It is well known that one in eight women will have breast cancer at some point in their lives. Up to 20% of these cases will be of a special, more aggressive type called Triple Negative breast cancer. This article will discuss what triple negative breast cancer is, and will elaborate on the following points: Triple negative breast cancer risk factors, symptoms, diagnosis, staging, treatment, prognosis, survival rates, life expectancy, metastasis, recurrence, diet, and the TNBC foundation.
What is Triple negative breast cancer?
Breast cancer refers to a disease characterized by the uncontrolled division and replication of cells within the breast, forming a mass that shouldn’t be there. Like all types of cancer, breast cancer is divided into two types: Benign and malignant. Benign tumors are those that, while still harmful and abnormal, lack the ability to spread or “metastasize” to other parts of the body after appearing in the breast. Malignant tumours, on the other hand, can metastasize and this is why they are considered much more dangerous. Indeed, a tumor that is confined to one body part can be removed through a surgical procedure, but a swelling that keeps spreading around and appearing in more than one location means that surgery most likely will not cure it.
So what does the Triple Negative part refer to? It means that the tumor cells lack three distinct and clinically relevant structures: Estrogen receptors, Progesterone receptors, and a gene called HER2. To understand what this means, we need to talk physiology.
Estrogen and progesterone are the primary female sex hormones. The brain contains a structure called the hypothalamus. This secretes a substance (Gonadotropin releasing hormone or GRH) that acts on another brain structure called the pituitary gland. The pituitary has many functions, and it performs these functions by releasing chemicals that get into the circulation, and thereby reach and stimulate different glands to produce their unique and essential hormones. This includes stimulating the adrenal gland to secrete cortisol, stimulating the thyroid gland to secrete T3 and T4, and stimulating the ovaries to produce Estrogen and progesterone. Normally, the two hormones are responsible for the regulation of the menstrual cycle, development of a feminine voice, production of milk in the mammary glands of the breast, support of the baby and placenta during pregnancy, the contouring of the female body, and many other functions.
For our purposes, there is a pathologic side to estrogen and progesterone when it comes to breast cancer. Some types of breast cancer are special in the fact that their cells contain receptors that are activated by the presence of the two female sex hormones. Think of it like a key going into a lock; when these cancer cells are affected by estrogen and progesterone, they grow in size. Since women normally continue to produce large amounts of estrogen and progesterone until the age of menopause, these types of breast cancer have an ample amount of stimulation to grow. There is a useful side to this feature, however. We can actually use the hormone receptors against the tumors. Certain medications, such as a drug called tamoxifen, are very similar in molecular structure to estrogen and progesterone. So similar, in fact, that they can trick the the hormone receptors present on the surface of the cancer cells into thinking that they are actually the female sex hormones that the tumor uses to grow. The only difference is that these drug molecules do not stimulate the tumor to grow. Instead, they fill up the hormone receptors of the cancer cells and prevent them from binding estrogen or progesterone. Like a plant whose water supply is cut, the tumor eventually shrinks and dies.
Not so in triple negative breast cancer. These tumors lack both estrogen receptors and progesterone receptors, thus they cannot be treated using any drug that mimics the two female sex hormones. This shortens the list of possible treatment modalities and so makes it more difficult to treat triple negative breast cancers.
The third and last part of the triad that characterizes triple negative breast cancer concerns the field of genetics. It was found that many patients who have breast cancer have a certain gene in their DNA called HER2, which stands for human epidermal growth factor receptor 2. It is also sometimes called HER2/neu. To explain the significance of the presence or absence of this gene, let’s take a look at what genes actually do.
