2.2. Study Procedures

Pregnant women with breast cancer were followed in the Breast cancer pregnancy unit that was composed by a Maternal–Fetal specialist, an Oncologist, and a Gynecologic surgeon. After the diagnosis of breast cancer and before and after CHT treatment, women have an exhaustive obstetrical and fetal evaluation that includes: blood pressure, weight, maternal wellbeing, and obstetric abdominal and vaginal ultrasound study using 6–4 MHz probes (Siemens Sonoline Antares, Siemens Medical, Erlangen, Germany). Estimated fetal weight, amniotic fluid index, and Doppler velocimetry; uterine artery pulsatility index (PI), umbilical artery PI and median cerebral artery PI, and maximum peak systolic velocity (Vmax MCA) were evaluated. Following obstetric evaluation, medical oncologist assesses whether potential toxicities derived from chemotherapy existed. Subsequently, if both evaluations (obstetrical and oncological) were correct, maternal blood was obtained and chemotherapy cycle was administered. The frequency of the blood tests was established by the chemotherapy schedule defined appropriately for each patient based on her tumor stage, patient’s characteristics, and weeks of pregnancy at the time of diagnosis. If there were concerns regarding maternal or fetal health, termination or delay of the chemotherapy were considered by the multidisciplinary team, or delivery was planned. If no specific concerns during treatment, delivery was planned and induced according to gestational age and CHT schedule to minimize any delay in maternal treatment. At the time of delivery, maternal and fetal cord blood was also obtained. Clinicians were blinded to angiogenic factors results.

Outcomes: Diagnostic criteria for preeclampsia were new onset of both hypertension (systolic blood pressure of 140 mmHg or above and/or diastolic blood pressure of 90 mmHg or above) and proteinuria (protein dipstick urinalysis result of 2+ or greater, or 300 mg protein per 24-h urine collection or greater, or protein in spot urine greater than or equal to 30 mg/dL, or protein/creatinine ratio greater than or equal to 30 mg/mmol) after 20 weeks’ gestation [17]. Suspicion of fetal anemia was defined if fetal Vmax MCA >1.55 MoM according to Mari et al. [18]. Fetal adverse outcomes were perinatal/fetal death, delivery before 34 weeks, intrauterine growth restriction, placental abruption, respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage.