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Saturday, June 3, 2017

Pregnancy After Breast Cancer Does Not Increase Recurrence Risk

​By Catlin Nalley

Long-term results from a multicenter, retrospective study confirm that pregnancy after breast cancer can be considered safe irrespective of ER status and should not be discouraged, according to data presented at the 2017 ASCO annual meeting, held June 2-6 (Abstract LBA10066).

"Our findings confirm that pregnancy after breast cancer should not be discouraged, even for women with ER-positive cancer," said lead study author Matteo Lambertini, MD, a medical oncologist and ESMO fellow at the Institut Jules Bordet in Brussels, Belgium, in a statement. "However, when deciding how long to wait before becoming pregnant, patients and doctors should consider each woman's personal risk for recurrence, particularly for women who need adjuvant hormone therapy."

Breast Cancer & Pregnancy

With a trend toward a delay in childbearing, breast cancer in young women often occurs before any reproductive plans can be completed (NCHS Data Brief 2016;(232):1-8). And, although half of newly-diagnosed women report interest in having children, Lambertini noted during a press briefing, less than 10 percent become pregnant following treatment (Cancer 2012;118(6):1710-1717).

"Having a family is one of the most important achievements in a person's life, however, for breast cancer survivor's this can be particularly challenging," Lambertini said. One of the main reasons for this, he noted, is because many people still believe that having a pregnancy in a patient with a prior history of breast cancer could lead to an increased risk of disease recurrence.

This is not a new concern for physicians or patients, especially among women with ER-positive disease. Since this subtype is fueled by estrogen, the worry is that hormone levels during pregnancy could lead to growth among any remaining cancer cells. Additionally, another concern for this patient population is the need to interrupt adjuvant hormone therapy before trying to become pregnant, according to ASCO.

Study Methodology

The study, which included 1,207 patients, is the largest study to investigate the safety of pregnancy after breast cancer and the only to address this question in women with ER-positive breast cancer, according to researchers.

The study enrolled women who had been diagnosed with non-metastatic breast cancer prior to 2008. Among this cohort, 57 percent had ER-positive cancer, and more than 40 percent had poor prognostic factors, such as large tumor size and cancer spread to the axillary lymph nodes, investigators reported.

Utilizing a case-control study design, 333 of the women included were pregnant and 874 were not. The pregnant cohort was matched (1:3) according to tumor and treatment characteristics, with patients without a subsequent pregnancy, Lambertini reported.

The primary endpoint was disease-free survival (DFS) in patients with ER-positive breast cancer. Secondary endpoints included DFS and overall survival (OS) in ER-negative and all patients irrespective of ER status, according to study authors. Researchers also evaluated the impact of induced abortion on breast cancer outcome. 

Researchers reported that the median time from diagnosis to conception was 2.4 years. According to study results, women with ER-positive breast cancer achieved pregnancy later than those with ER-negative disease; 23 percent of ER-positive patients had a pregnancy beyond 5 years from diagnosis as compared to 7 percent in those with ER-negative disease.

Key Findings

After a median follow-up of approximately 10 years, researchers observed no difference in DFS between women who became pregnant and those who did not with ER-positive breast cancer (hazard ratio [HR] 0.94; 95% confidence intervals [CI] 0.70-1.26; p = 0.68), ER-negative (HR 0.75; 95% CI 0.53-1.06; p = 0.10), and all patients (HR 0.85; 95% CI 0.68-1.06; p = 0.15).

Results showed no difference between the two cohort in patients with ER-positive disease (HR 0.84; 95% CI 0.60-1.18; p = 0.32). However, researchers reported a significant improved OS in the pregnant cohort for ER-negative breast cancer patients (HR 0.57; 95% CI 0.36-0.90; p = 0.01). This group had a 42 percent lower chance of dying than those who did not become pregnant.

"It's possible that pregnancy could be a protective factor for patients with ER-negative breast cancer, through either immune system mechanisms or hormonal mechanisms, but we need more research into this," Lambertini noted, in a statement.

Secondary analyses of DFS were also conducted in entire study population for pregnancy outcome, pregnancy interval since diagnosis, and breastfeeding status. Researchers observed no difference in DFS compared to non-pregnant women, regardless of whether the women completed pregnancy or had an abortion, became pregnant less than 2 years or more than 2 years from diagnosis, and whether the patients had breastfed. Additionally, data on breastfeeding, while limited, suggests it is feasible, even after breast surgery.

Concluding his presentation, Lambertini stressed that the "findings should serve as a strong basis for counseling women inquiring into the safety of future conception."

"Breast cancer disproportionally affects young women at a time in their lives when they may be starting or growing their families. For years, both patients and doctors have held concerns that having a baby after a breast cancer diagnosis can put a woman at risk for a cancer recurrence, whether her cancer is ER-positive or negative," emphasized Erica L. Mayer, MD, MPH, expert commentator at the ASCO press briefing. "This long-term follow-up data that Dr. Lambertini has just presented provides a great reassurance for young breast cancer survivors and their doctor's that choosing to have a pregnancy after a breast cancer diagnosis is safe and acceptable to do."

Future Research

While the results of these study are promising, future research is needed in areas not addressed in this retrospective analysis.

This study has limited information on the utilization of assisted reproductive technologies, such as in vitro fertilization, among breast cancer survivors, and the HER2 status was unknown in about 80 percent of the study population, noted ASCO. Further research on the effect of pregnancy on health outcomes of women with BRCA mutations, a group that typically develops the disease at the younger age, is also required.

The work of Lambertini and his colleagues has laid the foundation for the IBCSG-BIG-NABCG POSITIVE trial (NCT02308085), a global study currently underway that is investigating the impact of interrupting adjuvant hormone therapy to allow for pregnancy in women with ER-positive breast cancer; the study will also provide further insight on the impact of reproductive technologies and breastfeeding.

Catlin Nalley is associate editor.