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Some Breast Cancers May Switch HER2 Status if They Come Back

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If breast cancer comes back — called recurrence by doctors — the HER2 status of the recurrent cancer may change from HER2-positive or HER2-negative to a new classification of HER2 status, called HER2-low, according to an Italian study.

The research was presented at the European Society for Medical Oncology Breast Cancer Virtual Congress 2021 on May 8, 2021.

What is HER2-low breast cancer?
About the study
What this means for you

What is HER2-low breast cancer?

The HER2 gene makes HER2 proteins. HER2 proteins are receptors on breast cells. Normally, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. But in about 10% to 20% of breast cancers, the HER2 gene doesn’t work correctly and makes too many copies of itself (known as HER2 gene amplification). All these extra HER2 genes tell breast cells to make too many HER2 receptors (HER2 protein overexpression). This makes breast cells grow and divide in an uncontrolled way. Breast cancers with HER2 gene amplification or HER2 protein overexpression are called HER2-positive.

Traditionally, breast cancers are classified as either HER2-positive or HER2-negative based on testing results. Two of the most common tests for HER2 status are:

  • IHC test (ImmunoHistoChemistry): The IHC test uses a chemical dye to stain the HER2 proteins. The IHC test gives a score of 0 to 3+ based on the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it’s considered HER2-negative. If the score is 2+, it’s considered borderline. If the score is 3+, it’s considered HER2-positive.
  • FISH test (Fluorescence In Situ Hybridization): The FISH test uses special labels that attach to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. While the FISH test is the most accurate, it is also more expensive and takes longer to return results, which is why doctors tend to first order an IHC test to see if they can determine HER2-positive status. With the FISH test, you get a score of either positive or negative (some hospitals call a negative test result “zero”).

HER2-low breast cancers have levels of HER2 proteins that are too low to be considered positive. They have IHC scores of 1+ or 2+ or a FISH score of negative. About half of breast cancers classified as HER2-negative have low HER2 expression.

Studies are underway to see if HER2-low breast cancers could be treated with anti-HER2 medicines, such as Herceptin (chemical name: trastuzumab) or Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki).

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About the study

This study — the first of its kind — wanted to know if the HER2 status of a recurrent breast cancer was different from the HER2 status of an initially diagnosed breast cancer, called a primary breast cancer by doctors.

The study included 575 people diagnosed with recurrent breast cancer at two hospitals in Italy. The researchers looked at samples of both the primary tumor and the recurrent tumor to determine the HER2 status of each.

Of the primary breast cancers:

  • 59% were hormone-receptor-positive and HER2-negative
  • 25% were either hormone-receptor-positive or hormone-receptor-negative and HER2-positive
  • 16% were hormone-receptor-negative and HER2-negative (triple-negative breast cancer)
  • 34% were considered HER2-low

Overall, 38% of the recurrent cancers had a different HER2 status compared with the primary cancers:

  • 15% of HER2-negative primary breast cancers switched to HER2-low recurrent breast cancers
  • 14% of HER2-low primary breast cancers switched to HER2-negative recurrent breast cancers
  • 9% of the recurrent cancers either became HER2-positive or were not HER2-positive anymore

Among primary breast cancers that were HER2-negative, the rate of HER2 switching was higher among hormone-receptor-positive, HER2-negative cancers than triple-negative cancers (45% vs. 35%).

“The results provide a whole new insight on how HER2-low tumors might evolve as a subgroup, possibly challenging the current dichotomy between HER2-positive and HER2-negative breast cancer,” said Federica Miglietta, M.D., of the University of Padova, who presented the research, in a statement. “Our findings stress the importance of re-testing HER2 expression on tumor relapse since it might provide the option of new therapeutic opportunities, currently in a trial, and hopefully in the near future, in the clinic.”

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What this means for you

This study underscores how important it is to have a sample of a recurrent breast cancer tumor undergo the same tests as the initially diagnosed breast cancer, including testing for HER2 status. If the HER2 status has changed, you may benefit from treatments that wouldn’t have helped treat the primary cancer.

It’s important to know that HER2-low is not an official type of breast cancer yet, and no medicines have been approved to treat HER2-low breast cancer. Still, studies are underway to see if current anti-HER2 medicines can help treat HER2-low cancers.

If you’ve been diagnosed with recurrent breast cancer — breast cancer that has come back after your initial diagnosis — it’s a good idea to talk to your doctor about this study and ask for a full pathological work-up on the recurrent breast cancer tumor.

Knowing all the characteristics of the recurrent breast cancer and how those characteristics might be different from the primary breast cancer will help you and your doctor make the best treatment choices for your unique situation.

If the primary breast cancer was HER2-negative and the recurrent breast cancer is HER2-low, you may want to consider being part of a clinical trial that is testing anti-HER2 medicines to treat HER2-low breast cancer.

Learn more about the benefits and risks of participating in a clinical trial.

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Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser


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