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What is Triple-Positive Breast Cancer?

breast cancer ribbon cartoon

In patients who have been diagnosed with breast cancer, doctors look at the breast cancer cells under the microscope. This is done using a biopsy sample or tumor if the patient has undergone surgery. Doctors also review the results of imaging and other tests to help them understand what type of breast cancer a patient has. Based on this, the medical team determines the breast cancer type. This information is important to decide on the most appropriate treatment in breast cancer patients. One of the labels that doctors give to breast tumors is triple-positive breast cancer. Continue reading to learn more about what this means in terms of treatment and survival rates.

What does triple-positive mean in breast cancers?

The type of breast cancer you have determines how your cancer will behave and what treatments are likely to be most effective. Doctors look at various things in breast cancer patients. One is the pathology report which shows where the breast cancer arises (milk ducts, milk-producing lobules, or connective tissues in the breast). Based on this, the cancer is labeled as invasive ductal carcinoma, invasive lobular carcinoma, or other breast cancers. 

Estrogen Receptor and Progesterone Receptor

Another factor that doctors evaluate is whether the breast cancer cells are sensitive to female hormones like estrogen and progesterone. Some cancer cells are ER-positive, meaning they have estrogen receptors fuelled by the female hormone estrogen to grow. About 80% of breast cancers are ER-positive. Treatment with anti-estrogen therapy in such breast cancers can stop the growth of the tumor. Similarly, progesterone receptor-positive breast cancers are labeled PR positive. They are sensitive to the female hormone progesterone. Hormone or endocrine therapy can block the growth of these breast cells with cancer. 

HER2 Gene

HER2 is a growth-promoting protein that is present in all breast cells. Some breast cancer cells have many copies of this gene HER2 (human epidermal growth factor receptor 2). Such breast cancers are called HER2-positive tumors, and around 25% of breast cancers are HER2-positive. Targeted therapies that shut down this gene are effective in killing these cancer cells. 

Triple Positive Breast Cancer

Triple-positive breast cancer is one in which the breast cancer cells are ER-positive, PR-positive, and HER2-positive. Triple positive breast cancers are also called group 2 or luminal B cancers. These tumors benefit from surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy against HER2. It is estimated that approximately 10% of breast cancers are triple positive. Meaning, they have hormone receptors (ER and PR) as well as HER2 gene amplification.

Other molecular subtypes include group 1 (luminal A) cancers that are ER and PR positive but HER2 negative. Group 3 cancers are HER2 positive but ER and PR negative. Group 4 breast cancers are negative for ER, PR, and HER2. They are also called triple-negative breast cancer.

Understanding your breast cancer’s chemical and genetic makeup helps your doctors choose the most effective treatment for you.

Which is the most aggressive form of breast cancer?

The most aggressive and serious type of breast cancer is metastatic breast cancer. Metastatic disease means the cancer has spread from the original tumor site to other parts of the body. Metastatic breast cancer, also called stage 4 breast cancer, has spread from the breast to other parts of the body, such as the liver, lungs, bones, or brain.

In terms of hormone receptor status, triple-negative cancer cells are more aggressive, tend to occur in younger patients, are often diagnosed at later stages, and are more likely to metastasize. Breast cancers that are HER2-positive also tend to be aggressive with lower survival rates. They frequently do not respond to hormonal therapy. However, triple-positive breast cancers that are estrogen receptor-positive, progesterone receptor-positive, and HER2 positive behave more like ER-positive and HER2-negative tumors. They tend to be less aggressive and more responsive to endocrine therapy (hormone therapy). Nonetheless, tumors that are triple positive tend to be more aggressive than those that are ER-positive alone. 

In general, cancer cells that are estrogen receptor-positive alone have the best prognosis or outcomes, followed by triple positive cancer cells, HER2 positive tumors, and triple-negative tumors (worst prognosis).

Keep in mind that each patient is unique, and their cancer can behave unexpectedly. Doctors can, however, provide a prognosis based on the tissue sample, imaging, lymph nodes, metastasis, and other factors.

How fast does triple-positive breast cancer grow?

Different types of breast cancer grow at different rates. Again, each patient is unique, and it is difficult to estimate how quickly breast cancer will grow. In general, triple-negative and HER2-positive tumors are fast-growing. Hormone receptor-positive (ER-positive and PR-positive tumors) grow more slowly. The stage of cancer (local disease vs. metastatic disease) is also reflected in the growth rate. Cancer that has spread to other organs is more likely to continue spreading. Higher grade tumors (cancer cells that look very different from normal breast cells) also tend to grow faster. The patient’s age is a factor. Younger patients tend to have more aggressive, faster-growing tumors than older women. Lastly, some women have genetic mutations associated with a higher risk of developing breast cancer at a young age. These mutations can be associated with more aggressive forms of breast cancer that spread faster.

Is chemo necessary for triple-positive breast cancer?

Triple positive breast cancers are treated with chemotherapy, neoadjuvant chemotherapy, surgery, radiation therapy, hormone drugs, and targeted therapy (HER2-directed therapy or drugs that target HER2). The medical team develops an individualized treatment plan for each patient based on various factors, including the tumor’s hormone receptor expression. Initial treatment may consist of surgery followed by other modalities. 

The National Comprehensive Cancer Network (NCCN) has a range of free resources for patients who wish to learn more about treatment options for their breast cancer.

Is hormone therapy effective for triple-positive breast cancer?

Triple positive breast tumors are both ER and PR positive. Therefore, hormone or endocrine therapy is effective against these types of breast cancer cells. Hormonal drugs prevent estrogen and progesterone hormones from attaching to the ER and PR receptors on the cancer cells. Thus, hormone therapy can reach cancer cells anywhere in the body, not just in the breast. However, it is ineffective against tumors that don’t have hormone receptors, such as triple-negative breast cancers.

It is worth noting that triple-positive cancers can behave differently from ER-positive or HER2-positive cancers alone. For example, there can be “crosstalk” between the receptors, making hormone therapy, such as anti-estrogen therapy, less effective in triple-positive tumors. Similarly, crosstalk between the receptors can make triple-positive breast cancers resistant to HER2-targeted therapy.

What is the survival rate of triple-positive breast cancer?

According to the American Cancer Society, the 5-year survival rate for localized breast cancer is 99%. For breast cancer with regional spread (to lymph nodes or nearby structures) the survival rate is 86%, and for breast cancer with metastasis (distant spread) is 28%. The overall survival rate for all stages is 90%. This means breast cancer patients are 90% as likely as healthy people to live for at least 5 years after their diagnosis of breast cancer.

In general, the behavior and survival rate for triple-positive breast tumors is similar to ER-positive/HER2-negative tumors. One study in California that looked at nearly 125,000 women with breast cancer found no major difference in survival rates between these types of tumors. Triple-negative tumors, in general, have a shorter survival rate compared to triple positive tumors. With that said, each patient and their cancer is unique. As noted, crosstalk between estrogen receptors and HER2 can lead to treatment resistance to hormonal therapies and HER2-directed treatments, reducing the survival rate. 

 

References:

  1. https://www.hindawi.com/journals/jce/2014/469251/
  2. https://www.mayoclinic.org/diseases-conditions/breast-cancer/in-depth/breast-cancer/art-20045654
  3. https://pubmed.ncbi.nlm.nih.gov/27644638/
  4. https://health.clevelandclinic.org/how-fast-does-breast-cancer-spread/
  5. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html
  6. https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html
  7. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-survival-rates.html