“Fertility Studies in Young Women with Breast Cancer”
by Dr. Ellen Warner, MD, M.Sc., FRCPC, FACP
For many years there has been a gap in research focusing on breast cancer patients who are aged 40 and younger. Since these women represent just over 5% of all breast cancer cases, they have generally constituted a very small subset of the patients enrolled in clinical trials, which has made it difficult to make progress in addressing the very unique medical and psychosocial issues of this population. A recent Canadian study called RUBY (Reducing the bUrden of Breast cancer in Young women), http://www.womensresearch.ca/ruby-study, jointly funded by the Canadian Breast Cancer Foundation and Canadian Institutes of Health Research, is attempting to change this situation. Over 4 years, 1200 women aged 40 and younger newly diagnosed with breast cancer at 32 cancer centres and hospitals across Canada will be enrolling in RUBY. Almost 200 women have enrolled to date and recruitment is well on target to be completed in 2019. The overall goal of this study is to improve the cure rate and quality of life of young women with breast cancer. RUBY has several sub-studies, two of which, SPOKE and GYPSY, relate to fertility issues.
Breast Cancer and Fertility
Most young women with breast cancer require chemotherapy before or after their breast surgery to destroy any breast cancer cells that may have already spread to other parts of the body. This chemotherapy, particularly the drug cyclophosphamide, permanently damages the ovaries. The result is that many women who have not completed their families at the time of their breast cancer diagnosis will be infertile after receiving chemotherapy or will be fertile for fewer years than other women their age. Fortunately, there are several fertility preservation procedures that can be done before chemotherapy is started, which will give most of these women a high chance of having a successful pregnancy in the future. These procedures generally consist of stimulating the ovaries with a short course of hormones, ‘harvesting’ eggs through the vagina, and freezing the eggs either before (if the woman doesn’t have a male partner) or after fertilization (embryo freezing). These procedures take less than 3 weeks and to date have not been shown to increase the risk of breast cancer recurrence.
About 80% of young breast cancer patients will require hormonal therapy instead of or in addition to chemotherapy. While hormonal therapy doesn’t damage ovaries, many women wish to receive two or more years of hormonal therapy before attempting pregnancy. During this time fertility declines (as it does with time in all women) and pregnancy may no longer be possible when the woman is ready to get pregnant.
It is now recommended that all newly diagnosed breast cancer patients who have not yet completed their families be referred to a fertility clinic, as soon as possible after being told their diagnosis, to discuss their fertility preservation options. Early referral gives the woman/couple more time to make complex social and financial decisions, avoids or minimizes chemotherapy delay, and allows time for an additional cycle of ovarian stimulation if the results are not optimal the first time. The ideal health care professional to make this referral is the breast surgeon (or a member of the surgical team) since the surgeon is usually the first specialist to see these women. However, studies in Canada and elsewhere show that most surgeons do not make these referrals and many women lose the opportunity for fertility preservation. This is tragic as studies show that young breast cancer survivors consider fertility to be the most important breast-cancer related issue after fear of recurrence.
Our SPOKE study (Surgeon and Patient Oncofertility Knowledge Enhancement) aims to educate Canadian breast surgeons about the importance of early fertility preservation referral and, using a variety of strategies, help remove any barriers to these referrals. Our goal is to ensure that every young breast cancer patient will be informed by someone from her surgical team about the potential impact of her treatment on her future fertility, and that a fertility preservation referral will be offered to any woman who has not definitely completed her family. We will be able to measure our success by comparing rates of fertility discussion and referral at the beginning and end of the 4 year RUBY enrollment period. Results of our baseline survey of the knowledge, attitudes and practices of Canadian breast surgeons about breast cancer and fertility have been presented at several major fertility and oncology conferences in Canada, the USA, and UK, and recently published in the journal Annals of Surgical Oncology. http://www.ncbi.nlm.nih.gov/pubmed/27431414
Since fertility preservation can be inconvenient, expensive (over $10,000 in many provinces) and emotionally difficult (‘Is my relationship with my partner stable enough that I’m comfortable freezing embryos or do I want to freeze my unfertilized eggs in case I have a new partner in the future?’), it would be extremely helpful to be able to know which women may not need fertility preservation because they are expected to remain fertile for many years after their chemotherapy is completed. We know that this is much more likely for younger women but right now we don’t know enough to be able to predict that a woman of any age is likely to retain her fertility. This is the goal of GYPSY (Giving Young women with breast cancer Predictors of Sterility after chemotherapY). We will try to see whether we can use a woman’s age, measures of her fertility before getting chemotherapy (including a blood test called AMH or antimullerian hormone), chemotherapy received, hormone therapy, and other factors, to create a nomogram to predict the likelihood of a newly diagnosed young breast cancer patient remaining fertile for at least 5 or 10 years after receiving her cancer treatment.
Because women today tend to delay starting their families, most young women have not completed their families at the time of a breast cancer diagnosis. Our SPOKE study aims to ensure that each one of these women has the opportunity to at least consider fertility preservation before starting chemotherapy or hormonal therapy. Even a brief fertility discussion gives these women a powerful message of hope for a normal, cancer-free life in the future. Our GYPSY study will enable women, along with their health care team, to make more informed decisions about fertility preservation.
Dr. Warner is a medical oncologist and Professor of Medicine at the University of Toronto who has been at the Sunnybrook Odette Cancer Centre since 1993, where her practice and research have been devoted to breast cancer. In 1994, she created a program for hereditary breast and ovarian cancer patients, which introduced genetic counseling and testing to the Odette Cancer Centre. Since 1997, she has led a study to explore the role of magnetic resonance imaging (MRI) in screening women with an inherited predisposition to develop breast cancer which has helped make annual MRI surveillance the standard of care for this very high risk population.
Dr. Warner is also the creator and director of PYNK: Breast Cancer Program for Young Women, an interdisciplinary clinical and research program for young breast cancer patients which was officially launched at Sunnybrook in 2008. This program, the only one of its kind in Canada, addresses the special medical and psychosocial needs of this population and has a major focus related research and knowledge transfer. Dr. Warner is a co-investigator of RUBY, a Canada-wide research program focusing on newly diagnosed breast cancer patients aged 40 and younger, and principal investigator of the RUBY fertility sub studies.