Ann H. Partridge, MD, MPH, FASCO
Lisa Campo-Engelstein, PhD
Kara N. Goldman, MD
“Cancer in young adults is more complicated in part [because of the risk of] infertility and premature menopause,” commented Ann H. Partridge, MD, MPH, FASCO, Interim Chair, Department of Medical Oncology; the Eric P. Winer, MD Chair in Breast Cancer Research, Dana-Farber Cancer Institute; and Professor, Harvard Medical School, Boston. Together with Lisa Campo-Engelstein, PhD, and Kara N. Goldman, MD, the expert panel discussed the importance of oncofertility in the delivery of high-quality cancer care at the U.S. Food and Drug Administration (FDA)-ASCO Virtual Workshop: Measuring Toxicity in Reproductive Organs During Oncology Drug Development.1 Dr. Campo-Engelstein is Director, Institute of Bioethics and Health Humanities Chair, and the Harris L. Kempner Chair in the Humanities in Medicine Professor at The University of Texas Medical Branch, Galveston. Dr. Goldman is Associate Professor of Obstetrics and Gynecology and Director of the Fertility Preservation program at Northwestern University Feinberg School of Medicine, Chicago.
Focus on Reproductive Justice
“Fertility has historically been seen as outside of medicine…, [and] as a personal moral failing…[that was] associated with the private realm and often conflated with women,” Dr. Campo-Engelstein remarked. “There is consensus among medical professionals that it is a medical condition…, [and] it is important to recognize it is something that happens to [both men and women].”
According to Dr. Campo-Engelstein, the World Health Organization broadly defines health as a state of complete physical, mental, and social well-being. Taken together with her observation that much of health care is focused on quality-of-life vs survival outcomes, she suggested the argument dismissing fertility care as a component of medicine cannot stand.
For some, pregnancy and starting a family are part of gender identity and contribute to self-actualization. Dr. Campo-Engelstein further noted that care for iatrogenic conditions is typically covered by insurance, such as in the case of gender-affirming breast reconstruction after mastectomy. For these reasons, she stated: “I want to claim that fertility care is gender-affirming care…[and that cancer-related anticipated infertility] should be treated like other iatrogenic conditions.”
“Reproductive justice is more than just the right to an abortion; it is the right to a whole range of appropriate activities, including having a child,” Dr. Campo-Engelstein remarked. “This is a social justice issue, and if we are committed to reproductive justice, we need to provide this to people like we do other types of care.”
Oncofertility Decisions Based on Data
“Clinical trial data are urgently needed to understand the gonadotoxic effects of anticancer therapies for two reasons,” Dr. Goldman commented. First, she emphasized that “giving patients the agency and information to make decisions [regarding fertility preservation] is critical, regardless of age, parity, or whether we think they may want to build a family.” Only after a referral to reproductive endocrinology, discussion of family-building goals, evaluation of ovarian function, and assessment of the risk of anticancer therapy can a patient make an informed decision to proceed.
The ASCO Fertility Preservation and Cancer policy brief highlights the medical necessity of fertility preservation in all patients undergoing cancer treatment and the importance of discussing such reproductive care as early as possible.2 Dr. Goldman compared the time-sensitive nature of fertility in the context of cancer to “pressing up against a completely immobile ceiling,” as the inevitable loss of ovarian reserve is sped up by radiation therapy and chemotherapy.
However, Dr. Goldman emphasized that the assessment of anticancer therapy–associated reproductive risks is based on insufficient data, which may lead patients to default to cryopreservation or fear the consequences if they’re unable to pursue such fertility care. “We know this impacts a patient’s comfort level in pursuing oncology care,” she added, highlighting the frequency of rejecting, shortening, or changing anticancer therapy in favor of preserving long-term fertility.
The second reason for the necessity of such clinical trial data is to assess the impact of anticancer treatment on the ovaries, ultimately aiming to protect long-term ovarian endocrine function, according to Dr. Goldman. “If we can uncover mechanisms of iatrogenic ovarian injury, this would help guide protective strategies that would protect not just fertility but ovarian function,” she stated.
