Study: Impact of breast cancer and BRCA mutations on fertility preservation

Relevance: Medium

Strength of Science: Medium

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

The goal of this study was to see  if there were differences in the number of mature eggs collected among three groups of women:

• Those with stage 1, 2 or 3 breast cancer with a BRCA mutation
• Those with stage 1, 2 or 3 breast cancer with no known mutation
• Healthy women with a BRCA mutation

This study looked at the number of eggs within the ovaries—this is known as ovarian reserve. It also looked at the number of eggs collected after ovarian stimulation. These values were compared among the three groups listed above.

Note that when we say “women,” we refer to people assigned female at birth.

Why is this study important?

Treatment for young people with breast cancer may include chemotherapy. However, chemotherapy can impact future fertility since it is toxic to the ovaries, the location in the body that stores eggs and produces important hormones. Fertility preservation offers an option to delay childbearing and family planning during treatment. However, the data is mixed on how well people with breast cancer respond to fertility medications that help to increase the number of eggs released (ovarian stimulation).

Some studies suggest that women with a BRCA mutation have fewer healthy eggs than people without a mutation.  This is called decreased ovarian reserve. However, the data are limited and inconsistent.

Fertility preservation options

Fertility preservation is the process of saving or protecting eggs or embryos so the person can use them in the future. There are different options available, including:

• Ovarian stimulation can increase the number of eggs that mature during a menstrual cycle. Doctors can then collect the eggs during an outpatient procedure. These eggs can be frozen  or joined with sperm to make embryos and frozen for later use. Visit this page for a more detailed description.
• An ovary (or a portion of the ovary) can be removed and frozen while undergoing toxic treatments and transplanted back into the body when people are ready to get pregnant. This is called ovarian tissue freezing, ovarian tissue banking or ovarian tissue cryopreservation.
• Using a medication during chemotherapy to help shut down and protect the ovaries and increase the chances of pregnancy. This is typically achieved with drugs called gonadotropin-releasing hormone agonists.

The standard of care is currently egg/embryo freezing when a delay of at least 12 days before beginning treatment is considered safe. Importantly, it has been shown that this delay has not impacted outcomes.

Protective drugs can be used in people who are not interested in fertility preservation but might want to reduce the risk of losing ovarian function.

For more on fertility and cancer treatment, visit our website here.

Study findings

A total of 85 people between the ages of 18 and 41 underwent 100 treatment cycles. Treatment cycles were tailored to their individual needs. Data for the study was collected from October 2012 to November 2021.

• 75 (88%) people had breast cancer
  • 55 (65%) did not have a BRCA mutation (Group 1)
  • 20 (23%) had a BRCA mutation (Group 2)
• 10 (12%) people did not have breast cancer but did have a BRCA mutation (Group 3)
  • 8 had a BRCA1 mutation
  • 2 had a BRCA2 mutation
  • Of the 10 with a BRCA mutation, 3 had preimplantation genetic testing.

To achieve the study goal of determining the whether there are differences in the number of mature eggs collected, the researchers needed to compare the number of mature eggs collected after ovarian stimulation among the three study groups.

 A specific hormone known as Anti-Müllerian hormone (AMH) can provide insight into a person’s ovarian health and egg supply. AMH levels were also measured before and after ovarian stimulation; the levels were then compared among the three study groups.

Among participants:

• The number of mature eggs collected did not differ greatly between the groups.
• The percentage of eggs that fertilized—joined together with a sperm cell – was similar in all three groups. Fifteen percent of participants returned for an embryo transfer.  Some participants in each of the groups became pregnant, resulting in a total of 8 live births.
• AMH levels did not differ between the three groups, suggesting no difference in ovarian health and egg supply.

The following table highlights the results of the study based on the three groups:

Overall, the findings from this study suggest that breast cancer and BRCA mutation status did not affect the number of mature eggs collected for fertility preservation and preimplantation diagnosis. The rates of egg maturity and fertilization, which is necessary for pregnancy, also appeared to be similar across the three groups.  This suggests no difference in the quality of the eggs retrieved among the three groups.

Since this study had a small number of participants, the authors suggest that it should be repeated with more participants. This will lead to stronger, more reliable conclusions that can help confirm the findings of this study.  

Pregnancy after breast cancer: The POSITIVE trial

A related but different study known as the POSITIVE trial showed that pausing hormone therapy to pursue pregnancy does not increase the short-term risk of early-stage cancer recurrence. Read more in our XRAY review here.

In a second analysis of the POSITIVE trial data, the study team looked at fertility preservation using ovarian stimulation. They found that fertility preservation did not impact breast cancer outcomes.  They noted that pregnancy rates were higher among participants who underwent egg/embryo freezing.

What does this mean for me?

Breast cancer is the most common cancer diagnosed in premenopausal women. Balancing cancer treatment with family planning goals can be difficult.

If you are a young woman with breast cancer, with or without a BRCA mutation, and you are considering family planning alongside cancer treatment, you have options. It is important to speak with your doctors before undergoing breast cancer treatment to learn about your fertility preservation options.

If you have a BRCA mutation and have not been diagnosed with breast cancer, you also have fertility preservation options. More information about fertility and family planning issues can be found here.

Talking to a fertility specialist can help you evaluate the options that are best suited to your needs.

Reference

Prokurotaite, E., Condorelli, M., Dechene, et al. Impact of Breast Cancer and Germline BRCA Pathogenic Variants on Fertility Preservation in Young Women. Life. 2023; 13(4):930.

Azim, H. A., et al.  Fertility preservation and assisted reproduction in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy. Journal of Clinical Oncology. 2024; 42(28), 2822-2832.

FORCE blog: "Previvor Decisions: Choosing Prophylactic Mastectomy" is the personal story of one BRCA previvor navigating risk-reducing surgery and pregnancy.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 10/31/24