Triple-negative breast cancer is a type of breast cancer that tests negative for the receptors that are commonly found in breast cancer.
These receptors include estrogen receptors (ER), progesterone receptors (PR), and HER2 protein. This means that the growth of the cancer is not promoted by the hormones estrogen and progesterone, or by the HER2 protein.
Since these hormones or proteins do not influence cancer cell growth, triple-negative breast cancer does not respond to hormonal therapy or medicines that target HER2 protein receptors.
Triple-negative breast cancers account for about 10-20% of all breast cancers. They are more aggressive as compared to receptor-positive breast cancers.
Intense research is being carried out to find new drugs and medicines which can effectively treat triple-negative breast cancer.
Meaning of the term Triple-negative breast cancer
Cell receptors are special proteins that are found inside as well as on the surface of cells. They can be present on all cells- normal as well as cancerous. These receptor proteins act as a means of communication between the cell and the substances circulating in the bloodstream allowing them to produce their effect on those cells. The circulating substances could be hormones, growth factors, neurotransmitters, cytokines, nutrients, etc.
For eg, hormones like estrogen or progesterone can exert their effect on the breast cells only if the breast cells possess those receptors on their surface. The hormone will attach to its receptors and provide instructions that help the breast cells to grow and function properly. If the breast cell does not have hormone receptors on its surface, the circulating hormone will not be able to produce any effect on the breast cell.
HER2 is a protein that stimulates cell growth in normal, healthy breast cells. In about 20 % cases of breast cancer, the HER2 gene doesn’t work correctly and makes too many copies of itself (known as HER2 gene amplification). This promotes rapid growth and division of cancer cells.
If untreated, HER2 positive breast cancers are much more aggressive than HER2 negative breast cancers. However HER2 positive cancer cells respond to drugs such as the monoclonal antibody trastuzumab (in combination with conventional chemotherapy), and this has dramatically improved its prognosis.
Cancer cells that do not have any of these three receptors (ER, PR, or HER2) are called triple-negative breast cancers. About 10-20% of all breast cancers are negative for both hormone receptors and excess HER2, which means they are triple-negative.
If breast cancer is receptor-positive, hormonal therapies and HER2-targeted therapies can inhibit the effects of estrogen, progesterone, and the HER2 protein on cancer cells. This can reduce or stop the growth of cancer cells.
If however, breast cancer is receptor-negative (or triple-negative), the cancer cell growth does not depend on hormones or HER2 protein and will not respond to hormonal therapies and HER2-targeted therapies.
Incidence of Triple-Negative Breast Cancer
Triple-negative breast cancer accounts for about 10-20% of all breast cancers.
Risk Factors for getting Triple-Negative Breast Cancer
It is more likely to affect the following women:
- Younger women (younger than 50 years of age)
- African American women and women of Hispanic descent
- Women with BRCA1 gene mutation
Signs and Symptoms
The signs and symptoms of triple-negative breast cancer are essentially the same as for all breast cancers. These include:
- A lump in the breast or the armpit which is usually hard and painless. The lump may be fixed to overlying skin which means that it does not move beneath the skin. It may even be attached to the underlying structures of the breast.
- Change in the skin over the breast, such as dimpling or redness or scaling and crusting of the skin of the breast.
- The skin may have a pitted appearance resembling an orange peel.
- Change in the size, shape or appearance of a breast.
- A newly inverted nipple. change in the shape or appearance of the nipple.
- Discharge from the nipple which could be bloody.
Read more about Breast Lump: Causes, Diagnosis, and Treatment
Diagnosing triple-negative breast cancer
Breast cancer is diagnosed by a combination of imaging tests (mammography or ultrasound) and biopsy.
Read Breast Cancer: Risk Factors, Classification, Diagnosis, and Treatment to know more about investigations for diagnosing breast cancer.
Once a diagnosis of breast cancer is made, the receptor status of the cancer cells is checked before deciding the appropriate treatment. The breast tumor tissue is subjected to further investigations.
