WECARE study update: Family history and contralateral breast cancer risk in young women

A study in the Journal of Clinical Oncology supported previous findings that young women with a family history of breast cancer are at higher risk of being diagnosed with a second breast cancer in the opposite breast. Risk was also affected by how young close relatives were at breast cancer diagnosis and whether those relatives had cancer in both breasts.

Background

Many factors affect a woman’s risk of developing breast cancer in her lifetime. One of the biggest factors is a family history. Women whose relatives have or had breast cancer are at higher risk of being diagnosed with breast cancer, depending on the number of affected relatives, how closely they are related, and their relatives’ ages at diagnosis.

In general, women diagnosed with breast cancer in one breast, called unilateral breast cancer, are more likely to be diagnosed with a second breast cancer than are their undiagnosed peers. But the risk of a second breast cancer developing in the remaining healthy breast, called contralateral breast cancer, is even higher for women with a breast cancer family history.

The Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study compared women diagnosed with a second breast cancer in their remaining breast with women who had been diagnosed with cancer in only one breast. The study had two parts: WECARE I and WECARE II:

• WECARE I’s findings showed the impact of breast cancer family history on the risk of developing a second breast cancer in the remaining breast. It looked at people who did and did not test positive for genetic mutations, such as BRCA1 and BRCA2, which are associated with higher breast cancer risk.
• WECARE II followed up on those findings with a larger population.

Design

WECARE II looked at 3,733 women from six cancer registries in the United States, Canada and Denmark. All women were under age 55 when diagnosed and had never been diagnosed with cancer before. Participants included women

• diagnosed with a first breast cancer that had not spread past the lymph nodes near the breast at the time of diagnosis, and
• who were diagnosed with a second breast cancer in the opposite breast at least one year after the first diagnosis.

The women were also given a test to find their polygenic risk score. This score is found by looking at over 100 common genetic changes that are associated with small increases in the risk for breast cancer. Each of these mutations alone accounts for a only small change in the risk of developing breast cancer, but a polygenic risk score considers how multiple changes may affect your overall risk. Not included in the polygenic risk score are some well-known mutations – such as those on the BRCA 1/2, ATM, CHEK2 and PALB2 genes – that are linked to larger changes in breast cancer risk. Mutations on these genes are tested separately, usually only when there is reason to believe a person may have one of these mutations. Everyone in these studies was given a polygenic risk score. Many were also tested for these well-known mutations as well, but not everyone.

The researchers collected detailed breast cancer family histories for each participant, including information on each relative’s age at diagnosis and whether the relative’s breast cancer was in one or both breasts. They identified each relative as either first degree or second degree:

• First-degree relatives are the participant’s mother, sister or daughter
• Second-degree relatives are the participant’s  grandmothers, aunts or half-sisters

Results

Overall, the researchers found through WECARE I and WECARE II that women with a family history of breast cancer had the highest risk of a second breast cancer in the opposite breast.

Researchers found in the updated WECARE results that

• for women diagnosed with breast cancer in one breast, but with no family history of breast cancer, there was a 4.3 percent chance of developing breast cancer in the opposite breast within the next 10 years
• having a family history of breast cancer led to a higher risk of a second breast cancer, but that risk was even higher if
  • your close relatives were under 40 when diagnosed and
  • if that relative had breast cancers diagnosed in both breasts
• the risk that a woman would be diagnosed with a second breast cancer in the opposite breast in the next 10 years was
  • 8.1 percent, if she had any first-degree relative diagnosed with breast cancer
  • 13.4 percent, if she had a first-degree relative who was diagnosed with breast cancer before turning 40
  • 14.1 percent, if she had a first-degree relative who was diagnosed with breast cancer in both breasts
  • 36.3 percent, if she had a first-degree relative diagnosed with cancer in both breasts before the age of 40

In a separate analysis of women who tested negative for genetic mutations linked to breast cancer risk, like those on the BRCA genes, a first-degree family history still raised a woman’s chance of developing a second breast cancer. But not everyone was tested for these specific genetic mutations so more study will be needed on these findings.

What this means for you

People of all ethnicities and backgrounds are diagnosed with breast cancer. Anyone with breast tissue can develop breast cancer, including men, meaning that no one is completely protected from breast cancer.

This study showed that a family history of breast cancer continues to be a strong and consistent risk factor for developing a second breast cancer, even if tests have found that you do not have the known gene mutations that are linked to a higher breast cancer risk. Knowing your family’s medical history can help you make informed decisions regarding your personal diagnosis and treatment options.

You can use this brief questionnaire to learn more about your cancer risk. The results can help find your risk of developing cancer and decide whether you should consider genetic counseling. A genetic counselor is a trained healthcare professional who can help you review your family’s health and cancer histories and decide whether to get genetic testing. Based on your diagnosis and family history, a genetic counselor can help you weigh the pros and cons of genetic testing and interpret test results if you decide genetic testing is right for you.

To learn more, refer to Types of Genetic Tests.

Reiner, AS, Sisti, J, John, EM, et al. Breast cancer family history and contralateral breast cancer risk in young women: An update from the women’s environmental cancer and radiation epidemiology study. Journal of Clinical Oncology. April 5, 2018; 36(15): 1513-1520. DOI: 10.1200/JCO.2017.77.3424.

This article was supported by the Grant or Cooperative Agreement Number 1 U58 DP005403, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services