Ayesha Munir, MBBS
Ami Chitalia, MD
Breast cancer is the most commonly diagnosed cancer in women of reproductive age. Approximately 10% of breast cancers are diagnosed in this age group.1 Young age at diagnosis is an adverse prognostic factor, and most young women will be offered chemotherapy and/or endocrine therapy, both of which have demonstrated a decrease in the risk of breast cancer recurrence and increased survival. However, most of these therapies damage ovarian function, thereby leading to infertility. Given that many young women who have been diagnosed with breast cancer desire future pregnancies, it is imperative that fertility preservation be addressed as early as possible and prior to commencing treatment.
In earlier studies that evaluated treatment preferences in young women, the majority of responders overwhelmingly stated they would prefer an alternative such as ovarian suppression to conventional chemotherapy for multiple reasons, including the risk of infertility.2 Many young women reported fertility as an important factor in making treatment decisions. These young women should thus be counseled about their fertility preservation options; this discussion should be initiated as early as possible, because some interventions require time and could delay the start of therapy. Ideally, all women of reproductive age with newly diagnosed breast cancer who have fertility concerns should meet with a reproductive endocrinologist.
Strategies for Preserving Fertility
Use of assisted reproductive technology—including cryopreservation of eggs, oocytes, spermatozoa, or ovarian tissue; egg donation; embryo donation; and gestational carrier—in patients with hormone receptor–positive cancers appears to be effective and safe.3 A study comparing reproductive outcomes in women with breast cancer showed that 22.8% of those who received fertility preservation had at least one live birth after breast cancer diagnosis, compared with 8.7% of women who did not receive fertility preservation.4 Previously, there had been concerns regarding hormone receptor–positive breast cancer recurrence with fertility preservation. Aromatase inhibitor–based stimulation protocols are now well established and may mitigate this concern.5
“Ideally, all women of reproductive age with newly diagnosed breast cancer who have fertility concerns should meet with a reproductive endocrinologist.”— Ayesha Munir, MBBS, and Ami Chitalia, MD
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Furthermore, menstruation cycle–independent stimulation protocols for oocyte collection now allow for more efficient fertility preservation. In some women, use of gonadotropin-releasing hormone (GnRH) agonists to suppress ovarian function during chemotherapy has been associated with resumption of ovarian hormone production after treatment completion.6,7 However, given the lower success rates compared with assisted reproductive technology, GnRH agonists are not recommended as a replacement for assisted reproductive technology and should be used only in women who decline assisted reproductive technology or who have issues such as a lack of access or time.3
In addition, primordial ovarian follicles do not possess GnRH receptors; therefore, it is difficult to conclude how much GnRH agonists can protect their function. It is important, however, to consider the long-term risks of bone loss and cardiovascular disease associated with premature ovarian failure. GnRH agonists may help to protect against these conditions, though conflicts in the data remain.
Study Limitations and Paucity of Data
A limitation of these studies is the use of unreliable surrogate outcomes for fertility.6,8 The best measure of fertility is live birth rate. The number of live births in these studies, however, is often small; therefore, statistical assessment is limited by sample size. Other markers associated with reproduction are also poor predictors of fertility. For example, resumption of menses is a poor predictor of fertility because women can have resumption of menses but still remain infertile. Another example is follicle-stimulating hormone levels, which fluctuate daily, vary across cycles, and cannot be compared unless they are measured on a particular day of the menstrual cycle.
“Early referral for fertility preservation counseling and assisted reproductive technology can have a significant impact on the quality of life of young women who have been diagnosed with breast cancer.”— Ayesha Munir, MBBS, and Ami Chitalia, MD
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There is a paucity of data on fertility preservation, especially follow-up studies assessing the long-term impacts of fertility preservation on survivors of cancer. Of note, chemotherapy regimens have not been compared with respect to fertility preservation outcomes. ASCO and the American Society for Reproductive Medicine have published recommendations on fertility preservation in patients with cancer that can be easily accessed.3,9
Early referral for fertility preservation counseling and assisted reproductive technology, if appropriate, can have a significant impact on the quality of life of young women who have been diagnosed with breast cancer. Oncologists should encourage their patients to participate in available registries and clinical trials that can help to further define the safety and efficacy of fertility preservation interventions.
DISCLOSURE: Dr. Munir reported no conflicts of interest. Dr. Chitalia has served as a consultant or advisor to ASCO.
Disclaimer: This commentary represents the views of the author and
may not necessarily reflect the views of ASCO or The ASCO Post.
1. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Female Breast Cancer. Available at https://seer.cancer.gov/statfacts/html/breast.html. Accessed March 25, 2021.
2. Fallowfield L, McGurk R, Dixon M: Same gain, less pain: Potential patient preferences for adjuvant treatment in premenopausal women with early breast cancer. Eur J Cancer 40:2403-2410, 2004.
3. Oktay K, Harvey BE, Partridge AH, et al: Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 36:1994-2001, 2018.
4. Marklund A, Lundberg FE, Eloranta S, et al: Reproductive outcomes after breast cancer in women with vs without fertility preservation. JAMA Oncol 7:86-91, 2021.
5. Azim AA, Costantini-Ferrando M, Oktay K: Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: A prospective controlled study. J Clin Oncol 26:2630-2635, 2008.
6. Moore HCF, Unger JM, Phillips KA, et al: Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 372:923-932, 2015.
7. Elgindy E, Sibai H, Abdelghani A, et al: Protecting ovaries during chemotherapy through gonad suppression: A systematic review and meta-analysis. Obstet Gynecol 126:187-195, 2015.
8. Sonmezer M, Oktay K: Overview of fertility and reproductive hormone preservation prior to gonadotoxic therapy or surgery. UpToDate. Updated December 6, 2020. Available at https://www.uptodate.com/contents/overview-of-fertility-and-reproductive-hormone-preservation-prior-to-gonadotoxic-therapy-or-surgery. Accessed March 25, 2021.
9. Practice Committee of the American Society for Reproductive Medicine: Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: A committee opinion. Fertil Steril 112:1022-1033, 2019.
Dr. Munir is a hematology and medical oncology fellow at Medstar Washington Hospital Center. Dr. Chitalia is Assistant Professor within the Division of Hematology and Medical Oncology at Medstar Washington Hospital Center, with a focus on the treatment of patients with breast cancer.