Triple-Negative Breast Cancer

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Triple-negative breast cancer is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein.

These results mean the growth of the cancer is not fueled by the hormones estrogen and progesterone, or by the HER2 protein. So, triple-negative breast cancer does not respond to hormonal therapy medicines or medicines that target HER2 protein receptors. Still, other medicines are used to successfully treat triple-negative breast cancer.

About 10-20% of breast cancers are triple-negative breast cancers. For doctors and researchers, there is intense interest in finding new medications that can treat this kind of breast cancer. Studies are trying to find out whether certain medications can interfere with the processes that cause triple-negative breast cancer to grow.

What is triple-negative breast cancer?

Cell receptors are special proteins found inside and on the surface of cells. These receptor proteins are the “eyes” and “ears” of the cells, receiving messages from substances in the bloodstream and then telling the cells what to do.

Hormone receptors inside and on the surface of healthy breast cells receive messages from the hormones estrogen and progesterone. The hormones attach to the receptors and provide instructions that help the cells continue to grow and function well. Most, but not all, breast cancer cells also have these hormone receptors. Roughly two of three breast cancers test positive for one or both of these hormone receptors. (For a more complete explanation, see the Hormone Receptor Status page.)

A smaller percentage of breast cancers — about 20% — make too much of the HER2 protein. In normal, healthy breast cells, the HER2 stimulates cell growth. When breast cancer cells have too much of the HER2 protein, however, the cells grow and divide too quickly. (For a more complete explanation, see the HER2 Status page.)

Hormonal therapies and HER2-targeted therapies disrupt the effects of estrogen, progesterone, and the HER2 protein on breast cancer, which can help slow or even stop the growth of breast cancer cells.

About 10-20% of breast cancers test negative for both hormone receptors and excess HER2 in the lab, which means they are triple-negative. Since hormones aren’t fueling the cancer’s growth, the cancer is unlikely to respond to hormonal therapy medicines, including tamoxifen and aromatase inhibitors. Triple-negative breast cancer also is unlikely to respond to medicines that target the HER2 protein, such as Herceptin (chemical name: trastuzumab), Kadcyla (chemical name: T-DMA or ado-trastuzumab emtansine), Nerlynx (chemical name: neratinib), Perjeta (chemical name: pertuzumab), or Tykerb (chemical name: lapatinib).

Three common features of triple-negative breast cancer

  • Triple-negative breast cancer is considered to be more aggressive and have a poorer prognosis than other types of breast cancer, mainly because there are fewer targeted medicines that treat triple-negative breast cancer. Studies have shown that triple-negative breast cancer is more likely to spread beyond the breast and more likely to recur (come back) after treatment.
  • It tends to be higher grade than other types of breast cancer. The higher the grade, the less the cancer cells resemble normal, healthy breast cells in their appearance and growth patterns. On a scale of 1 to 3, triple-negative breast cancer often is grade 3.
  • It usually is a cell type called “basal-like.” “Basal-like” means that the cells resemble the basal cells that line the breast ducts. Basal-like cancers tend to be more aggressive, higher grade cancers — just like triple-negative breast cancers. Most but not all basal-like breast cancers are triple negative, and most but not all triple-negative breast cancers are basal-like.

Who gets triple-negative breast cancer?

Anyone can be diagnosed with triple-negative breast cancer. Still, researchers have found that it is more common in:

  • Younger people. Triple-negative breast cancer is more likely to be diagnosed in people younger than age 50. Other types of breast cancer are more commonly diagnosed in people age 60 or older.
  • African-American and Hispanic women. Triple-negative breast cancer is more likely to be diagnosed in African-American women and Hispanic women. Asian women and non-Hispanic white women are less likely to be diagnosed with this type of cancer.
  • People with a BRCA1 mutation. About 70% of breast cancers diagnosed in people with an inherited BRCA mutation, particularly BRCA1, are triple-negative.

If you are diagnosed with triple-negative breast cancer

It can be upsetting and scary to find out that you’ve been diagnosed with a type of breast cancer that is often more aggressive than other types and isn’t a good candidate for treatments that target the hormone receptors or HER2 protein.

Still, it’s important to remember that the lack of hormone receptors and excess HER2 protein are just two factors that you and your doctor will take into consideration when deciding on a treatment plan. The stage and grade of the cancer are also crucial to your prognosis.

It’s also important to remember there are therapies available that can treat triple-negative breast cancer.

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Treatment for triple-negative breast cancer

Triple-negative breast cancer is typically treated with a combination of surgery, radiation therapy, and chemotherapy.

Neoadjuvant chemotherapy

Research has shown that when triple-negative breast cancer is treated with chemotherapy before surgery — what doctors call neoadjuvant chemotherapy — and there is a pathologic complete response, disease-free survival and overall survival are better.

One way for doctors to judge the effectiveness of neoadjuvant treatment is to look at the tissue removed during surgery to see if any active cancer cells are present. If no active cancer cells are present, doctors call it a “pathologic complete response” or pCR.

Disease-free survival is how long a person lives without the cancer recurring. Overall survival is how long a person lives whether or not the cancer recurs.

PARP inhibitors

PARP inhibitors, such as Lynparza (chemical name: olaparib) and Talzenna (chemical name: talazoparib), have been approved to treat advanced-stage HER2-negative breast cancer in people with a BRCA1 or BRCA2 mutation.

The poly ADP-ribose polymerase (PARP) enzyme fixes DNA damage in both healthy and cancer cells. Research has shown that medicines that interfere or inhibit the PARP enzyme make it even harder for cancer cells with a BRCA1 or BRCA2 mutation to fix DNA damage. This makes it harder for the cancer cells to survive. In other words, a PARP inhibitor makes some cancer cells less likely to survive their DNA damage.

Immunotherapy

Research also suggests that the immunotherapy medicine Tecentriq (chemical name: atezolizumab) combined with the chemotherapy Abraxane (chemical name: albumin-bound paclitaxel or nab-paclitaxel) improves outcomes for people diagnosed with advanced-stage triple negative breast cancer compared to Abraxane alone.

Immunotherapy medicines work by helping your immune system work harder or smarter to attack cancer cells. Tecentriq is an immune checkpoint inhibitor medicine, which means it targets a specific protein that helps cancer cells hide from the immune system, in this case, the PD-L1 protein. By inhibiting PD-L1, Tecentriq essentially allows immune system cells to “see” the cancer cells and kill them.

You can visit Treatment and Side Effects for more information about surgery, radiation therapy, chemotherapy, targeted therapies such as PARP inhibitors, and immunotherapy.

Clinical trials using these and other therapies could play a key role in improving the treatment of triple-negative breast cancer. Talk to your doctor if you think you might be interested in taking part in a clinical trial.

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Pathology Report ThumbnailYour Guide to the Breast Cancer Pathology Report is an on-the-go reference booklet you can fill out with your doctor or nurse to keep track of the results of your pathology report. Order a free booklet by mail or download the PDF of the booklet to print it at home.


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