Breast Cancer

What is Breast Cancer?

Breast cancer is the most common cancer in the United Kingdom. Every year 48,000 new cases are diagnosed there. Of these, 80% are over 50 but younger women, and in rare cases, men, can also get breast cancer. Breast cancer is the leading cause of death for women aged 34 to 54.

Electron micrograph of a single breast cancer cell.

The normal breast

The breasts of a woman are made up of fat, supportive (connective) tissue and tissues with glands called lobes. These lobes are milk glands where breast milk is produced. These are connected to the nipple by a network of milk ducts.

Both breasts may be slightly different from each other. They change throughout a woman’s life and often feel different at different times in the month because of hormonal changes. Just before periods they may feel lumpy and they may feel softer, smaller and more lax as the woman ages.

Under the skin, an area of breast tissue extends into the armpit (axilla). This is called the tail of the breast. The armpits also contain a collection of lymph nodes which are part of the lymphatic system. There are also lymph nodes just beside the breastbone and behind the collarbones. These drain the breast tissues and are affected in breast diseases and inflammatory conditions. The lymph nodes are connected by a network of tiny lymphatic tubes. Lymph flows through the lymphatic system.

This picture shows the lobes and ducts inside the breast. It also shows the lymph nodes near the breast.

What is cancer?

The body is made up of billions of tiny cells. Normally, cells grow and multiply in a tightly regulated fashion. New cells are only made when and where they are needed. When cancer occurs the cells’ growth cycle goes haywire making them multiply uncontrollably. Cells become cancer cells because of damage to DNA. This leads to formation of a lump that may be benign or non-cancerous or aggressive it its growth – termed malignant or cancerous.

What is breast cancer?

Breast cancer is a malignant tumor that starts in the cells of the breast. A malignant tumor is capable of invading surrounding tissues or spreading or metastasizing to distant areas of the body. The disease occurs almost entirely in women, but men can get it, too. 

Symptoms of breast cancer

Breast cancer can have a number of symptoms but usually shows as a lump or thickening in the breast tissue. Other common symptoms may include deformity, ulcers and discharge from the nipple.

Types of breast cancer

There are several varieties of breast cancer. These can affect various parts of the breast. Breast cancer is often divided into non-invasive and invasive types.

Non-invasive breast cancer

Non-invasive breast cancer is also known as cancer or carcinoma in situ, or pre-cancerous cells. This is seen in the ducts of the breast and does not have the ability to spread outside the breast. This form of cancer rarely shows as a lump in the breast and is usually found on a routine check up with a mammogram. The most common type of non-invasive cancer is ductal carcinoma in situ (DCIS).

Invasive cancer

Invasive cancer is more aggressive and spreads outside the breast. The most common form of breast cancer is invasive ductal breast cancer. This type develops around the ducts of the breast and accounts for about 80% of all cases of breast cancer and is sometimes called 'no special type'.

Other types of breast cancer

Less common varieties of breast cancer include invasive lobular breast cancer, inflammatory breast cancer and Paget’s disease of the breast.

Breast cancer diagnosis

Breast cancer is detected on routine screening using mammograms or after a breast lump is followed up with investigations. After a lump is found an ultrasound and mammogram is advised and a tissue sample is take from the lump using Fine needle aspiration cytology (FNAC). This is then analysed to assess whether malignant cells are present and confirm the diagnosis of cancer.

The cancer is also tested if it contains Estrogen receptors in which case it is termed ER positive cancer. Other organs, abdomen, lungs, brain, bones etc. are examined using imaging techniques like CT scan and MRI to detect possible spread of the cancer.

Breast cancer treatment

Breast cancer is treated using a combination of surgery, chemotherapy and radiotherapy. Some cases of breast cancer may also be treated using biological or hormone treatments. There is a good chance of recovery if it is detected in its early stages. For this reason, it is vital that women check their breasts regularly for any changes and always get any changes examined by their doctors.

Breast Cancer Classification

Breast cancers can be classified on the basis of four schemes. Each of these schemes classify the cancers based on different criteria and serve a different purpose. Some of these are:

Classification based on pathology

The cancer is classified according to its cellular structure and microanatomy. This is the commonest for of classification or typing the breast cancer.

This picture shows ductal carcinoma in situ.
This picture shows cancer cells spreading outside the duct. The cancer cells are invading nearby tissue inside the breast.

Classification according to grade

The pathologist classifies the cancer according to grade. A ''well-differentiated'' tumor for example is low grade and resembles normal tissue. A ''poorly differentiated'' tumor is composed of disorganized cells and, therefore, does not look like normal tissue and is termed high grade. Some are ''moderately differentiated'' or intermediate grade as well.

Classification based on stage of cancer

This is the most commonly used scheme of determining the stage of cancer and the TNM staging that takes into account the Tumor size, lymph Node involvement and Metastasis or spread of the cancer.

Protein & gene status

All breast cancers these days are tested for expression, or detectable effect, of the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins. These tests utilize principles of immunohistochemistry and once the status of these proteins it known, prognosis can be predicted and certain novel therapies may be chosen for treatment.

Histological appearance

Breast cancer is usually, but not always, primarily classified by its histological appearance. Some of the histological types include:

Ductal Carcinoma in situ (DCIS)

This signifies a very early form of cancer that has not spread. DCIS is a type of early breast cancer inside of the ductal system that has not attacked the nearby tissue. It is one of the common types of non-invasive cancer

Infiltrating or invasive ductal carcinoma (IDC)

This is the most common type of breast cancer. It starts in the milk ducts and spreads to surrounding tissues. This can also spread to other parts of the body via lymph channels and blood stream.

Medullary carcinoma

This forms around 15% of all breast cancers. It affects middle aged women more commonly and the cellular histology resembles the medulla (gray matter) of the brain.

Lobular Carcinoma in situ (LCIS)

This is a rarer form of non-invasive tumor. It usually does not develop into invasive cancer. LCIS is more of a “marker” or signal that breast cancer may develop. LCIS has recently been renamed lobular neoplasia.

