breast-cancer
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What is Breast cancer?

In breast cancer, a malignant (cancerous) tumour begins to grow in the cells of the breast. A cancerous tumour is a mass of cells that is growing abnormally and out of control, and is able to invade other tissues. Breast cancer primarily occurs in women, but can also happen in men. 

The normal breast

Components of the breast

Breasts are composed of glands that produce breast milk (called lobules), small tubes (called ducts) that bring the milk from lobules to the nipple, connective tissue, fatty tissue, blood vessels and lymph vessels. Breast cancer usually arises from cells that are in the lining of the ducts. Rarely, cancer can start in cells that are in the lining of lobules. When cancer starts in cells in other breast tissues, they are no longer classified as breast cancer, but as sarcomas and lymphomas.

Pink Ribbon ImageThe lymph system

Lymph nodes are small clumps of tissue shaped like beans that contain infection-fighting immune cells. They are connected by vessels that carry a clear liquid called lymph. Together, lymph nodes and lymph vessels make up the lymphatic system, and are a main way that breast cancer can spread to other parts of the body. Lymph vessels from the breast mostly carry lymph to nodes under the arm (axillary nodes), around the collarbone (supraclavicular and infraclavicular nodes), and in the chest near the breast bone (internal mammary nodes).




Cells from a breast cancer tumour can break off from the tumour and travel through lymph vessels to lymph nodes. Once this occurs, it becomes more likely for cancer cells to reach other parts of the body, with the risk increasing with the number of affected lymph nodes. Lymph nodes can be removed to check for cancer cells, and their presence determines the treatment plan.

Benign breast lumps

Breast lumps are not always cancerous (these are called benign lumps). Although benign lumps are abnormal tissue, they do not leave the breast to invade other tissues, and are not dangerous to health. However, they can indicate an increased risk for breast cancer.

Cancer types

Carcinoma

This type of cancer starts in the cells in the lining of organs, including the breast.

Adenocarcinoma

This type of carcinoma begins in gland tissue, which produces and secretes specific fluids. For example, cancers that start in the ducts and lobules that make breast milk are adenocarcinomas. This is the most common type of breast cancer and will be the focus of this breast cancer overview.

Sarcoma

This type of cancer begins in connective muscle, fat or vascular (blood vessel) tissue. It is rare for breast cancer to be of this type.

Breast cancer types

The more common types of breast cancer will be covered here. Breast cancer can be a combination of several of the types below.

Ductal carcinoma in situ (DCIS)

In DCIS, there are abnormal cells growing in the lining of a duct, but they have not grown through (invaded) into the breast tissue, and are not able to reach the lymph nodes or other parts of the body. Since there is no invasion, this type of cancer is also called non-invasive. DCIS may change into invasive cancer later, and is a pre-cancer. DCIS is detected by mammograms.

 Invasive (also known as infiltrating) ductal carcinoma (IDC)

IDC is the most common type of breast cancer. Abnormal cells begin growing in the lining of a duct, and go on to invade breast tissue. Cancer cells are able to reach lymph nodes and from there, get carried to other organs.

Invasive (or infiltrating) lobular carcinoma (ILC)

ILC begins in the lining of lobules and invades breast tissue, spreading to lymph nodes and other organs.

Inflammatory breast cancer (IBC)

IBC is rare. In this type of breast cancer, a lump or tumour is not present. IBC affects the skin of the breast, leading to redness, warmth, and thick, pitted, and scaly skin. The affected breast can swell and feel harder, tender, and/or itchy.

The symptoms of IBC match those of an infection. Due to the lack of a tumorous lump, mammograms do not pick up IBC. IBC is more likely to spread and more deadly than other types of breast cancer.

Risk factors

There are several factors that are connected with your chance of getting breast cancer. It is important to note that they do not determine for certain whether or not someone will get breast cancer.

