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PURPOSE Young women with germline BRCA mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with BRCA mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations. PATIENTS AND METHODS This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline BRCA mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors. RESULTS Of 1,252 patients with germline BRCA mutations ( BRCA1, 811 patients; BRCA2, 430 patients; BRCA1/2, 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; P = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; P = .66) were observed between the pregnancy and nonpregnancy cohorts. CONCLUSION Pregnancy after breast cancer in patients with germline BRCA mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility.

e24057 Background: Female patients undergoing anticancer treatment are at elevated risk of ovarian damage including development of POI. AMH is a key serum biomarker of ovarian reserve. However, its role to identify risk of POI in cancer patients prior to and after treatment is less well understood. Methods: A systematic literature search for AMH in women with cancer was conducted up to 30 August 2020, with formal bias assessment. We aimed at evaluating AMH as a biomarker of ovarian reserve and POI before and after anticancer treatment. Exploratory subgroups were based on age, cancer type and length of follow-up. Results: : Eighty publications (including 7,708 patients) were included in this analysis. All papers reporting AMH before and after treatment reported a large reduction in AMH following treatment, in both adult and paediatric populations. Effect sizes varied depending on the treatment and diagnosis, but ranged from 42% to below the limit of detection, and many reported declines of ≥90%. A majority (25/34, 74%) of studies also reported at least partial recovery of AMH at follow-up. Pre-treatment AMH correlated with post-treatment levels in all studies and younger patient age with higher post-treatment AMH in 21/29 (72%) studies. In 18/32 (58%) publications, oligo/amenorrhea correlated with lower post-treatment AMH. No studies reported correlations between post-treatment AMH and pregnancy, although pregnancy was reported in some patients with low or undetectable AMH. 70% of publications found that within-study variations in treatment (estimated by chemotherapy or radiotherapy type, dosage, duration and/or number of cycles) correlated with AMH reductions and degree of recovery, indicating its potential value as a marker of gonadotoxicity. In women with breast cancer, recovery of AMH was reported in some patients in 10/18 publications; however, AMH levels showed no recovery in many patients receiving alkylating agents or cyclophosphamide-based chemotherapies. In lymphoma, patients receiving ABVD-based regimens had at least partial post-treatment recovery of AMH at follow-up compared with those receiving cyclophosphamide-containing regimens. 16/20 (80%) publications in pediatric cancer patients showed significant reductions in AMH compared with pre-treatment levels or controls. The diagnostic value of post-treatment AMH for POI was supported in 5/5 (100%) studies. AMH levels measured 1–2 years after treatment appeared to be equally reliable at indicating longer-term menstrual outcomes as studies with longer followup. Conclusions: AMH levels were strongly impacted by anticancer treatment, with recovery in some women determined by treatment regimen, age, and pretreatment AMH level. There was evidence for its role in diagnosis of POI, nut further studies are required to clarify its value to assist in patient management.

We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up., SCOPUS: ar.j, info:eu-repo/semantics/published

5572 Background: The PARPi Olaparib has been approved in maintenance setting of recurrent platinum-sensitive and BRCA mutated, ovarian cancer (OC) patients. However, according to the striking results of SOLO 1 trial, it could be shortly proposed even to newly diagnosed BRCA mutated OC women. We report the results of the implementation of tumor BRCA test in diagnostic setting within the frame of institutional workflow for the management of OC patients. Methods: 223 women with OC were consecutively referred over 25 months to tumor BRCA test. The test was requested by gynecologic oncologist at the diagnosis of non-mucinous and non-borderline OC, upon discussion on the implications of the test result and written consent collected for each patient. Formalin-fixed paraffin embedded (FFPE) specimens of OC were tested using the automatized “Oncomine BRCA Research Assay” Next Generation Sequencing (NGS) panel. The tumor BRCA test was also performed on 5 archetypal cytological samples from ascites. Results: All the cases were considered adequate for the NGS analysis according to the tumor cell content (more than 10%) and the DNA yield extracted (more than 10 ng). The tumor BRCA test had a successful rate of 99.1% . The median Turn-Around Time (TAT) was 17 calendar days, from 33 days of the first trimester to 14 days of the last trimester of this analysis. Overall BRCA1 or BRCA2 pathogenic (P)/likely pathogenic (LP) mutations were found in 62 (28.1%) cases and variants of uncertain significance (VUS) in 25 (11.3%) cases, including 3 cases with a BRCA1 P variant and a concurrent BRCA2 VUS alteration. In detail, 47 P/LP variants and 16 VUS were identified in BRCA1 whereas 15 P/LP mutations and 9 VUS occurred in BRCA2. Complete concordance in tumor BRCA test results were seen between ascites cytological samples and matched tumors. Conclusions: The tumor BRCA test could be implemented in routine diagnostic setting, at diagnosis of non-mucinous and non-borderline OC. The test could be performed on FFPE specimens, had an high successful rate and a TAT compatible with clinical needs. The promising data on cytological samples will be confirmed in larger series.

