Blog Post October 30, 2018

Can we do a better job of preserving fertility and ovarian function for young breast cancer survivors? [and how genomic research can help]

Young women with a new cancer diagnosis are faced with a number of challenges. These patients (and their providers) are often anxious to begin treatment right away. The problem is that many young women haven’t started or completed their families at the time of their diagnosis. It turns out that discussing options for fertility preservation with a specialist has been shown to be an important factor contributing to a woman’s quality of life during and after her cancer journey.

The role of genomics in preserving fertility

There is promise in current research. Genomic and fertility researchers are searching for targets for new treatments that, when given along with chemotherapy or radiation, will protect ovarian function and fertility. Increasing our understanding of the biological pathways damaged or disrupted by radiation and chemotherapy will lead to new drug development that will be protective of these pathways. Radiation and some chemotherapies, including cyclophosphamides and platinum-based therapies, among others damage ovaries in different ways, such as inducing DNA damage, creating vascular interference, or inappropriately activating primordial follicles. The end result is the same – loss of ovarian reserve and premature ovarian failure. Providing a targeted adjuvant therapy that protects the dormant follicle pool may become the preferred strategy because of the dual benefit of fertility and ovarian function preservation.

Researchers are also involved in precision medicine efforts to help identify which women are at greatest risk of premature ovarian failure during treatment. Precision medicine has led to advancements in cancer care: somatic tumor testing for identifying targeted treatments in many types of cancer (see Exploring Somatic Cancer Panel Testing), and in breast cancer specifically, helping to identify when chemotherapy would be most beneficial (e.g. OncotypeDX® or MammaPrint®). Right now, only age and type of treatment can help predict the level of risk for premature ovarian failure and infertility. But what if the key to stratifying risk is in our genome? That is where JAX researcher Ewelina Bolcun-Filas, Ph.D., is looking for answers. She is searching for genetic risk and protective factors which could identify patients at risk and reveal pathways that protect others. Her group is also examining the role of the checkpoint kinase CHK2 in the survival of immature eggs exposed to radiation and chemotherapy. The research is showing promise for young women undergoing cancer treatment.

What you can do now to improve care

The American Society of Clinical Oncologists (ACSO) guidelines on fertility preservation recommend that health care providers caring for adult and pediatric cancer patients address the possibility of infertility as early as possible, before treatment starts. Providers should refer patients who express an interest in fertility preservation (and those who are ambivalent) to reproductive specialists. Referral to counseling services with a specialty in fertility issues may also be recommended if the patient is experiencing significant stress.

A national, comprehensive resource is the Oncofertility Consortium, an interdisciplinary initiative that addresses the complex health care and quality-of-life issues that concern young cancer patients whose fertility may be threatened by their disease or its treatment. Local to the Jackson Laboratory for Genomic Medicine, the University of Connecticut’s Center for Advanced Reproductive Services is a member of the Consortium. Through collaborations with researchers, medical specialists in reproductive endocrinology and oncology have access to new and developing techniques in fertility preservation.

A helpful resource to facilitate these discussions is the validated “Pathways” decision aid. This tool outlines fertility preservation options and evidence-based guidance and interactive activities to support decision-making. When the provider-patient relationship is supported in this way, patient motivations are acknowledged, and reduced decisional conflict can optimize satisfaction with the overall treatment plan.

Studies of cancer survivors also provide insight into the most important issues to address around fertility. Survivorship care plans are routinely provided to patients, and include a summary of their treatments and what to expect going forward. Advocates are recommending including a discussion of any reproductive effects. Gorman, et al, developed a plan that was relevant for breast cancer survivors, including information to help them understand and assess their infertility risk, detailed evidence about safety of pregnancy after breast cancer, birth outcomes, and the impact of cancer, genetic status, and treatments on fertility. Women felt having this information would encourage them to initiate conversations with their providers about their hopes and concerns.

For women with known or suspected hereditary cancer conditions, such as BRCA1/2 carriers, reproductive decision making can be even more complicated. These women should be informed of the possible preconception, embryo and prenatal genetic testing options available to them and their families. Genetic counselors can help women access resources, understand their options, and facilitate decision-making around these complex issues.

So for women with a new cancer diagnosis, making space in the initial busy time between diagnosis and starting treatment for discussions about fertility preservation and protecting ovarian function will improve patients’ quality of life during and after treatment.

Do you want to learn more about the potential of genomics in cancer care? The Jackson Laboratory for Genomic Medicine, with generous funding from the Connecticut Breast Health Initiative, Inc., hosted a three-part educational series "Beyond Genetics: Genomics in Breast Cancer Diagnosis, Treatment, and Research." This series provided those touched by breast cancer information about the role of genomics to help them make informed decisions regarding their own, or a loved one's care. Learn more about Dr. Bolcun-Filas’ research by accessing her presentation in this series.