The breast is a milk factory in which the lobules make the milk and the ducts carry the milk to the nipples. Virtually all breast cancer begins in this milk ductal system.
Cancer occurs when a normal cell stops functioning properly and begins to grow and divide uncontrollably. This process doesn't occur in a day, or in a week, or in a month, or even in a year. It often takes decades or more for a normal cell to acquire the properties necessary to start acting like a cancer cell.
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The first step to understanding cancer is becoming familiar with the following terms:
- Cell: The cell is the structural and functional unit of all living organisms. It is estimated that the human body contains 100,000 billion cells.
- Nucleus: The nucleus is the central part of the cell. It contains DNA and RNA and is responsible for the cell's growth and reproduction.
- DNA (deoxyribonucleic acid): The DNA in the nucleus codes all the information in our body and is responsible for transferring genetic characteristics. With the same system of four bases (like four letters), everything that's alive is programmed. These four bases, or nucleotides, are adenosine (represented by the letter A), thymine (T), cytosine (C), and guanine (G). The nucleotides combine in pairs, and this pairing is very precise, like a tiny jigsaw puzzle. A and T fit together, as do G and C, and that can never vary.
- Gene: The base pairs of DNA come together in a chain to form a gene. Genes are the basic biological units of heredity. Genes are arranged in a long row, side by side, to form a chromosome.
- Chromosome: Normal human cells have 46 chromosomes that are arranged in 23 pairs. All the chromosomes together form the genome — a human being.
- Protein: A large molecule that performs a variety of essential functions in the cell. Proteins are the body's building blocks.
- RNA (ribonucleic acid): DNA doesn't work alone. It has a partner, called RNA. RNA duplicates each gene and translates the genetic code it contains in its DNA into a protein. The production of RNA determines how much protein will be produced and therefore the levels of expression of a particular protein.
Putting this together
The DNA that forms each gene in a chromosome is a code for creating a protein. But the DNA can't make that protein alone. It needs RNA to translate the code and produce the protein. You can think of it this way: DNA holds the precious family recipe for making, in this case, protein. RNA is the copy that you use in the kitchen to make the protein.
Now that you know about DNA, RNA, and proteins, it's time to learn about the cell cycle.
The Cell Cycle
Cell division, which is termed mitosis, is carefully orchestrated in a process called the cell cycle. The active cell cycle is divided into four different phases. The quiescent phase, G0, is the phase most cells are usually in. They're just sitting around, doing nothing. Then something wakes them up and says, "Time to divide!" sending them into the first active phase, called G1. During this phase, which lasts approximately nine hours, the cells prepare to divide.
Before a cell can move on to the next phase, it is inspected to ensure that it is free of any serious mutations. If mutations are present, the cell must repair them before the G1 checkpoint will allow it to move on to the second active phase, which is called the S phase. During the S phase, which lasts about six hours, the cell replicates its entire genetic material, which results in two sets of paired chromosomes. The cell then enters the third active phase, which is called G2. This phase, which takes about four hours, involves another quality control inspection, and, if necessary, repair. It is the final checkpoint before the cell enters the mitosis, or M, phase, where it will divide and become two cells.
All cells, including cancer cells, go through the same cell cycle. Now that you are familiar with what goes on inside the cell and the cell cycle, the next step is to look at how cancer develops.
How Cancer Develops
A cancerous cell is a normal cell that has stopped functioning properly and is now growing and dividing uncontrollably. This occurs when normal processes break down. What happens?
Mutations Develop: A mutation is an error that can occur when the wrong nucleotide—A, T, C, or G—gets inserted into a gene as it's being created. A mutation can also occur if a nucleotide is deleted. A person can be born with a mutation. Mutations also develop throughout a person's lifetime. Most mutations will never cause a problem. It is estimated that thousands of DNA errors are detected and repaired during the cell division process.
One mutation by itself isn't enough for a normal cell to stop functioning properly. It takes a series of mutations for a cell to transform from normal to cancerous. This is why most cancers, including breast cancer, are more likely to occur as people age.
Where the mutation occurs is also important. For example, P53 is a tumor suppressor gene that works at the G1 checkpoint. Like any other gene, P53 can become mutated. If this occurs, the G1 checkpoint will no longer function properly. This allows cells that contain mutations and should have been sent back for repairs through, increasing the possibility that a cell will collect enough mutations to become cancer.
A mutation can also develop in an oncogene, a gene that is involved with cell division. Oncogenes involved in breast cancer typically encourage cells to divide faster. One oncogene that comes into play in breast cancer is epidermal growth factor receptor 2. In the US this is commonly known as HER2 (or HER-2 or Her-2/neu); in Europe it is called erB2 or erb-b2. When a mutation occurs in HER2, the gene becomes amplified. This means that the cell carries 10 to 60 copies of the gene instead of just one. Too many genes result in too many HER2 receptors on the cell's surface and an excess of HER2 protein. This extra protein causes the cell to replicate more than it should. Breast cancer tumors that have this gene amplification are called HER2-positive.