Infiltrating Lobular Carcinoma (ILC)

This is the second most common type of breast cancer after invasive ductal carcinoma. The cancer begins in the lobules or lobes and spreads to other parts of the body. There is initial appearance of a thickening in the upper-outer section of the breast. These are usually positive for estrogen and progesterone receptors and thus may be treated successfully with hormone therapy.

Tubular carcinoma

The cancer cells appear like tiny tubules. This type of breast cancer is typically found in women aged 50 and above. This tumor responds well to treatment

Mucinous carcinoma or colloid

This is rare type of invasive breast cancer that rarely spreads to the lymph nodes. The cancer cells produce mucus and these cells are distinct from normal cells under a microscope. The mucous and cancer cells combine to form jelly-like tumors. 

Paget’s disease

This leads to an eczema-like change in the skin of the nipple. There is itchiness, scaling and oozing discharge from the nipple. 90% of the women who experience these symptoms have an underlying breast cancer. Paget’s Disease can occur at any age but will more likely occur in women who are in their 50s.

Inflammatory breast cancer

This is a rare but aggressive type of breast cancer. The cancer leads to blockage of the lymph vessels in the skin of the breast. The cancer appears to cover the breast over a large area like a sheet rather than a lump. The breast appears swollen, red and inflamed.

Triple negative breast cancer

Breast tumor that is negative for estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins.

Metastatic breast cancer

This is a later stage of breast cancer when it has spread to other organs like liver, brain, bones etc.

Breast Cancer Causes

The exact causes of breast cancer are not well understood. However, there are several risk factors that raise the possibilities of breast cancer. Of these risk factors some may be modified or changed like lifestyle factors while others are non-modifiable.
The causes and risk factors of breast cancer are outlined as follows –

Non-modifiable risk factors

Age

The risk of breast cancer rises with age and most cases are diagnosed in women over 50 years of age and those who have had their menopause. Eight out of 10 cases of breast cancer occur in women over 50. This means that all women between 50 and 70 years of age should be screened for breast cancer every three years. Women over the age of 70 are also likely to get breast cancer and may need regular screening.

Gender

Although women are more at risk of getting breast cancer, this cancer can also occur rarely among men. Women are 100 times more likely to get breast cancer than men.

Breast density

The normal breast contains lobules that produce milk and ducts that carry it. This glandular tissue contains a higher concentration of breast cells than other breast tissue and thus makes the breast dense. Women with more dense breast tissue may have a higher risk of developing breast cancer because there are more cells that can become cancerous. High breast density also makes diagnosis of a breast lump difficult using a mammogram. Younger women tend to have denser breasts and with age the glandular tissue in the breast decreases and is replaced by fat reducing its density.

Family history

Women who have a close relative with breast cancer or ovarian cancer have a higher risk of developing breast cancer. Although most of the breast cancers are not hereditary there are genes that determine the likelihood of getting breast cancer. This includes genes like BRCA1 and BRCA2 that can increase the risk of developing both breast and ovarian cancer. It is possible for these genes to be passed on from a parent to their child. A third gene (TP53) is also associated with increased risk of breast cancer. Other genes that have been implicated include P53, P65 and ATM. Women who have two or more close relatives from the same side of the family that includes mother, sister or daughter who have had breast cancer under the age of 50 are eligible for genetic screening to look for these genes and regular surveillance and breast cancer screening.

Those with a previous history of breast cancer

Women who have had breast cancer in one breast earlier are more likely to get breast cancer of the other breast or the same breast again.

Those with previous benign breast tumors

Usually a benign or non-cancerous lump in the breast do not indicate breast cancer. However, some of the benign breast changes may precede breast cancer. This includes atypical ductal hyperplasia (cells growing abnormally in ducts) and lobular carcinoma in situ (abnormal cells inside the breast lobes).

Exposure to estrogens

Breast cancers, especially those that are sensitive to hormones, are stimulated to grow by the female hormone estrogen. Women, who have begun their periods at a younger age and entered menopause at a late age, are exposed to longer duration of estrogen secretion from the ovaries compared to those who have had a shorter reproductive period in life. In the same way, not having children, or having children later in life, may slightly increase the risk of developing breast cancer because their exposure to estrogen is uninterrupted by pregnancy.

Height

Taller women are more likely to develop breast cancer than someone who is shorter than average. This may be due to interactions between genes, nutrition and hormones. The exact reason is unknown.

Modifiable risk factors

Being overweight or obese

Those who are overweight or obese are more at risk of developing breast cancer. It is hypothesized that these women may be having higher levels of estrogen in their blood. And women who are overweight or obese after the menopause have higher production of estrogen.

Alcohol intake

Women who take high amounts of alcohol are more likely to get breast cancer. For every 200 women who regularly have two alcoholic drinks a day, three more is diagnosed with breast cancer compared to same number of women who do not drink at all.

Exposure to radiation

Imaging studies like X rays and CT scans may raise the risk of getting breast cancer slightly. Women who have been exposed to radiation therapy for cancers earlier are at a greater risk of breast cancer.

Hormone replacement therapy (HRT)

Women who are on HRT need to take pills containing estrogen, progesterone or both. HRT is associated with slightly increased risk of developing breast cancer. Both combined HRT and oestrogen-only HRT can increase the risk of breast cancer, although the risk is slightly higher with combined HRT. There are around 19 extra cases of breast cancer for every 1,000 women taking combined HRT for 10 years. The risk reduces after stopping HRT.

Exposure to Diethylstilbesterol (DES) 

Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40. This drug was given to the women in the 1940s - 1960s.

Breast cancer and breast implants

Risk of breast cancer is not raised by breast implants (those approved by regulatory authorities), using antiperspirants, exposure to pesticides and wearing underwired bras.

Breast Cancer Pathophysiology

Cancer Pathophysiology

There are trillions of cells in the body. These cells have a tightly regulated cell cycle that controls their growth, maturity, division and death. During childhood normal cells divide faster to allow the person to grow. Once adulthood is reached the cells divide to replace worn-out cells and to repair injuries. This cell division and growth is controlled by the cellular blue print or DNA and genes that lie within the cell’s nucleus.