552Background: A randomized, controlled clinical trial is the optimal method to evaluate the effect of an experimental therapy. However a single arm trial can be used when randomization is infeasib...

e13097Background: Several studies have addressed gestational and neonatal outcomes of chemotherapy during pregnancy (CDP) and demonstrated increased complications as pre-eclampsia and intrauterine ...

TPS596Background: Retrospective evidence suggests that pregnancy after BC does not negatively impact disease outcomes in pts with ER+ BC and is safe for the offspring. Young BC pts are often diagno...

Purpose To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor–negative or stage III tumor with five or more positive axillary nodes. Patients and Methods Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2 plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). Results After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor–positive tumors benefited significantly from DI-EC. Conclusion There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.

LBA10066 Background: Physicians and pts remain concerned on the safety of pregnancy following BC, particularly in women with history of ER+ disease. Previously, we showed no detrimental effect of pregnancy on BC outcome within the first 5 years following conception (Azim et al. JCO 2013). Here, we report long-term follow-up data. Methods: In this multicenter retrospective study, pts with pregnancy after BC (pregnant cohort) were matched (1:3) according to tumor and treatment characteristics with pts without subsequent pregnancy (non-pregnant cohort). To adjust for guaranteed time bias, each non-pregnant pt should have been disease free for a minimum time not inferior to the time elapsing between BC diagnosis and conception in the matched pregnant one. Primary endpoint was disease-free survival (DFS) in pts with ER+ BC. Secondary endpoints were DFS and overall survival (OS) in ER-negative and all pts irrespective of ER status. We also evaluated the impact of induced abortion on BC outcome. Results: The study included 1,207 pts, 333 pregnant and 874 non-pregnant. A total of 57% of pts had ER+ BC. After 12.5 years from conception, no DFS difference was observed between pregnant and non-pregnant pts with ER+ BC (hazard ratio [HR] 0.94; 95% confidence intervals [CI] 0.70-1.26; p = 0.68), ER- BC (HR 0.75; 95% CI 0.53-1.06; p = 0.10), and all pts (HR 0.85; 95% CI 0.68-1.06; p = 0.15). There was no OS difference between the 2 cohorts in pts with ER+ BC (HR 0.84; 95% CI 0.60-1.18; p = 0.32), but a significant improved OS was observed in the pregnant cohort for ER- pts (HR 0.57; 95% CI 0.36-0.90; p = 0.01) yielding a significant overall estimate (HR 0.72; 95% CI 0.55-0.94; p = 0.02). Abortion did not have any impact on outcome (HR 0.80; 95% CI 0.56-1.13; p = 0.20), irrespective of ER status. Conclusions: This is the largest study addressing the safety of pregnancy in pts with history of ER+ BC. Long-term follow-up confirms that pregnancy is safe and should not be discouraged irrespective of ER status. Our results further strengthen the rationale of the ongoing IBCSG-BIG-NABCG POSITIVE trial (NCT02308085) addressing the role of temporary interruption of adjuvant endocrine therapy to allow pregnancy.

TO THEEDITOR:Van Calsteren et al 1 recently reported a retrospective analysis of 215 patients with cancer who were diagnosed and managed during the course of pregnancy. They showed that managing patients with cancer during pregnancy is feasible and is not associated with an increased risk of fetal malformations. However,theauthorsstatedtheirconcernsregardingthehighincidence of preterm deliveries, which reached 54.2% in their series. They emphasized that preterm delivery is associated with high risk of medicalcomplications,whichcouldhaveseriousconsequenceson fetal morbidity and mortality. In an attempt to reduce this risk, they proposed delaying adjuvant therapy for patients with early breast cancer until fetal maturity, even if this would entail holding therapy up to 3 months. They referred to a mathematical model suggesting that delaying adjuvant therapy in gestational breast cancer could be an acceptable approach. 2 They also suggested that if chemotherapy is considered, delivery should be delayed until fetal maturity rather than fetal viability. We completely agree with the second proposition provided the proper selection of the agents administered during the course of gestation. Nevertheless, although we acknowledge that delaying adjuvant therapy for patients with breast cancer is reasonable in some cases, it remains questionable for many others as a result of the typically aggressive biology of gestational breast cancer. It has been shown that almost 50% of patients with breast cancer diagnosed during pregnancy are diagnosed with locally advanced, node-positivedisease. 3 Furthermore,delayingadjuvantchemotherapy beyond 3 weeks from surgery was shown to be detrimental in patients with endocrine unresponsive tumors. 4 Thus, chemotherapy should not be delayed in pregnant patients with breast cancer whoneedit.Theexceptionwouldbeforpatientsdiagnosedduring the first trimester, in which the incidence of fetal malformation is as high as 20%. 5 Of 83 patients diagnosed with gestational breast cancer, only six infants (7%) had a birth weight below the 10th percentile for gestational age. Other studies showed similar results as well. 6,7 Hence,itisnotclearthatpatientswithearlybreastcancerarethose at significant risk of preterm delivery if exposed to chemotherapy during the pregnancy course. We believe it is hard to generalize conclusions and caution should be taken when dealing with less aggressive settings (eg, adjuvant breast cancer), in which we could compromise their treatment for fear of a risk, which seems to be low anyway in their case. We have recently conducted a systematic review of literature on theuseofdifferentsystemictherapiesinthetreatmentofpatientswith

