Breast cancer is categorized according to hormone receptor and HER2 status. Triple-positive breast cancer has higher-than-typical levels of hormone receptors and HER2.

After skin cancer, breast cancer is the most common cancer in people assigned female at birth. In fact, it accounts for 30% of new cancers diagnosed in this group each year, according to the American Cancer Society (ACS).

After diagnosis, breast cancer is characterized according to its hormone receptor (HR) status and its HER2 status. Triple-positive breast cancer (TPBC) is positive for both types of HRs as well as for HER2.

This article takes a deeper look at what TPBC is, how it’s diagnosed and treated, and what the outlook is for someone who has received a diagnosis.

TPBC is breast cancer in which cancer cells are found to have higher-than-typical levels of:

Estrogen and progesterone receptors are found at higher-than-typical levels on some breast cancer cells. The binding of estrogen and progesterone to these receptors promotes cell growth.

HER2 is a protein that’s found in normal breast tissue but can be seen at higher levels in some breast cancers. Breast cancers with excess HER2 tend to be more aggressive, growing and spreading faster.

The overall prevalence of TPBC isn’t well documented. However, the SEER database of the National Cancer Institute notes that 10% of breast cancers are HR-positive and HER2-positive.

A 2018 article that looked at the therapeutic challenges of triple-positive breast cancer, found that among 114 HR+/HER2+ cases:

  • 71% were triple positive
  • 21% were ER+/PR-/HER2+
  • 8% were ER-/PR+/HER2+

The exact risk factors for TPBC specifically aren’t known. One 2021 study found that the following factors were associated with an increased risk of HR-positive, HER2-positive breast cancer:

Risk factors for HR-positive breast cancer

Prolonged exposure to estrogen and progesterone may increase the risk of HR-positive breast cancers. Examples of risk factors related to hormones include:

The ACS also notes that behavioral risk factors like engaging in low amounts of physical activity and frequent, heavy use of alcohol are linked with an increased risk of HR-positive breast cancers.

Risk factors for HER2-positive breast cancer

Being an older age is a risk factor for breast cancer in general. However, some research suggests that younger individuals are more likely to be diagnosed with HER2-positive breast cancer.

Additional risk factors for breast cancer

In addition to the factors discussed above, further risk factors for breast cancer in general include:

When breast imaging, such as with a mammogram or breast ultrasound, finds a concerning area, the only way to know for sure if it’s cancerous is to collect a breast biopsy.

The biopsy sample is examined under a microscope to look for cancer. If cancer is found, tests can be done on it to further characterize the cancer. These include tests for HR and HER2 status:

  • Immunohistochemistry (IHC): HR and HER2 status is typically determined using IHC. This uses a special stain that identifies the levels of HRs and HER2 on the surface of cancer cells.
  • Fluorescence in situ hybridization (FISH): FISH uses a fluorescent dye to find extra copies of the HER2 gene. Extra copies of this gene can indicate that cancer cells have higher levels of HER2 protein on their surface.

Multigene panels can also look into the genetics of the cancer. OncotypeDX testing helps doctors determine if additional treatment is needed after surgery. Further genetic testing, such as Myriad MyRisk can help test for mutations such as BRCA 1 or 2.

Additional imaging tests like CT scan, MRI scan, or PET scan can determine how far the cancer has spread.

There are several aspects to the treatment of TPBC. Let’s look at these now.

Surgery for triple-positive breast cancer

One of the main treatments for breast cancer in general is surgery to remove as much of the cancer as possible. Depending on the type of cancer or the size of the tumor, this may involve breast-conserving surgery or mastectomy.

Hormone therapy and targeted therapy for triple-positive breast cancer

Because TPBC has HER2 and both HRs on its cells, it can be treated with targeted therapy and hormone therapy. These treatments may be given:

  • before surgery to help shrink a tumor
  • after surgery to help destroy remaining cancer cells and prevent cancer from coming back
  • before and after surgery
  • as the main component of treatment if surgery isn’t possible or you choose not to have surgery

Hormone therapy aims to block estrogen and progesterone from attaching to their receptors. When these hormones cannot bind to their receptors, it can help to slow or stop the growth of the cancer.

Targeted therapy is directed at inhibiting certain markers associated with cancer cells. There are many targeted therapies aimed at HER2-positive cancers, such as:

  • monoclonal antibodies that target HER2, like trastuzumab (Herceptin)
  • HER2-specific antibodies linked to chemotherapy drugs, such as fam-trastuzumab deruxtecan (Enhertu)
  • kinase inhibitors that block HER2 signaling like lapatinib (Tykerb)

Some targeted therapies can also help hormone therapy to work better, according to the ACS. Examples include CDK4/6 inhibitors like palbociclib (Ibrance) or mTOR inhibitors like everolimus (Afinitor).

A challenge to the treatment of TPBC is the potential “crosstalk” between the biological pathways associated with HRs and HER2. This can make treatment with hormone therapy or targeted therapy less effective.

A 2021 review points out that some TPBCs may need to be treated with both hormone therapy and HER2-directed targeted therapy. A 2020 review notes that trials of treatments targeting both the HR and HER2 pathways are an area of major interest.

Other treatments for triple-positive breast cancer

Additional treatments that may be a part of your TPBC treatment include:

The outlook for someone with TPBC can depend on several factors. These include:

  • the specific type of breast cancer you have
  • the stage of your cancer
  • how fast the cancer is growing and spreading
  • the genetics of your cancer
  • the type of treatment used and how the cancer responds to it
  • whether the cancer is a new diagnosis or a recurrence of a previous cancer
  • your age, overall health, and menopausal status

The table below shows the 5-year survival rates for breast cancer that’s HR-positive and HER2-positive, according to the SEER database.

SEER stage5-year relative survival rate
localized to the breast99.1%
spread to regional tissues89.8%
spread to distant tissues45.6%

A 2022 study found within the population studied, the 5-year overall survival for TPBC was 96.7%, compared to 82.7% for HR-negative, HER2-positive breast cancer.

TPBC is breast cancer that has higher-than-typical levels of estrogen receptors, progesterone receptors, and HER2 protein. HR and HER2 status are determined during breast cancer diagnosis.

Surgery is used to treat many breast cancers. TPBC can also be treated with hormone therapy or targeted therapy. However, careful consideration must be used, as TPBC can be resistant to hormone therapy or targeted therapy alone.

Every person with breast cancer is different. If you’ve been diagnosed with TPBC, talk with your oncologist about what that means for your individual treatment plan and outlook.