The PREgnancy and FERtility (PREFER) study: an Italian multicenter prospective cohort study on fertility preservation and pregnancy issues in young breast cancer patients

Matteo Lambertini, Paola Anserini, Valeria Fontana, Francesca Poggio, Giuseppina Iacono, Annalisa Abate, Alessia Levaggi, Loredana Miglietta, Claudia Bighin, Sara Giraudi, Alessia D'Alonzo, Eva Blondeaux, Davide Buffi, Francesco Campone, Domenico F Merlo, Lucia Del Mastro, Matteo Lambertini, Paola Anserini, Valeria Fontana, Francesca Poggio, Giuseppina Iacono, Annalisa Abate, Alessia Levaggi, Loredana Miglietta, Claudia Bighin, Sara Giraudi, Alessia D'Alonzo, Eva Blondeaux, Davide Buffi, Francesco Campone, Domenico F Merlo, Lucia Del Mastro

Abstract

Background: Fertility and pregnancy issues are of key importance for young breast cancer patients. Despite several advances in the field, there are still multiple unmet needs and barriers in discussing and dealing with these concerns. To address the significant challenges related to fertility and pregnancy issues, the PREgnancy and FERtility (PREFER) study was developed as a national comprehensive program aiming to optimize care and improve knowledge around these topics.

Methods: The PREFER study is a prospective cohort study conducted across several Italian institution affiliated with the Gruppo Italiano Mammella (GIM) group evaluating patterns of care and clinical outcomes of young breast cancer patients dealing with fertility and pregnancy issues. It is composed of two distinctive studies: PREFER-FERTILITY and PREFER-PREGNANCY. The PREFER-FERTILITY study is enrolling premenopausal patients aged 18-45 years, diagnosed with non-metastatic breast cancer, who are candidates to (neo)adjuvant chemotherapy and not previously exposed to anticancer therapies. The primary objective is to obtain and centralize data about patients' preferences and choices towards the available fertility preserving procedures. The success and safety of these strategies and the hormonal changes during chemotherapy and study follow-up are secondary objectives. The PREFER-PREGNANCY study is enrolling survivors achieving a pregnancy after prior history of breast cancer and patients diagnosed with pregnancy-associated breast cancer (PABC). The primary objectives are to obtain and centralize data about the management and clinical outcomes of these women. Patients' survival outcomes, and the fetal, obstetrical and paediatric care of their children are secondary objectives. For both studies, the initial planned recruitment period is 5 years and patients will remain in active follow-up for up to 15 years. The PREFER-FERTILITY study was first activated in November 2012, and the PREFER-PREGNANCY study in May 2013.

Discussion: The PREFER study is expected to support and improve oncofertility counseling in Italy, to explore the real need of fertility preserving procedures, and to acquire prospectively more robust data on the efficacy and safety of the available strategies for fertility preservation, on the management of breast cancer survivors achieving a pregnancy and of women with PABC (including the possible short- and long-term complications in their children).

Trial registration number: ClinicalTrials.gov identifier: NCT02895165 (Retrospectively registered in August 2016).

Keywords: Breast cancer; Fertility preservation; Pregnancy; Pregnancy-associated breast cancer; Young patients.

Figures

Fig. 1
Fig. 1
Suggested algorithm for physicians dealing with fertility issues. POF premature ovarian failure; LHRHa luteinizing hormone-releasing hormone analogs; CT chemotherapy
Fig. 2
Fig. 2
Suggested algorithm for the management of patients with breast cancer diagnosed during pregnancy

