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Breast cancer is an uncontrolled growth of cells in the breast. To better understand the disease, it helps to understand how cancer in general develops.
Cancer occurs as a result of abnormalities (mutations) in the genes responsible for controlling the growth and maintaining the health of cells. These genes are present in each and every cell in our bodies. Normally cell growth occurs via an orderly process: healthy new cells replace old or defective ones. Unfortunately, over time, mutations can alter the genes in our cells controlling growth / replication of a cell. That altered cell then gains the ability to keep dividing with the body being unable to control or inhibit the process, producing more cells exactly like it and forming a growth (tumor).
A tumor can be benign (rarely dangerous to health) or malignant (cancer). Benign tumors are not cancerous: their cells closely resemble the original cell in appearance, they grow slowly, and they do not invade nearby tissues or spread to other distant organs of the body. Malignant tumors are cancerous. Growth of these malignant cells is usually much faster than in a benign tumor, their appearance can alter substantially from the original cell and their behaviour is less predictable. These malignant cells can eventually spread beyond the original tumor to other organs in the body (metastatic disease).
The term “breast cancer” refers to a malignant growth or tumor that has developed from cells in the breast. Breast cancer can either begin in the cells of the lobules of the milk-producing glands (lobular breast cancer), or in the ducts that drain milk from the glands to the nipple (ductal breast cancer). Less commonly, breast cancer can begin in the ‘in-between’ or stromal tissues, which include the fatty and fibrous tissue that connects the different glands of the breast (i.e. Phyllodes tumour).
If left unchecked, cancer cells can invade nearby healthy breast tissue and invade lymphatic channels and blood vessels. The underarm lymph nodes (glands) would be the first organs that filter the lymphatic channels draining the breasts. Tumor cells trapped here will present as enlarged glands in the armpit and implies a more advanced stage of disease. If cancer cells get into the blood vessels, they then have a pathway into other parts of the body. Distant organs mostly affected would be the liver, lungs, bone and occasionally the brain. Once cancer has spread to these distant organs the patient has metastatic disease. This implies very advanced disease and generally carries a poor prognosis.
Breast cancer is always caused by a genetic abnormality or aberration (a “mistake” in the genetic material). Mostly (90%) breast cancers are due to genetic abnormalities that occur as a result of the normal ageing process and the “wear and tear” of the cell. However, 5-10% of cancers are due to an inherited abnormality.
A risk factor is any factor that makes it more likely that you will get a certain disease, such as cancer. Having one risk factor, or even many, does not necessarily mean that you will get the disease. Many women with no apparent risk factors for getting breast cancer will develop the disease, whereas most women who have one or more breast cancer risk factors will never develop the disease.
There are different kinds of risk factors. Some factors, like a person's age or race, can't be changed and are therefore termed ‘non-preventable’. Others are linked to cancer-inducing environmental factors and some are related to personal behaviours
, such as smoking, excessive alcohol intake and an unhealthy diet. These factors are termed ‘preventable’
Simply being female is the main and most important risk factor for developing breast cancer. Men are about 100 times less likely to develop breast cancer.
The risk of cancer increases with age. By far the majority of invasive cancers occur in women older than 55 years of age.
BRCA1 and BRCA2: Hereditary breast cancer accounts for only 5-10% of all breast cancer cases. The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 and BRCA2 genes.
Having one first-degree relative (mother, sister, or daughter) with breast cancer approximately doubles a woman’s risk. Having 2 first-degree relatives increases her risk about 3-fold.
However, most (over 85%) women who develop breast cancer do not have a family history.
A woman with previous breast cancer has a 3- to 4-fold increased risk of developing a new cancer in the other breast or in another part of the same breast should she have had breast-conserving treatment.
Overall, Caucasian women are slightly more likely to develop breast cancer than are African women, but African women are more likely to die of this cancer.
Women diagnosed with certain benign breast conditions might have an increased risk of breast cancer. Some of these conditions are more closely linked to breast cancer risk than others. These benign breast conditions are often divided into 3 general groups, depending on how they affect this risk.
LCIS (also called lobular neoplasia) is sometimes grouped with ductal carcinoma in situ (DCIS) as a non-invasive breast cancer, but it differs from DCIS. It doesn’t seem to become an invasive cancer if it is left untreated. Women with this condition do have a 7- to 11-fold increased risk of developing invasive cancer in either breast. Therefore, women with LCIS should have regular mammograms and doctor visits.