Cancer begins when cells in a part of the body start to grow out of control. All types of cancer, irrespective of their origin, occur due to this disturbed growth of cells that leads to formation of tumours and lesions. In addition, the cancer cells possess some rogue like properties:

  • They have longer life spans and instead of dying continue to grow and form new, abnormal cells
  • Cancer cells can also invade other tissues. This is something that normal cells cannot do. This property is called metastasis.
  • Cancer cells grow into tumors that are supplied by a new network of blood vessels. This is called angiogenesis and is unique in maintaining the blood supply and supply of nutrients to the cancer cells.

What makes a normal cell turn cancerous?

A normal cell can become a cancer cell if it undergoes damage to the DNA. Since it is the DNA that regulates the cells’ cycle of growth and death and any changes or damage to DNA affects the cell.

For most cells if the DNA is damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired and the damage is propagated to newer abnormal cells that are born of the defective cell.

Damaged DNA by mutation can also be inherited from parents or relatives. DNA damage can also occur due to exposure to toxins like cigarette smoking, alcohol etc.

Breast Cancer Pathophysiology

Breast cancer is a malignant tumor that starts in the cells of the breast. Like other cancers, there are several factors that can raise the risk of getting breast cancer. Damage to the DNA and genetic mutations can lead to breast cancer have been experimentally linked to estrogen exposure. Some individuals inherit defects in the DNA and genes like the BRCA1, BRCA2 and P53 among others. Those with a family history of ovarian or breast cancer thus are at an increased risk of breast cancer.

The immune system normally seeks out cancer cells and cells with damaged DNA and destroys them. Breast cancer may be a result of failure of such an effective immune defence and surveillance.

These are several signalling systems of growth factors and other mediators that interact between stromal cells and epithelial cells. Disrupting these may lead to breast cancer as well.

Breast Cancer Diagnosis

Breast cancer is diagnosed on routine screening procedures or after detection of symptoms. For example, women who notice nipple changes or changes in their breast or feel a lump in their breast may consult their physicians who may follow up the lesion to diagnose the tumor as cancerous or non-cancerous.

Diagnosis of breast cancer involves:

Examination of the breast and surrounding lymph nodes

Both breasts, nipples and lymph node in the armpits, under the collar bone and neck are examined. The lump or skin changes are noted. If the lump appears to be fixed to the skin over it or tissues and chest wall under it, it is most likely to be cancerous.

Mammogram

A mammogram is an X ray of the breast. Mammograms are routinely employed to screen women over 50 for breast lumps and cancer.

Breast ultrasound

Women under 35 need breast ultrasound scan only. This is because younger women have denser breasts, which means a mammogram is not as effective as ultrasound in detecting cancer. Ultrasound uses high-frequency sound waves to produce an image of the inside of the breast tissues. An ultrasound also helps to detect if the breast lump contains solid cells or liquid like mucous.

Biopsy

This involves taking a sample of tissue cells from the breast tissues or breast lump and examining them under the microscope to see if they are cancerous. Breast biopsy may be of more than one type. Initially a small amount is taken from the lump using a fine needle. This is called FNAC or Fine needle aspiration cytology. Needle biopsy is the most common type of biopsy. If the lump is not clearly defined imaging studies like ultrasound or X-ray but sometimes MRI may be used to guide the needle for the biopsy. Larger amounts of tissues can be taken for biopsy using core biopsy or excisional tissue biopsy. Samples or whole of lymph nodes from the armpits may also be taken as biopsy to detect spread to the lymph nodes. A biopsy of the tumor is the surest way of diagnosing the type and grade of breast cancer.

Computerized tomography scan (CT scan), Magnetic Resonance imaging (MRI), X rays and liver ultrasound for metastasis

These are needed to check whether the cancer has spread to the lungs or liver. An MRI scan of the breast may be needed to clarify or to assess the extent of disease within the breast. A bone scan may be recommended to check if the cancer has spread to the bones. Similarly blood tests are recommended to check for adequate functioning or involvement of the liver and kidneys as well.

Hormone receptor test

This is a test that determines the specific types of treatment that will be useful for a patient. Breast cancer cells can be stimulated to grow by female hormones like estrogen and progesterone in some women who have estrogen receptors (ER) or progesterone receptors (PR) on their tumor. These women respond to therapies that stop the effects of the hormones or by lowering the level of these hormones. This is known as hormone therapy.

HER2/neu protein test

While in some women hormones can encourage the growth of some breast cancers, other types are stimulated by a protein called human epidermal growth factor receptor 2 (HER2). These types of cancer may be treated using drugs to block the effects of HER2. This type of targeted therapy is called biological therapy.

Staging of breast cancer

Once the cancer is diagnosed, it is divided as per the histological or cellular type. Next the cancer is staged. Early detection means an early stage of cancer that is usually amenable to treatment.  Late stage cancers are usually advanced and have already spread to vital organs and may mean a shortened lifespan and non-responsiveness to therapy.

A simplified version of staging is:

  • Sometimes, ductal carcinoma in situ (DCIS) is described as Stage 0.
  • Stage 1 indicates that the tumour measures less than 2cm and the lymph nodes in the armpit are not affected.
  • In stage 2 the tumour measures between 2cm and 5cm or the lymph nodes in the armpit are affected, or both.
  • In stage 3 the tumour measures between 2cm and 5cm and may be attached to structures in the breast, such as skin or surrounding tissues. The lymph nodes in the armpit are affected.
  • In stage 4 the tumour is of any size and the cancer has spread to other parts of the body.

Grading of the cancer

The cancer is graded as well. A ''well-differentiated'' tumor for example is low grade and resembles normal tissue. A ''poorly differentiated'' tumor is composed of disorganized cells and, therefore, does not look like normal tissue and is termed high grade. Some are ''moderately differentiated'' or intermediate grade.

The TNM staging system may also be used to describe breast cancer. It can provide accurate information about the diagnosis. T describes the size of the tumour, N describes whether cancer has spread to the lymph nodes and M gives an indication of whether the cancer has spread to other parts of the body.

Breast Cancer Screening

Screening means looking for the cancer or ailment before a person has any symptoms. This can help find cancer at an early stage. If any abnormality is detected early, it may be easier to treat. By the time symptoms appear, cancer may have begun to spread and may become more difficult to treat increasing health care costs and shortening lifespan.

Breast cancer screening

Breast screening is a method of detecting breast cancer at a very early stage. A mammogram is the first step in screening. It is an x-ray of each breast taken while carefully compressing the breast. The mammogram can detect small changes in breast tissue that may need further investigations to check for cancer.

When to screen for breast cancer

In the United Kingdom, most women receive their first invitation to attend for a mammogram at the local breast screening unit sometime between their 50th and 53rd birthdays. The screening invitations are sent out every three years till a woman is 70.

Women under 50 are not currently offered routine screening. Studies have shown that routine screening in the 40 to 50 age group is less effective. After menopause the glandular part of the breast reduces and is replaced by fatty tissues. This makes the breast less dense and makes interpretation with mammograms easier.

Example breast imaging technology

Digital mammography however is better for screening younger women and women with denser breasts, and is equally effective as film mammography in older women. Women over 70 are not sent routine invitations, but may request three-yearly screening visits.

At the screening unit

Before mammography, a detailed history of breast diseases in the woman or in her family is obtained. All women are taught to be breast aware between two screening visits. This means all women have different consistencies and “feel” of their breasts. They should be aware of how their normal breast feels to be able to detect an abnormality at the earliest. All women are taught to regularly perform Breast Self-Exam.

Mammogram

The mammogram is a low dose x-ray. Each breast is placed in turn on the x-ray machine and gently but firmly compressed with a clear plate. This lasts for a few seconds and is harmless. This pressure helps to keep the breast still and get a clearer picture using lowest amount of radiation. It may be slightly uncomfortable or painful much like while measuring blood pressure and is less painful than a blood test. The mammograms are examined and the results sent to the woman and her practitioner.

Further investigations

If the mammograms show positive findings, the woman is asked to return for further investigations. These may include:

  • a clinical examination
  • mammograms at different angles or with magnification
  • examination using breast ultrasound
  • an MRI image
  • fine needle aspiration or core biopsy
  • open or excisional biopsy

Treatment options

Once cancer is confirmed the woman is referred to a consultant surgeon for a discussion of the options available to her. This is essential before making any decisions on treatment.

Treatment may involve surgery, likely to be followed by radiotherapy, chemotherapy or hormone therapy or a combination of these. The exact course of treatment will depend on the type of cancer found and the woman's personal preferences.

Those at high risk

All women identified as being at higher risk include those with a family history of breast cancer (in their mother, daughter or sister). They need to be assessed for their exact risk and their risk management options need to be discussed with them. These women may be screened with digital X-ray mammography and magnetic resonance imaging. They may also need genetic screening looking for genetic mutations such as those for BRCA1 and BRCA 2.

Breast Cancer Management

Breast cancer treatment has advanced to a stage that, if detected early, most women may survive much longer than they did a few decades ago.

Who provides breast cancer treatment?

Care for breast cancer involves a multidisciplinary team or a team of specialists who work together to provide the best care and therapy. The team usually includes specialist cancer surgeon or an oncosurgeon, an oncologist (who specializes in cancer chemotherapy), a radiation therapist, a radiologist, pathologist, a reconstructive surgeon or a plastic surgeon, a specialist nurse, occupational therapist, diet advisor or nutritionist, a psychologist or psychiatrist and a social worker.

Deciding on treatment options

Once diagnosed, the first step is discussion with the oncologist on the available treatment options and possible outcome or prognosis with and without treatment.

Treatment depends on the stage and grade of the cancer, general health, whether the woman has undergone menopause and personal preferences.

Use of hormonal and biological therapy also necessitates certain tests. If these tests (for example Estrogen receptor positivity or positivity for HER2/neu proteins) are positive, hormonal or biological therapies may be initiated.

Main treatment options

The main treatment options include :

  • Surgery
  • Radiotherapy
  • Chemotherapy
  • Hormone therapy
  • Biological therapy (targeted therapy)

These may be used alone or in combination.

Surgery

Surgery is usually the first step in treatment of breast cancer. The type of surgery depends on the type and extent of breast cancer. Surgery is usually followed by chemotherapy or radiotherapy or, in some cases, hormone or biological treatments.

There are two types of surgery for breast cancer. One of these is to remove the cancerous lump or tumor alone. This is called breast-conserving surgery.

Breast conserving surgery may be a lumpectomy or wide local excision. For this, just the tumour and a little surrounding breast tissue is removed. It may also be a partial mastectomy or quadrantectomy, in which up to a quarter of the breast is removed. The type of breast conserving surgery depends on the type of cancer, size of the tumour, amount of surrounding tissue that is affected and size of the breasts.

The other type is surgery to remove the whole breast, which is called a mastectomy. After a mastectomy the breast may be reconstructed surgery to recreate the breast that was removed. Here the nipple is also removed.

If the cancer has not obviously spread, a lymph node from the armpit is also removed along with the breast. It is called sentinel lymph node biopsy (SLNB). However if the cancer has spread to lymph nodes a more extensive removal (clearance) of lymph nodes from the armpits is needed.

Radiotherapy

This mode of treatment involves use of controlled doses of radiation to kill cancer cells. It is generally given after surgery and chemotherapy to kill any remaining cancer cells. Radiotherapy is usually begun around a month after surgery or chemotherapy.

Radiotherapy sessions are usually three to five days a week, for three to six weeks. Each session lasts only a few minutes. The duration and intensity of radiotherapy depends on the type of cancer. Some women may not need to have radiotherapy at all. Radiotherapy may be directed to the affected breast after a breast conserving surgery, or may be directed to the chest wall and lymph nodes.

The side effects of radiotherapy include irritation, soreness, burns and darkening of the skin, fatigue and lymphoedema or fluid accumulation in the arm due to blockage of lymph channels.

Chemotherapy

This modality of therapy involves using anti-cancer drugs to kill the cancer cells. Chemotherapy is usually used after surgery to destroy any cancer cells that have not been removed. This type of chemotherapy is called adjuvant chemotherapy. Sometimes chemotherapy may also be given before surgery to shrink the tumor before surgery. This is called neo-adjuvant chemotherapy.

