal outcome, breast feeding). Overall, available data support pregnancy and breast feeding after breast cancer as safe and feasible for women at low risk of recurrence. This retrospective and population-based evidence is, however, frequently incomplete; usually not representative of the entire population, it can be biased by patients’ related effects or underpowered and is often not controlled for biological factors and risk determinants in the statistical model used. Before making any definitive assumption on this delicate and fundamental aspect of a woman’s life after breast cancer, we should demonstrate without any reasonable doubt that the scattered information available today is scientifically sound. The Breast International Group and North American Breast Cancer Group are planning a global prospective study in young women with endocrine responsive, early breast cancer who desire pregnancy, to assess both patients’ and pregnancy outcomes. The trial will include an observational phase investigating the feasibility and impact of a temporary treatment interruption to allow conception and an experimental phase investigating the optimal duration of the subsequent endocrine treatment after delivery or the last failed attempt to get pregnant.
Similar content being viewed by others
References
Brinton LA, Sherman ME, Carreon JD, Anderson WF (2008) Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst 100(22):1643–1648
Goldhirsch A, Gelber RD (2004) Breast cancer in young women. In: Harris JR, Lippman ME, Morrow M et al (eds) Diseases of the breast, 3rd edn. Lippincott Williams & Wilkins, MD, pp 1339–1349
Kroman N, Jensen MB, Wohlfahrt J et al (2000) Factors influencing the effect of age on prognosis in breast cancer: population based study. BMJ 320:474–478
Aebi S, Castiglione M (2006) The enigma of young age. Ann Oncol 17(10):1475–1477
Anders CK, Hsu DS, Broadwater G et al (2008) Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 26:3324–3330
Sant M, Allemani C, Berrino F (2004) European concerted action on survival and care of cancer patients (EUROCARE) working group. Breast carcinoma survival in Europe and the United States. Cancer 100(4):715–722
Cancello G, Maisonneuve P, Rotmensz N et al (2010) Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol 21(10):1974–1981
Smigal C, Jemal A, Ward E et al (2006) Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin 56:168–183
Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684
Smith I, Procter M, Gelber RD et al (2007) 2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36
Ventura SJ, Abma JC, Mosher WD, Henshaw SK (2008) Estimated pregnancy rates by outcome for the United States, 1990–2004. National Center for Health Statistics. Natl Vital Stat Rep 56(15):1–25
Prioux F (2005) Late fertility in Europe: some comparative and historical data. Rev Epidemiol Sante Publique 53(2):2S3–2S11
Heck KE, Schoendorf KC, Ventura SJ, Kiely JL (1997) Delayed childbearing by education level in the United States, 1969–1994. Matern Child Health J 1(2):81–88
Partridge AH, Gelber S, Peppercorn J et al (2004) Web-based survey of fertility issues in young women with breast cancer. J Clin Oncol 22:4174–4183
Ruddy KJ, Gelber S, Ginsburg ES et al (2011) Menopausal symptoms and fertility concerns in premenopausal breast cancer survivors: a comparison to age- and gravidity-matched controls. Menopause 18(1):105–108
Thewes B, Meiser B, Taylor A et al (2005) Fertility- and menopause-related information needs of younger women with a diagnosis of early breast cancer. J Clin Oncol 23:5155–5165
Duffy CM, Allen SM, Clark MA (2005) Discussions regarding reproductive health for young women with breast cancer undergoing chemotherapy. J Clin Oncol 23:766–773
Holleb AI (1965) Breast cancer and pregnancy. CA Cancer J Clin 15:182–183
Azim HA, Peccatori FA, de Azambuja E, Piccart MJ (2011) Motherhood after breast cancer: searching for la dolce vita. Expert Rev Anticancer Ther 11(2):287–298
de Bree E, Makrigiannakis A, Askoxylakis J (2010) Pregnancy after breast cancer. A comprehensive review. J Surg Oncol 101(6):534–542
Azim HA Jr, Santoro S, Pavlidis N et al (2011) Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. EJC 47(1):74–83
Mueller BA, Simon MS, Deapen D et al (2003) Childbearing and survival after breast carcinoma in young women. Cancer 98(6):1131–1140
