Study: Some Women With Cancer in One Breast May Be More Likely to Develop It in the Other

  • Women who have had breast cancer once may be at an increased risk of getting it again in the other breast if they have certain genetic mutations, a new study found.
  • BRCA1, BRCA2, PALB2, and CHEK2 genes can raise someone's risk of getting breast cancer a second time, as can their age, race, and menopausal status.
  • Having a more robust understanding of a person's risk will make it easier for physicians and patients to make decisions about how to best screen for and treat their breast cancers.

Women who have had breast cancer in one breast may be at a higher risk of developing it in the other if they carry specific genetic mutations, new research shows.

The findings come from a study published earlier this month in the Journal of Clinical Oncology, which followed women previously diagnosed with breast cancer who also carried one of five different gene mutations: BRCA1, BRCA2, CHEK2, PALB3, and ATM. The women were also treated with ipsilateral surgery.

Women who carried BRCA1, BRCA2, or CHEK2 gene mutations had a higher chance developing breast cancer again in the opposite breast, known as contralateral breast cancer, or CBC.

Results from the study—one of the largest to help estimate contralateral breast cancer risk—can add another level of detail and personalization for breast cancer patients.

“Now we can provide a more individualized or personalized risk estimate of contralateral breast cancer in germline mutation carriers,” study co-author Siddhartha Yadav, MD, MBBS, assistant professor of oncology at the Mayo Clinic, told Health. “We can combine all of these factors and come up with a number to give a patient, or sort of a precise estimate of saying, ‘This is most likely what your risk of developing a second breast cancer is.’”

female doctor talking to female patient in office.

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New Information About Genetic Risks for Breast Cancer 

As researchers are learning more about some of the genetic mutations associated with breast cancer, Dr. Yadav and his coauthors wanted to determine to what extent these gene changes might make a woman more susceptible to getting breast cancer a second time. Specifically, they looked at the well-known BRCA1 and BRCA2 genes, plus others called CHEK2, PALB2, and ATM. 

The researchers followed a cohort of 15,104 women with genetic risks for breast cancer that was reflective of the typical population of breast cancer patients. The average age of first breast cancer diagnosis was 62 years, and on average, the study followed up with these women after 11 years. This allowed researchers to determine how many people had gotten breast cancer for a second time, and the approximate risk associated with each gene mutation.

“BRCA1 and 2 mutation carriers, if they have first breast cancer they [have an] approximately three fold or higher likelihood of developing a second breast cancer in the opposite breast,” Dr. Yadav said. “For CHEK2 we found that their risk is approximately two fold increased.”

For those with the PALB2 gene, there was only an increased risk if the person was first diagnosed with estrogen receptor negative (ER negative) breast cancer, a specific type that does not use the hormone estrogen to grow. The ATM gene did not appear to increase the risk of contralateral breast cancer.

The study builds on what is already known about breast cancer and the varying types of genes that influence risk, said Amanda Woodworth, MD, FACS, CPE, director of breast health for USC and Henry Mayo Hospital and associate professor of clinical surgery at Keck Medicine of USC.

“One of the things people don’t realize is we all have BRCA1 and BRCA2 genes. It’s just whether or not there’s a mutation that exists in those genes that results in either failure of the body to suppress tumors from happening,” she told Health. “Or if you’re, with those genetic mutations, allowing cancers to spread more easily.”

Even among these mutations, there are varying levels of risk for getting breast cancer a first time. The five genes included in the study can fall on a sliding scale—BRCA1 and BRCA2 are associated with a 50% chance of being diagnosed with breast cancer, Dr. Yadav said. For PALB2 it’s around 30% to 50%, and it’s about 20% for ATM and CHEK2.

This information is not new. But it’s also important that physicians understand how each of these genes might affect a woman’s risk of getting breast cancer a second time. 

