Triple-negative Breast Cancer | Symptoms, Diagnosis, Treatment and More

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.