For young women with a history of breast cancer, there’s at least one thing about which they might stop worrying. In general, pregnancy does not increase the risk of cancer recurrence. That’s the main finding of the largest trial to date on this subject. Leaders of the American Society of Clinical Oncology featured this result at the society’s annual meeting in Chicago.
Historically, many doctors advised women not to get pregnant after early-stage breast cancer and, if they became pregnant, to terminate the pregnancy. They feared that hormones of pregnancy could stimulate residual breast cancer cells, leading to recurrence. This concern held especially true for women who had estrogen receptor positive (ER+) tumors.
Now, there’s ample data to assuage most concerns. Among 1207 women with breast cancer before age 50, those who later delivered babies experienced no more likelihood of recurrence than did women who didn’t bear more children. All women in the registry had localized breast tumors diagnosed by 2008; the new analysis updates an earlier publication regarding the same women. Follow-up in the current report extends to 10 years.
“The odds of survival and relapse in the women who got pregnant and delivered, versus those who did not, were the same in this study,” said Dr. Dan Hayes. He’s a breast cancer specialist and researcher at the University of Michigan in Ann Arbor. We spoke last month, when he was ASCO president and planning for the conference.
Like some obstetricians, Hayes keeps a photo gallery in his office with pictures of patients’ babies, he told me. “This is something I care deeply about. This is more than just another abstract.”
A quarter of women with breast cancer are of child-bearing age. That’s why this study is so important, Hayes emphasized. “The issue is whether women who’ve had breast cancer can safely get pregnant and deliver,” he said. “These data further suggest it’s safe to tell your patients that if they want to get pregnant, fine.”
“I think women who wish to become pregnant can strongly consider it,” But Hayes added a note of caution. “I wouldn’t be quite so certain.” The study is limited by its retrospective nature, he wrote by subsequent email. “The nice thing about it is the long follow-up.” However, the registry started prior to modern anti-estrogen therapy. There’s concern about the time, years, during which women might stop anti-estrogen therapy to become pregnant and deliver. The safety data are most clear for women who had ER negative tumors, he indicated.
Dr. Matteo Lambertini, a medical oncologist and ESMO fellow at the Institut Jules Bordet in Brussels, Belgium, presented the paper in Chicago “Breast cancer in young women often occurs before completion of reproductive plans,” he said at the press briefing. “Around 40 to 50% of those younger women desire a future pregnancy at the time of breast cancer diagnosis, yet less than 10% of them manage to become subsequently pregnant,” he said.
“The main message is the safety of pregnancy in breast cancer survivors, regardless of the pregnancy interval, ER status, timing of pregnancy, and breast feeding,” Lambertini said. The observational trial also looked at abortion, which had no effect. “Abortion need not be considered as a therapy,” he stated. “Pregnancy should not be discouraged.”
At the press meeting in Chicago, Dr. Richard Schilsky of ASCO raised a point of clarification: The study authors use the term “safety” with respect to risk of recurrence of breast cancer. “It’s very clear that these women are not at greater risk for recurrence,” he stated. The report doesn’t address other possible complications of pregnancy in women with a history of breast cancer.
The new paper updates an observational report on 1207 relatively young women with various forms and localized stages of breast cancer: 57% had ER positive disease; over 40% had poor prognostic features for tumor recurrence, such as having cancer cells found in the lymph nodes, or large tumors. For each of 333 women who became pregnant after breast cancer, investigators matched 3 non-pregnant women with similar tumors and ages.
Among the women who became pregnant after breast cancer, disease-free survival equaled that in the control group. For those who had ER+ breast cancer, overall survival was not affected by pregnancy. For women who had ER negative tumors, subgroup analysis suggests a survival benefit of pregnancy. (This correlation might be explained by healthier women after breast cancer being more likely to become pregnant and deliver, ES.) The long-term analysis is sponsored by the Breast Cancer International Group (BIG) with NIH support and involvement of physicians in Europe and Boston.
Pregnancy and sexual health are among the biggest concerns for young women after a breast cancer diagnosis, said Dr. Don Dizon. He’s a medical oncologist at Massachusetts General Hospital who specializes in gynecologic cancer and sexuality after cancer. The new paper builds on previous reports that pregnancy is not associated with lesser outcomes,” he wrote by email. “It is the largest analysis of women with ER-positive tumors. There are no negative outcomes associated with pregnancy even in this group, which is reassuring.”
“Patients are appropriately nervous about pregnancy after breast cancer, but I think clinicians have a greater worry for their patients,” Dizon wrote. This fear may be exaggerated, he suggested.
“These data are very helpful,” said Dr. Hope Rugo by email. She’s a medical oncologist and professor of medicine at the University of California San Francisco who specializes in breast cancer and clinical trials. “These are large datasets and reassuring numbers.”
I asked Rugo if she had any concerns about the study’s limitations. “Patients who attempt pregnancy generally tend to have lower risk disease,” she responded. Some bias is inevitable. “Of course, the decision to pursue pregnancy is an individual one, so that the control group cannot be fully matched.” The accumulated data demonstrate similar outcomes with and without pregnancy. “This reassurance must be moderated by the patient’s own individual risk of recurrence,” she wrote.
Now that we know pregnancy is generally safe, the issue patients face is how long to wait after a breast cancer diagnosis, Rugo considered. For patients with hormone receptor negative disease, pregnancy decisions are comparatively straightforward because recurrences generally occur within the first 3-5 years after diagnosis. A concern for women after treatment for hormone-sensitive breast cancer—apart from pregnancy per se—is stopping anti-estrogen therapy. Oncologists typically prescribe anti-estrogen treatment for 5 to 10 years after diagnosis, to reduce chances of relapse.
“Decisions about when to stop hormone therapy can be quite difficult,” Rugo wrote. All three specialists—Hayes, Rugo and Dizon—referred to an ongoing, prospective observational POSITIVE trial of pregnancy in women with a history of ER + breast cancer. The international study will analyze whether it’s safe for pre-menopausal women to stop anti-estrogen therapy for a few years to pursue pregnancy and childbirth.
Rugo encourages young women with breast cancer to discuss the possibility of future pregnancy with their doctors before starting treatment. It’s “good to keep all options open,” she wrote. “First, preserving fertility is important. We refer all patients interested in preserving fertility to our fertility group (gynecologists).” Patients should consider egg-harvesting before starting chemotherapy or hormone therapy for early stage breast cancer, she wrote.
“The second issue is when to attempt pregnancy,” Rugo wrote. “For patients with triple negative disease, I recommend at least a 3-year window from completing chemotherapy for early stage disease.” After treatment of hormone receptor positive breast cancer, advice varies. “The recommendation must be individualized and tailored to the patient’s risk of recurrence, so that exposure to hormone therapy is maximized.”
“We need data,” Dizon concluded. For young women after ER+ breast cancer, the question is how long they should wait before attempting pregnancy. This issue matters particularly for women who might take ovarian suppression as a treatment and for many women who take extended endocrine therapy. Dizon also referred to the POSITIVE study. “I think the ongoing clinical trial, once completed, will be incredibly important.”