Sankila R, Heinavaara S, Hakulinen T (1994) Survival of breast cancer patients after subsequent term pregnancy: “healthy mother effect”. Am J Obstet Gynecol 170:818–823
Rajkumar L, Guzman RC, Yang J et al (2004) Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments. Breast Cancer Res 6(1):R31–R37
Yuri T, Tsukamoto R, Miki K et al (2006) Biphasic effects of zerona on the growth of estrogen receptor-positive human breast carcinoma cells. Oncol Rep 16(6):1307–1312
Janerich DT (2001) The fetal antigen hypothesis: cancers and beyond. Med Hypotheses 56(1):101–103
Andrieu N, Goldgar DE, Easton DF et al (2006) Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS). JNCI 98(8):535–544
Del Mastro L, Catzeddu T, Venturini M (2006) Infertility and pregnancy after breast cancer: current knowledge and future perspectives. Cancer Treat Rev 32(6):417–422
Ives A, Saunders C, Bulsara M, Semmens J (2007) Pregnancy after breast cancer: population based study. BMJ 334(7586):194–198
Partridge AH, Gelber S, Peppercorn J et al (2008) Fertility and menopausal outcomes in young breast cancer survivors. Clin Breast Cancer 8(1):65–69
Walshe JM, Denduluri N, Swain SM (2006) Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 24(36):5769–5779
Faddy MJ, Gosden RG (1995) A mathematical model of follicle dynamics in the human ovary. Hum Reprod 10:770–775
Partridge AH, Ruddy KJ (2007) Fertility and adjuvant treatment in young women with breast cancer. Breast 16(S2):S175–S181
Oktay K, Sönmezer M (2008) Fertility issues and options in young women with cancer. Recent Results Cancer Res 178:203–224
Jung M, Shin H, Rha S et al (2010) The clinical outcome of chemotherapy-induced amenorrhea in premenopausal young patients with breast cancer with long-term follow-up. Ann Surg Oncol 17(12):3259–3268
Abusief ME, Missmer SA, Ginsburg ES et al (2010) The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer 116(4):791–798
Partridge A, Gelber S, Gelber RD et al (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. EJC 43:1646–1653
Partridge AH, Ruddy KJ, Gelber S et al (2010) Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril 94(2):638–644
Kroman N, Jensen MB, Melbye M et al (1997) Should women be advised against pregnancy after breast cancer treatment? Lancet 350:319–322
Velentgas P, Daling JR, Malone KE et al (1999) Pregnancy after breast carcinoma: outcomes and influence on mortality. Cancer 85:2424–2432
Gelber S, Coates AS, Goldhirsch A et al (2001) Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer. J Clin Oncol 19:1671–1675
Blakely LJ, Buzdar AU, Lozada JA et al (2004) Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence. Cancer 100(3):465–469
Langagergaard V, Gislum M, Skriver MV et al (2006) Birth outcome in women with breast cancer. Br J Cancer 94(1):142–146
Dalberg K, Eriksson J, Holmberg L (2006) Birth outcome in women with previously treated breast cancer–a population-based cohort study from Sweden. PLoS Med 3(9):e336
Lee SJ, Schover LR, Partridge AH et al (2006) American Society of Clinical Oncology: American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 24:2917–2931
Lee S, Ozkavukcu S, Heytens E, Moy F, Oktay K (2010) Value of early referral to fertility preservation in young women with breast cancer. J Clin Oncol 28(31):4683–4686
Porcu E, Bazzocchi A, Notarangelo L et al (2008) Human oocyte cryopreservation in infertility and oncology. Curr Opin Endocrinol, Diabetes Obesity 15:529–535
Oktay K, Buyuk E, Rodriguez-Wallberg KA, Sahin G (2010) In vitro maturation improves oocyte or embryo cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation. Reprod Biomed Online 20(5):634–638
Oktay K, Buyuk E, Libertella N et al (2005) Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 23:4347–4353
West ER, Shea LD, Woodruff TK (2007) Engineering the follicle microenvironment. Semin Reprod Med 25(4):287–299
Donaldson SS, Link MP, Weinstein HJ et al (2007) Final results of a prospective clinical trial with VAMP and low-dose involved-field radiation for children with low risk Hodgkin’s disease. J Clin Oncol 25:332–337
Blumenfeld Z, Avivi I, Eckman A et al (2008) Gonadotropin-releasing hormone agonist decreases chemotherapy-induced gonadotoxicity and premature ovarian failure in young female patients with Hodgkin lymphoma. Fertil Steril 89:166–173