  • Women get breast cancer much more often than men.
  • Risk increases with age.
  • Caucasian women have a higher risk of breast cancer than African-American women, although the disease is more deadly for African-American women.
  • Some genetically inherited mutations, especially in the BRCA1 and BRCA2 genes, increase the risk of getting breast cancer.
  • Family history. If close relatives have had or have breast cancer, your risk of breast cancer is higher.
  • Medical history. Having had cancer in one breast increases the likelihood of getting a new cancer in the other breast.
  • Breast density. The presence of more gland tissue and less fatty tissue in the breast increases the risk of breast cancer.
  • Benign (non-cancerous) breast conditions. Benign breast lumps and changes increase the risk of cancer.
  • Lobular carcinoma in situ (LCIS). LCIS is when cancer-like cells are found in lobules, but they are non-invasive. LCIS is not classified as cancer or pre-cancer. Having LCIS increases the risk of getting breast cancer.
  • Having started menstruating before the age of 12, or having menopause after the age of 55 increases the risk of breast cancer.
  • Exposure to radiation. Having had radiation treatment in the chest area in the past increases the risk of breast cancer significantly.
  • DES treatment. Having taken diethylstilbestrol (DES) while pregnant causes a slight increase in the risk of breast cancer.
  • Not having children, or having had children after the age of 30 slightly increases the risk of breast cancer, while having multiple pregnancies or pregnancy under the age of 30 decreases the risk of breast cancer.
  • Birth control use. Birth control pills and use of an injectable birth control, Depo-Provera, slightly increases breast cancer risk. The increased risk reduces over time after stopping birth control.
  • Hormone therapy. The use of combined hormone therapy (estrogen and progesterone) after menopause increases breast cancer risk. This increased risk reduces over time after stopping hormone therapy.
  • Not breastfeeding increases breast cancer risk, while breastfeeding reduces it. Breastfeeding for 1.5 to 2 years reduces breast cancer risk the most.
  • Alcohol consumption. Any alcohol consumption increases breast cancer risk.
  • Women who are obese or overweight after menopause have a greater risk of breast cancer.
  • Tobacco use. The increased risk of breast cancer due to smoking appears to affect only specific groups (e.g., women who began to smoke before their first pregnancy).

Symptoms

Symptoms of breast cancer include:

  • A new mass or lump in the breast (the most common symptom). These lumps can be painless or tender, soft or hard, rounded or uneven.
  • Swelling of any part of the breast or all of the breast
  • Skin irritation
  • Skin dimpling
  • Pain in the breast(s)
  • Pain in the nipple(s)
  • Nipple reversal (turning inward)
  • Thickening, scaliness and redness of the breast skin or nipple
  • Abnormal nipple discharge
  • Swelling or lumps in the lymph nodes under the arms and/or collarbone (even without the obvious presence of a lump in the breast)

Breast cancer screening

Mammograms are recommended for screening to find breast cancer before it has begun to cause symptoms. This helps to find breast cancer early, which improves the effectiveness and predicted outcome of treatments.

Breast cancer diagnosis

In addition to a review of your symptoms and a physical examination, tests to determine the presence of breast cancer include:

Imaging

There are several methods used to image and examine the tissue of the breast.

  • X-rays are used to image the breast. Breasts are positioned between two plates that flatten them so that the tissue is spread out for imaging. A picture is then taken. This is repeated for different positions of the breast. Although uncomfortable, each position only lasts a few seconds. The entire process takes a total of around 20 minutes.

Mammograms can either be used to screen the breast for breast cancer, or to diagnose breast cancer. If a lump that looks like cancer is detected on a mammogram, a biopsy (a sample of the breast tissue) is required to determine if there are cancer cells.

  • Sound waves and their echoes are used to create an image of the breast. Ultrasounds involve spreading a gel on the breast and placing a small wand-like instrument on the area. Ultrasounds are used to inspect a specific area of interest in the breast that was identified by a mammogram. It is able to distinguish between cysts and tumours. Lymph nodes can also be examined using ultrasound.
  • MRI (magnetic resonance imaging). Detailed cross-sections of the body are obtained using radio waves and strong magnets, with the patient lying face-down on a special platform in a tube-like machine. MRIs can be used both for screening for breast cancer and for looking at areas of interest found by a mammogram. It is also used for sizing of tumours.

Biopsy

Biopsies give further information about the presence of breast cancer. They are the only way to obtain a diagnosis of breast cancer. Biopsies involve removal of cells from the areas of concern identified by imaging tests so that the presence of cancer cells can be determined.

  • Lymph node biopsy. When there are swollen lymph nodes under the arms, a needle may be used to obtain tissue from them to check for cancer cells. Entire lymph nodes can also be surgically removed to be checked, sometimes multiple lymph nodes at once.
  • Breast tissue biopsy. Most commonly, a needle is used to remove tissue from an area identified to have a problem. A doctor can feel the lump to determine where it is, or use an imaging test. When a needle biopsy doesn’t provide an answer about whether cancer is present, the lump (part or all of it) may need to be surgically removed.

Lab examination of biopsy tissue

Tissue from biopsies are examined in laboratories to determine whether cancer is present. If cancer is present, the information from lab tests give your doctor information about what kind of cancer it is, how fast it is growing, and how best to treat it.

  • When cancer is detected, it gets a grade between 1 and 3. Lower grade cancer is more like the normal tissues of the breast and are less invasive. The grade of the cancer helps to predict how well the cancer can be treated.
  • Hormone receptors. Proteins in cells are able to attach to hormones present in the blood through proteins called hormone receptors. Breast cancer cells sometimes have receptors for the hormones estrogen and progesterone, which cause them to grow faster. Tumour biopsies are tested for the presence of these hormone receptors. If they are present in a tumour, the cancer is called estrogen or progesterone receptor-positive, or hormone receptor-positive. These cancers are slower-growing and more responsive to hormone treatment than hormone receptor-negative cancers. 2/3 of breast cancers are hormone receptor-positive.
  • HER2/neu. 1/5 of breast cancers show an abnormally increased amount of a specific protein, HER2/neu. These cancers are called HER2-positive and are treated using drugs that specifically target HER2/neu.
  • Gene expression pattern. Certain patterns of many genes examined at the same time give an indication of how likely a cancer is to return after treatment. Gene pattern tests give guidance for future treatments. Two tests are available: Oncotype DX® and MammaPrint®. These tests are not informative for all breast cancers.

Testing for breast cancer spread

Testing for the spread of breast cancer is not done if the cancer was caught early. It is usually done if there is some cause for concern about spreading (e.g., symptoms, physical exam results, tumour size).

  • Chest x-ray. This is used to check for cancer in the lungs.
  • Bone scan. This is used to check for cancer in bones.
  • Computed tomography (CT) scan. A series of X-rays of the body from different angles is taken with a ring-like machine. The X-rays are computationally combined to create detailed pictures of the chest and abdomen area. This shows whether there is cancer in other organs. Contrast agents are either drank or given intravenously to enhance imaging.
  • As described above, MRI uses radio waves and strong magnets to create images of the body.
  • Ultrasound can be used on different parts of the body to check for cancer.
  • Positron emission tomography (PET). A radioactive sugar is given intravenously and spreads throughout the body. Since cancer cells use a lot of sugar, the radioactivity will be strongest near tumours. A special imaging device is used to determine these “hot spots.” PET is useful for determining where exactly a cancer has spread. It can be combined with CT.

Breast cancer staging

Staging involves determining how widespread a cancer is when it is first diagnosed. This helps determines how it can be best treated. The stage of a cancer depends on whether it is invasive, tumour size, the number of lymph nodes affected, and if it has spread to other areas of the body. Stage 0 indicates non-invasive breast cancer, and stages I-IV describe invasive breast cancers. Lower numbers indicate less spread and less advanced cancer. Sub-stages are indicated using letters A, B and C, with a lower letter indicating a better stage. Cancers of each stage are treated similarly and have similar predicted outcomes.

TNM

TNM is another breast cancer staging system. T and the numbers after it indicate the size of the tumour, N and the numbers after it indicate whether lymph nodes are affected, and M and the numbers after it indicate if there has been spread of the cancer to other organs (metastasis).

Treatment

Below are the main types of treatment for breast cancer.

Surgery

Surgery is usually used to remove as much of the primary breast tumour as possible. In addition, it can be used to find cancer cells in lymph nodes and to reshape the breast after surgery.

  • Breast-conserving surgery (BCS) (also known as lumpectomy or partial mastectomy). Part of the breast is removed, depending on the location and size of the tumour. The tissue that is removed is examined for cancer cells around the edges. If found, further surgery is needed to remove more tissue that may be cancerous. Radiation therapy is usually done after BCS to try to kill any cancer cells that may be left.
  • The entire breast is removed in this surgery, and sometimes also nearby tissue. A simple mastectomy is when only the breast is removed, while a radical mastectomy includes removal of muscles of the chest wall underneath the breast (if cancer is also present there). A modified radical mastectomy also involves removal of lymph nodes.

Lymph node surgery

To determine if there is cancer in the lymph nodes under the arms (the axillary lymph nodes), the lymph nodes can be removed for examination. This helps to stage the cancer and decide on treatment.

  • Axillary lymph node dissection. 10-40 lymph nodes are removed, usually during mastectomy or BCS.
  • Sentinel lymph node dissection and biopsy. To check for cancer in axillary lymph nodes without removing a lot of them, a radioactive marker and/or blue dye is injected into the breast tumour. The marker and/or dye is carried to the nodes that directly receive lymph from the tumour, and these are detected and removed. If these sentinel nodes are found to have cancer, additional lymph nodes are surgically removed and examined for cancer cells.

Radiation

In radiation therapy, X-rays or high-energy particles are used to kill cancer cells, either after or before a surgery. It is usually given after BCS and chemotherapy, and is used in the treatment of cancer that has spread to other organs.

  • External beam radiation. Radiation is targeted to the area with cancer from outside the body using a machine. This type of radiation is the most commonly used for breast cancer.
  • Radioactive pellets is implanted into the breast. This can also be combined with external beam radiation. A radiation-emitting device can also be implanted temporarily into the space that is created by BCS (called intracavitary brachytherapy).

Chemotherapy

Cancer-killing drugs are injected, or administered orally in pill or liquid form. The drugs are able to reach throughout the body by traveling in the bloodstream, and can act on cancer that has spread to multiple organs. Because the drugs also kill normal cells, side effects include hair loss, fatigue and nausea.

Hormone therapy

In hormone receptor-positive cancers, estrogen increases tumour growth. Hormone therapy can be used to prevent estrogen’s effects, or lower estrogen levels. This type of therapy includes:

  • Estrogen receptor inhibitors. These drugs block estrogen receptors, and include Tamoxifen, Faslodex® and toremifene.
  • Aromatase inhibitors (AIs). These drugs prevent the production of estrogen by fat tissue, and include Arimidex, Aromasin and Femara. Estrogen levels are only lowered by these drugs after menopause.
  • Luteinizing hormone-releasing hormone (LHRH) analogues. These drugs shut down ovaries to lower estrogen levels.
  • Surgical removal of ovaries. Removing the ovaries can decrease estrogen production in women that have not experienced menopause.

Targeted therapy

By elucidating the gene changes that are involved in cancer, drugs have been developed that can directly target these changes. Because of their specific action, side effects are usually less severe. Most of these drugs target the HER2/neu protein.

Bone-directed therapy

Drugs to treat cancer that has spread from the breast to bone include bisphosphonate drugs (e.g., Aredia® and Zometa®), and denosumab (e.g., Xgeva® and Prolia®). These drugs help to prevent the weakness and pain in bones caused by cancer.

Adjuvant and neoadjuvant therapy

After surgery, when most or all of the cancer appears to have been removed, further treatment may still be given to kill undetectable cancer cells that may be present in the bloodstream and can still form new tumours. This treatment is called adjuvant therapy. Adjuvant therapy can involve systemic treatment or radiation therapy.

If treatment is given to shrink a tumour before surgery, it is called neoadjuvant therapy.

Follow-up on treatment

Close follow-up is required after treatment to ensure continuing health. This involves mammograms, and MRIs in the case of carriers of BRCA1 or BRCA2 gene mutations. Regular exercise to maintain a healthy body weight is recommended. Any smoking or alcohol consumption is not recommended.

Palliative treatment

Some cancer is not cured by many different treatments and becomes resistant to treatment. At this point, treatment is given to maintain comfort and relieve symptoms (e.g., pain and nausea), and is called palliative treatment.

 

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References

Carol DeSantis, Jiemin Ma, Leah Bryan, Ahmedin Jemal. “Breast Cancer Statistics, 2013” CA Cancer J Clin. 2014;64(1):52-62. doi: 10.3322/caac.21203.

Link: http://onlinelibrary.wiley.com/doi/10.3322/caac.21203/pdf

Catherine Downs-Holmes & Paula Silverman. “Breast Cancer: Overview & updates.” Nurse Pract. 2011;36(12):20-26. doi:10.1097/01.NPR.0000407602.29522.d7.

Link: http://journals.lww.com/tnpj/pages/articleviewer.aspx?year=2011&issue=12000&article=00008&type=abstract

James L. Khatcheressian, Patricia Hurley, Elissa Bantug et al. “Breast Cancer Follow-Up and Management After Primary Treatment: American Society of Clinical Oncology Clinical Practice Guideline Update” J Clin Oncol. 2013;31(7):961-965. doi: 10.1200/JCO.2012.45.9859.

Link: http://jco.ascopubs.org/content/31/7/961.short

 

Written By: Anna Zhou



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