Triple Positive Breast Cancer: Prognosis and Treatments

HER2-positive, ER-positive, and PR-positive

Jennifer Welsh is a Connecticut-based science writer and editor with over ten years of experience under her belt. She's previously worked and written for WIRED Science, The Scientist, Discover Magazine, LiveScience, and Business Insider.

Gagandeep Brar, MD, is a board-certified hematologist and medical oncologist in Los Angeles, California.

Triple-positive breast cancer has three features that influence its prognosis and set it apart from other subtypes of breast cancer. It grows in response to two hormones and makes a lot of a protein called human epidermal growth factor receptor 2 (HER2).

While these features mean cancer grows fast, it also means that it has many treatment options. It responds to both hormone treatments and targeted treatments against HER2. However, new research suggests that it may not respond as well to these drugs as other breast cancers with HER2.

While triple-positive breast cancer can be aggressive, the outlook for this type of cancer is better than triple-negative breast cancer and cancers with HER2 but without hormone receptors. Triple-negative breast cancers have the lowest survival rate of all breast cancer subtypes.

This article explains the general outlook for triple-positive breast cancers and what you can do to improve your prognosis and quality of life. The article also covers how many people survive triple-positive breast cancer and how likely it is to return.

Isaac Lane Koval/Corbis/VCG / Getty Images

Triple-positive is one of the many subtypes of breast cancer. The subtypes are defined by their molecular characteristics—the proteins they make and the genes they express. The two main proteins that define a subtype are the hormone receptors and the HER2 protein.

The cell's hormone receptors are proteins on its surface that see signals from hormones and make cancer cells grow. The most critical hormones in breast cancers are estrogen and progesterone. Cancers can be hormone receptor-positive (HR-positive), which means the cancer cells have estrogen receptors (ER), progesterone receptors (PR), or both.

Cancer cells with hormone receptors are typically slow growing and respond well to treatments that block the hormone signals.

HER2 is a growth-promoting protein expressed by some breast cancers. About 15% to 25% of breast cancers make a lot of HER2.

HER2-positive breast cancers grow and spread quickly, but there are treatments targeted at them. These treatments give people with HER2-positive cancers more options.

According to the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Result (SEER) cancer database, the four molecular subtypes of breast cancer are:

In approximately 7% percent of cases in the NCI database, the subtype is unknown.

Triple-positive breast cancers fall under the HR-positive/HER2-positive subtype, a heterogeneous group of cancers. HR-positive/HER2-positive breast cancer includes cancers that are:

HR-positive/HER2-positive cancers are typically given a higher score that indicates how abnormal cancer cells look in the lab (grade) than HR-positive/HER2-negative cancers. They also have worse outcomes.

Triple-positive breast cancer falls under the HR-positive/HER2-positive category because it's HR-positive and HER2-positive. A small portion of these cancers and triple-positive cancers have some unique features because they have both ER and PR.

Triple-positive and other HR-positive/HER2-positive cancers are generally more aggressive and have a slightly less positive outlook than other breast cancers. However, the outlook for triple-positive breast cancer is better than it is for triple-negative breast cancer.

There is not a lot of specific data on triple-positive breast cancer prognosis. In a small study of people with triple-positive breast cancers, 5.9% died within 33 months of diagnosis.

Generally, HR-positive cancers have a better prognosis because they respond to hormone therapies. They also typically grow slower than HR-negative cancers. While they may recur, this normally does not happen for many years after treatment.

HER2-positive cancers generally have a worse prognosis than HER2-negative cancers. However, this might change with the development of targeted therapies against HER2.

According to NCI data, the five-year relative survival rate for HR-positive/HER2-positive female breast cancer is 90.7%.

NCI data is also broken down by how advanced the disease is when diagnosed:

HR-positive/HER2-negative breast cancers have the best survival statistics of all breast cancer subtypes. HR-positive/HER2-positive, which includes triple-positive breast cancers, have the second-best survival pattern. HR-negative/HER2-positive cancers have worse survival rates, and HR-negative/HER2-negative (triple-negative) have the worst.

A 2018 study that specifically looked at triple-positive breast cancer in Korea found a survival rate between that of HR-positive/HER2-negative and HER2-enriched subtypes, similar to the rates from the NCI database.

Triple-positive breast cancers can come back, but they’re usually slower to recur than other types of breast cancer. They often come back more than five years after initial treatment, which may give people a false sense of security. On the other hand, HER2-positive/ER-negative cancers typically come back before five years.

