BackgroundFertility 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.MethodsThe 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.DiscussionThe 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 numberClinicalTrials.gov identifier: NCT02895165 (Retrospectively registered in August 2016).

CASE REPORTS Case 1In this case, the couple had been referred to our center for prenatal diagnosis because the mother was affected by Holt-Oram syndrome. Since the referral was in the second trimester, targeted ultrasound and fetal echocardiography were performed at the time of amniocentesis. The skeletal abnormality consisted of a bifid thumb, while an enlarged right atrium, not associated with tricuspid insufficiency, was detected on fetal echocardiography (Figure 1). The results of molecular analysis on amniocytes confirmed that the fetus was affected by Holt-Oram syndrome and the couple opted for termination of pregnancy. Case 2A pregnant woman was referred to our center at 22 weeks of gestation because of fetal ventricular disproportion and right atrial enlargement. In this case, on fetal echocardiography, a large foramen ovale flap and significant enlargement of the right atrium were noted (Figure 2a). Tricuspid regurgitation was also absent in this case. On follow-up echocardiography carried out at 28 gestational weeks, the right atrial enlargement was confirmed and, in addition, two tiny muscular ventricular septal defects were detected (Figures 2b and c). The pregnancy went to term and a female neonate weighing 3030 g was delivered by Cesarean section. The neonate was clinically stable, but on external examination a threephalangeal thumb was noted. Neonatal echocardiography confirmed both the right atrial enlargement and the two small muscular ventricular septal defects. The foramen ovale remained patent and follow-up echocardiography

In fetuses with tetralogy of Fallot, ductal diameter can be reduced even up to prenatal closure. Prenatal ductal morphology assessment may be useful for improving management of patients with moderate right ventricular outflow obstruction and small ductus arteriosus who may become cyanotic at birth.

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