BREAST CANCER OVERVIEW 

The breast as we know is the bulgy (protuberant) organ that lies over the second to the sixth rib of the human chest (mainly focused on women). Men also have this organ but the prominence is not that appreciated in most, as that of women.

The projection or protuberant nature of the breast in women is as a result of a number of different tissues housed beneath the skin. The tissues are arranged as:

  1. The skin: Outermost covering of the breast.
  2. The ligaments (Cooper’s Ligaments): Fibrous (tough) tissues connecting the skin anteriorly to the structures of the chest wall posteriorly. This maintains the structure of the breast. The ligaments are also known as Cooper’s ligament.
  3. Pectoralis muscles: One of the contractile (squeezable) muscles beneath the breast.
  4. Fatty tissues
  5. Lobules: The basic functional unit of the breast, which performs the mammary function; production of milk.
  6. Ductules: These are small canals, draining content from the lobules to the main duct of the breast.
  7. Duct: The main canal which receives secretions from ductules, stores the content temporarily, and excrete it during lactation (milk expulsion). It also has an ampulla (dilated portion) which ensures the storage of milk.
  8. Areola: It contains involuntary muscles and has sebaceous glands which lubricate the nipple.
  9. Nipples: It is the pointed part of the breast with a tough skin. It also has erectile tissues which cause erection of the nipple when stimulated.
  10. Blood and lymphatic vessels.

Whenever there is a malignancy in any of the cells of the breast, it is termed breast cancer. Also, there is an extension of breast tissues to the axilla (armpit), which anatomist or surgeons term as the Axillary Tail Of Spence, named after Scottish surgeon James Spence.

WHAT IS A BREAST CANCER?

Breast cancer occurs when there is an uncontrolled abnormal growth of the cells of the breast and like most cancers, it has the potential of invading or spreading to other body parts. Alteration (mutations) of genes responsible for cell growth and cell death is the hallmark of cancerous breast tissue.

Cancer of the breast tissue commonly occurs in the lobules or the ductules, but occasionally fatty tissue or tough(fibrous) connective tissue of the breast are involved.

 

CLASSIFICATIONS OF BREAST CANCER

 

  1. Breast cancers are grouped into different categories based on whether they stay in the breast alone or move to other parts of the body. These are:
  • Local (cancer cells confined to the breast).
  • Invasive (Directly and violently puncture into neighboring structures).
  • Metastatic (spread to other parts of the body far away from the breast).
  1. Based on the the type of breast cells that cancer originates from. These are:
  • Ductal (from the ductules of the breast).
  • Lobular (from the lobules of the breast ).

This basis of classification is the source of the names of the various types of breast cancers.

TYPES OF BREAST CANCERS

 

  1. Ductal Carcinoma In situ.
  2. Lobular Carcinoma In situ.
  3. Invasive Ductal Carcinoma.
  4. Invasive Lobular Carcinoma.
  5. Metastatic breast cancers.
  6. Other types of breast cancers.

 

  1. Ductal Carcinoma In Situ (DCIS): This refers to cancerous cells of the duct that are confined within it. The term in situ explains the fact that these changed cells stay in their original place, and do not invade neighboring organs. This condition is precancerous or of a low grade cancerous ability; having the ability to invade other tissues if not treated in time. Normally patients are asymptomatic, with no significant symptoms manifesting. Since they are asymptomatic, they are commonly detected during screening of the breast.
  2. Lobular Carcinoma In situ (LCIS): These are precancerous cells that grow in the lobules (milk-producing cells) of the breast. The cells are also confined to the lobule hence, in situ.
  3. Invasive Ductal Carcinoma(IDC): This cancer type begins in the ducts of the breast and spreads beyond the ducts to other tissues of the breast. They are capable of invading other neighboring tissues. It is the most common type of breast cancer, and has several subtypes depending on the appearance of the cancerous cells. These types are :
  • Mucinous Carcinoma of the breast: This refers to cancer of the mucin-producing cells within the duct of the breast. These cancerous cells appear histologically (under a microscope) as a mixture of cells suspended in mucus. Hence, this cancer can also be called colloid carcinoma of the breast.
  • Tubular Carcinoma of the breast: These duct cancerous cells invade tissues and organs. The cancerous cells are made up of pipe-shaped (tube-shaped) structures called tubules.
  • Medullary Carcinoma of the breast: This is an invasive carcinoma originally from the ducts of the breast. It is named so because the cells look like the medulla oblongata of the brain stem (part of the brain continuous with the spinal cord).
  • Papillary Carcinoma of the breast: The cancerous cells in this type have clearly outlined margins or well-defined borders and are made up of small digitated (fingerlike) protrusions. It invades other tissues in the breast from the duct and other closely related organs.
  • Cribriform Carcinoma of the breast: The cells invade the supporting (connective) tissues of the breast (the stroma) and leave holes between the tumor cells, among the ductules and lobules forming perforations that characteristically resemble Swiss Cheese, and so are aptly described as possessing a Swiss Cheese Appearance.
  1. Invasive Lobular Carcinoma: The origin of this cancer is in the lobules of the breast and it invades nearby tissues and organs.
  2. Metastatic breast cancers: Cancerous cells that break out and spread to distant organs through blood (hematogenous) and lymph (lymphatic spread) from the breast. The most common organs that the cancer cells spread to are the liver, brain, bones, and lungs. This usually results in the abnormal detection of breat cells in other organs. Early detection of local precancerous changes helps to prevent metastasis or direct invasions. In contrast, there are cases that standout, with patients diagnosed with a breast cancer secondary to metastasis from another origin. This presentation, known as De novo metastatic breast cancer; implies the the breast cancer was metastatic from the onset. Simply speaking, the patient was diagnosed with breast cancer that spread to other organs from the very start.

OTHER TYPES OF BREAST CANCERS

These breast cancers are uncommon and deviate from the classification according to spread, invasion or original cellular location.

  1. Paget’s disease of the nipples: The cancer begins in the ducts of the breast and presents superficially on the nipples and the areola (a small circular area around the nipples) in the form of eczema (scaly, red, itchy ). This eczematous presentation on the nipple and areola do not respond to local treatment. It has the tendency of wearing away the nipple if not treated in time. Hence, the inherent cancer is diagnosed clinically.
  2. Angiosarcoma of the breast: This is a cancer of the blood and lymph vessels of the breast. Angio(relating to lymph or blood vessels) and sarcoma, a type of cancer.
  3. Phyllodes tumor: This type of tumor is rare. It affects the connective tissues of the breast. They are mostly benign(non-invasive or non-metastatic), but are capable of spreading on a few occasions. Sometimes known as cystosarcoma phyllodes, they commonly occur in women over the age of 40 and can cause ulcerations on the skin due to pressure and shearing or friction (pressure necrosis). The cancerous cell growth has the appearance of a leaf, hence the name phyllodes, a derivative of the word Phyllo, Greek for leaf.
  4. Inflammatory breast cancer: Breast cancers which make the breast swollen, red, and warm, as opposed to the classical presentation of forming palpable masses or lumps. These cancers are rare but grow rapidly. They thefore require immediate medical attention. This cancer occurs when cells growrapidly, preventing lymphatic drainage by blocking lymph nodes. It is often misdiagnosed as mastitis; the inflammation of the breast, usually by microbial infection, as the presentation is almost identical.
  5. MOLECULAR SUBTYPES OF BREAST CANCER

This is classified based on the biological characteristics of the cancer cells. This classification is focused on cancer cells’ genetic expression of receptors for estrogen and progesterone hormones and/or human epidermal growth factor receptor (HER2) . This classification is very important for the prognosis of cancer. The types include:

  1. Luminal A: These cancer cells are positive for hormone receptors (estrogen and progesterone receptor positive ) but negative HER2. There is a low amount of Ki-67 proteins, which control proliferationof cancer cells. This makes this type a low grade cancer, with lower cell proliferation and a consequently better prognosis.
  2. Luminal B: These cancer cells have a relatively low expression of hormone receptors (Estrogen and progesterone) but a positive HER2. The proliferative marker Ki-67 is increased. These cancers have a higher growth rate, hence a worse prognosis than luminal A.
  3. Triple-negative: The cancerous cells are negative for progesterone and estrogen receptors and negative for HER2. This type of cancers does not necessarily need hormones to grow and subsequently gows very quickly and is very difficult to treat. The rapid growth of this cancer is due to inactivation of tumor suppressor protein; a protein that prevents the growth of cancer cells. This cancer is also called basal-like breast cancer.
  4. HER2-enriched breast cancers: This cancer is negative for the two hormone receptors (estrogen and progesterone receptors) and positive for HER2. This cancer has a rapid growth rate, relative to the luminal cancers and consequently has a very poor prognosis. The management of this type is not as difficult when compared to the triple negative cancer.
  5. Normal-like breast cancer: These cancers are just like Luminal A cancers but with a prognosis that is a little worse than the Luminal A cancers.

 

  1. MALE BREAST CANCER

This is a rare cancer type that happens in men. The ducts are commonly involved and to a lesser extent, there is involvement of the lobules since men have very few lobules. It normally occurs in older men.

EPIDEMIOLOGY

Breast cancer is the most common cancer in women, according to the Centers for Disease Control and Prevention (CDC). Breast cancer makes up 22.9% of invasive cancers in women and 458,503 worldwide deaths were recorded in 2008 due to breast cancer. The expected amount of cancers to be diagnosed in 2015 in the United States alone, was about 232,000 according to the American Cancer Society. Breast cancer is quite rare in men.

CAUSES

The cause of most breast cancers is not clearly understood, but it is normally based on these two factors:

  1. Genetic mutations.
  2. Environmental factors such as infections, lifestyle habits, exposure to carcinogens and hormonal influences.

PATHOPHYSIOLOGY

This refers to changes and deviation in the normal cell division, maturity, and growth that cause normal breast cells to become cancerous. Alterations or mutation in the genes responsible for regulating breast cell growth are regularly implicated. The deviation from normal function may cause:

  1. Breast cells to grow rapidly than normal.
  2. Abnormal cells ignore signals to self-destruct, and thus refuse to die.
  3. The abnormal cells grow into a mass (tumor).
  4. The cells get bigger and invade nearby organs or spread to other body parts.

RISK FACTORS

The main risk factors of breast cancer include:

  • Age: Advanced age increases the tendency of developing breast cancer (around age 55 upward).
  • Gender: Females are at a higher risk than males.
  • Thick breast: Heavy breast tissues pose a high risk of developing breast cancer and also negatively impact screenings.
  • Previous history of breast cancer.
  • A family history of breast cancer.
  • Excessive alcohol intake.
  • Chronic smoking.
  • Radiation exposure.
  • Very late menopause: Around age 55 increases risk.
  • Very early menstruation: Around age 12 and below.
  • Genetic mutations: Inheritance of a mutated BRCA1 and BRCA2 genes.
  • Hormonal Replacement Therapy.
  • Late Pregnancy with first child.

CLINICAL MANIFESTATIONS 

EARLY MANIFESTATIONS

There usually are not any symptoms during the early stages but some women may present with a lump in the breast. Early signs and symptoms include:

  • Lump in the breast or thickening of breast tissue.
  • Pain in the breast.
  • Skin changes on the breast (redness and dimpling).
  • Swelling in breast tissues.
  • Peeling of breast skin.
  • Discharge from the nipple, that is not breast milk.
  • Bloody discharge from the nipple.
  • Inverted nipple.
  • A sudden change in the size and shape of the breast.

PROGNOSIS

The outcome of breast cancer is dependent on a lot of factors. A very common predictor of disease outcome for breast cancer is the Nottingham Prognostic Index; a grading system based on the following criteria: Tumor Size, Lymph Node Involvement, Grade of the Tumor. Other prognostic factors include:

  • Invasive or Metastatic potential (location of tumor).
  • Histological grade of the tumor.
  • Measures of tumor proliferation (S-phase fraction).
  • Growth factor Analysis

ROUTES OF BREAST CANCER

This depicts the various means cancerous cells  can migrate from their original source to nearby or distant tissues and organs.

  • Local Invasion: The violent puncture of cancerous breast cells into surrounding tissues and nearby organs.
  • Hematogenous spread: Spread of cancer cells to distant organs in blood through blood vessels.
  • Lymphatic spread: Spread to distant organs through the lymph vessels into lymph nodes (commonly, the axillary and internal mammary lymph nodes).

STAGES OF BREAST CANCER

This is done to determine the severity of breast cancer and the best method of treatment approach. These factors are to be considered when staging breast cancers.

  • Invasive or noninvasive (local).
  • Size of the tumor (large or small).
  • Lymph node involvement.
  • Spread of cancer cells to nearby tissues or not.

*Based on these categories, breast cancer is grouped into these five stages

  1. Stage O: Cancers cells remain in local tissues with no invasion or metastasis. Examples include 1. Ductal Carcinoma In Situ (DCIS) and Lobular Carcinoma in Situ (LCIS).
  2. Stage 1 is grouped into two.
  • Stage 1A: Tumor size is about 2cm or less and has no lymph node involvement.
  • Stage 1B: Tumor size is less than 2cm or not in the breast, but in nearby lymph nodes.
  1. Stage 2 grouped into two.
  • Stage 2 A: Size is less than 2cm and has spread to 1 to 3 nearby lymph node, or Size is 2 to 5cm with no lymph node involvement.
  • Stage 2B: Size of the tumor is between 2 to 5cm in 1 to 3 armpit lymph nodes, or the Size is bigger than 5cm with no lymph node involvement.
  1. Stage 3 has three groups
  • Stage 3A: Tumor in 4-9 armpit lymph nodes or expanded the lymph nodes in the breast. These tumors are more than 5 centimeters and are in armpit lymph nodes (1 to 3 of them ) in any of the bones of the breast region.
  • Stage 3B: Tumor is in less than 10 lymph nodes with an invasion of chest wall and skin.
  • Stage 3C: Cancer cells in more than 10 armpit lymph nodes or the internal breast lymph nodes.
  1. Stage 4: Cancer cells travel to distant lymph nodes and organs and can be of any size. This type is called metastatic breast cancer.

DIAGNOSIS OF BREAST CANCER

In addition to your presenting symptoms and signs, a physical examination, radiographic imaging, and a breast biopsy must be done before a confirmative diagnosis can be made.

  • Physical examinations: Inspection and palpation (pressing) of the breast to check for lumps or any other abnormalities.
  • Mammography: Radiographic images taken from two plains might show abnormality in the tissues of the breast. Best used in women after the age 35years or those with less dense breast tissue.
  • Breast Ultrasound: Ultrasound imaging is commonly used in young women below the ages of 35years old or those with dense breast tissue. It can differentiate a solid and liquid tumor. As a result, it serves as a good tool for detecting cancer, with a high value of accuracy but is usually user dependent.
  • Breast Biopsy: Used normally if there are no positive results in the mammography or ultrasound. Tissues from the affected part of the breast are taken for studies to detect the precise changes in the breast cells.
  • Breast MRI: Mostly by injection of a dye to serve as a contrast medium for a contrast enhanced Magnetic Resonance Image of the internal tissues of the breast.

PREVENTION

  • Early screening by mammography.
  • Avoid excessive alcohol intake.
  • Eat healthy.
  • Regular exercises.
  • Maintain a healthy body weight.
  • Stop postmenopausal hormonal therapy.

*There are various procedure people with very high risk can undertake to reduce the risk of getting breast cancer.

  • Preventive chemotherapeutic drugs: Estrogen and progesterone blockers.
  • Prophylactic mastectomy: Removing breast tissue to reduce the risk of breast cancer.

TREATMENT OF BREAST CANCER

  1. Surgery: This is the most common and helpful treatment for breast cancer. There are different types of surgical procedures used based on the extent or stage of cancer.
  • Lumpectomy: This is removal of the cancerous lump of breast tissue and it is usually described as a breast preserving procedure.
  • Mastectomy: The entire breast tissue is removed, or total removal of both breasts(double mastectomy).
  • Sentinel node excision/biopsy: Some limited number of lymph nodes are removed to check for the presence of tumors or cancers.
  • Axillary lymph node dissection: This is performed when there is a tumor in the sentinel lymph node biopsy. Extra lymph nodes are removed to prevent tumor spread.
  1. Radiation therapy: Use of high energy rays to destroy cancer cells. Transmission of the rays from a source within the body is known as Brachytherapy.
  2. Chemotherapy: Medications given before or after breast cancer surgery. Medications used to prevent cancer spread or to prevent recurrence of cancer are referred to as adjuvant chemotherapy.
  3. Hormonal therapy: These drugs block estrogen and progesterone action by; decreasing synthesis, inhibiting the binding of the hormones to their receptors, and/or destruction their receptors. These drugs are grouped as:
  • Selective Estrogen Receptor Modulators (SERM): They block estrogen from binding to cancer cells which are positive for estrogen receptor, causing a halt in cell growth and ensure cancer cells shrink. Eg: Raloxifene.
  • Aromatase inhibitors or Estrogen synthase inhibitors: Aromatase is an enzyme which converts androgens into estrogen. Inhibition of this enzyme prevents the production of estrogen from androgen hormones like testosterone, hence reducing the amount of estrogen in the body. This drug works mostly in postmenopausal women. Eg: Letrozole.
  • Estrogen receptor degrader: These drugs block estrogen from binding to receptors on the cancerous cells by destroying the estrogen receptors and cause the destruction of the cancerous cells. Used in women after menopause. Eg: Fulvestrant.
  • Targeted Chemotherapy: These drugs target specific properties in the cancerous cells that make them grow rapidly and also refuse to die. These drugs kill cancer cells by destroying those properties. Eg: Trastuzumab blocks the human epidermal growth factor from binding to its receptors (HER2) on the cancer cells and cause the death of the cancer cells.