Meme Kanseri Sonrası Fertilite Korunması ve Gebelik
Özet
Meme kanseri, reprodüktif çağdaki genç kadınlarda sıkça görülen ve tedavi süreçlerinin gonadotoksik etkileri nedeniyle doğurganlığı doğrudan tehdit eden önemli bir sağlık sorunudur. Standart kemoterapi, radyoterapi ve hormonal tedaviler over rezervini azaltarak kalıcı ya da geçici kısırlığa yol açabilmektedir. Bu nedenle, ASCO ve ESMO gibi uluslararası kılavuzlar, tanı alan tüm genç hastalara tedavi öncesinde fertilite korunması seçeneklerinin sunulmasını önermektedir. Günümüzde uygulanan temel yöntemler arasında, menstruel döngünün herhangi bir fazında başlatılabilen oosit ve embriyo kriyoprezervasyonu en başarılı seçenekler olarak öne çıkmaktadır. Zaman kısıtlaması olan veya hormonal uyarının istenmediği durumlarda over dokusu dondurulması ve in vitro maturasyon (IVM) gibi alternatif ya da deneysel yöntemler de tercih edilmektedir. Erkek hastalar için ise sperm kriyoprezervasyonu en güvenilir yaklaşımdır. Çalışmalar, tedavi sonrasında elde edilen gebeliklerin kanser nüksü riskini artırmadığını ve sağ kalımı olumsuz etkilemediğini net bir şekilde ortaya koymaktadır. Ancak, geçmişte kanser tedavisi almış kadınlarda düşük, erken doğum ve intrauterin gelişme geriliği gibi obstetrik komplikasyonların görülme oranı normale göre daha yüksektir. Bu durum, multidisipliner bir yaklaşım ve hastaların tedavi öncesinde kapsamlı şekilde bilgilendirilmesini zorunlu kılmaktadır.
Breast cancer is a highly prevalent malignancy among young women of reproductive age, posing a direct threat to future fertility due to the gonadotoxic nature of oncological treatments. Standard systemic chemotherapy, radiation, and endocrine therapies frequently lead to temporary or permanent ovarian insufficiency, significantly reducing the chances of natural conception. Consequently, prominent international guidelines, including ASCO and ESMO, strongly advocate that fertility preservation counseling be integrated into the initial treatment planning for all young patients. Among established methods, oocyte and embryo cryopreservation stand out as the most reliable strategies, enhanced by "random-start" protocols that prevent unnecessary delays in cancer therapy. For situations where hormonal stimulation is contraindicated or restricted by time, alternative approaches such as ovarian tissue cryopreservation and in vitro maturation (IVM) provide viable solutions. For male breast cancer patients, semen cryopreservation remains the gold standard. Extensive clinical data indicates that subsequent pregnancy does not compromise oncological prognosis or increase recurrence rates, even in hormone receptor-positive cases. Nevertheless, survivors exhibit a higher incidence of adverse obstetric outcomes, including premature delivery, miscarriage, and intrauterine growth restriction. Comprehensive pre-treatment counseling and robust multidisciplinary collaboration are essential to optimize patient care.
Referanslar
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29. doi:10.3322/caac.21208
Socialstyrelsen. Statistikområden, cancer. Accessed October 20, 2020. https://sdb. socialstyrelsen.se/if_can/
Coleman MP, Forman D, Bryant H, et al; ICBP Module 1Working Group. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet. 2011;377(9760):127-138. doi:10.1016/S0140-6736 (10)62231-3
Letourneau JM, Ebbel EE, Katz PP, et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2012;118(6):1710- 1717. doi:10.1002/cncr.26459
Azim HA Jr, Peccatori FA, de Azambuja E, Piccart MJ. Motherhood after breast cancer: searching for la dolce vita. Expert Rev Anticancer Ther. 2011;11(2): 287-298. doi:10.1586/era.10.208
Azim Jr HA, Santoro L, Pavlidis N, et al. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer 2011;47:74–83.
Valachis A, Tsali L, Pesce LL, et al. Safety of pregnancy after primary breast carcinoma in young women: a meta-analysis to overcome bias of healthy mother effect studies. Obstet Gynecol Surv 2010; 65:786–93.