Chemotherapy is usually administered as an outpatient or day care basis. The drugs are usually given through an intravenous line or as tablets. Chemotherapy sessions may be once every two to three weeks, over a period of four to eight months. Often three drugs are used together in a chemotherapy regimen.

Side effects of chemotherapy include anemia, bone marrow depression, propensity for infections, bleeding tendencies, loss of appetite, nausea and vomiting, hair loss, mouth ulcers etc.

Hormone therapy

Some breast cancers are stimulated to grow by the hormones oestrogen or progesterone that are the natural female hormones in the body. These cancers contain estrogen and progesterone receptors (ER or PR). These are called hormone-receptor-positive cancers. Hormone therapy works by lowering the levels of hormones in the body thereby stopping the growth of these cancers.

Hormone therapy is usually given after surgery and chemotherapy, but it is sometimes given before surgery to shrink a tumour. In women who have poor health and cannot withstand surgery, chemotherapy or radiotherapy, hormone therapy may be the only option. Usually hormone therapy lasts for up to five years after surgery.

Drugs used include Tamoxifen. Tamoxifen stops estrogen from binding to estrogen-receptor-positive cancer cells. It may be taken as pills. Another group of drugs are called aromatase inhibitors like Ansatrozole, Exemastane and Letrozole. These are offered to women who have has their menopause. These drugs block the enzyme aromatase that helps in the formation of estrogen.

In addition to drugs, the ovaries that produce estrogen may also be supressed using drugs like goserelin, which is a luteinising hormone-releasing hormone agonist (LHRHa) or by surgery and radiation to kills the cells of the ovary.

Biological therapy

Sometimes some individuals have breast cancers that are stimulated to grow by a protein called human epidermal growth factor receptor 2 (HER2). These cancers are called HER2-positive. There are targeted therapies that works by stopping the effects of HER2 and by activating the immune system to fight off the cancer.

Notable among these drugs includes trastuzumab. Trastuzumab, also known by the brand name Herceptin, is usually used after chemotherapy. It is a monoclonal antibody. The trastuzumab antibody targets and destroys cancer cells that are HER2-positive. It is given as an intravenous drip.

Psychological support

Treatment of breast cancer also involves familial and psychological support to the women. After therapy follow up focuses not only on possible relapse of the cancer but also to restore self-esteem and relationships.

Breast Cancer Prognosis

Prognosis of outlook of any cancer depends on several factors. Notable among these is how early the cancer is detected and treated. The stage of the cancer thus at the beginning of therapy determines the outlook of a breast cancer patient.

Overall, in the UK, more than 85% diagnosed with breast cancer live for at least 5 years after diagnosis. More than 75% live for at least 10 years.

Over years, with the development of medicines and surgical procedures for breast cancer treatment the outlook for breast cancer has continued to improve. The number of women dying from breast cancer has gone down significantly in the last 20 years in the UK mainly because of efficient and early screening and detection of the cancer.

Some of the most important factors that determine survival of a breast cancer patient include:

  • Location of the tumor and how far it has spread
  • Grade of the tumor
  • Stage of the tumor
  • Hormone receptor positive or negative status
  • Presence of tumor markers
  • General condition and age of the patient

Remission and relapse

Once a cancer recedes and is undetectable after initial therapy, the patient is said to be in remission. If breast cancer comes back, it is usually within the first 2 years. Breast cancer can come back 10 or 20 years after initially remission. This is, however, rare and the more time that passes since diagnosis, the less likely it is that the cancer will come back.

Outlook of breast cancer based on grade of cancer

Just like outlook of breast cancer depends on staging of the cancer, it is also dependent on grade of the cancer. A ''well-differentiated'' tumor for example is low grade and resembles normal tissue. A ''poorly differentiated'' tumor is composed of disorganized cells and, therefore, does not look like normal tissue and is termed high grade. Some are ''moderately differentiated'' or intermediate grade.

This is important because high grade cancers may be faster growing and more likely to spread. The Nottingham Prognostic Index (NPI) that determines outcome or prognosis of breast cancer is based on grade of the cancer. 

Outlook of breast cancer depending on stage

The earlier a breast cancer is diagnosed, the smaller it is likely to be and the lower the chance that it has spread.

The numbers below come from the National Cancer Data Base, and are based on people who were diagnosed with breast cancer in 2001 and 2002.

Stage

5-year Survival Rate

0

93%

I

88%

IIA

81%

IIB

74%

IIIA

67%

IIIB

41%*

IIIC

49%*

IV

15%

*These numbers are correct as written (stage IIIB shows worse survival than stage IIIC).

Outlook of Ductal carcinoma in situ (DCIS)

In DCIS the cancer cells are present within the ducts of the breast. So there is very little risk of the cancer cells spreading. Treatment for DCIS usually means a certain cure.

Outlook of hormone receptor positive or negative status

About 75% of breast cancers are estrogen receptor-positive (ER-positive, or ER+). About 65% of ER-positive breast cancers are also progesterone receptor-positive (PR-positive, or PR+). Cells that have receptors for one of these hormones, or both of them, are considered hormone receptor-positive.

These cancers are sensitive and responsive to hormone therapy. Hormone therapy includes tamoxifen or aromatase inhibitors. Hormone receptor-negative tumors are referred to as hormone resistant.

A better outlook is seen in women who have hormone receptor-positive tumors because these cells grow more slowly than receptor-negative cells. In addition, women with hormone receptor-positive cancer have more treatment options.

Outlook of tumours positive for tumor markers

Tumor markers are proteins found in blood or urine when cancer is present. Tumor markers relevant for breast cancer prognosis includeHER2, CA 15-3, CA 27.29, CEA, ER, PgR, uPA, and PAI-1. HER2-positive cancer usually occurs in younger women and is more quickly-growing and aggressive than other types of breast cancer. The HER2 marker is present in about 20% of cases of invasive breast cancer. Those with HER2 positive tumors respond to trastuzumab (Herceptin) or lapatinib (Tykerb).