For example, in the 2018 Korean breast cancer study, people with an average follow-up of a bit over six years had the following rates of recurrence:

The primary treatment for breast cancers of all kinds is surgery to either remove the cancerous lump (breast-conserving surgery) or the entire breast (mastectomy). Surgery can also involve removing and testing lymph nodes in the chest for cancer.

In addition to surgery, breast cancer treatment can also include:

For triple-negative breast cancers, chemotherapy might be needed before or after surgery if your cancer is advanced (stage 2 or stage 3) or has genetic signals that suggest it may come back after treatment.

In addition, many breast cancers are treated with radiation after surgery to make sure all of the cancer is killed. This is usually done when a person opted for breast-conserving surgery or cancer was found in four or more lymph nodes.

In addition to these typical treatments for breast cancers, triple-positive breast cancers can also benefit from HER2-targeted and hormone therapies.

HER2 therapy targets cells that express high levels of the HER2 protein. Therapies that specifically target HER2 include monoclonal antibodies, antibody-drug conjugates, and kinase inhibitors.

Monoclonal antibodies are manufactured versions of immune system proteins called antibodies that bind to cellular proteins (in this case, HER2). Examples include:

Antibody-drug conjugates are anti-cancer drugs glued to antibodies targeting HER2. They find the cancer cells using HER2, block the HER2 signal, and drop off deadly drugs. Examples include:

Kinase inhibitors block the signals that the HER2 protein uses to tell the cells to grow. Examples include:

In addition to HER2 therapies, triple-positive cancers may respond to hormone therapy. These drugs stop or block hormones from reaching the cancer cells. They may stop your body from making hormones or binding to the cancer cells' receptors. These halt the growth signals that the hormones are sending to cancer.

These drugs are typically taken for many years after other treatments have stopped because they help reduce the chance that cancer will return. Hormone therapy, also called endocrine therapy, for breast cancer may include selective estrogen receptor modulators (SERMs) that block estrogen signals in the breast tissue but act like estrogen in other tissues. SERMs include:

Selective estrogen receptor degrader (SERD) can turn down the estrogen signals throughout the body. Examples include:

Aromatase inhibitors turn down the body's production of estrogen. They are only for post-menopausal people. Examples include:

One complicating factor is recent evidence that triple-positive breast cancers may not react as well to HER2 and hormone therapies as other cancers that are only HER2-positive or only HR-positive.

Targeting both pathways for treatment seems to cause "crosstalk" within the cancer cells, which appears to lower the efficacy of both types of treatment. According to an Italian study of people with triple-positive breast cancer, this is most evident in triple-positive cancers that express high levels of both hormone receptors.

In a 2018 Korean study, the HER2-targeted drug trastuzumab did not improve overall survival among people with triple-positive breast cancer. However, it did increase survival for people with the HER2-enriched subtype.

There is still debate about how effective HER2 or hormone therapies are against triple-positive breast cancers. They may prolong survival, even if they are less effective. Other HER2 treatments may work better than trastuzumab.

Breast cancer is most treatable—and curable—when it's caught early. The best way to improve your breast cancer prognosis is to get screening mammograms regularly when your healthcare providers suggest and follow up with them about any concerning symptoms.

The less advanced your cancer is when it's found, the more accessible treatment is and the better your outlook—no matter the subtype.

If you’ve already been diagnosed with triple-positive breast cancer, consider these steps to improve your outlook:

Triple-positive breast cancers are a newly recognized and unique subset of hormone receptor-positive and HER2-positive breast cancers. They make up a small portion of all breast cancers.

While there are many treatment options, this subtype of cancer's unique molecular characteristics may make some treatments less effective than they would be for other breast cancers.

Generally, the survival rate for triple-positive breast cancers is better than for triple-negative breast cancers but lower than it is for breast cancers that do not have high levels of HER2.

Any diagnosis of breast cancer is distressing. While triple-positive breast cancer can be aggressive, it will be comforting to know that it has many treatment options and an overall good outlook.

Several factors influence a tumor's aggression, including its biological makeup, size, stage (how far it has spread), etc. Here are some key takeaways about the aggressiveness of different breast cancers:

Triple-positive breast cancer is a more aggressive subtype of cancer, as it has a lot of growth-promoting HER2 proteins. In a study of 85 people in the United States with triple-positive breast cancer, 58.9% had cancer in their lymph nodes when they were first diagnosed.

Chemotherapy is often used to treat triple-positive breast cancer, especially at stage 2 or 3. It can be used before surgery or after.

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By Jennifer WelshJennifer Welsh is a Connecticut-based science writer and editor with over ten years of experience under her belt. She's previously worked and written for WIRED Science, The Scientist, Discover Magazine, LiveScience, and Business Insider.