Oktay K, Harvey BE, Loren AW (2018) Fertility Preservation in Patients With Cancer: ASCO clinical practice guideline update summary. J Oncol pract 14(6):381–385
Paluch-Shimon S, Cardoso F, Partridge AH, Abulkhair O, Azim HA, Bianchi-Micheli G et al (2020) ESO–ESMO 4th International consensus guidelines for breast cancer in young women (BCY4). Ann Oncol 31(6):674–696
Rosenberg SM, Newman LA, Partridge AH. Breast Cancer in Young Women: Rare Disease or Public Health Problem? JAMA Oncol. 10 2015;1(7):877–878.
Pavlidis N, Pentheroudakis G. The pregnant mother with breast cancer: diagnostic and therapeutic management. Cancer Treat Rev. 10 2005;31(6):439–447.
Moore HC, Unger JM, Phillips KA, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 3 5 2015;372(10):923–932.
Christinat A, Pagani O. Fertility after breast cancer. Maturitas. 11 2012;73(3):191–196.
Lambertini M, Goldrat O, Clatot F, Demeestere I, Awada A. Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art. Curr Opin Oncol. 7 2017;29(4):243–252.
Ruddy KJ, Gelber SI, Tamimi RM, et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol. 4 10 2014;32(11):1151–1156.
Oktay K, Harvey BE, Partridge AH, et al. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 7 1 2018;36(19):1994–2001.
Paluch-Shimon S, Pagani O, Partridge AH, et al. ESO-ESMO 3rd international consensus guidelines for breast cancer in young women (BCY3). Breast. 10 2017;35:203–217.
Peccatori FA, Azim HA Jr., Orecchia R, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 10 2013;24 Suppl 6:vi160–170.
Jeruss JS, Woodruff TK. Preservation of fertility in patients with cancer. N Engl J Med. 2 26 2009;360(9):902–911.
Ruddy KJ, Guo H, Barry W, et al. Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial). Breast Cancer Res Treat. 6 2015;151(3):589–596.
Lambertini M, Goldrat O, Clatot F, Demeestere I, Awada A. Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art. Curr Opin Oncol. 7 2017;29(4):243–252.
Ganz PA, Land SR, Geyer CE Jr., et al. 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. 3 20 2011;29(9):1110–1116.
Zhao J, Liu J, Chen K, et al. What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis. Breast Cancer Res Treat. 5 2014;145(1):113–128.
Lambertini M, Campbell C, Bines J, et al. Adjuvant Anti-HER2 Therapy, Treatment-Related Amenorrhea, and Survival in Premenopausal HER2-Positive Early Breast Cancer Patients. J Natl Cancer Inst. 6 5 2018.
Abusief ME, Missmer SA, Ginsburg ES, Weeks JC, Partridge AH. The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer. 2 15 2010;116(4):791–798.
Zagouri F, Sergentanis TN, Chrysikos D, Papadimitriou CA, Dimopoulos MA, Bartsch R. Trastuzumab administration during pregnancy: a systematic review and meta-analysis. Breast Cancer Res Treat. 1 2013;137(2):349–357.
Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351(9114):1451– 1467.
Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–816.
Palomar Rios A, Gascón A, Martínez JV, et al. Sperm preparation after freezing improves motile sperm count, motility, and viability in frozen-thawed sperm compared with sperm preparation before freezing-thawing process. J Assist Reprod Genet 2018; 35:237.
Dahhan T, Balkenende E, van Wely M, et al. Tamoxifen or letrozole versus standard methods for women with estrogen-receptor positive breast cancer undergoing oocyte or embryo cryopreservation in assisted reproduction. Cochrane Database Syst Rev 2013; :CD010240.
Rodgers RJ, Reid GD, Koch J, et al. The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review. Hum Reprod 2017; 32:1033.
Mitwally MF, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod 2003; 18:1588.
Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001; 75:305.
Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 7 1 2013;31(19):2500–2510.
Ozkaya E, San Roman G, Oktay K. Luteal phase GnRHa trigger in random start fertility preservation cycles. J Assist Reprod Genet. 6 2012;29(6):503–505.