Outlook based on general condition and age of the patient

Frail and elderly patient with poor helth often have poorer outcome and lowered capacity to withstand therapy for breast cancer and respond adequately to therapy.

Breast Cancer Epidemiology

Breast cancer is the most common cancer in women worldwide after skin cancer. It represents 16% of all cancers in women. This rate is twice that of colorectal cancer and cervical cancer and about three times that of lung cancer. Death rates are also 25% greater than that of lung cancer in women.

Incidence of breast cancer around the world

All around the world the incidence of this cancer shows varied rates. The rates are low in less-developed countries and greatest in the more-developed countries. Breast cancer is related to age with only 5% of all breast cancers occur in women under 40 years old.

In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows:

  • Eastern Asia – 18 per 100,000 women
  • South Central Asia - 22 per 100,000 women
  • Sub-Saharan Africa – 22 per 100,000 women
  • South-Eastern Asia – 26 per 100,000 women
  • North Africa - 28 per 100,000 women
  • Western Asia - 28 per 100,000 women
  • South and Central America - 42 per 100,000 women
  • Eastern Europe - 49 per 100,000 women
  • Southern Europe - 56 per 100,000 women
  • Northern Europe - 73 per 100,000 women
  • Oceania - 74 per 100,000 women
  • Western Europe - 78 per 100,000 women
  • North America - 90 per 100,000 women

In the United Kingdom

Breast cancer has been the most common cancer in the UK since 1997. It accounts for 31% of all new cases of cancer in females. In 2010, there were 49,961 new cases of breast cancer in the UK. There are 157 new breast cancer cases for every 100,000 females in the UK. The rates are lower in Northern Ireland than in England, Wales or Scotland.

Higher incidence rates are seen among older women, supporting a link with hormonal status. Between 2008 and 2010, an average of 45% of cases were diagnosed in women aged 65 years and over, and 80% were diagnosed in the 50s and over. Nearly half (48%) of female breast cancer cases are diagnosed in the 50-69 age group. Incidence is lower among women from low socioeconomic strata.

The lifetime risk of developing breast cancer in the UK is estimated to be 1 in 8 for women. Among all detected cases 41% in 2009 were detected as stage 1, 45% at stage II, 9% at stage III and 5% at stage IV.

In the United States

In the US, around 1 in 8 women carry a lifetime risk of invasive breast cancer. In 2011, an estimated 230,480 new cases of invasive breast cancer were expected to be diagnosed in women in the U.S., along with 57,650 new cases of non-invasive (in situ) breast cancer. In addition, around 39,520 women in the U.S. were expected to die in 2011 from breast cancer.

There was a steady decline in breast cancer incidence from 1999 to 2005. The decrease was seen only in women aged 50 and older. This could be due to reduced use of hormone replacement therapy (HRT) by women.

Those with a family history of breast cancer are at double the risk of developing the cancer. About 15% of women who get breast cancer have a family member diagnosed with it. About 5-10% of breast cancers can be linked to gene mutations (abnormal changes) inherited from one’s mother or father. The most common mutations are those of BRCA 1 and BRCA 2. Women with these mutations have up to an 80% risk of developing breast cancer during their lifetime.

For women in the U.S., breast cancer death rates are higher than those for any other cancer, besides lung cancer. However, death rates are on the decline due to advances in therapeutics against breast cancer.

White women are slightly more likely to develop breast cancer than African-American women. However, in women under 45, breast cancer is more common in African-American women than white women. Asian, Hispanic, and Native-American women have a lower risk of developing and dying from breast cancer.

In Australia

Breast cancer is the most common cancer among Australian women after melanoma or skin cancers. Breast cancers accounted for 28.2 per cent of all new cancers in women in 2008. Breast cancer is the second leading cause of cancer-related death in Australian women, accounting for 15.5 per cent of all cancer deaths in women in 2007.

The average age at diagnosis is usually around 60 years. The risk of developing breast cancer increases with age. The number of new cases of breast cancer diagnosed in women has increased from 5,310 in 1982 to 13,567 in 2008 and by 2020, it is estimated that there will be 17,210 new cases of breast cancer diagnosed in women. Breast cancer is the most common cancer in Aboriginal and Torres Strait Islander women.

History of Breast Cancer

Breast cancer has been known to mankind since ancient times. It has been mentioned in almost every period of recorded history. Because of the visible symptoms especially at later stages the lumps that progress to tumors have been recorded by physicians from early times. This is more so because, unlike other internal cancers, breast lumps tend to manifest themselves as visible tumors.

Earlier, however, it was a matter of taboo and embarrassment that meant detection and diagnosis was rare. The mention of breast cancers in literature beyond medical journals and books was rare. Involvement of more women and actively bringing out the disease into the open is a recent phenomenon that is around three or four decades old. In the 1990’s the symbol of breast cancer - the pink ribbon – brought out a revolution against this cancer.

Ancient Greece and Egypt

Ancient Egyptians were the first to note the disease more than 3,500 years ago. The condition was described fairly accurately in both Edwin Smith and George Ebers papyri. One of the descriptions refers to bulging tumors of the breast that has no cure.

In 460 B.C., Hippocrates, the father of Western Medicine, described breast cancer as a humoral disease. He postulated that the body consisted of four humors - blood, phlegm, yellow bile, and black bile. He suggested that cancer was caused by the excess of black bile. In appearance of the breast cancer too black, hard tumors are seen that burst forth if left untreated to yield a black fluid. He named the cancer karkinos, a Greek word for “crab,” because the tumors seemed to have tentacles, like the legs of a crab.

Thereafter in A.D. 200, Galen described the cancer as well. He also suggested excessive black bile but, unlike Hippocrates, he postulated that some tumors were more dangerous than others. He suggested medications like opium, castor oil, licorice, sulphur, salves etc. for medicinal therapy of the breast cancers. During this time of history breast cancer was a disease that affected the whole body and thus surgery was not considered.

