Study: Women can have safe pregnancies after breast cancer treatment

IN-DEPTH REVIEW OF RESEARCH

Study background

The continued trend toward delaying families until later in life means that more women are diagnosed with breast cancer before completing their families. Long-term outcomes and survival of early-stage patients have improved over the last several decades. For women of reproductive age, understanding how breast cancer and related treatment affect family planning, fertility and pregnancy outcomes would allow better decision-making.

Fifteen to 75 percent of young women who receive chemotherapy during their breast cancer treatment have amenorrhea (loss of menstrual periods).  About 27 to 75 percent of these young women recover the ovarian function needed for conception. Poorvu and colleagues followed the pregnancy histories of women under age 40 who were diagnosed with breast cancer to understand their family planning choices and experiences. Only 36 percent were interested in having children within five years of their cancer diagnosis. Of these women, nine percent tried to become pregnant, and 70 percent of those attempts were successful.  Another prospective cohort study of women diagnosed with breast cancer showed that among women who attempted to get pregnant after breast cancer treatment, half were able to conceive by intercourse alone.

In this meta-analysis, researchers reviewed all published studies on pregnancy after breast cancer to understand the impact of breast cancer treatment on pregnancy rates as well as pregnancy and cancer outcomes for mothers and children.

Researchers of this study wanted to know

Researchers wanted to know whether women who had breast cancer treatment had different chances of becoming pregnant, different pregnancy outcomes or were at different personal risk than women who had not become pregnant.

Populations looked at in this study

This meta-analysis looked at all published studies involving the questions examined. The populations of these studies varied.

Study design

Dr. Eva Blondeaux presented the results of the PROSPERO study at the 2020 San Antonio Breast Cancer Symposium. To know what happens when women get pregnant after their breast cancer treatment, these researchers looked systematically at all published studies on this topic. They included studies that reviewed patients’ histories (retrospective studies) or tracked patients forward in time (prospective studies). They excluded case reports of individuals or studies with fewer than 10 patients. They also excluded studies of pregnancy within a year of breast cancer treatment. For evaluation of chances of pregnancy, seven studies were included. For understanding pregnancy outcomes, nine studies were included. For evaluation of disease-free survival and overall survival, 11 and 21 studies were included, respectively.

Study findings

What are the chances of becoming pregnant?
Among 48,513 women who had breast cancer treatment compared to 3,289,113 healthy women:

• 60% fewer pregnancies occurred.
  • It is unknown whether this decreased number of pregnancies reflects difficulties in becoming pregnant or decreased choice to attempt pregnancy after breast cancer treatment.
  • Among women with other types of cancer and intact reproductive systems, rates of pregnancy were lower only for women who survived cervical cancer (67% decreased pregnancies) or all cancer combined (35% decreased pregnancies).

What are the risks of pregnancy complications and the impact on infant safety?
Compared to 4,814,452 healthy women, the following results were identified among 3,240 women who were treated for breast cancer:

• No differences were found in the rates of pregnancy complications, completed pregnancies or spontaneous abortions (miscarriages).

• The rate of C-sections modestly increased (by 14%).
• No increase in birth defects/congenital abnormalities among infants was identified.
• Infants of mothers who had breast cancer treatment were more likely to:
  • have lower birth weight (relative risk was 1.5 or 50% increased risk)
  • be born prematurely (relative risk was 1.45 or 45% increased risk)
  • be born small for gestational age (relative risk was 1.16 or 16% increased risk).
  • It is important to note that these situations (low birth weight, preterm birth and small size for gestational age) are not common in healthy women. Even though these rates were increased in women after breast cancer treatment, the absolute number of these types of births was low.
  • Low birth weight and small size for gestational age occurred mostly among women who had been treated with chemotherapy.
    • Women who had chemotherapy had a 62% increased risk of having an infant with low birth weight, while women treated for breast cancer without chemotherapy had no significant increase in the risk of having an infant with low birth weight.
    • Women who had chemotherapy had a 51% increased risk of having an infant who was small for its gestational age, while women treated for breast cancer without chemotherapy had no significant increase in the risk of having infants with low birth weight (and perhaps had less risk).
    • Similar rates of premature birth occurred whether or not women had chemotherapy.

How does pregnancy affect cancer recurrence and survival?

Pregnancy is safe for women after breast cancer treatment. For disease-free survival analysis, studies included 2,003 women who became pregnant after breast cancer treatment compared to 37,779 women who did not become pregnant after breast cancer treatment:

• The rate of cancer recurrence was similar. Pregnancy did not elevate a woman’s risk of cancer returning and disease-free survival (DFS) was similar. Pregnancy after breast cancer was linked to a decreased rate of recurrence (21% less than among women who became pregnant compared to those who did not.)

For overall survival analysis, studies included 3,261 women who became pregnant after breast cancer treatment compared to 58,238 women who did not become pregnant after breast cancer treatment:

• The overall survival was better among women who became pregnant (48% improvement)
• The overall survival of women with BRCA mutations was greater (15% improvement with pregnancy) than women who had a pregnancy after their breast cancer treatment, although it was more modest than in the whole group of women with and without BRCA mutations.
• These results were true regardless of node status or hormone-receptor status.
  • Women who were treated for hormone receptor-positive cancer and then became pregnant had similar disease-free survival as women who did not become pregnant after their breast cancer treatment.
  • Women who had hormone receptor-negative cancer and then became pregnant had better disease-free survival than women who did not become pregnant after their breast cancer treatment (28% decreased risk).
  • Overall survival was better among women who became pregnant after treatment regardless of whether their treatment included chemotherapy. However, those who did not have chemo had better survival (42% increase) than those who had chemo (29% increase). This difference may reflect the severity or aggressive nature of women’s cancer.

Strengths and limitations

Strengths

• This study looked at 39 published studies including over 48,513 women with breast cancer and 3,289,113 healthy women. The size of the patient groups provides confidence in the findings.
• Researchers were able to assess the consistency of results between published studies to see confirmation of results.
• Sufficient patients with different nodal, hormone receptor or mutation status participated so that researchers could look at pregnancy in these subgroups.

Limitations

• Race or ethnic information about study participants was not indicated. Whether any of these aspects of pregnancy differ between women of different races or ethnic backgrounds is unknown.
• The studies did not look at women with breast cancer who had inherited mutations in genes other than BRCA1 and BRCA2.

Context

This meta-study broadly confirmed many smaller studies that found pregnancy after breast cancer treatment is possible, safe for mothers and their children and does not alter longer-term cancer recurrence or outcomes. When Lambertini et al (2020) looked at early-stage breast cancer patients under age 40 with BRCA mutations, 19 percent became pregnant and most had a safe pregnancy. Pregnancy after breast cancer was uneventful for both mothers and children with no long-term effects on the mother's cancer outcomes. This is similar to outcomes for breast cancer survivors without BRCA mutations.

Conclusions

Pregnancy after breast cancer treatment is a feasible goal for women who want to start or expand their families. Women are less likely to become pregnant after breast cancer treatment, although it is unclear if this is by choice or a limited ability to conceive.

Once pregnant, pregnancy and delivery are similar to healthy women, although the rate of C-sections is modestly increased. Infants born after their mother's breast cancer treatment are at increased risk of being premature, of low birth weight or small for birth age but no increased rate of birth defects was seen. Breast cancer survivors who became pregnant had similar risks of recurrence and survival as survivors who did not become pregnant. Overall, this new research suggests that pregnancy is a safe choice for women after breast cancer treatment but may require closer monitoring.

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posted 6/24/21