Sonmezer M, Turkcuoglu I, Coskun U, Oktay K. Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles. Fertil Steril. 5 2011;95(6):2125 e2129–2111.
Moravek MB, Confino R, Smith KN, et al. Long-term outcomes in cancer patients who did or did not pursue fertility preservation. Fertil Steril. 2 2018;109(2):349–355.
Cobo A, Meseguer M, Remohi J, Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. Hum Reprod. 9 2010;25(9):2239–2246.
Ho JR, Woo I, Louie K, et al. A comparison of live birth rates and perinatal outcomes between cryopreserved oocytes and cryopreserved embryos. J Assist Reprod Genet. 10 2017;34(10):1359–1366.
Kim SS, Klemp J, Fabian C (2011) Breast cancer and fertility preservation. Fertil Steril 95(5):1535–1543
Stoop D, Cobo A, Silber S (2014) Fertility preservation for age-related fertility decline. Lancet 384(9950):1311–1319
Donnez J, Dolmans MM (2009) Cryopreservation of ovarian tissue: an overview. Minerva Med 100(5):401–413
Sonmezer M, Oktay K (2010) Orthotopic and heterotopic ovarian tissue transplantation. Best Pract Res Clin Obstet Gynaecol 24(1):113–126
Pacheco F, Oktay K (2017) Current success and efficiency of autologous ovarian transplantation: a meta-analysis. Reprod Sci 24(8):1111–1120
Cruz MR, Prestes JC, Gimenes DL, Fanelli MF (2010) Fertility preservation in women with breast cancer undergoing adjuvant chemotherapy: a systematic review. Fertil Steril 94(1):138–143
Cha KY, Chian RC (1998) Maturation in vitro of immature human oocytes for clinical use. Hum Reprod Update 4(2):103–120
Rao GD, Tan SL (2005) In vitro maturation of oocytes. Sem Reprod Med 23(3):242–247
Lim KS, Chae SJ, Choo CW, Ku YH, Lee HJ, Hur CY et al (2013) In vitro maturation: clinical applications. Clin Exp Reprod Med 40(4):143–147
Huang JY, Tulandi T, Holzer H, Tan SL, Chian RC (2008) Combining ovarian tissue cryobanking with retrieval of immature oocytes followed by in vitro maturation and vitrification: an additional strategy of fertility preservation. Fertil Steril 89(3):567–572
Cao YX, Chian RC (2009) Fertility preservation with immature and in vitro matured oocytes. Semin Reprod Med 27(6):456–464
Chian RC, Huang JY, Gilbert L, Son WY, Holzer H, Cui SJ et al (2009) Obstetric outcomes following vitrification of in vitro and in vivo matured oocytes. Fertil Steril 91(6):2391–2398
Xiaofu Zhang, Jingxin Niu, Tuanjie Che, et al. Fertility preservation in BRCA mutation carriers-efficacy and safety issues: a review. Reprod Biol Endocrinol 2020 Feb 18;18(1):11. doi: 10.1186/s12958-019-0561-0.
Lambertini M, Goldrat O, Toss A et al. Fertility and pregnancy issues in BRCA-mutated breast cancer patients. Cancer Treat Rev 2017; 59: 61–70.
Lambertini M, Goldrat O, Clatot F et al. Controversies about fertility and pregnancy issues in young breast cancer patients. Current state of the art. Curr Opin Oncol 2017; 29(4): 243 252.
Hourvitz, A. et al. Intracytoplasmic sperm injection (ICSI) using cryopreserved sperm from men with malignant neoplasm yields high pregnancy rates. Fertil. Steril. 90, 557–563 (2008).
Chung, K. et al. Sperm cryopreservation for male patients with cancer: an epidemiological analysis at the University of Pennsylvania. Eur. J. Obstet. Gynecol. Reprod. Biol. 113 (Suppl. 1), S7–S11 (2004).
Fossa, S. D. & Magelssen, H. Fertility and reproduction after chemotherapy of adult cancer patients: malignant lymphoma and testicular cancer. Ann. Oncol. 15 (Suppl. 4), iv259–iv265 (2004).