Women who have had more menstrual cycles (starting early menstruations and/or going through menopause later) have a slightly higher risk of breast cancer. The increase in risk is probably due to a longer lifetime exposure to the hormones estrogen and progesterone.
Having no children or having your first child after the age of 30 slightly raises your breast cancer risk. Having many pregnancies and becoming pregnant at a young age reduces your breast cancer risk. Pregnancy reduces a woman's total number of lifetime menstrual cycles and thus exposure to the hormones estrogen and progesterone, which may explain this effect.
Oral contraceptive use: Studies have found that women using birth control pills have a slightly higher risk of breast cancer than women who have never used them. This risk seems to go back to normal over time once the pills are stopped.
Depot-medroxyprogesterone acetate (DMPA; Depo-Provera®) is an injectable form of progesterone that is given once every 3 months as birth control. Women currently using this form of contraception seem to have a higher risk, but the risk decreases to normal levels again 5yrs after stopping the treatment.
Hormone therapy with estrogen (sometimes combined with progesterone) has been used for many years to help relieve the symptoms of menopause and prevent osteoporosis (weakening of the bones).
There are 2 main types of hormone therapy. For women who still have a uterus (womb), doctors generally prescribe a combination of estrogen and progesterone (known as combined hormone therapy or HT). For those women who've had a hysterectomy, estrogen alone can be prescribed. This is commonly known as Estrogen Replacement Therapy (ERT) or just estrogen therapy (ET).
Combined Hormone Therapy: Using combined HT after menopause increases the risk of getting breast cancer. This increase in risk can be seen after as little as 2 years of use. A woman's breast cancer risk seems to return to that of the general population within 5 years of stopping combined treatment.
Estrogen therapy (ET): There is no apparent increase in the risk of developing breast cancer if estrogen alone is used after menopause. In fact, some research has shown that women who have had their uterus removed and who is on estrogen therapy actually have a decreased risk of breast cancer. Women taking estrogen seem to have more problems with strokes and other blood clots. When used long term (>10 years), some studies have shown that ET increases the risk of ovarian cancer.
Although ET does not seem to increase breast cancer risk, it does increase the risk of heart disease, blood clots and stroke. At this time there appear to be very little reason to use post-menopausal hormone therapy (either combined HT or ET), other than possibly for the short-term relief of menopausal symptoms. If a woman in conjunction with her doctor decide to try hormone therapy for symptoms of menopause, it is usually best to use it at the lowest dose needed to control symptoms and for as short a time as possible.
Some studies suggest that prolonged breastfeeding (1½ to 2 years) may slightly lower breast cancer risk. It may be that breastfeeding reduces a woman's total number of lifetime menstrual cycles and thus exposure to estrogen and progesterone.
Being overweight or obese after menopause increases breast cancer risk. After menopause (when the ovaries has stopped making estrogen), most of a woman's estrogen comes from fat tissue. Having more fat tissue obviously raises estrogen levels thereby increasing breast cancer risk.
There is growing evidence that exercise reduces breast cancer risk. In one study from the Women's Health Initiative, as little as 1.25 to 2.5 hours per week of brisk walking per week reduced a woman's risk by 18%.
There is a clear link to alcohol use and an increased risk of developing breast cancer. The risk increases with the amount of alcohol consumed. Women who consume 1 alcoholic drink a day have a very small increase in risk. Compared with non-drinkers, those who have 2 to 5 drinks daily have about a 1½ times increase in risk.
More and more women are deciding to learn whether or not they have an abnormality in what have come to be known as the “breast cancer genes,” BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two). Women who inherit a mutation in either of these genes — from their mothers or their fathers — have a much higher-than-average risk of developing breast cancer and ovarian cancer. Men with these mutations have an increased risk of breast cancer, especially if the BRCA2 gene is affected, and possibly of prostate cancer. Many inherited cases of breast cancer have been associated with these two genes.
The function of the BRCA genes is to keep breast cells growing normally and prevent any cancer cell growth. But when these genes contain the mutations that are passed from generation to generation, they do not function normally and breast cancer risk increases. Abnormal BRCA1 and BRCA2 genes may account for up to 5 – 10% of all breast cancers, or 1 out of every 10 – 20 cases.
Most people who develop breast cancer have no family history of the disease. However, when a strong family history of breast and/or ovarian cancer is present, there may be reason to believe that a person has inherited a BRCA1 or BRCA2 mutation. Some people choose to undergo genetic testing to find out. A genetic test involves giving a blood sample that can be analysed to pick up any abnormalities in these genes.