Breast cancer in the 17th and 18th Century

Until the 17th century Galen’s theories on breast cancer were believed. In 1680, French physician Francois de la Boe Sylvius began to challenge the humoral theory of cancer. He hypothesized that cancer did not come from an excess of black bile. He suggested it came from a chemical process that transformed lymphatic fluids from acidic to acrid. In 1730s, Paris physician Claude-Deshais Gendron also rejected the systemic theory of Galen and said that cancer developed when nerve and glandular tissue mixed with lymph vessels.

In 1713 Bernardino Ramazzini's developed a hypothesis that high frequency of breast cancer in nuns was due to lack of sex. Ramazzini said that without regular sexual activity, reproductive organs, including the breast may decay and develop cancers. Yet another researcher Friedrich Hoffman of Prussia postulated that women who had regular sex but still developed cancer were practicing “vigorous” sex. This could be leading to lymphatic blockage.

Other theories included Giovanni Morgagni blaming curdled milk, Johanes de Gorter blaming pus-filled inflammations in the breast, Claude-Nicolas Le Cat from Rouen blaming depressive mental disorders, Lorenz Heister blaming childlessness, and yet others blaming sedentary lifestyle.

It was in 1757 when Henri Le Dran, a leading French physician suggested that surgical removal of the tumor could help treat breast cancer, as long as infected lymph nodes of the armpits were removed. Claude-Nicolas Le Cat argued that surgical therapy was the only method to treat this cancer. This lasted well into the twentieth century and led to the creation of the radical mastectomy or extensive removal of the breast.

The 19th and 20th Century

By mid-nineteenth century, surgery was the available option for breast cancer. The development of antiseptic, anesthesia and blood transfusion during this time also made survival after a surgery more possible.

William Halstead of New York made radical breast surgery the gold standard for the next 100 years. He developed radical mastectomy that removed breast, axillary nodes (nodes in the armpits), and both chest muscles in a single en bloc procedure or in a single piece to prevent spread of the cancer while removing each of these individually.

Radical mastectomy was the mainstay of treatment for the initial four decades of the twentieth century. Although radical mastectomy helped women survive longer, especially if performed early, many women did not choose it since it left them disfigured. In addition there were problems like a deformed chest wall, lymphedema or swelling in the arm due to lymph node removal and pain.

In 1895, Scottish surgeon George Beatson discovered that removing the ovaries from one of his patients shrank her breast tumor. As this caught on, many surgeons began removing both ovaries and performing a radical mastectomy for breast cancers. This reduction of the tumor after removal of the ovaries was due to the fact that estrogen from ovaries helped in growth of the tumor and their removal helped reduce the size of the tumor.

What came next was that in these women without ovaries, estrogen was produced by the adrenal glands. In 1952 Charles Huggins began removing a woman’s adrenal gland (adrenalectomy) in an effort to starve the tumor of estrogen. Rolf Lefft and Herbert Olivecrona began removing the pituitary gland – another site of estrogen production stimulation.

Development of the systemic theory

In 1955, George Crile suggested that cancer was not localized but rather is spread throughout the body. Bernard Fisher also suggested the capability of cancer to metastasize. In 1976, Fisher published results using simpler breast-conserving surgery followed by radiation or chemotherapy. He noted that these were just as effective as radical mastectomy.

With advent of modern medicine, by 1995, less than 10 percent of breast cancer-inflicted women had a mastectomy. This time also saw the development of novel therapies for breast cancer including hormone treatments, surgeries and biological therapies. Mammography was also developed for early detection of the cancers. Scientists then isolated the genes that cause breast cancer: BRCA 1, BRCA2 and ATM

Breast Cancer Society and Culture

Origin of the pink ribbon

In 1982, Nancy G. Brinker formed the Susan G. Komen Breast Cancer Foundation. She formed it to honor her sister who was fighting the cancer. The organization was dedicated to fighting breast cancer and originated the Race for the Cure fitness walk and fundraiser in 1983.

This race since then is an international event, with more than 1.6 million participants in over 140 races. In 1990 the race was held in Washington, D.C. where the Komen Foundation distributed pink visors to participants. The following year, at a walk in New York City, the organization handed out symbolic pink ribbons. Since then the pink ribbon has become a symbol of fight against breast cancer.

Breast cancer then and now

For many years breast cancer was shut behind closed doors with many women too embarrassed or scared to get themselves examined or checked by their physicians for breast cancer. This has often led to late detection of the cancer and has caused innumerable deaths due to this cancer.

Even today many cultures worldwide, especially in developing countries in Asia or under developed countries in Africa getting screened or even checked for breast cancer is not routinely practiced.

In the West, the breast cancer advocacy movement began in the 1990’s and it brought forth many issues regarding getting second opinions before surgery, less invasive surgical procedures, breast reconstruction and use of prosthetics for artificial breast after surgery. The advocacy movement supported individual opinions and helped support them to make informed choices regarding treatment. This led to other advances in patient care as well.

National Breast Cancer Awareness Month

National Breast Cancer Awareness Month is observed in October for survivors, family and friends of survivors and/or victims of the disease. For whole of this month, the symbolic pink ribbon is worn to salute and recognize the struggle against this deadly and common cancer.

Breast cancer awareness also has its roots in breast awareness and propagation of breast self-exam by all women over 50. Awareness of one’s own breast is sometimes the first step in detecting an abnormality in the breast and seeking investigation and support.

Pink for October is an initiative started by Matthew Oliphant. It asks the sites willing to help make people aware of breast cancer to change their template or layout to include the color pink. This may lead to increase worldwide awareness regarding breast cancer. The patron saint of breast cancer is Agatha of Sicily.

Breast cancer in men

After the pink ribbon came, the pink and blue ribbon that went out to spread the message that men can get breast cancer too, albeit rarely. It was designed by Nancy Nick, President and Founder of the John W. Nick Foundation in 1996.

In 2009 Out of the Shadow of Pink, A Man's Pink and the Brandon Greening Foundation for Breast Cancer in Men came together to make third week of October as Male Breast Cancer Awareness Week.