Schlegel, P. N. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum. Reprod. 14, 131–135 (1999).
Hsiao, W. et al. Successful treatment of postchemotherapy azoospermia with microsurgical testicular sperm extraction: the Weill Cornell experience. J. Clin. Oncol. 29, 1607–1611 (2011).
Schrader, M. et al. “Onco-tese”: testicular sperm extraction in azoospermic cancer patients before chemotherapy-new guidelines? Urology 61, 421–425 (2003).
Miro Kasum, Lidija Beketić-Orešković, Parvin F Peddi, Slavko Orešković, Rebecca H Johnson. Fertility after breast cancer treatment. Eur J Obstet Gynecol Reprod Biol 2014 Feb; 173:13-8. doi:10.1016/j.ejogrb.2013.11.009. Epub 2013 Nov 17.
Rena Yamazaki, Masanori Ono, Tomoharu Sugie, Masafumi Inokuchi, Satoko Ishikawa, Yuki Horage, Yasuyuki Kojima, Takeshi Iwasa, Tetsuaki Hara, Yumi Nagata, Keiichi Kato, Yasuhito Michikura, Takeshi Kuramoto, Soko Uchida, Akihito Horie, Hiroshi Fujiwara, Toshiya Matsuzaki. Case-based survey: The impact of breast-cancer treatment on fertility in Japan. J Obstet Gynaecol Res 2022 Mar;48(3):553-562. doi: 10.1111/jog.15132. Epub 2021 Dec 21.
M Condorelli, M De Vos, S Lie Fong, C Autin, A Delvigne, F Vanden Meerschaut, C Wyns, R Imbert, C Cheruy, J Bouziotis, E de Azambuja, A Delbaere, M Lambertin, I Demeestere. Impact of ARTs on oncological outcomes in young breast cancer survivors. Hum Reprod 2021 Jan 25;36(2):381-389. doi: 10.1093/humrep/deaa319.
Lambertini M, Blondeaux E, Bruzzone M, Perachino M, Anderson RA, de Azambuja E, Poorvu PD, Kim HJ, Villarreal-Garza C, Pistilli B, Vaz-Luis I, Saura C, Ruddy KJ, Franzoi MA, Sertoli C, Ceppi M, Azim HA Jr, Amant F, Demeestere I, Del Mastro L, Partridge AH, Pagani O, Peccatori FA. Pregnancy After Breast Cancer: A Systematic Review and Meta-Analysis. J Clin Oncol. 2021 Oct 10;39(29):3293-3305. doi: 10.1200/JCO.21.00535. Epub 2021 Jul 1.
Soo Youn Bae, Jihyoun Lee, Ji Sung Lee, Jae Sun Yoon, Ku Sang Kim, Yoo Seok Kim, Zisun Kim, Jun Won Min, Eun-Jung Shim, Ilkyun Lee, Min Hyuk Lee, Sungmin Park. Prognosis of pregnancy after breast cancer diagnosis according to the type of treatment: A population-based study in Korea by the SMARTSHIP group. Breast 2022 Jun; 63:46-53. doi: 10.1016/j.breast.2022.03.005. Epub 2022 Mar 11.
Group IBCS. Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer (POSITIVE) 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT02308085.
Orit Kaidar-Person, Rakefet Yoeli-Ullman, Nir Pillar, Shani Paluch-Shimon, Philip Poortmans, Yaacov R Lawrence. Obstetric complications at time of delivery amongst breast cancer survivors: A population-based cohort study. Breast 2022 Apr; 62:170-178. doi: 10.1016/j.breast.2022.02.008. Epub 2022 Feb 15.
Valentina D'Ambrosio, Flaminia Vena, Daniele Di Mascio, Ida Faralli, Lucia Musacchio, Chiara Boccherini, Roberto Brunelli, Maria Grazia Piccioni, Pierluigi Benedetti Panici, Antonella Giancotti. Obstetrical outcomes in women with history of breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 2019 Dec;178(3):485-492. doi: 10.1007/s10549-019-05408-4. Epub 2019 Aug 26.