A sample of breast cancer cells obtained by doing a fine needle aspiration, needle biopsy, lumpectomy, or tumor removed during mastectomy is used for performing these tests. The tumor cells are stained by immunohistochemical stains for the evaluation of receptor status. If the cells do not have estrogen or progesterone receptors, and also do not make too much of the HER2 protein, the cancer is considered to be triple-negative breast cancer.
Prognosis of Triple-Negative Breast Cancer
It is more aggressive and has a poorer prognosis than other breast cancers.
Since it does not respond to hormonal or HER2 targeted therapies, fewer treatment options are available to treat it. There are greater chances of metastasis ( spreading to distant organs) as well as recurrences (coming back after treatment).
Also, it has a higher grade than other breast cancers. Higher grade means that the cancer cells are less likely to resemble normal, healthy breast cells both in their appearance and growth patterns. High-grade cancers or grade 3 or poorly differentiated cancers are more aggressive and have the worst prognosis.
It usually is a “basal-like” cancer. This means that the cells resemble the basal cells that line the breast ducts. Similar to triple-negative breast cancers, basal-like cancers are higher-grade cancers and more aggressive. Most of the basal-like breast cancers are triple-negative and vice versa.
Though aggressive, triple-negative breast cancer can be treated with a combination of surgery, radiation therapy, and chemotherapy.
However, it does not respond to hormonal therapy including drugs like tamoxifen and aromatase inhibitors. It also does not respond to medicines that target the HER2 protein, such as Herceptin (trastuzumab), Kadcyla (T-DMA or ado-trastuzumab emtansine), Nerlynx (neratinib), Perjeta (pertuzumab), or Tykerb (lapatinib).
Triple-negative breast cancers are treated with chemotherapy. These cancers show a better response to chemotherapy than hormone receptor-positive breast cancers.
Chemotherapy is usually given before surgery (also called neoadjuvant chemotherapy). This produces better response and increases disease-free survival.
Usually, a combination of drugs is given in a specific number of cycles over a set period of time. Common drugs include Capecitabine (Xeloda), Carboplatin, Cisplatin, Cyclophosphamide, Docetaxel, Doxorubicin, etc.
Platinum-based chemotherapy drugs like carboplatin and cisplatin are effective in triple-negative breast cancer women who have a BRCA1 or BRCA2 gene mutation.
The tumor and some surrounding healthy tissue are removed during an operation. The axillary lymph nodes, which are under the arm are also usually removed. It includes:
- Mastectomy (removing the entire breast)
- Double mastectomy (removing both the breasts): this is done in cases where cancer has spread to both the breasts
- Lymph node removal
Since breast cancer frequently involves the axillary nodes, these lymph nodes are removed to examine whether they have been involved by cancer or not.
High-energy rays are delivered to the affected part of the body to kill the cancer cells. The most common type of radiation treatment is external-beam radiation therapy which is given from a machine outside the body.
It is usually given after surgery to lower the risk of recurrence in the breast. If there is cancer in the axillary lymph nodes, radiation therapy may be given to the same side of the neck or underarm near the breast or chest wall.
PARP (poly ADP-ribose polymerase) inhibitors, such as Lynparza (olaparib) and Talzenna (talazoparib), are used to treat advanced-stage HER2-negative breast cancer in women with a BRCA1 or BRCA2 gene mutation.
This includes drugs that stimulate the body’s immune system to fight cancer cells. It can also be used to reduce the side effects of other cancer treatments.
An example is the drug atezolizumab (Tecentriq) which blocks a protein called PD-L1. The expression of the PD-L1 protein on the tumor cell surface helps the tumor cells to escape immunosuppression. Atezolizumab in combination with the chemotherapy drug Abraxane (paclitaxel) is given as a first-line treatment for unresectable, metastatic triple-negative, PD-L1-positive breast cancer.
Numerous research is going on regarding newer treatment modalities for triple-negative breast cancer. The patient can enroll and take part in a clinical trial.