“When a patient develops breast cancer and we treat them, they’re still left with this gene for the rest of their life that can cause a new breast cancer in the other breast. And so what do we do about that? That’s the question,” Mark Moasser, MD, professor of medicine at the Helen Diller Family Cancer Center at UC San Francisco, told Health

Other Factors That Play a Role 

Beyond its primary findings, the study also explained how the risk of developing a second breast cancer has a lot to do with other factors, most of which are age-related.

“Your age at first breast cancer diagnosis matters quite significantly,” Dr. Yadav said. “If a 30-year-old germline mutation carrier develops breast cancer, then her risk is much higher of developing a second breast cancer compared to a woman who develops first breast cancer at the age of 65.”

In a similar vein, researchers also found that the risk of developing contralateral breast cancer was higher for premenopausal women with genetic mutations than for postmenopausal women.

In general, this is because breast cancer in younger women is more likely to be hereditary than in older women.

“Their body, in some way, has allowed for a breast cancer to occur at a much younger age than what you would typically expect,” Dr. Woodworth said. “We know that those women are going to be at a higher risk—and it’s not a huge risk, but it is a little bit higher risk—of developing a second breast cancer in the future.”

Because of this, race also played a part in a person’s risk of getting contralateral breast cancer, the study found. Black women—who have disproportionately high mortality rates from breast cancer—tend to get the disease at a younger age, Dr. Woodworth said, which again made them just slightly more likely to get contralateral breast cancer in some instances.

A Call For More Personalized Screening & Treatments

Only about 5% to 10% of breast cancers are linked to these specific gene mutations, but experts agree it’s important to have a better system for determining a person’s true risk of contralateral breast cancer, following an initial diagnosis.

Using the information from this study, Dr. Yadav hopes that people can get a better idea of their individual risk of developing cancer again if they’ve already had it.

“If we know exactly what the risk is, then we can sort of target the risk,” he said. “Do we need to do [an] MRI, or do we even need to go as far as saying, maybe let’s remove the breast so that we prevent a second breast cancer from happening?”

A part of that equation will likely be the breast cancer patient’s age, Dr. Moasser added, in addition to the specific type of gene mutation that’s causing the cancer in the first place.

The study should also support the idea that genetic testing among people who have breast cancer should be more widespread, Dr. Woodworth said.

Many physicians follow guidelines that say only those with a strong family history of breast cancer or those who get cancer when they’re very young should get genetic testing. But people who fall outside of those criteria may not get the chance to know if they might have BRCA1, BRCA2, CHEK2, or any other mutations.

“The American Society of Breast Surgeons has put out a statement that they think all women who’ve been diagnosed with breast cancer should be offered genetic testing. And that’s been my own practice for a decade,” she said. “It’s so that we can identify someone at the time of diagnosis if there’s an increased risk for developing future cancers.”

Someone who had breast cancer caused by an ATM gene mutation, for example, would have no heightened risk of developing contralateral breast cancer. But the same wouldn’t be the case for a first cancer caused by BRCA1 or 2, or CHEK2. Having that information would be incredibly valuable as doctors and patients figure out next steps after a diagnosis.

“I am a huge advocate for self-[advocacy],” Dr. Woodworth said. “This hammers home the point about the importance of offering genetic testing when somebody is first diagnosed with breast cancer, so that both their treating physicians and the patient can make an educated decision.”

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  1. Yadav S, Boddicker NJ, Na J, et al. Contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol. Published online January 9, 2023. doi:10.1200/JCO.22.01239

  2. Centers for Disease Control and Prevention. Breast cancer in young women.

  3. Williams DR, Mohammed SA, Shields AE. Understanding and effectively addressing breast cancer in African American women: Unpacking the social contextCancer. 2016;122(14):2138-2149. doi:10.1002/cncr.29935

  4. Centers for Disease Control and Prevention. Hereditary breast cancer and BRCA genes.

  5. Centers for Disease Control and Prevention. Genetic testing for hereditary breast and ovarian cancer.

  6. American Society of Breast Surgeons. Consensus guideline on genetic testing for hereditary breast cancer.

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