Breast Cancer
Overview
What is breast cancer?
Breast cancer occurs when changes called mutations take place in the genes that regulate cell growth, causing breast cells to multiply uncontrollably. Most breast cancer forms either in the lobules, the glands that produce milk, or the ducts that bring the milk from the glands to the nipple. Less often, cells in the fatty or fibrous connective tissue of the breast can become cancerous. Cancer cells may invade surrounding healthy breast tissue. In addition, cancer cells may migrate to the lymph nodes in the armpit and, from there, spread to other parts of the body. This spreading process is called metastasis.
Worldwide, breast cancer is the most common invasive cancer in women. In the United States, breast cancer is second only to skin cancer as the most common cancer. Breast cancer is far more common in women than men. The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries, especially the United States. Age is an important factor in breast cancer. Only 5% of all breast cancers occur in women under 40 years old, while around 80% occur in women age 50 or older. Black women are usually diagnosed with breast cancer at a younger age than white women.
Over the last 50 years the incidence of breast cancer significantly increased, a trend associated with modern lifestyles (see Prevention, below). Fortunately, better awareness, better screening and earlier intervention with the latest treatments has seen a steady decline in age-adjusted incidence and deaths in women over the last two decades. Breast cancer survival rates vary widely based on many factors, including the type of breast cancer, early diagnosis, age, gender and race. The good news is that breast cancer survival rates are improving steadily. Forty years ago the 5-year survival rate was 75.2%. Ten years ago, it was 90.6%. When diagnosed at a localized, early stage the 5-year survival rate of some breast cancers can be up to 99%. Alas, 5-year survival of patients with advanced, metastatic cancers is around 30%.
Causes
Causes of breast cancer
Breast cancer occurs when some breast cells begin to grow abnormally. These cells divide more rapidly than healthy cells do and continue to accumulate, forming a lump or mass. Cells may spread (metastasize) through your breast to your lymph nodes or to other parts of your body.
Breast cancer most often begins with cells in the milk-producing ducts (invasive ductal carcinoma). Breast cancer may also begin in the glandular tissue called lobules (invasive lobular carcinoma) or in other cells or tissue within the breast.
Various hormonal, lifestyle and environmental factors that may increase the risk of breast cancer (see Risk Factors, below). Yet, some people who have no risk factors develop cancer, while other people with risk factors do not. It seems that breast cancer is caused by a complex interaction of genetic makeup and environment.
Approximately 5-10% of breast cancers have been linked to gene mutations passed from one generation to the next in a family. A number of such inherited mutated are recognized. The most well-known are two genes, breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2), which significantly increase the risk of both breast and ovarian cancer. If there is a strong family history of breast and other cancers, a blood test may help to identify specific mutations in BRCA or other genes that are being passed through your family. However, genetic testing by genealogy companies is very unreliable. A genetic counselor can review your family health history, and discuss the benefits, risks and limitations of genetic testing to assist you with shared decision-making.
Symptoms
Symptoms of breast cancer
Most breast cancers cause a lump to grow. However, not all lumps are cancerous, and need to be checked out by a doctor. In the early stages of breast cancer there may be no symptoms because a tumor may be too small to be felt, although they may be seen on a screening mammogram. The first sign is usually a lump in the breast that was not there before.
Different types of breast cancer may cause a range of symptoms. The most common signs and symptoms include:
Breast Lump
A new breast lump or thickening that feels different from the surrounding tissue
Change In Breast Appearance
Change in the size, shape or appearance of a breast
Breast pain
Changes to the skin
Changes to the skin over the breast, such as dimpling, redness or pitting
Peeling
Peeling, scaling, crusting or flaking of the pigmented area of skin surrounding the nipple (areola) or breast skin
Inverted nipple
A newly inverted nipple
Swollen area on breast
Swollen, red areas formed on the top of the breast, possibly with no lump
Discharge
Discharge from the nipple other than breast milk
Swelling in your armpit
A lump or swelling in your armpit
It should be emphasized that most symptoms of breast disorders, including most lumps, are not caused by breast cancer. Fewer than 20% of lumps are cancerous, and benign breast diseases such as infection (mastitis) and fibroadenoma of the breast most commonly cause these symptoms. A doctor’s consult is required the exclude breast cancer.