References

    1. National Cancer Institute - Surveillance, Epidemiology and End Results Program. . Accessed 7 May 2017.
    1. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104:386–405. doi: 10.1093/jnci/djr541.
    1. Rosenberg SM, Newman LA, Partridge AH. Breast cancer in young women: rare disease or public health problem? JAMA Oncol. 2015;1:877–878. doi: 10.1001/jamaoncol.2015.2112.
    1. Azim HA, Partridge AH. Biology of breast cancer in young women. Breast Cancer Res. 2014;16:427. doi: 10.1186/s13058-014-0427-5.
    1. Lambertini M, Pinto AC, Ameye L, Jongen L, Del Mastro L, Puglisi F, et al. The prognostic performance of adjuvant! Online and Nottingham prognostic index in young breast cancer patients. Br J Cancer. 2016;115:1471–1478. doi: 10.1038/bjc.2016.359.
    1. Poggio F, Levaggi A, Lambertini M. Chemotherapy-induced premature ovarian failure and its prevention in premenopausal breast cancer patients. Expert Rev Qual Life Cancer Care. 2016;1:5–7. doi: 10.1080/23809000.2016.1139458.
    1. Ruddy KJ, Gelber SI, Tamimi RM, Ginsburg ES, Schapira L, Come SE, et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol. 2014;32:1151–1156. doi: 10.1200/JCO.2013.52.8877.
    1. Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2500–2510. doi: 10.1200/JCO.2013.49.2678.
    1. Peccatori FA, Azim HA Jr, Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi160–170.
    1. Paluch-Shimon S, Pagani O, Partridge AH, Bar-Meir E, Fallowfield L, Fenlon D, et al. Second international consensus guidelines for breast cancer in young women (BCY2) Breast. 2016;26:87–99. doi: 10.1016/j.breast.2015.12.010.
    1. Lambertini M, Goldrat O, Barragan-Carrillo R, Viglietti G, Demeestere I, Villarreal-Garza C. Viable options for fertility preservation in breast cancer patients: a focus on Latin America. Rev Investig Clin. 2017;69:103–113.
    1. Biglia N, Torrisi R, D’Alonzo M, Codacci Pisanelli G, Rota S, Peccatori FA. Attitudes on fertility issues in breast cancer patients: an Italian survey. Gynecol Endocrinol. 2015;31:458–464. doi: 10.3109/09513590.2014.1003293.
    1. Letourneau JM, Ebbel EE, Katz PP, Katz A, Ai WZ, Chien AJ, et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2012;118:1710–1717. doi: 10.1002/cncr.26459.
    1. Stensheim H, Cvancarova M, Møller B, Fosså SD. Pregnancy after adolescent and adult cancer: a population-based matched cohort study. Int J Cancer. 2011;129:1225–1236. doi: 10.1002/ijc.26045.
    1. Lambertini M, Del Mastro L, Pescio MC, Andersen CY, Azim HA, Peccatori FA, et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med. 2016;14:1.
    1. Smith LH, Dalrymple JL, Leiserowitz GS, Danielsen B, Gilbert WM. Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997. Am J Obstet Gynecol. 2001;184:1504–1513. doi: 10.1067/mob.2001.114867.
    1. Stensheim H, Møller B, van Dijk T, Fosså SD. Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a study-based cohort study. J Clin Oncol. 2009;27:45–51. doi: 10.1200/JCO.2008.17.4110.
    1. Andersson TM-L, Johansson ALV, Hsieh C-C, Cnattingius S, Lambe M. Increasing incidence of pregnancy-associated breast cancer in Sweden. Obstet Gynecol. 2009;114:568–572. doi: 10.1097/AOG.0b013e3181b19154.
    1. Lee YY, Roberts CL, Dobbins T, Stavrou E, Black K, Morris J, et al. Incidence and outcomes of pregnancy-associated cancer in Australia, 1994-2008: a population-based linkage study. BJOG. 2012;119:1572–1582. doi: 10.1111/j.1471-0528.2012.03475.x.
    1. Eibye S, Kjær SK, Mellemkjær L. Incidence of pregnancy-associated cancer in Denmark, 1977-2006. Obstet Gynecol. 2013;122:608–617. doi: 10.1097/AOG.0b013e3182a057a2.
    1. Merlo DF, Ceppi M, Filiberti R, Bocchini V, Znaor A, Gamulin M, et al. Breast cancer incidence trends in European women aged 20-39 years at diagnosis. Breast Cancer Res Treat. 2012;134:363–370. doi: 10.1007/s10549-012-2031-7.
    1. Loibl S, Schmidt A, Gentilini O, Kaufman B, Kuhl C, Denkert C, et al. Breast cancer diagnosed during pregnancy: adapting recent advances in breast cancer Care for Pregnant Patients. JAMA Oncol. 2015;1:1145–1153. doi: 10.1001/jamaoncol.2015.2413.
    1. Nilsen RM, Leoncini E, Gastaldi P, Allegri V, Agostino R, Faravelli F, et al. Prevalence and determinants of preconception folic acid use: an Italian multicenter survey. Ital J Pediatr. 2016;42:65. doi: 10.1186/s13052-016-0278-z.
    1. Pentheroudakis G, Pavlidis N. Cancer and pregnancy: poena magna, not anymore. Eur J Cancer. 2006;42:126–140. doi: 10.1016/j.ejca.2005.10.014.
    1. Loibl S, Han SN, von Minckwitz G, Bontenbal M, Ring A, Giermek J, et al. Treatment of breast cancer during pregnancy: an observational study. Lancet Oncol. 2012;13:887–896. doi: 10.1016/S1470-2045(12)70261-9.
    1. Amant F, Van Calsteren K, Halaska MJ, Gziri MM, Hui W, Lagae L, et al. Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: an observational study. Lancet Oncol. 2012;13:256–264. doi: 10.1016/S1470-2045(11)70363-1.
