Oncologist and author of the new study presented at #ESMOBreast24
“More and more evidence has shown the safety of assisted reproductive technology, whether performed before or after cancer treatments”
Fertility, explained by the European Society of Medical Oncology (ESMO), is one of the main concerns of women who suffer from breast cancer at a young age, before having had children, because the treatment can stop the functioning of the ovaries. and trigger menopause. One way to preserve fertility is to freezing oocytes or embryos before starting breast cancer treatment.
Increasing estrogen hormone levels with the use of drugs to stimulate the ovaries to obtain eggs for fertility preservation techniques before starting breast cancer treatment could increase the risk of cancer recurrence in the future. In this context, This new study aimed to shed light on whether fertility treatments are safe or not in breast cancer patients. and, specifically, in those with pathogenic variants in the BRCA genes, which inhibit malignant tumors, cancer, in humans.
Assisted reproduction techniques (ART) in young women with high-risk genes who have survived breast cancer do not have an increased risk of cancer recurrence, nor negative consequences on pregnancies or babies born after the process, according to what is clear from the first global study presented last Thursday at ESMO Breast Cancer 2024.
After its presentation, Dr. Matteo Lambertini, associate professor and consultant of Medical Oncology at the University of Genoa and the IRCCS Policlinico San Martino Hospital in Genoa (Italy), explains, in an interview with OKSALUD, that “the results are very promising. and we have the first evidence that the use of fertility procedures is safe in young women with pathogenic or probably pathogenic alterations in the germline BRCA1 or BRCA2 genes. Dr. Lambertini is the principal investigator of this new study along with Dr. Ann Partridge, Professor of Medicine at Harvard Medical School and Vice President of Medical Oncology at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston (United States).
QUESTION.- Why did you decide to undertake this study?
ANSWER.- Fertility preservation and, in particular, controlled ovarian stimulation (CSO) for cryopreservation of oocytes and/or embryos before chemotherapy is the standard treatment for young women with breast cancer and planning incomplete family. Pregnancy after adequate treatment and follow-up does not appear to affect the prognosis of breast cancer, not even in patients with hormone receptor-positive disease or in carriers of pathogenic variants or probable pathogenic variants (VP) of BRCA1/2 in the germ line.
In recent years, increasing evidence has shown the safety of assisted reproductive technology (ART) performed before or after cancer treatments in patients with a history of breast cancer. However, evidence on the use and safety of ART in breast cancer patients carrying germline BRCA1/2 VP is very limited. Addressing the safety of ART is essential for all young patients who cannot conceive spontaneously after breast cancer treatment and who may need to resort to ART to achieve pregnancy.
For all these reasons, and taking into account that there are still many concerns among physicians about the safety of ART procedures, it is vitally important to understand the need for the use of ART in BRCA1/2 carriers and whether it can impact the cancer prognosis.
Q.- Indeed, until now it was a taboo topic to preserve fertility in the case of patients with pathogenic variants in the BRCA genes, due to their increased risk of breast cancer and other types of cancer…
A.- That’s right, as I mentioned in the previous answer. In fact, in the case of patients with breast cancer and BRCA PV, in addition to concerns (due to the breast neoplasia itself) of being exposed to hormonal manipulation for fertility techniques, there were other concerns related to their risk of developing other primary breast and non-breast malignancies.
For all these reasons, and taking into account that there are still many concerns among physicians about the safety of ART procedures, it is vitally important to understand the need for the use of ART in BRCA1/2 carriers and whether it can impact the cancer prognosis
Q.- What have been the methodological bases of the research and the time in which it was developed?
A.- Data from almost 5,000 women aged 40 or younger with pathogenic alterations in genes have been analyzed. BRCA1/2 diagnosed with breast cancer, in 78 cancer centers around the world between 2000 and 2020. The researchers compared the risk of breast cancer recurrence in 107 of these women who had a pregnancy through ART with 436 who conceived naturally.
Q.- And what have been the main results?
A.- The results showed no significant difference in breast cancer recurrence in women who underwent ART compared to those who had a baby without ART, after being followed for an average of just over 5 years after conception. The study also showed no statistically significant differences in pregnancy complications, although women who conceived with ART had more spontaneous abortions and fewer induced abortions than those who conceived naturally or in babies born to these women.
Q.- Can we conclude after this research that assisted reproduction is safe for young people with high-risk genes who overcome breast cancer?
A.- Yes. In terms of survival outcomes, antiretroviral therapy to achieve pregnancy appeared to be safe in young BRCA1/2 carriers with breast cancer with no signs of worsening maternal prognosis.
Q.- So, the use of products for the preservation of fertility (eggs or embryos) before undergoing breast cancer treatment or after overcoming it is safe for the mother. And for the baby?
A.- We have also shown that access to ART procedures can be considered safe for the baby. Specifically, we showed no differences in pregnancy outcomes between patients who conceived spontaneously or with the use of ART procedures.
However, a slightly higher incidence of spontaneous abortions was observed among patients in the ART group compared to patients who conceived spontaneously (11.3% vs. 8.8%, respectively). These results may reflect the significant difference in the median age at pregnancy in the two study groups (37.1 years in the ART group and 34.3 years in the non-ART group). Age is a powerful predictor of the spontaneous abortion rate, which could increase up to 20% with advanced maternal age. The opposite was observed in the case of induced abortion (0.9% versus 8.3%, respectively). Knowing the suboptimal use of contraceptive methods in young women with breast cancer, patients who conceive spontaneously could have experienced an unwanted pregnancy and then opted for an induced abortion.
Q.- Furthermore, the study’s conclusions suggest that women “may want to use ART for preimplantation genetic diagnosis in order to select embryos that do not carry the same risk genes to avoid transmitting a potential risk of cancer.” of hereditary breast to the next generation. Could it be a first step in the fight against breast cancer before conceiving?
A.- In our study, data on preimplantation genetic diagnosis (PGD) were not collected. However, in women interested in avoiding BRCA1/2 PV transmission, PGT-M should be offered. However, it is important to remember that being a BRCA1/2 PV carrier does not mean having cancer, but only a predisposition to the development of cancer. Therefore, for ethical reasons, we cannot and should not impose access to PGT-M for all patients.
Q.- What implications do the findings of this research have in clinical practice? The sample of women studied for this case does not seem to be too large, being a study carried out all over the world…
A.- Indeed, but this is not the case. We have brought together centers from around the world to collect data on young women under 40 years of age with pathogenic alterations in BRCA. Although the number of women in the study groups of this research may seem small, it must be taken into account that only 5-6% of all breast cancer cases occur in this single group of patients and, of them, about one in six have BRCA.