Tumors that are ‘malignant’ can metastasize and lodge in other tissues and organs in the body, causing symptoms dependent on the location of metastasis. Commonly, these include bone, liver, lung, and brain, although other sites may be involved. A cancer that has spread is said to be ‘invasive’ and is categorized as the most advanced ‘stage 4’ cancer (see Breast cancer staging, below). The symptoms of stage 4 cancer depend on where the tumor settles. Most common are unexplained weight loss, bone and joint pain, jaundice and neurological symptoms. These are called non-specific symptoms because they could be caused by other illnesses.
Diagnosis
Diagnosis of breast cancer
Detection of a lump or other abnormalities in the breast can be achieved self-examination or by a clinician. However, a lump large enough to detect may have been growing for several years, so feeling for a lump is not particularly effective. Therefore, women are recommended to have a mammogram (breast X-ray) every 2 years after the age of 50, according to national and international guidance. Other approaches include ultrasound and magnetic resonance imaging (MRI). Screening is performed in otherwise healthy women to provide the earliest diagnosis in the belief that this will lead to better outcomes. Nevertheless, some doctors question the value of routine screening because of exposure to radiation and false positives results.
Most breast cancers are confirmed by examination of a small sample, called a biopsy, using a microscope. Some more specialized laboratory analysis are also used. Samples of fluid within the lump are obtained by ‘fine needle aspiration and cytology’ (FNAC). Clear fluid is more likely to come from a cyst rather than cancer, while cloudy or bloody samples may contain cancer cells and require further testing. The combination of physical examination of the breasts, mammography and FNAC can accurately diagnose most breast cancer. Other samples that can be taken are ‘core biopsies’, tiny samples of tissue, for microscopic examination. In special circumstance an excisional biopsy, surgical removal of the entire lump, is performed.
The most common types of breast cancer are categorized as ‘invasive’, when the tumor has invaded or spread to nearby tissues in the breast, or ‘non-invasive’ (or in situ) when the tumor has not spread.
The common types of breast cancer are:
- Invasive ductal carcinoma (IDC) is the most common type of breast cancer. This type of breast cancer begins in the breast’s milk ducts and then invades nearby tissue in the breast. Once the breast cancer has spread to the tissue outside your milk ducts, it can begin to spread to other nearby organs and tissue.
- Ductal carcinoma in situ (DCIS) is a noninvasive condition. With DCIS, the cancer cells are confined to the ducts in the breast and have not invaded the surrounding breast tissue.
- Invasive lobular carcinoma (ILC) first develops in your breast’s lobules (milk-producing glands) and invades nearby tissue.
- Lobular carcinoma in situ (LCIS) is cancer that grows in the lobules of the breast but has not invaded the surrounding tissue.
Less common types of breast cancer include:
- Inflammatory breast cancer. This is a rare (only seen in less than 5% of breast cancer diagnosis) yet aggressive form of breast cancer. Swollen, red areas form on the top of the breast are a result of a blockage of lymph vessels by cancer cells. This type of breast cancer more commonly affects younger women, obese women and African American women. Because inflammatory breast cancer does not cause a lump there can sometimes be a delay in diagnosis.
- Paget disease of the nipple. This cancer begins in the ducts of the nipple, and affects the skin and areola of the nipple.
- Phyllodes tumor. This is a very rare type of breast cancer, growing in the connective tissue of the breast. Most phyllodes tumors are benign, but some are cancerous.
- Angiosarcoma. These cancers grow on the blood or lymph vessels in the breast.
- Metaplastic carcinoma. This very rare breast cancer arises in ductal cells and invades surrounding tissues. However, it comprises different cell types. It is the most aggressive type of breast cancer.
- Papilliary and medullary carcinomas. These are rare forms of invasive ductal carcinoma.