The decision to have a genetic screening test is a complex one to make. A positive result will have far reaching complications for the patient in terms of raising the possibility of prophylactic mastectomies and oophorectomy as well as the possible implications with regards to life insurance policies, etc. A positive result will also have consequences for siblings and offspring. Therefore the decision to have a genetic test must preferably be made in conjunction with your surgeon and genetic counsellor and with the support of your family.
The most reliable way to diagnose breast cancer is to use a combination of modalities, sometimes also referred to as the ‘triple test’. This consists first and foremost of a thorough history and clinical examination, followed by a mammogram and lastly a ‘fine needle aspiration’ (FNA) to obtain cells from the suspicious area of breast tissue. This will lead to diagnosis in the majority of cases. In a few special instances it might be necessary to substitute the mammogram for a breast MRI scan or the FNA for a larger biopsy of the tumor.
Once the diagnosis is confirmed we need to determine the severity of the breast cancer, both locally (in the breast itself) and also systemically, (whether the disease has spread to other organs). This process is commonly referred to as staging of the cancer. The local staging of the tumor and also whether lymph nodes (glands) in the axilla (armpit) are involved can be readily determined by physical examination. To determine whether systemic spread has occurred a minimum of a CT scan of the chest and abdomen as well as a bone scan will be necessary.
Breast cancer is one of the most studied diseases in the field of medicine. This has lead to a large body of scientific evidence to guide the treatment of the disease. However, every patient will still have her/his treatment individualized to ensure the best possible outcome for the patient. These decisions are usually best made by a multi-disciplinary team consisting of a radiologist, surgeon and an oncologist, taking into account the patient’s personal preferences. In broad terms the treatment can be divided in local and systemic therapy.
Local therapy includes the treatment of the breast itself as well as the axilla(armpit). Breast tumors have traditionally been treated with a total mastectomy (removal of all the breast tissue, skin and nipple-areola). We now know that this is not necessary in all cases. As long as certain pre-requisites are met a tumor excision coupled with local breast irradiation (breast conservation therapy) can offer similar cure rates to a mastectomy. There may however be contraindications to breast conserving therapy, which will be explained to you by your surgeon, should they be applicable. Treatment of the axilla depends largely on whether there are lymph nodes (glands) palpable or not.
In the presence of palpable glands a standard axillary dissection is routinely performed to remove all the lymph nodes in the axilla. This is done to control the axillary disease as well as to gain information to help guide the systemic treatment of the disease.
In the absence of palpable glands a sentinel lymph node biopsy is performed. The sentinel node is the first node in the axilla draining the breast. If this node is free of cancer there is very little chance that the other axillary nodes will be involved. The sentinel node is identified by injecting a special radioactive substance into the tumor or behind the nipple. Following this the patient is taken to theatre and the sentinel node (which will concentrate the radioactive marker) is identified with a gamma camera and resected. After full histological examination a decision will then be made whether to proceed with an axillary dissection.
Radiotherapy (irradiation) is also employed to reduce the local recurrence rate. This is usually administered to the operative field after wound healing has occurred.
Although breast cancer always starts off as a local growth in the breast it will at some stage spread to the rest of the body. Even if all the screening tests for cancer spread is clear it is mostly advisable to still treat systemically (the whole body/patient) except in cases where the cancer is really detected very early. Systemic treatment has 3 components:
From the above information it is obvious that one of the main ‘driving forces’ of breast cancer is exposure to the hormones estrogen and progesterone. Once a diagnosis of breast cancer is made, cancer tissue will be obtained (either by resection the cancer or by doing a biopsy) which will then be tested to determine whether the cancer is hormone responsive. If the cancer is responsive you will be treated with some form of endocrine therapy to block the effects of the body’s naturally occurring estrogen and thereby slow or stop the growth of the cancer. It is most often used as an adjuvant therapy to help reduce the risk of the cancer coming back after surgery, but it can be used as neoadjuvant (before surgery) treatment, as well. It is also used to treat cancer that has come back after treatment or has spread. Endocrine therapy may include one of the following:
Tamoxifen is a type of drug called a selective estrogen-receptor modulator (SERM). In breast tissue it blocks estrogen from attaching to estrogen receptors and therfore it functions as an anti-estrogen. Tamoxifen can reduce the risk of cancer recurrence by 50% and is usually given for a period of 5 years as a once daily pill. Tamoxifen can also be used to treat stage IV or metastatic breast cancer, as well as to reduce the risk of the development of breast cancer in women at high risk.