DNA (Deoxyribonucleic acid) consists of tiny particles called nucleotides. DNA can be divided into discrete segments called genes. Each gene functions to generate a set of amino acids that combine to form larger compounds called polypeptides that ultimately coalesce into proteins. The resulting proteins have hundreds of functions ranging from creating a person’s bodily organs to their blood components, secretions, neurotransmitters, and so on and so forth. However, a gene can turn into an unwanted guest if instead of helping the body function optimally, it starts to support tumor growth. A gene that has an accidental mutation may turn into what is called an oncogene. The word’s etymology shows the nature of these abnormal genes, as “Onco” is the same latin prefix used in the field of cancer treatment: Oncology. Thus, these tumors generate bad proteins that are associated with tumor growth. Indeed, patients with breast cancer who test positive for the presence of the HER2 gene have a bad prognosis and are more likely to experience a recurrence of the tumor after having had it surgically removed. However, the upside is that like in tumors with estrogen receptors and progesterone receptors, some medications can supress the HER2 gene, and thus prohibit the tumor cells from receiving its vital growth factors. Synthetically created “monoclonal antibodies” target and attack the oncogene, and are thus able to reduce the tumor growth and contribute to reaching a cure for the breast cancer.
This is unfortunately not the case for triple negative breast cancer, though. Since it has no oncogene that can be targeted, its growth is more difficult to inhibit, and the number of available treatments for it shrinks.
Continue reading to learn about risk factors for triple negative breast cancer now.
Risk factors for triple negative breast cancer
Triple negative breast cancer is more common in women who are under 40 years of age, those of African American descent, and those who test positive for the presence of a harmful mutant gene called BRCA 1 (short for BReast CAncer).
Triple negative breast cancer symptoms
The symptoms caused by triple negative breast cancer are the same as the ones that are caused by other breast cancer types. Thus, these manifestations can be divided into three groups: The first group concerns the symptoms caused by the presence of the cancer at its original location inside the breast tissue. Group number two is about the symptoms caused by the swelling as a result of its spread or metastasis to far away body sites. The third and final group of symptoms includes the effects caused by the cancer on the whole body as a result of the chemical substances that the tumor synthesizes within its cells.
Symptoms caused by the tumor at its primary location include breast pain, the feeling of the presence a lump or mass within the breast, an abnormal discharge or secretion from the nipple, the turning inwards of the nipple, or any other visible physical deformity altering the breast’s shape.
Triple negative breast cancer metastasis can cause a variety of symptoms, which depend on the location to which the tumor has spread. For example, breast cancer that spreads to the bone can cause bony pain and swelling, as well as a propensity for fractures even after minor trauma. A tumor that metastasizes to the lungs may cause difficult breathing and coughing up blood. It is very difficult to diagnose a metastatic tumor without a radiological study and an tissue biopsy.
Lastly, breast cancer whether triple negative or not, can cause the patient to have a fever, become fatigued and worn out, and to sweat profusely at night, in addition to the symptoms caused by any hormones created by the tumor cells’ protein synthesizing machinery.
Diagnosis of triple negative breast cancer
There’s no way around the fact that triple negative breast cancer is a more aggressive form of the disease. Thus, the important of an early diagnosis of the tumor, if possible, cannot be overemphasised. Left to its own devices, this form of breast cancer will most likely spread to different body parts, and a patient whose body shows multiple tumors has a poor prognosis and is not curable through surgery.
With that being said, the diagnostic process begins with the patient explaining her complaints to the physician, including when she first started feeling any discomfort, the side where the symptoms are present, and any relevant family history, such as that of a close relative who had suffered from breast cancer.
Next, the patient’s top half is unclothed and the physician inspects the breast in question. He/She may palpate the breast thoroughly to detect the presence of a solid mass, and then note the specific characteristics of said swelling, including its approximate size, shape, consistency, surface, and whether it is tender or not among many other traits. This may be accompanied by a physical examination of the lymph nodes around the breast, such as those residing in the armpit. Since these lymph nodes constantly drain fluid from the affected breast, they are more likely to be diseased in the presence of breast cancer in the breast in question.
The third and most important aspect of triple negative breast cancer diagnosis are the investigations. We start with the least invasive and most basic procedure: An imaging study.
Like other cancers and even non-cancerous diseases, a plain X-ray, a CT (Computed tomography) scan, or an MRI (Magnetic resonance imaging) scan of the chest can be done. However, due to the importance and prevalence of breast cancer, a specific imaging modality was created to allow easier and more accurate diagnosis of this disease: The mammogram. This investigation entails the placement of the diseased breast between two curved acrylic plates that compress its tissue, then waves of electromagnetic radiation are aimed and fired at the breast from multiple angles. The compression of the breast, while it can cause some temporary discomfort, flattens and thins out the breast tissue, which helps the radiation to penetrate it more thoroughly, resulting in a clearer and more accurate final image. In addition, since the rays are shot from more than one angle, this gives the physician a view of the breast and its contents from multiple sides, allowing him/her to discern overlapping structures, and to visualize artefacts that may be difficult to find when looking from one viewpoint only. There are even new technological advances that improve the effectiveness of mammography, such as what is known as 3D mammography. Instead of taking two radiographic images of the breast from two angles, 3D mammography or digital breast tomosynthesis uses a revolving camera that shoots all around the breast, giving the radiologist an even better view of the potential mass.
A mammogram is a cheap, effective, and widely available diagnostic tool that has saved many women’s lives, however the other imaging studies do have some value as well. For example, an MRI is better than a mammogram when diagnosing a patient who has surgically augmented breasts (breast implants).
After the radiological study that has been used detects an abnormal mass within the breast, a part of the swelling must be extracted and studied under a powerful microscope. This can be done through a small incision in the breast, or through a tissue biopsy needle.
Whatever the method employed, the tumor tissue sample is sliced, stained, and put onto a small glass slide for microscopic examination. This allows the pathologist to look at the tumor cells in detail, noting any abnormal characteristics that may be found. This is a necessary step to determine the histological type of the cancer, which has a huge impact on the prognosis, survival rates, and treatment methods used.
Another important piece of information regarding the prognosis is the “stage” of the tumor. This is based on the tumor size, whether or not it has spread to the lymph nodes nearby, and whether or not it has spread to other sites beyond the original tumor location in the breast. For reference, this is a simplified version of the different stages of triple negative breast cancer:
Stage 0 triple negative breast cancer: The cancer cells are only present inside the mammary gland ducts, and show no evidence of invasion of the surrounding tissues. Thus, breast cancer of this stage is described as “non-invasive”. No distant metastases are present.
Stage 1 triple negative breast cancer: The cancer becomes invasive. It is no longer confined to the breast ducts, on the contrary it starts to encroach upon the other parts of the breast, but only minimally. The nearby lymph nodes may or may not be affected, and the tumor size does not exceed 2cm. No distant metastases are present.
Stage 2 triple negative breast cancer: The tumor size may become as large as 5cm, and/or more lymph nodes are involved and have larger tumor foci. No distant metastases are found.
Stage 3 triple negative breast cancer: The tumor size is greater than 5cm with no upper limit, and the cancer may have invaded the chest wall or the skin covering the area. More lymph node groups may be affected. No distant metastases are present.
Stage 4 triple negative breast cancer: Simply put, any breast cancer that has metastasized beyond its original location into other body parts is defined as a stage 4 cancer, regardless of its size.
Triple negative breast cancer treatment
Even though triple negative breast cancer is a more vicious form of the disease, there are multiple lines of treatment available for it, and long-term remission is possible. These can be classified into surgical procedures, chemotherapy, radiotherapy, and immunotherapy.
1) Triple negative breast cancer surgery
Triple negative breast cancer surgery can be simply divided into two main surgical operations: Lumpectomy and mastectomy. As the name implies, a Lumpectomy entails the removal of the abnormal lump only, with the remaining part of the breast left untouched. This is appropriate if the tumor is found to be small in size and single. On the other hand, a large tumor that shows calcific deposits or invades the skin will most likely require a mastectomy, which is the removal of the entire breast. This may be followed by breast reconstruction in the same surgery or in a later operation to help restore the breast’s normal appearance.