The type of cancer the patient has determines treatment options, as well as the likely long-term outcome.
| Breast cancer type | Relative Incidence | Overall 5yr Survival |
|---|---|---|
| Ductal carcinoma in situ | 23% | 97-100% |
| Lobular Carcinoma in situ | 6% | 97-100% |
| Tubular/cribriform carcinoma | 4% | 97-100% |
| Mucinoid (colloid) carcinoma | 1.5% | 97-100% |
| Invasive ductal carcinoma | 54% | 80-90% |
| Invasive lobular carcinoma | 7% | 80-90% |
| Medullary carcinoma | 1.5% | 80-90% |
| Papillary carcinoma | 0.5% | 80-90% |
| Metaplastic carcinoma | 0.5% | 55-60% |
| Other carcinomas | 2% |
Categorizing
Categorizing breast cancer
Several approaches are used to categorize breast cancer. These include tumor staging, receptor status and DNA analysis. Determining how much a tumor has grown and spread is important to guide treatment.
Breast cancer staging depends on the size of the tumor (T for tumor size), whether it has spread to the lymph nodes in the armpit (N for nodes) and whether it has spread beyond the lymph nodes to other parts of the body (M for metastasis). A higher TNM score is associated with worse outcome.
The main stages are:
Stage 0 breast cancer
Pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
Stage 1 breast cancer
Primary tumor smaller than 2cm, cancer cells may or may not be found in lymph nodes
Stage 2 breast cancer
Tumor smaller than 2 cm has spread to 1–3 nearby lymph nodes, or is larger than 2cm but has not spread to any lymph nodes
Stage 3 breast cancer
Primary tumor can be any size may have spread to 4–9 or more axillary and other lymph nodes, and may have invaded the chest wall or skin locally
Stage 4 breast cancer
‘Metastatic’ cancer that has spread beyond the breast and regional lymph nodes
When metastatic spread is suspected in stage 4 cancer, imaging studies such as PET scans, CT scans and bone scans may be used. However, if the tumor is unlikely to have spread, the risks of exposure to ionizing radiation using these procedures may outweigh the benefits.
Breast cancer cells have ‘receptors’ that bind messenger molecules such as hormones. These control cell growth and behavior. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and a receptor for human epidermal growth factor 2 (HER2).
Cancer cells that have estrogen receptors are called ER positive (ER+) depend on estrogen for their growth, and can be treated with drugs to block estrogen effects (e.g. tamoxifen). Generally, ER+ tumors have a good outcome. HER2+ breast cancers grow more aggressively than HER2- breast cancers, but they do respond to drugs such as the monoclonal antibody trastuzumab (in combination with conventional chemotherapy) quite effectively. Cells that do not have any ER, PR or HER2 are called triple-negative, although they frequently do express receptors for other hormones such as androgen and prolactin. Unfortunately, triple negative breast cancers are the most aggressive and have a poorer prognosis.
DNA analysis. DNA testing of various types are now being used to compare normal cells to breast cancer cells. The specific changes in a particular breast cancer can be used to classify the cancer in several ways, and may assist in choosing the most effective treatment for that DNA type.
Treatment
Treatment of breast cancer
Surgery is the most common treatment for breast cancer. Many women have additional treatments, such as radiation and chemotherapy, often in combination with hormone therapy or immunotherapy.
Surgery is used to remove breast cancer tissue:
- Lumpectomy removes only the tumor and some surrounding tissue.
- Quadrantectomy removes a larger portion of the breast including the tumor and nearby tissue
- Mastectomy removes an entire breast. In a double mastectomy, both breasts are removed. In contralateral prophylactic mastectomy both breasts are removed because of the higher risk of developing cancer on the other side.
- Removal of lymph nodes. The number of lymph nodes removed depends on how far the cancer has spread.
External radiation therapy
High-powered beams of radiation are used to target and kill cancer cells. Most radiation treatments use external beam radiation from a large machine outside of the body.
Internal radiation therapy (brachytherapy)
Cancers may be irradiated from inside the body to destroy cancer cells. Radioactive pellets are placed near the tumor site and remain there for a short time.
Chemotherapy is a drug treatment used in stage 2-4 breast cancer to destroy cancer cells, particularly in ER- tumors. Older drugs such as doxorubicin and fluorouracil block DNA synthesis in dividing tumor cells. The newest drugs target growth pathways that are overactive in cancer cells. Some people may undergo chemotherapy on its own, but this type of treatment is often used along with other treatments, especially surgery (adjuvant chemotherapy). Patients may be given chemotherapy before surgery (neo-adjuvant therapy) to shrink the tumor and reduce the extent of surgery. Chemotherapy has side effects, which may limit therapy.
Estrogen and progesterone, two female hormones, can stimulate the growth of ER+ and PR+ breast cancer tumors. Hormone therapy either blocks the body’s production of these hormones (aromatase inhibitors such as anastrozole and letrozole), or blocks the hormone receptors on the cancer cells (tamoxifen) to slow or stop the growth of breast tumors..
Monoclonal antibodies can target particular cellular processes. Certain treatments are designed to attack specific abnormalities or mutations within cancer cells. Herceptin (trastuzumab) and Perjeta (pertuzumab) prevent the HER2 protein from binding to its receptor, slowing the growth of HER2+ tumor cells. Other monoclonal antibodies and engineered proteins are designed to enable immune response strong enough to destroy the tumor. These new approaches are particularly promising.
Risk
Risk factors for breast cancer
Several risk factors increase the chances of getting breast cancer, although individuals with these risk factors do not necessarily develop the disease. Some risk factors can be affected by a change in behavior and are called ‘modifiable’ risk factors. Other risk factors are fixed and are called ‘non-modifiable’ risk factors.
- Age. The risk for developing breast cancer increases with age. Most invasive breast cancers are found in women over age 55.
- Gender. White women are 100 times more likely to develop breast cancer than white men, and black women are 70 times more likely to develop breast cancer than black men.
- Genes and inheritance. Women who have certain BRCA1 and BRCA2 gene mutations are more likely to develop breast cancer than women who don’t, but having these mutations does not inevitably cause breast cancer. Other gene mutations may also affect your risk. Having a close female relative (mother, grandmother, sister or daughter) who has had breast cancer is associated with an increased risk for developing it. However, the majority of women who develop breast cancer have no family history of the disease.
- Personal history of breast cancer. Having breast cancer in one breast increases the risk of developing cancer in the other breast. Similarly, certain precancerous breast conditions such as lobular carcinoma in situ (LCIS) or atypical hyperplasia of the breast carries an increased risk of breast cancer.
- Menstruation and menopause. Early menstruation, having a period before age 12, increase breast cancer risk. Late menopause, after age 55, increases the likelihood of breast cancer.
- Hormone therapy. Women who took or are taking postmenopausal estrogen and progesterone medications to reduce their signs of menopause symptoms have a higher risk of breast cancer. The risk of breast cancer decreases when women decrease or stop taking these medications.
- Pregnancy. Women who give birth to their first child after age 35 have an increased risk of breast cancer. Women who never became pregnant or never carried a pregnancy to full term are more likely to develop breast cancer.
- Having dense breast tissue. Dense breast tissue increases the risk of breast cancer and makes mammograms hard to read.
- Drinking alcohol. Drinking excessive amounts of alcohol raises risk.
- Radiation exposure. Receiving radiation treatments to the chest as a child or young adult has been associated with breast cancer later in life.
- Obesity. Maintain a healthy weight. Being obese increases the risk of breast cancer.
- Physical activity. Regular exercise on most days of the week reduces risk.
- Healthy diet. Women who eat a Mediterranean diet may have a reduced risk of breast cancer. This diet focuses on fruits and vegetables, whole grains, legumes, and nuts, healthy fats and fish instead of red meat.
Measures
Preventative measures in patients at high risk of breast cancer
Patients at very high risk through family history, genetics or precancerous breast conditions may benefit from preventative measures.
Preventive medications (chemoprevention)
Estrogen-blocking medications, such as selective estrogen receptor modulators and aromatase inhibitors, reduce the risk of breast cancer in women with a high risk of the disease. These medications may have serious side effects, and are reserved for women who have a very high risk of breast cancer.
Preventive surgery
An extreme option for women at very high risk is ‘prophylactic bilateral mastectomy’ (surgical removal of both breasts) before cancer appears. Patients with cancer in one breast are at risk of developing cancer in their other breast. These patients can elect to have a ‘prophylactic contralateral risk-reducing mastectomy’ or CRRM, removal of the unaffected breast to reduce the risks of cancer in the second breast.