Cells with Mutations That Should Die Don't: All cells have the ability to kill themselves. This programmed cell death, or cell suicide, is called apoptosis, and it is designed to occur when there is something wrong with the cell itself—such as too many mistakes, or mutations, in the DNA. Cancer cells acquire the ability to evade apoptosis, which allows them to keep replicating endlessly.
Cells Keep Dividing Endlessly: Cells are not supposed to keep dividing forever. They are only supposed to divide for a set number of times. At the very end of each chromosome is a section called the telomere. Each time a cell divides, it snips off a little bit of the telomere. When the telomere gets really short, it sends a message to the cell to stop dividing. Telomerase is an enzyme in the body that can lengthen the telomere. Cancer cells use telomerase to keep the telomere from getting too short. This allows the cancer cell to replicate endlessly.
Cells & Their Community
For a cancer to occur a cell has to "mutate" and its behavior has to change. We used to think that was all it took. But we now know that this is not enough by itself to create cancer. The mutated cells are in a neighborhood of other cells—fat cells, immune cells, blood, etc.—known collectively as the stroma. If these cells are all well behaved, they will have a good influence on the mutated cell, which will coexist peacefully with them, and no disease will occur. But if the neighborhood is not so "law abiding" and stimulates or at least tolerates bad behavior, there may be trouble. The combination of the mutated cells and the stimulating, or tolerant, neighborhood will create breast cancer. (fig 4.2).
Does this mean you can have mutated cells and no cancer? The answer is a surprising yes. In fact, we probably all walk around with mutated cells in our bodies, as we get older. This means that if we knew the right environment, the reverse would be possible as well: we might be able to keep the cancer stem cells from misbehaving. I find this new way of thinking about cancer very exciting because it explains a lot and gives me a new way to think about the disease, its cause and risk factors. We can also figure out what affects the community around the mutated cell. Since the community is also composed of cells, they too can undergo mutations and alter their behavior. (fig 4-3)
Inside the Breast: From Precancer to Invasive Breast Cancer A person can have millions of cells with mutations in his or her body and not have cancer. For someone to have cancer, the cells must be replicating endlessly. Further, this mass of cells has to break out of the area where these cells are supposed to be and invade into other areas.
Virtually all breast cancer begins in the breast duct. A diagnosis of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) means that there are cancer cells in the breast, but they are still contained within the breast duct or lobule. They have not invaded into another area. This is why DCIS and LCIS are called precancers. If a woman is diagnosed with invasive cancer, it means the cancerous cells have broken out of the duct and invaded the surrounding tissue.
Most invasive breast cancers have been present for 8 to 10 years by the time they have been detected on a mammogram or physical exam. During that time there is plenty of opportunity for the cancer cells to get out of the breast and spread to the rest of the body. Sometimes the immune system takes care of these cells and sometimes it doesn't.
If cancer cells were content with only invading nearby tissue, cancer would be easy to cure. But they aren't. Their next goal is to make new blood vessels to support themselves (a process called angiogenesis), get out of the breast territory, and establish new homes for themselves in other parts of the body. This is called metastasis.
In order to metastasize, cancer cells have to evade the body's immune system, make new blood vessels, travel through the bloodstream, figure out what organ to go to, break out of the blood vessel, get into the new organ, and set up a new home. But even when early metastasis has occurred, it doesn't necessarily spell doom. Let's say that the cell has successfully made the journey to the lung. Once it arrives there it has to establish a new home by making new blood vessels. It's possible that other cells in the lung may be able to keep these invaders under control. The cells then act normally until something happens—a change in the lung's environment, or a new genetic alteration occurs that allows the breast cancer cells to grow in the lung. This might explain why some women will have a recurrence of breast cancer many years after the first diagnosis. Those cells were there from the beginning but were dormant until the right conditions induced them to grow again.
Frequently Asked Questions
What are some of the symptoms of breast cancer?
When it first develops, breast cancer typically has no symptoms. However, as the tumor grows, you may notice:
- a lump in your breast or under your arm
- swelling in your armpit
- pain or tenderness in your breast
- an indentation on the breast
- changes in the size, shape, texture or temperature of the breast
- changes in the nipple or a bloody or mucousy discharge.
Inflammatory breast cancer is a rare type of breast cancer that does have symptoms. It causes the breast to become red or develop a texture that looks like the skin of an orange. These symptoms are all too easily initially mistaken for a breast infection. If you develop them, you should see a breast specialist.
A scaly rash on the nipple could be a sign of Paget’s disease, a form of breast cancer that shows up in the nipple as an itchiness and scaling that doesn't get better. Usually Paget's disease presents as redness, mild scaliness, and flaking of the nipple skin and gradually goes on to crusting, ulceration, and weeping. It can be itchy, hypersensitive, and painful. It's often mistaken for eczema of the nipple—a far more common occurrence