    1. Amant F, Vandenbroucke T, Verheecke M, Fumagalli M, Halaska MJ, Boere I, et al. Pediatric outcome after maternal cancer diagnosed during pregnancy. N Engl J Med. 2015;373:1824–1834. doi: 10.1056/NEJMoa1508913.
    1. Quinn GP, Vadaparampil ST, Gwede CK, Reinecke JD, Mason TM, Silva C. Developing a referral system for fertility preservation among patients with newly diagnosed cancer. J Natl Compr Cancer Netw. 2011;9:1219–1225. doi: 10.6004/jnccn.2011.0102.
    1. Kelvin JF, Reinecke J. Institutional approaches to implementing fertility preservation for cancer patients. Adv Exp Med Biol. 2012;732:165–173. doi: 10.1007/978-94-007-2492-1_13.
    1. Reinecke JD, Kelvin JF, Arvey SR, Quinn GP, Levine J, Beck LN, et al. Implementing a systematic approach to meeting patients’ cancer and fertility needs: a review of the fertile hope centers of excellence program. J Oncol Pract. 2012;8:303–308. doi: 10.1200/JOP.2011.000452.
    1. Partridge AH, Ruddy KJ, Kennedy J, Winer EP. Model program to improve care for a unique cancer population: young women with breast cancer. J Oncol Pract. 2012;8:e105–e110. doi: 10.1200/JOP.2011.000501.
    1. Clayman ML, Harper MM, Quinn GP, Reinecke J, Shah S. Oncofertility resources at NCI-designated comprehensive cancer centers. J Natl Compr Cancer Netw. 2013;11:1504–1509. doi: 10.6004/jnccn.2013.0177.
    1. Goossens J, Delbaere I, Van Lancker A, Beeckman D, Verhaeghe S, Van Hecke A. Cancer patients’ and professional caregivers’ needs, preferences and factors associated with receiving and providing fertility-related information: a mixed-methods systematic review. Int J Nurs Stud. 2014;51:300–319. doi: 10.1016/j.ijnurstu.2013.06.015.
    1. Kelvin JF, Thom B, Benedict C, Carter J, Corcoran S, Dickler MN, et al. Cancer and fertility program improves patient satisfaction with information received. J Clin Oncol. 2016;34:1780–1786. doi: 10.1200/JCO.2015.64.5168.
    1. Lambertini M, Anserini P, Levaggi A, Poggio F, Del Mastro L. Fertility counseling of young breast cancer patients. J Thorac Dis. 2013;5:S68–S80.
    1. Oktay K, Turan V, Bedoschi G, Pacheco FS, Moy F. Fertility preservation success subsequent to concurrent Aromatase inhibitor treatment and ovarian stimulation in women with breast cancer. J Clin Oncol. 2015;33:2424–2429. doi: 10.1200/JCO.2014.59.3723.
    1. Kim J, Turan V, Oktay K. Long-term safety of Letrozole and Gonadotropin stimulation for fertility preservation in women with breast cancer. J Clin Endocrinol Metab. 2016;101:1364–1371. doi: 10.1210/jc.2015-3878.
    1. Lambertini M, Pescio MC, Viglietti G, Goldrat O, Del Mastro L, Anserini P, et al. Methods of controlled ovarian stimulation for embryo/oocyte cryopreservation in breast cancer patients. Expert Rev Qual Life Cancer Care. 2017;2:47–59. doi: 10.1080/23809000.2017.1270760.
    1. Donnez J, Dolmans M-M, Pellicer A, Diaz-Garcia C, Ernst E, Macklon KT, et al. Fertility preservation for age-related fertility decline. Lancet. 2015;385:506–507. doi: 10.1016/S0140-6736(15)60198-2.
    1. Wallace WHB, Smith AG, Kelsey TW, Edgar AE, Anderson RA. Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation. Lancet Oncol. 2014;15:1129–1136. doi: 10.1016/S1470-2045(14)70334-1.
    1. Moore HCF, Unger JM, Phillips K-A, Boyle F, Hitre E, Porter D, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015;372:923–932. doi: 10.1056/NEJMoa1413204.
    1. Lambertini M, Boni L, Michelotti A, Gamucci T, Scotto T, Gori S, et al. Ovarian suppression with Triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial. JAMA. 2015;314:2632–2640. doi: 10.1001/jama.2015.17291.
    1. Lambertini M, Ceppi M, Poggio F, Peccatori FA, Azim HA, Ugolini D, et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies. Ann Oncol. 2015;26:2408–2419. doi: 10.1093/annonc/mdv335.01.
    1. Lambertini M, Cinquini M, Moschetti I, Peccatori FA, Anserini P, Valenzano Menada M, et al. Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology. Eur J Cancer. 2017;71:25–33. doi: 10.1016/j.ejca.2016.10.034.
    1. Azim HA, Jr, Kroman N, Paesmans M, Gelber S, Rotmensz N, Ameye L, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31:73–79. doi: 10.1200/JCO.2012.44.2285.
    1. Dalberg K, Eriksson J, Holmberg L. Birth outcome in women with previously treated breast cancer--a population-based cohort study from Sweden. PLoS Med. 2006;3:e336. doi: 10.1371/journal.pmed.0030336.
    1. Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ. 2007;334:194. doi: 10.1136/bmj.39035.667176.55.
    1. Pagani O, Ruggeri M, Manunta S, Saunders C, Peccatori F, Cardoso F, et al. Pregnancy after breast cancer: are young patients willing to participate in clinical studies? Breast. 2015;24:201–207. doi: 10.1016/j.breast.2015.01.005.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi