Cancer during pregnancy: Optimize treatment, minimize risks, ‘meet patients where they are’
Click Here to Manage Email Alerts
Approximately one in 1,000 pregnant women will be diagnosed with cancer, and incidence of pregnancy-associated cancer is on the rise as maternal age increases.
Cancer during pregnancy carries unique physical and emotional challenges for patients, while forcing clinicians to make a series of complex decisions to try to balance optimal treatment timing and efficacy with the need to minimize risks to the mother and fetus.
In addition, the U.S. Supreme Court’s Dobbs v. Jackson Women's Health Organization decision in 2022 — which allows states to establish parameters regarding abortion — has created legal obstacles to the delivery of cancer treatment to some pregnant women depending on where they live.
“Every case is incredibly nuanced, and myriad factors go into the decision-making,” Katherine Van Loon, MD, MPH, professor of medicine at University of California, San Francisco, with expertise in the management of gastrointestinal cancers, told Healio.
Healio spoke with leaders in the oncology field about the factors that must be considered when trying to optimize cancer treatment during pregnancy; the unique challenges that arise with use of newer treatments, such as immunotherapies or targeted agents; the importance of clinician empathy; and the need for more robust data to guide decision-making.
‘A new phenomenon’
The cancers most frequently diagnosed during pregnancy tend to be those that are more prevalent among younger women. These include breast, cervical, thyroid, colon and ovarian cancers, as well as melanoma, lymphoma and leukemia.
“Most often, cancer during pregnancy is detected with a symptom,” Ann H. Partridge, MD, MPH, founder and director of the Program for Young Adults with Breast Cancer and director of the adult survivorship program at Dana-Farber Cancer Institute, told Healio. “There might be a change in the breast or underarm, a lump or bump, or an area of redness or rash that doesn’t go away.”
However, pregnancy may confound diagnosis because it can be associated with similar symptoms — such as fatigue or breast tenderness — as the malignancy itself.
In some cases, an incidental finding of occult cancer occurs during routine prenatal sequencing tests.
A trial led by NCI and National Institute of Childhood Health and Disease is enrolling asymptomatic women with abnormal noninvasive prenatal testing results. These participants will undergo MRI and work-up for potentially undiagnosed cancers.
“This is rare, but it’s happening more as we increasingly do these tests,” Partridge said. “Right now, clinicians look at a patient’s genetics and look for the most likely cancer. If it could be breast cancer, typically we would try breast imaging, while obviously trying to avoid harm to the fetus. It’s fantastic that there is a study looking into this, because [it] is truly uncharted clinical territory.”
However, prenatal testing varies in its specificity, according to Brandon Hayes-Lattin, MD, FACP, medical director of the adolescent and young adult oncology program at Oregon Health & Science University’s Knight Cancer Institute.
“A variety of potential results that come from prenatal screening may indicate either an increased risk for cancer or actual cancer,” Hayes-Lattin said in an interview. “There may be a finding that is highly suggestive of an active malignancy but, much more often, the [results] suggest a predisposition toward cancer. Because it’s such a new phenomenon, there aren’t established guidelines for a work-up in this situation.”
Treatment decision-making
The effort to optimize cancer treatment during pregnancy depends on multiple factors, with the goal to balance effective treatment for the mother with potential risks to the fetus or patient.
Certain cancer treatments can be administered during pregnancy, Van Loon said.
“I have taken care of multiple patients who were diagnosed with colorectal cancer in the second or third trimester of pregnancy,” she said. “Chemotherapy for colon cancer can be administered safely during pregnancy. We actually now know that the risks for prematurity are worse for the fetus than in utero exposure to chemotherapy. So, in those instances, we’ve treated the mother’s cancer until the fetus is full term and then safely delivered a healthy baby.”
This is not possible for other cancers, she said. For example, trastuzumab (Herceptin, Genentech) — a therapy shown to confer a significant survival benefit to patients with HER2-positive breast cancer — is not safe during pregnancy.
“In that instance, decisions need to be made about timing of cancer care for the mother, or termination of the pregnancy may be considered if the fetus is not yet viable,” Van Loon said. “If the fetus is viable, we may opt to deliver the baby early, exposing the fetus to risks of prematurity.”
Hayes-Lattin said he frames discussions about cancer treatment with pregnant women by first addressing the standard treatments, expected outcomes and prognosis for a patient in the same situation who is not pregnant.
“That should be the baseline for the start of the conversation,” he said. “It helps women understand their situation and, frankly, it also helps us to have better information when weighing whether to pursue terminating the pregnancy.”
Hayes-Lattin then addresses the additional risks standard treatments may pose to the fetus and the patient.
Next, he reviews individual medications and treatment regimens known to increase risk to the baby or mother.
In many cases, these treatment decisions exist in “a gray zone,” Hayes-Lattin said.
“There isn’t a giant or robust database on the risks for many chemotherapy drugs in pregnancy, including risk to the fetus,” he said. “This is difficult when counseling a patient.”
Historically, the approach to treating pregnant women with cancer has been to use good judgment around the mechanism of the drug(s) needed for treatment, Partridge said.
“We want to consider how a treatment might or might not impact a developing fetus, and weigh that against the risks of delaying treatment,” she said. “Sometimes we can do a surgery and wait. In other cases, we can’t wait — either we treat or the mother dies.”
Hayes-Lattin emphasized that the safety of certain treatments may depend upon when they are initiated in the course of the pregnancy.
“The risk can be dramatically different in the first trimester versus later in the pregnancy, so we have to look at the risks and benefits of delaying therapy,” he said.
New drugs, new questions
ASCO has formed a task force aimed at writing formal guidelines for the multidisciplinary management of cancers and pregnancy, Van Loon said.
“There is a table in there specifically about drug classifications, where we conducted a review of all the existing literature about known teratogenic risks [for] different drug classifications,” she said. “We summarized what’s been published about safety versus risk of certain drugs.”
However, the rapid evolution of cancer treatment — including the adoption of new drug classes — can compound potential confusion about what regimens are safe or effective to use for pregnant women.
“One of the challenges is that there are so many new agents, and while concurrent pregnancy and cancer does happen, it’s not common enough for us to have updated information,” Hayes-Lattin said. “Oftentimes, the best information we can give a patient about the risks and benefits of various treatments are based on animal studies or are theoretical, based on the biology of how the medication works.”
Although the risks cytotoxic chemotherapy may pose to a fetus have long been noted, the risks posed by newer treatments are not always well understood, Hayes-Lattin said.
“Medications like immune checkpoint inhibitors, tyrosine kinase inhibitors, and other immunologic or targeted therapies can also have significant consequences during pregnancy,” he said. “These are often contraindicated.”
Partridge agreed, noting new agents have helped extend survival and conferred other benefits but potentially complicate decision-making in cases of pregnancy, where the impacts of these medications are not yet fully understood.
“We don’t have a long history, or a body of literature, to inform decisions around treatment during a pregnancy,” she said. “It becomes a complicated situation where we’re trying to determine what we know about a particular drug and how likely it is to be a safe option.”
Although concerns around treating cancer during pregnancy tend to be focused on cytotoxic chemotherapy and other curative treatments, clinicians should consider the potential risks of all medications prescribed during the course of treatment, Hayes-Lattin said.
“We have to think about supportive care medications, as well, whether it’s antiemetics, antibiotics or any other agents,” he said. “There are obviously resources for looking up pharmaceutical agents across any class, but it can get confusing. There’s no easy answer.”
Enabling future pregnancy
For young women with breast cancer, the need for adjuvant endocrine therapy can put plans for pregnancy on indefinite hold.
Partridge and colleagues conducted the prospective nonrandomized POSITIVE trial, in which women aged 42 years or younger with stage I to stage III hormone receptor-positive breast cancer temporarily stopped endocrine therapy to attempt pregnancy.
“We know these women are at risk for recurrence,” Partridge said. “We don’t want to make them put their lives on hold, but we also don’t want to compromise their breast cancer outcomes.”
Researchers followed 497 women for potential pregnancy; of this group, 74% had at least one pregnancy and 63.8% had at least one live birth. Among the 365 babies born, 8% had low birth weight and 2% had birth defects.
After 1,638 patient-years of follow-up, 44 women experienced a breast cancer event. Results showed comparable 3-year recurrence rate between those who paused endocrine therapy and a comparative external control cohort from the SOFT/TEXT trials (8.9% vs. 9.2%).
“The good news — at least on early follow-up — is there doesn’t appear to be a significant worsening of breast cancer outcomes compared with a target that we set for safety, as well as a historical, well-matched calculated control analysis,” Partridge said.
‘Meet patients where they are’
Regardless of the decisions a pregnant woman ultimately makes about cancer treatment, clinicians should remember to empathize with the stress and fear she likely is experiencing.
Part of that empathy is reserving judgment, Partridge said.
“It’s important to remember that patients come from all kinds of places with regard to their expectations around their pregnancy and future fertility,” she said. “We, as oncologists, may feel like that person shouldn’t keep the baby and compromise treatment in some settings. However, we need to meet patients where they are.”
Clinicians also should avoid voicing discouragement toward patients who express interest in pursuing a future pregnancy, Partridge said.
“There is nothing worse than when patients are diagnosed with a life-changing illness like cancer, and then we’re all of a sudden swatting them down proverbially about something as important to them as having another child,” she said. “For many women, this offers them hope for the future. It’s about what they want to do with their lives. We need to consider that and keep an open mind.”
Arming patients with valuable, empowering information about their options is another way to provide emotional support, Van Loon said.
“When treatment for cancer is incompatible with pregnancy, our responsibility as clinicians is to give the patient all the information she needs, and then it really becomes her decision about how to prioritize her own health and the pregnancy,” she said.
Hayes-Lattin emphasized the importance of involving a multidisciplinary team in the effort to provide emotional support to patients navigating cancer during pregnancy.
Social workers, nurses, pharmacists and obstetricians specializing in high-risk pregnancy can play key roles in helping patients through this challenging time.
“It’s also valuable for these patients to connect with other patients who have been in the same situation,” Hayes-Lattin said. “A number of services, often run by nonprofit organizations, can help connect these patients either to other stories or scenarios, or even directly to other patients who can understand and help.”
The path forward
As the number of new agents in the cancer treatment armamentarium continues to grow, clinicians likely will face evolving challenges related to treating patients during pregnancy.
It is incumbent upon oncologists to educate themselves about how best to assist their patients, Partridge said.
“This is a particularly tricky area because it’s so sensitive, and even though it might seem to me like it happens a lot, it’s actually a fairly rare occurrence,” she said. “It’s not the average person walking into the oncologist’s office who is either pregnant at diagnosis or wants to be pregnant after diagnosis.”
There are data repositories that offer useful information about cancer in pregnancy, Partridge said. One example is the INCIP Project, run by Netherlands Cancer Institute.
“The more we can learn and educate each other, the better we’ll be able to take care of our patients,” she said. “We also need to recognize that this problem isn’t going away. In fact, young adult cancers are increasing, so we’re going to see more of this globally in the coming decades.”
Hayes-Lattin highlighted the value of advocacy and the need for guidelines around coexisting pregnancy and cancer. He also noted the need for further research into risk stratification for both mother and fetus within the context of cancer.
“There’s an opportunity to create a real-world registry system to better learn and track what is happening,” he said. “We want to get as much information as possible so we can develop and promote expert medical guidelines.”
References:
- American Cancer Society. Cancer during pregnancy. Available at: https://www.cancer.org/cancer/managing-cancer/making-treatment-decisions/cancer-during-pregnancy.html. Accessed Feb. 23, 2024.
- Cottreau CM, et al. J Womens Health (Larchmt). 2019;doi:10.1089/jwh.2018.6962.
- NCI. When prenatal DNA tests point to cancer (press release). Available at: https://www.cancer.gov/news-events/cancer-currents-blog/2023/pregnancy-prenatal-testing-finds-cancer. Published May 17, 2023. Accessed Feb. 23, 2024.
- Partridge AH, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2212856.
- Silverstein J, et al. JCO Oncol Pract. 2020;doi:10.1200/OP.20.00077.
For more information:
Brandon Hayes-Lattin, MD, FACP, can be reached at OHSU Knight Cancer Institute, 3485 Bond Ave., Building 2, Portland, OR 97239; email: hayeslat@ohsu.edu.
Ann H. Partridge, MD, MPH, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email: ann_partridge@dfci.harvard.edu.
Katherine Van Loon, MD, MPH, can be reached at Helen Diller Family Comprehensive Cancer Center, 550 16th St., 6th Floor, Box 3211, San Francisco, CA 94143-1770; email: katherine.vanloon@ucsf.edu.
Collapse
Click Here to Manage Email Alerts