Assisted Reproduction Treatments are Safe in Young Breast Cancer Survivors with High-risk Genes

M. Lambertini¹, I.M. Magaton², A-S. Hamy-Petit³, S. Linn⁴, R. Bernstein Molho⁵, F.A. Peccatori⁶, A. Ferrari⁷, E. Carrasco⁸, S. Paluch-Shimon⁹, E. Agostinetto¹⁰, M. Venturelli¹¹, I.V. Vaz Luis¹², K.R. Rodriguez-Wallberg¹³, H.J. Kim¹⁴, K. Sorouri¹⁵, M. Bruzzone¹⁶, I. Demeestere¹⁷, H. Azim¹⁸, A.H. Partridge¹⁹, E. Blondeaux^20
1Medical Oncology, University of Genova – IRCCS San Martino, Genova, Italy, ²Gynecology Endocrinology & Reproductive Medicine, Universitätsklinik für Frauenheilkunde – Inselspital Bern, Bern, Switzerland, ³Medical Oncology, Hopital René Huguenin – Institut Curie, Saint-Cloud, France, ⁴Medical Oncology Dept, NKI-AVL – Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands, ⁵Oncology Dept., Chaim Sheba Medical Center, Ramat Gan, Israel, ⁶Gynecologic Oncology Dept., IEO – Istituto Europeo di Oncologia IRCCS, Milan, Italy, ⁷Department of Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, ⁸Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain, ⁹Oncology, Hadassah University Hospital – Ein Kerem, Jerusalem, Israel, ¹⁰ATPT, Institute Jules Bordet, Brussels, Belgium, ¹¹Department of Oncology and Hematology, Azienda Ospedaliero – Universitaria Policlinico di Modena, Modena, Italy, ¹²Medical Oncology Department, Institut Gustave Roussy, Villejuif, Cedex, France, ¹³Oncology-Pathology Department, Karolinska Universitetssjukhuset Huddinge – Reproduktionsmedicin, Huddinge, Sweden, ¹⁴Surgery, Asan Medical Center – University of Ulsan, Seoul, Korea, Republic of, ¹⁵Medical Oncology, DFCI – Harvard Medical School, Boston, USA, ¹⁶Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy, ¹⁷Gynecology, ULB – Université Libre de Bruxelles, Brussels, Belgium, ¹⁸Medical, Emergence Therapeutics France SAS, Marseille, France, ¹⁹Medical Oncology, Dana Farber Cancer Institute, Boston, USA, ²⁰Epidemiology unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy

Background: Very limited evidence is available on the safety of assisted reproductive techniques (ART) in breast cancer (BC) patients harboring BRCA1/2 pathogenic variants (PVs). Hence, concerns remain among physicians counseling young BRCA carriers with BC on the safety of ART use.

Methods: This is an international, multicenter, hospital-based, retrospective cohort study including women harboring known BRCA1/2 PVs and diagnosed at ≤40 years with stage I-III BC between January 2000 and December 2020 (NCT03673306). This analysis explored safety of ART to achieve a pregnancy. Maternal and fetal outcomes were compared between patients achieving a pregnancy spontaneously (spontaneous pregnancy group) vs. using ART (ART group).

Results: Out of 4732 patients included across 78 centers worldwide, 543 with a pregnancy after BC entered the present analysis. Among them, 436 conceived naturally and 107 using ART. In the ART group, 45 (42.1%) underwent oocyte/embryo cryopreservation at BC diagnosis, 33 (30.8%) ovarian stimulation following use of anticancer therapies, 21 (19.6%) embryo transfer following oocyte donation and for 8 ART type was missing. As compared to the spontaneous pregnancy group, patients in the ART group were significantly older at the time of conception (37.1 vs. 34.3 years), had more often hormone receptor-positive BC (43.4% vs. 30.8%) and a longer median time from BC diagnosis to conception (4.2 vs. 3.3 years). No statistically significant differences in pregnancy complications were observed between cohorts (p=0.382). However, patients who conceived with ART had more miscarriages (11.3% vs. 8.8%) and less induced abortion (0.9% vs. 8.3%) than those who conceived spontaneously. At a median follow up of 9.1 years (IQR 6.4-13.4), no detrimental effect of ART on disease-free survival (DFS) was observed with 13 and 118 DFS events in the ART and spontaneous pregnancy groups, respectively (log-rank p=0.147; HR 0.64, 95% CI 0.36-1.14; adjusted HR 0.72, 95% CI 0.38-1.33).

Conclusions: This global study showed that ART to have a pregnancy appears to be safe in BC survivors harboring BRCA1/2 PVs, with no apparent worsening of maternal prognosis or fetal outcomes.

Clinical trial identification : NCT03673306

Editorial acknowledgement : Not applicable

Legal entity responsible for the study: Institut Jules Bordet

Funding: AIRC

Disclosure: M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead.
 S. Paluch-Shimon: Financial Interests, Institutional, Advisory Board, Advisory board, invited speaker, honoraria, travel: Roche; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Pfizer, Novartis, AstraZeneca; Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Exact sciences, Eli Lilly; Financial Interests, Institutional, Other, Advisory board, speaker’s bureau, consultancy: Medison; Financial Interests, Institutional, Advisory Board, Advisory board, speaker’s bureau: MSD; Financial Interests, Institutional, Advisory Board: Gilead; Financial Interests, Personal and Institutional, Research Grant, Research grant for an RFP independent research put out by SPCC and Pfizer: SPCC (Shared Progress in Cancer Care).
 I.V. Vaz Luis: Financial Interests, Institutional, Invited Speaker: Amgen, Pfizer/Edimark, Pfizer/Edimark, AstraZeneca; Financial Interests, Institutional, Advisory Board, Consulting/ AB: Novartis; Financial Interests, Institutional, Expert Testimony: Sandoz; Financial Interests, Personal, Other, Travelling: Novartis; Financial Interests, Institutional, Other, Research Funding: Resilience; Financial Interests, Institutional, Funding: Resilience; Non-Financial Interests, , Member, Member of WG: ASCO.
 H. Azim: Financial Interests, Personal, Other, Consultant: Diaccurate; Financial Interests, Personal, Invited Speaker: Astra Zeneca; Financial Interests, Personal, Full or part-time Employment, ended June 2022: PIERRE FABRE SANTE SA; Financial Interests, Personal, Full or part-time Employment, Biotech focused on R&D – no commercial activities Ended June 2021: Innate Pharma; Financial Interests, Personal, Officer, Biotech focused on R&D – no commercial activities: Emergence Therapeutics; Financial Interests, Personal, Stocks/Shares: Innate Pharma; Non-Financial Interests, , Member: American Society of Clinical Oncology.
 E. Blondeaux: Financial Interests, Institutional, Research Grant, Research grant to my Institution for a research project: Gilead Science.
 All other authors have declared no conflicts of interest.