Lugano, Switzerland, 16 May 2024 – Assisted reproductive techniques (ART) in young women with high-risk genes who have survived breast cancer do not increase the risk of cancer recurrence or adversely affect the resulting pregnancies and babies, show results from a global study reported at ESMO Breast Cancer 2024 (1).
“This study provides the first evidence that use of fertility procedures is safe in young women with germline pathogenic/likely pathogenic variants in the BRCA1 or BRCA2 genes, which are known to increase the risks of developing breast and other cancers,” said Matteo Lambertini, Associate Professor and Consultant in Medical Oncology at the University of Genova, and IRCCS Policlinico San Martino Hospital, Genova, Italy, who will present the study. (2) “The results provide reassuring evidence for these women and their doctors to consider when discussing the risks and benefits of using ART to preserve their chances of having a baby following completion of anticancer therapies,” he suggests.
Fertility is a major concern for women developing breast cancer at a young age before they have had children, because treatment can stop the ovaries from working and trigger the menopause. One way a woman can preserve her fertility is to freeze oocytes (eggs) or embryos before starting breast cancer treatment. (3) These techniques generally involve use of fertility drugs to stimulate the ovaries to produce eggs, but this increases levels of the hormone oestrogen.
“We have previously been concerned that increasing hormone levels for fertility preservation techniques before starting breast cancer treatment may increase the risk of cancer recurrence in the future. There has been even more concern in women with pathogenic variants in the BRCA genes because of their increased risk of breast cancer and other cancers. And so strategies to preserve fertility were often not even discussed with these patients,” explained Lambertini. “This was the main rationale for our study: to provide the evidence on whether fertility treatments are safe in patients with breast cancer and, specifically in those with pathogenic variants in the BRCA genes, or not.” “In light of these results, now when we counsel a young woman with breast cancer who has such variants, we can safely discuss the use of fertility preservation before starting treatment, without major concern,” Lambertini added, proposing that these findings will have immediate implications for clinical practice.
The new study analysed data for nearly 5000 women with BRCA1/2 pathogenic variants who were diagnosed with breast cancer aged 40 years or younger at 78 cancer centres across the world between 2000 and 2020. Researchers compared the risk of breast cancer recurrence in 107 of these women who had a pregnancy using ART with 436 who conceived naturally. Results showed no significant difference in breast cancer recurrence in women undergoing ART compared to those having a baby without ART after following them up for an average of just over 5 years after conception. The study also showed no statically significant differences in pregnancy complications, although women conceiving with ART had more miscarriages and less induced abortions than those conceiving naturally, or on the babies born to these women.
“The main take-home message from this study is that there is no increased risk of breast cancer recurrence with assisted reproductive techniques in young women with BRCA pathogenic variants having a pregnancy after breast cancer. We also found that these procedures are safe for the baby: having a pregnancy with the use of fertility procedures does not increase the risk of complications,” said Lambertini. He acknowledged that the numbers of women in the study groups may appear small, but he pointed out that only 5-6% of all cases of breast cancer occur in young women under 40 and, of these, around one in six have BRCA pathogenic variants. (4) “We put together centres from all over the world to collect data on this unique group of patients,” he explained.
“These findings add really reassuring information for this subgroup of young breast cancer patients,” agreed Ann Partridge, Professor of Medicine at Harvard Medical School and Vice-Chair of Medical Oncology at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, USA, a co-author of the study. She added, “We always worry a little more about the patients with BRCA pathogenic variants, because not only do they have a risk of recurrence like all breast cancer patients, but they also have a higher risk of a new cancer not related to the original breast cancer.”
Dr. Partridge considered the study provides very useful information for doctors to discuss with young women with early breast cancer and a BRCA1/2 variants to help them make decisions about fertility treatments. “These new data provide reassuring evidence that pursuing fertility preservation before undergoing breast cancer treatment or using the products of fertility preservation (eggs or embryos) or undergoing fertility preservation after surviving breast cancer, all appear to be safe from a cancer standpoint and in terms of the baby’s outcome,” she said.
Dr. Partridge added that there is an additional reason why young women with BRCA1/2 breast cancer may want to use ART, in addition to overcoming infertility. “These women might want to use ART for pre-implantation genetic diagnosis to select embryos that do not carry the same risky genes to avoid passing on a potential risk of hereditary breast cancer to the next generation.”
Notes to Editors
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References
- Lambertini M, Magaton IM, Hamy-Petit A-S et al. Safety of assisted reproductive techniques in young BRCA carriers with a pregnancy after breast cancer: results from an international cohort study. Abstract 266O. ESMO Breast Cancer 2024.
- Proffered Paper session 2 - Thursday, 14 May 2024, 16:45 to 18:05 (CEST) in Berlin Hall.
- Lambertini M, Peccatori FA, Demeestere I, et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines†. Ann Oncol. 2020;31(12):1664-1678. doi: 10.1016/j.annonc.2020.09.006
- Copson ER, Maishman TC, Tapper WJ, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018;19(2):169-180. doi:10.1016/S1470-2045(17)30891-4
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. Blondeaux20
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.