2) Triple negative breast cancer chemotherapy
Chemotherapy entails the use of very powerful drugs that are taken by mouth or through an injection, which reach the tumor cells wherever they are in the body and destroy them. This line of therapy is therefore useful in treating a patient with metastatic disease. Chemotherapy can be used before surgery to shrink the tumor, making the operation easier to perform. This is called neoadjuvant therapy. It can also be used after the operation, in order to eliminate any remaining tumor cells, thus decreasing the risk of recurrence of the breast cancer. There are, however, a number of side effects that occur when using most chemotherapeutic drugs, most commonly nausea, vomiting, and diarrhea. The physician may prescribe one drug or multiple chemotherapy medications to create a drug regimen that is tailored to the patient’s specific type of breast cancer while attempting to minimize the side effects as well.
3) Triple negative breast cancer radiotherapy
Radiotherapy is the use of high power radiation waves that are aimed and fired at the tumor for long periods of time in order to eliminate it. This line of treatment probably won’t cure the tumor by itself, but when used in conjunction with the other treatment methods may decrease the risk that the disease appears again after treatment.
4) Immunotherapy for triple negative breast cancer
Immunotherapy is a treatment method that depends on the body’s own immune system. It is the usage of certain drugs that stimulate the immune cells, putting them on high alert so that they attack any tumor cells vigorously. This is particularly useful when the tumor has spread in the patient’s body, making surgery less useful.
As noted previously, hormonal treatments such as drugs which block estrogen and progesterone receptors do not work in triple negative breast cancer cases.
Triple negative breast cancer survival rate, life expectancy, and prognosis
Usually, the survival rate of any type of cancer is measured in terms of how many patients remain alive 5 years after diagnosis. Thus, the 5 year survival rates for triple negative breast cancer are as follows:
- 5 year survival rate for women with triple negative breast cancer that has not spread outside the breast is 91%
- 5 year survival rate for women who also have affection of the surrounding lymph nodes is 65%
- 5 year survival rate for women with triple negative breast cancer that has metastasized beyond the original site is 11%
- 5 year survival rate for women who have had a recurrence of the disease after treatment is 27%
- 5 year survival rate for triple negative breast cancer in general is 77%. Meanwhile, the survival rate for other types of breast cancer is higher at 93%
The prognosis of this disease is less promising than for other types of breast cancer within the first 5 years after diagnosis. Afterwards, the outlook is quite similar in both. Different histological types of breast cancer have different prognostic outcomes, and a tumor that is diagnosed early is more likely to be cured than one that is diagnosed late.
Triple negative breast cancer recurrence
Reappearance of a triple negative breast cancer is most common in the first few years after completion of treatment. If the first five years pass without incident, the chances of recurrence become much lower.
Triple negative breast cancer recurrence after a lumpectomy often necessitates the removal of the entire breast, and using additional lines of treatment.
Triple negative breast cancer recurrence after mastectomy, on the other hand, is treated by chest wall surgery, and by adding more treatments methods such as radiotherapy. Even though the diseased breast is gone, the local lymph nodes may still be harbour some cancer cells that had spread earlier.
Triple negative breast cancer diet
A healthy diet is important in preventing and managing any type of cancer. Make sure to limit processed meat, fast food, and food rich in salt and sugar. Try also to increase your share of fruits, vegetables, fibre, and wholegrain foods.
Can you be cured from triple negative breast cancer?
Yes. It is possible to cure this form of breast cancer. But the chances of long-term remission are dependent on many factors, such as the time of diagnosis, the histological type of the tumor, and the stage of the cancer.
Triple negative breast cancer foundation (TNBC Foundation)
Established in 2006, this non-profit organization aims to raise public awareness of triple negative breast cancer. They also sponsor clinical research and lab studies dedicated to finding new, effective, and safe treatments for the disease. The foundation was created in honor of a patient who was diagnosed with triple negative breast cancer. Since then the foundation has raised millions of dollars and continues to have a pioneering role in the fight against triple negative breast cancer.