589 Background: Given the rising trend of delaying pregnancy to later in life, more women are diagnosed with breast cancer during pregnancy. Management is still controversial and relies on expert guidelines. Thus the experience of single centres with high patients’ volume remains of interest. Methods: All breast cancer patients (pts) diagnosed at the European Institute of Oncology (IEO) in Milan were included in a specific registry since 1995. Results: Out of 8340 patients < 47 y/o registered up to Dec 2012, 167 were diagnosed during pregnancy (2%). Median age was 36 years (24-47y). Median gestational age was 18 weeks (1-38 w). 73 % pts had a pT1-2 tumor, with positive nodes in 48%. 9,6% had luminal A, 38% luminal B, 26% basal like and 16% HER2+ tumors, according to St Gallen criteria. 29/167 pts (17%) opted for an induced abortion. Of the remaining 97 pts, 81 (84%) underwent definitive surgery during pregnancy; 58 (72%) and 23 pts (28%) had quadrantectomy and mastectomy, respectively. Immediate breast reconstruction was performed in 13 cases. Sentinel node procedure (SLN) was performed in 42 pts (52%), with positive axilla in 10 pts. 41 pts (51%) received chemotherapy during pregnancy. Regimens included weekly epirubicin (24 pts), EC/AC (12 pts), FAC/FEC (3 pts), q21 epirubicin (2 pts). No G3-G4 toxicities were reported. No pregnancy complications were observed, with the exception of 1 case of premature delivery at 28 weeks. Median gestational age at delivery was 36 weeks (29-40 w). No major malformations were observed. Gestational age at birth and birth-weight were similar in babies who received chemotherapy in-utero (36 w and 2555g) and in babies who did not receive gestational chemotherapy (37w and 2600g). At a median follow-up of 42 months (range: 1-178 m), all children had normal neurological and physical development with no late adverse effects observed. Conclusions: Managing breast cancer during pregnancy should follow standard practice as in non-pregnant pts. Surgeries like SLN and breast reconstruction were performed with no serious complications. Our results further emphasize the safety of anthracycline-based gestational chemotherapy without major effects on pregnancy course or fetal health.

e19520 Background: The role of FDG-PET for staging and response assessment in Hodgkin lymphoma (HL) is still evolving. We report our experience with the intent of evaluate prognostic role of 18FDG-PET in terms of long term complete remission (CR). Methods: We retrospectively analysed 65 consecutive pts affected by newly diagnosed HL. Median age was 36 yrs. Histology included 50 classical and 10 lymphocyte predominance HL. According to Hasenclever index, 58 out of 65 pts were considered at low risk, 5 at intermediate and 2 at high risk. 30/65 pts showed good prognosis (defined as IA-IIA, < 3 nodal sites, ERS < 50) and received 4 cycles of VBM followed by involved field (IF) radiotherapy (RT); the remaining 35 pts received hybrid ChlVPP/ABVVP for 6 cycles followed by IF RT in case of bulky disease. All patients underwent 18FDG-PET scans at diagnosis, after the fourth cycle in the VBM group, after the third cycle in the ChlVPP/ABVVP (interim 18FDG-PET), at the end of treatment in all patients. Fisher exact test was used to compare percentages between groups. Results: CR was recorded in 60 (92%) pts. Interim 18FDG-PET was negative in 52 out of 65 pts (80%), all in CR at the end of treatment. Eight out of 13 pts with positive interim 18FDG-PET obtained a CR at the end of treatment (100% versus 62%, Fisher exact text p18FDG-PET was negative in 5 of them, positive in 1 case. Two deaths occurred, one among pts with negative and one with positive interim 18FDG-PET. After a median follow-up of 30 months, 3-year freedom from treatment failure was 83% and 62% in pts with negative and positive interim 18FDG-PET, respectively (Log-rank test p18FDG-PET demonstrate a predictive role regarding the achievement of CR and treatment failure, at least as relevant as Hasenclever index, but failed to predict clinical result in 12 (18%) pts. Its role in defining the best therapeutical approach in HL pts must be further investigated in randomized clinical trials. No significant financial relationships to disclose.

6699 Background: Pegfilgrastim (PEG) is a new growth factor able to stimulate granulocyte production with a single injection. Basing on a biomathematical model showing a relationship between PEG se...

9596 Background: We investigated the incidence and prognostic relevance of tumor cell detection (TCD) in G-CSF-mobilized peripheral blood progenitor cells collections (PBPCC), using Cytokeratyn (CK...