HER2-Negative vs. HER2-Positive Breast Cancer

HER2-negative and HER2-positive are types of breast cancer that share some things in common, but they have plenty of differences, too. Which kind you have can affect the treatment you get.

Cancer is uncontrolled cell growth. Breast cancer means these cells started in the breast, though they may spread to nearby tissue and organs and eventually to anywhere in the body.

HER2 stands for human epidermal growth factor receptor-2. It's healthy in normal amounts, but too much may be a sign of a certain type of breast cancer.

Most people with breast cancer have a normal amount of this protein, which means you are HER2-negative. But about 1 in 5 cases are HER2-positive, which means your levels are unusually high.

If you have breast cancer, your doctor will likely test your HER2 to figure out if you're "negative" or "positive."

The Role of HER2 Proteins in Breast Cancer

HER2 proteins come from the HER2 gene. These proteins play a role in healthy breast cells by controlling how fast they divide, grow, and repair themselves.

But sometimes, the HER2 gene makes too many copies of itself. This leads to too many HER2 proteins in your breast cells, a situation called "protein overexpression." The result is breast cells that divide and grow too quickly.

Special tests help your doctor know whether your breast cancer is HER2-positive. Compared with HER2-negative breast cancers, HER2-positive breast cancers tend to:

  • Grow more quickly
  • Spread more easily
  • Return more often (called recurrence)

But they also respond well to certain "targeted medications."

Your HER2 status can change as your cancer grows or returns. That is, HER2-positive cancer can become HER2-negative and vice versa. You and your doctor may decide to retest for HER2 over time or if your cancer comes back after treatment.

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How HER2 Affects Treatment

Treatment for breast cancer depends in part on the stage and type and is different in each case, but typically involves some combination of surgery, radiation, chemotherapy, or other drug therapies. These other drug therapies depend partly on whether your cancer is HER2-positive. If it is, certain medications can work well, such as:

Monoclonal antibodies. These are lab-made versions of immune system substances designed to attach to HER2 protein on breast cancer cells.

Antibody-drug conjugates. These drugs target chemotherapy directly to HER2 protein on cancer cells.

Kinase inhibitors. These medications stop proteins like HER2 from sending signals.

How HER2 Affects Breast Cancer Stage

There are a number of things that affect the stage of your breast cancer. Whether you are HER2-positive or HER2-negative is one. Others are:

  • Size of tumor and if it's grown into tissue around it
  • Whether there's cancer in your lymph nodes
  • Whether cancer has spread beyond the breast
  • The tumor's grade (a score that measures what the cells look like and how fast they grow)
  • Whether cancer cells have receptors for the hormones estrogen and progesterone

It can be hard to figure out your stage because of the number of factors your doctor must consider. Every case is different, but there are general guidelines for each stage, and your HER2 status can make quite a bit of difference. For example, you might have breast cancer with:

  • Tumor that is 2 to 5 centimeters
  • No cancer cells detected in lymph nodes

If you're HER2-positive you're likely at stage IIA. If you're negative, you're probably still stage I.

Stage IIB could mean:

  • Tumor that is 2 to 5 centimeters
  • Cancer cells or clumps up to 2 millimeters in one or more lymph nodes

But even with these signs, you could still be at stage I if you're HER2-positive (and also positive for estrogen-receptor and progesterone-receptor)

A stage III fast growing (grade 3) tumor that's bigger than 5 centimeters might still be at stage IIA if you're positive for:

  • HER2
  • Estrogen-receptor
  • Progesterone-receptor
WebMD Medical Reference Reviewed by Melinda Ratini, DO, MS on May 26, 2020

Sources

SOURCES:

American Cancer Society: "Targeted Therapy for Breast Cancer," "Treatment of Breast Cancer by Stage," "Breast Cancer Grades," "Survival Rates for Breast Cancer," "Breast Cancer HER2 Status."

American Joint Committee on Cancer: "Physician to Physician AJCC 8th Edition Breast."

American Society of Clinical Oncology: "Breast Cancer - Metastatic: Statistics."

Breastcancer.org: "HER2 Status," "Breast Cancer Stages."

Mayo Clinic: "HER2-positive breast cancer: What is it?"

University of Rochester Medical Center: "Breast Cancer: Grades and Stages."

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