Beck-Fruchter R, Weiss A, Shalev E (2008) GnRH agonist therapy as ovarian protectants in female patients undergoing chemotherapy: a review of the clinical data. Hum Reprod Update 14:553–561
Oktay K, Sonmezer M, Oktem O et al (2007) Absence of conclusive evidence for the safety and efficacy of gonadotropin-releasing hormone analogue treatment in protecting against chemotherapy-induced gonadal injury. Oncologist 12:1055–1066
Badawy A, Elnashar A, El-Ashry M et al (2009) Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. Fertil Steril 91:694–697
Gerber B, von Minckwitz G, Stehle H et al (2011) Effect of luteinizing hormone-releasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study. J Clin Oncol 29(17):2334–2341
Anderson RA, Cameron DA (2011) Pre-treatment serum anti-mullerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer. J Clin Endocrinol Metab 96(5):1336–1343
Su HI, Sammel MD, Green J et al (2010) Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors. Cancer 116(3):592–599
Anderson RA, Themmen APN, Al Qahtani A et al (2006) The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Human Reprod 10:2583–2592
Scheffer GJ, Broekmans FJ, Looman CW et al (2003) The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. Hum Reprod 18:700–706
Lutchman Singh K, Muttukrishna S, Stein RC et al (2007) Predictors of ovarian reserve in young women with breast cancer. Br J Cancer 96:1808–1816
Gorman JR, Usita PM, Madlensky L, Pierce JP (2009) A qualitative investigation of breast cancer survivors’ experiences with breastfeeding. J Cancer Surviv 3:181–191
McCullough L, Ng A, Najita J et al (2010) Breastfeeding in survivors of Hodgkin lymphoma treated with chest radiotherapy. Cancer 116(20):4866–4871
Moran MS, Colasanto JM, Haffty BG et al (2005) Effects of breast-conserving therapy on lactation after pregnancy. Cancer 11:399–403
Azim HA Jr, Bellettini G, Gelber S, Peccatori FA (2009) Breast-feeding after breast cancer: if you wish, madam. Breast Cancer Res Treat 114(1):7–12
Azim HA Jr, Bellettini G, Liptrott SJ et al (2010) Breastfeeding in breast cancer survivors: pattern, behaviour and effect on breast cancer outcome. Breast 19(6):527–531
Helewa M, Levesque P, Provencher D et al (2002) Breast Disease Committee and Executive Committee and Council, Society of Obstetricians and Gynaecologists of Canada. Breast cancer, pregnancy, and breastfeeding. J Obstet Gynaecol Can 24(2):164–180
Camune B, Gabzdyl E (2007) Breast-feeding after breast cancer in childbearing women. J Perinat Neonat Nurs 21(3):225–233
Rosenberg R, Levy-Schwartz R (2003) Breast cancer in women younger than 40 years. Int J Fertil 48(5):200–205
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365:1687–1717
Cuzick J, Ambroisine L, Davidson N et al (2007) Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 369:1711–1723
International Breast Cancer Study Group (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
Swain SM, Jeong JH, Geyer CE Jr et al (2010) Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 362:2053–2065
Acknowledgments
The authors express their gratitude to Mrs Kris Vantongelen for coordinating the work of the Breast International Group and North American Breast Cancer Group Endocrine Working Group. The Breast International Group and the North American Breast Cancer Group Collaboration is supported by a grant of The Breast Cancer Research Foundation.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was conducted on behalf of the Breast International Group (BIG) and North American Breast Cancer Group (NABCG) Endocrine Working Group. The members of this group are included under Appendix.
Appendix
Appendix
Members of the Breast International Group and North American Breast Cancer Group Endocrine Working Group: Aron Goldhirsch and Larissa Korde (Co-Chairs), Kathy Albain, Sunil Badve, John Bartlett, David Byrd, Kristine Calhoun, Peter Dubsky, Matthew Ellis, Richard Gelber, Michael Gnant, Olivia Pagani, Ann Partridge, Peggy Porter, Mahasti Saghatchian-d’Assignies, Christos Sotiriou, Laura van’t Veer, Eric Winer.
Rights and permissions
About this article
Cite this article
Pagani, O., Partridge, A., Korde, L. et al. Pregnancy after breast cancer: if you wish, ma’am. Breast Cancer Res Treat 129, 309–317 (2011). https://doi.org/10.1007/s10549-011-1643-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-011-1643-7