Preserving Fertility in BRCA-Positive Breast Cancer

Matteo Lambertini, MD

As part of our coverage of the European Society for Medical Oncology (ESMO) 2017 Congress, held in Madrid, we are speaking with Matteo Lambertini, MD, a medical oncologist and ESMO fellow at the Institut Jules Bordet in Brussels, who specializes in the care of women with breast cancer. At a session on novel supportive and palliative care research results, Dr. Lambertini discussed a study on fertility-preserving procedures for women with BRCA-positive breast cancers (abstract 1541O_PR).

-Interviewed by Anna Azvolinsky

Cancer Network: Dr. Lambertini, can you talk about the general issue of fertility preservation for women with breast cancer who are of child-bearing age? What do clinicians and patients have to keep in mind?

Dr. Lambertini: Breast cancer is the most frequent malignancy in women of reproductive age and thanks to the major advances in oncology practice that we have had over the past years, young women with breast cancer now have excellent survival. So, maintenance of good long-term quality of life represents a crucial goal to be accomplished when managing these patients. We know that in premenopausal patients, anticancer treatment can be associated with the added burden of potential premature ovarian failure and subsequent infertility. The concern related to the possible loss of fertility can add significant anxiety and emotional strain during treatment decision making for these patients. As indicated by young women and advocates, fertility preservation is, in fact, a priority and concern for these patients. Therefore, as recommended by major guidelines, onco-fertility counseling to discuss the risk of premature ovarian failure and available fertility preservation options should be considered standard of care in all newly diagnosed breast cancer patients.

Cancer Network: Are BRCA-positive patients unique in any sense? Are there specific considerations for those BRCA-positive patients who would like to undergo fertility preservation?

Dr. Lambertini: Up to 10% of the cases of breast cancer diagnosed in young patients is related to a hereditary condition and, in most of the cases, this is caused by the presence of a germline mutation in the BRCA genes, BRCA1 and BRCA2. We know that patients that carry a deleterious BRCA mutation have an increased lifetime risk of developing breast cancer and other forms of cancer, but preclinical data also suggest that the presence of a BRCA mutation can be associated with impaired ovarian function, meaning that these patients may have an increased risk of fertility-related problems and increased ovarian aging. If these women develop a cancer-for example, breast cancer-during their reproductive years, and they require the use of anticancer treatment, this treatment can further negatively impact their ovarian function and fertility. Moreover, we have to consider that in BRCA-mutated patients, the significant risk of developing ovarian cancer makes them candidates to receive prophylactic gynecologic surgery at a young age, before the age of 40. This can narrow the fertility of these women.

Cancer Network: Your study assessed various fertility-preserving procedures for these patients. Can you talk about which ones you and your colleagues studied and what you found with respect to later reproductive potential after cancer treatment?

Dr. Lambertini: As mentioned, there are strong and rational preclinical data suggesting the possible negative impact of carrying a BRCA mutation on fertility potential. However, there is very little data on the reproductive potential and performance with respect to fertility-preserving procedures in this specific subgroup of women. To acquire more insights into this unmet medical issue, we conducted the present study that we presented at ESMO to evaluate the reproductive potential and performance of cryopreservation procedures in BRCA-mutated breast cancer patients.

This was a retrospective analysis of two prospective studies investigating oocyte cryopreservation in one study, and ovarian tissue cryopreservation in the other, in newly diagnosed breast cancer patients. To evaluate baseline ovarian reserve, we used the anti-Müllerian hormone levels, which is considered the best marker for ovarian reserve, and measured these levels before the start of cryopreservation strategies. We then compared oocyte cryopreservation and ovarian tissue cryopreservation between patients with breast cancer with or without a germline BRCA mutation. This study included 101 patients, of whom 29 were BRCA-mutated and 72 had no mutation. The main take-home message from this study is that fertility-preserving procedures in BRCA-mutated breast cancer patients are feasible: both oocyte and ovarian tissue cryopreservation are feasible in patients carrying a germline BRCA mutation. We also reported on a live birth in a patient with a BRCA2 mutation who underwent ovarian tissue transplantation at the end of treatment. However, despite showing the feasibility of these procedures, we observed a consistent trend for a reduced reproductive potential and performance for both cryopreservation procedures in BRCA-mutated breast cancer patients as compared with patients without a BRCA mutation.

Cancer Network: What questions does this study raise? Are you currently addressing these with newer studies or do you plan to start a new study in the near future?

Dr. Lambertini: Our study showed that young women with BRCA-mutated breast cancer may have a reduced reproductive potential, and fertility preservation procedures may be characterized as having a lower performance in this setting, in line with the preclinical data available. Although no solid conclusion can be drawn from our study because of the small numbers of patients, it does raise awareness about the possible need for personalized approaches for young women with BRCA-mutated breast cancer who are having fertility-preserving procedures before starting anticancer treatment. We believe that our study suggests the need for further larger reproduction studies to improve the onco-fertility counseling and the success of available fertility preservation options in this patient subgroup.

Cancer Network: Thank you so much for joining us today, Dr. Lambertini.

Dr. Lambertini: Thank you very much.