Dr. Goldman and her team investigated mTOR inhibition as one of these protective strategies. “[We] found that co-treatment with cyclophosphamide resulted in normalization of primordial follicle counts, antimüllerian hormone, and litter size [in mice],” she remarked.
The future presents an opportunity for a paradigm shift in protecting ovarian function, Dr. Goldman concluded. She advocated for the consideration of offering a fertoprotective agent alongside fertility preservation and intervention.
Pregnancy After Cancer: Is It Safe and Feasible?
“[Cancer] is not easy for most people, but it is even harder for our youngest patients [because of] fertility and menopause issues,” commented Dr. Partridge. “We have to support [young adults with cancer]…in order to help them optimize their potential future fertility.”
She furthermore posed a critical question: Is it safe to remain fertile and become pregnant after cancer? Concerns include the need for effective contraception in patients not desiring pregnancy; cancer and treatment-related comorbidities; the risk of concurrent relapse and pregnancy; and the potential negative impact of pregnancy on the risk of recurrence in particular disease settings (eg, hormonally driven breast cancer).
In addition, Dr. Partridge highlighted the potential for anticancer treatment–induced altered fetal development in inadvertently pregnant patients, with the current understanding of such outcomes being “based on animal models and biologic plausibility.” An article published by ASCO this past year provided guidelines for the optimal timing of fetal exposure, though she acknowledged “we still have a lot of work to do in terms of the research.”3
“[Treating patients with cancer during -pregnancy] often requires modifying standard treatment algorithms, aiming for the most effective treatment for the women with cancer while minimizing risks to the fetus,” Dr. Partridge remarked. She further noted that the previously mentioned ASCO publication may also guide such approaches.3
Returning to focus on the safety of pregnancy in patients with hormonally driven breast cancer, Dr. Partridge presented the results of the prospective POSITIVE trial. This study evaluated whether endocrine therapy may be interrupted to attempt conception in those with estrogen receptor–positive disease. A total of 74.0% and 63.8% of patients had at least one pregnancy and live birth, respectively.4
The trial population showed a similar recurrence rate compared with an external control cohort. In an 18-month landmark analysis, those who did vs did not become pregnant demonstrated a lower risk of recurrence. “[The idea that fertility causes the cancer to ‘blow back,’ especially in the special setting of estrogen receptor–positive disease], is getting debunked,” she stated.
Regarding the feasibility of fertility and pregnancy after cancer, a range of potential outcomes have been reported for both men and women, and there may be anatomic and physiologic or hormonal limitations. Although much is known, according to Dr. Partridge, there are still gaps in our understanding of the risks to fertility.
“[Based on a critical review], most studies [regarding cancer treatment–related infertility] are retrospective,” Dr. Partridge remarked. “We need to measure these things prospectively.” Furthermore, she advocated for the consideration of the ASCO recommendations on fertility preservation in assessing and addressing risk.5
“[In addition to making sure to assess the risk of infertility], we need to remove unnecessary barriers within our health systems,” Dr. Partridge concluded. “Fertility preservation providers need to ‘clear the decks’ for these patients.”
DISCLOSURE: Dr. Partridge receives royalties for coauthoring the Breast Cancer Survivorship section of UpToDate. Dr. Campo-Engelstein reported no conflicts of interest. Dr. Goldman serves on a scientific advisory board for WndrHLTH.
REFERENCES
1. Campo-Engelstein L, Goldman K, Partridge A: Oncofertility: Measuring toxicity in reproductive organs during oncology drug development: An FDA-ASCO Virtual Workshop. Session 3. Presented October 8, 2024.
2. ASCO: Policy brief: Fertility preservation and cancer. Available at https://society.asco.org/sites/new-www.asco.org/files/content-files/advocacy-and-policy/documents/2022-Fertility-Preservation-Brief.pdf. Accessed November 6, 2024.
3. Sorouri K, Loren AW, Amant F, et al: Patient-centered care in the management of cancer during pregnancy. Am Soc Clin Oncol Educ Book 43:e100037, 2023.
4. Partridge AH, Niman SM, Ruggeri M, et al: Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med 388:1645-1656, 2023.
5. Lee SJ, Schover LR, Partridge AH, et al: American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 24:2917-2931, 2006.