Aromatase inhibitors (AIs): The following drugs stop estrogen production in post-menopausal women and are used to treat both early and advanced breast cancer: anastrozole (Arimidex®), letrozole (Femara®) and exemestane (Aromasin®). These drugs work by blocking an enzyme (aromatase) that naturally occurs in fat tissue and is responsible for producing small amounts of estrogen in post-menopausal women. They are only effective in women whose ovaries aren’t working (like after menopause). These drugs are taken daily as pills. So far, none of these drugs seems to be superior to the others. They do seem to have fewer side effects than Tamoxifen and can be used in the adjuvant therapy of post-menopausal women.
Ovarian ablation: In pre-menopausal women, the ovaries, which are the main source of estrogens, may be removed or shut down with medication. This effectively makes the woman post-menopausal. This may allow other hormone therapies to work more effectively. This is most often used to treat metastatic breast cancer in pre-menopausal women. Permanent ovarian ablation can be done by one of 3 routes: They can be surgically removed. This operation is called an oophorectomy. Specific drugs called luteinizing hormone-releasing hormone (LHRH) analogs, such as leuprolide (Lupron®) or goserelin (Zoladex®) may also be used. These drugs stop the signal that the body sends to ovaries to make estrogens. They can be used alone or in combination with tamoxifen as hormone therapy in pre-menopausal women. Lastly, the use of conventional chemotherapy may well suppress ovarian function irreversibly, thereby inducing early menopause.
Chemotherapy is the use of specific cancer killing drugs given either intravenously or orally in an attempt to treat the patient systemically (whole body). The aim is to ‘kill off’ cancer cells that has escaped from the primary cancer but is as yet clinically undetectable. This can be done either in combination with surgery (as is mostly done) with the intent to cure the patient or it can be used alone in cases where cure is not possible (the aim here would be to delay the progression of the disease). If used in conjunction with surgery it can be given either before (neoadjuvant therapy) or after (adjuvant therapy) surgery. There is no survival difference to giving chemo before or after surgery. Giving chemo before surgery may shrink larger tumors so that breast conservation surgery might be possible. The other advantage is that the response to the chemotherapy drugs can be evaluated clinically. If the tumor does not shrink with the first set of drugs, other chemotherapy drugs might be indicated. These days there are a variety of chemotherapy drugs available and multiple drugs are usually given in combination. Which combination is best is still to be determined and remains a ongoing theme for laboratory studies and clinical trials.
Chemotherapy drugs attack cells that divide quickly, which is why they are effective against cancer cells. Other cells in the body: the bone marrow, the lining of the mouth and intestines and the hair follicles, also divide quickly. These cells will also be affected by chemotherapy, which is why side effects develop. The severity of side effects is difficult to predict and will depend on the type of drugs used, the amount given, and the length of the treatment. The most common of the possible side effects include:
Chemotherapy is usually given in cycles, with each period of treatment followed by a period of rest where the body is given time to recover. The total length of treatment is usually between 3 – 6 months, but will be determined by your oncologist and also guided by your response to the therapy.
Breast cancer is one of the most studied diseases of our time. This has lead to a much better understanding of the changes that occur at a genetic level when breast cancer develops. This understanding has made it possible for scientists to develop newer drugs that specifically target these changes. The development of these drugs represents a new avenue of attack in the treatment of breast cancer and also has the advantage of fewer and less severe side effects when compared to conventional chemotherapy.
Unfortunately not all cancers will respond to immunological therapy. Only 1 in 5 cancers will have larger than normal amounts of the growth-promoting protein known as HER2/neu (or just HER2) expressed on the surface of their tumour cells. Trastuzumab is a type of drug known as a monoclonal antibody — a man-made version of a very specific immune system protein. When the HER2 receptor is present (this can be tested for) Trastuzumab will bind to it and help slow the growth of the tumour. It can also stimulate the patient’s own immune system to better fight the cancer.
Breast reconstruction is usually done by a plastic surgeon. It can be done at the time of the mastectomy (immediate reconstruction) or it can be done at a later stage (delayed reconstruction). It can be done using the patients own tissue also referred to as autologous (own tissue) flap surgery or it can be done with the help of breast implants. Deciding which of these options is best for you will depend on a number of clinical factors as well as your own personal preference.