Breast Cancer Symptoms

The most common symptom of breast cancer is the feeling the presence of a lump or an area of thickened tissue over the breast. Of the lumps nearly 90% are benign or not cancerous but all lumps and abnormalities need to be checked for cancer by using Fine needle aspiration cytology (FNAC) and other biopsy techniques. Breast cancer still remains one of the most commonly diagnosed cancer among women and kills thousands worldwide each year.

Breast awareness

The most common way that a potential problem is detected is by regular breast examination by self. The key is for the woman to know what 'normal' is - then changes can be noticed. All women should practise breast awareness. This means the knowledge of the structure, feel and appearance of their breasts.

Warning symptoms

Warning symptoms of breast cancer that can be identified include:

  • Lump within the breast. This may be a lump that is fixed to the skin above it or the chest wall and structures underlying it. A fixed lump is more often than not a sign of cancerous tumor.
  • Thickened tissue over the skin of the breast.
  • A change in the size or shape of one or both breasts.
  • Formation of dimples over the skin of the breast especially when arms are raised or moved. This is due to the attachment of the tumor to the skin overlying it. The dimples give the breast a pitted appearance and the skin change is called Peau d’orange or orange peel appearance.
  • Change in the shape and appearance of one or both nipples. Commonly in cases of a tumour underneath the nipple causes it to be flattened, and alters its appearance. On lifting both arms upwards the position of the nipple may deviate for example.
  • Discharge from one or both nipples. The discharge may be clear, yellow, green or even blood tinged.
  • Rash or sores around the nipple.
  • A lump or more in the armpits, under the collar bone etc. This is a swollen lymp node. Although there are numerous reasons why a lymph node may be swollen, it is best to get checked for breast abnormalities and diseases as well.
  • Pain in either of the breast or armpits not related to periods.
  • Due to extensive lymph node involvement the lymph flow from the arm may be disrupted. This leads to swelling of the arm(s) next to the affected breast.
  • Symptoms of spread of the cancer and an advanced cancer include bone pain or easy fractures, skin ulcers, weight loss, fatigue, convulsions or seizures etc.

Detecting breast cancer in dense breasts

This article is about the problem of detecting tumors in dense breasts, and how many states are tackling the problem by requiring doctors to tell women that mammograms don’t work well for those who have dense breasts. I will also discuss effective solutions to this problem.

But first, I want to tell the story of Nancy Cappello, Ph.D. a former Connecticut state department of education administrator from Woodbury, Connecticut. Like many women, Dr. Cappello began having yearly mammograms starting at age 40. Year after year, her mammograms came up negative. Cappello assumed that everything was fine.

It wasn’t. In 2004, when she was 51, Cappello had her yearly mammogram. As usual, it looked normal. Just six weeks later, however, her doctors felt a lump in her breast. She had cancer. By then, the advanced-stage cancer had already spread to 13 lymph nodes. Even then, though, another mammogram still couldn’t find the tumor. Cappello needed multiple surgeries, chemotherapy, radiation and hormone treatment.

Cappello was stunned that her cancer was missed by mammogram and diagnosed at such a later stage. Only after asking her doctors why the mammogram did not find her cancer was she told that she had dense breast tissue—and that mammograms have a hard time spotting tumors in such breasts. She did some digging in the scientific research, and discovered that has been a huge issue for decades. Seventy-four percent of patients between 40 and 49 years old have dense breasts, according to one study. (1)

Dense breasts, Cappello learned, have lots of glandular or connective tissue. That kind of tissue blocks X-rays and shows up as white on mammograms. Cancer also looks white on mammograms. That’s why tumors are hard to spot in women with dense breasts.

In contrast, breasts that aren’t dense have more fat. They show up on mammograms as black. So the white tumors in non-dense breasts are easier to see.

The surprising fact is that it is impossible to know if a breast is dense or not just by touching it. The only way to know for sure is to have a mammogram.

Cappello was outraged to learn these facts. She decided to do something about it. She started an activist organization, Are You Dense, Inc. (AreYouDense.org), to warn other women. “How many women are like me and had normal mammograms and may have a hidden intruder stealing their life?” she asked. (2)

What American women needed, she decided, were doctors routinely informing women of this critical breast health issue. After being told by several doctors in CT that they were “not ready” to do this Cappello began to press lawmakers to pass such legislation. Testifying before the Connecticut state legislature in 2009, she said: “I live each day knowing that my late stage diagnosis could have been prevented IF someone (especially those I depend on – my doctors – my caregivers) had told me that I have dense breast tissue.” (3)

Her education and outreach campaign, including a second organization focusing on legislative and regulatory efforts, Are You Dense Advocacy, Inc. has been successful. Connecticut passed the country’s first measure requiring disclosure of dense breasts, the Breast Density Law, in 2009. Since then, five more states—Texas, Virginia, New York, California and Hawaii—have passed similar laws, and the U.S. Congress is considering the measure.

The New York law, for example, took effect January 19, 2013. It states that mammography patients with dense breasts must be told:

“Your mammogram shows that your breast tissue is dense. Dense breast tissue is very common and is not abnormal. However, dense breast tissue can make it harder to find cancer on a mammogram and may also be associated with an increased risk of breast cancer. This information about the result of your mammogram is given to you to raise your awareness. Use this information to talk to your doctor about your own risks for breast cancer. At that time, ask your doctor if more screening tests might be useful, based on your risk. A report of your results was sent to your physician.”

Thanks to laws like these and to the awareness campaigns launched by activists like Cappello, the word is getting out that mammograms don’t work for women with dense breasts. The American Cancer Society’s own guidelines explain that “dense breast tissue can also make it harder for doctors to spot problems on mammograms.” (4)

At the same time, there is a continuing controversy over the effectiveness of mammograms in general. A study published in the New England Journal of Medicine in November of 2012 argued that mammograms cause substantial harm by falsely raising alarms in many women, leading to unnecessary worry, biopsies and treatment. Woman are also justifiably concerned about radiation exposure from mammograms.

Clearly mammograms just aren’t doing the job. So what’s the solution?

Cappello believes for women with dense breast tissue it is critically important to supplement a mammogram with another screening tool —such as an ultrasound. “When women with dense breasts supplement their yearly mammogram with an ultrasound, the combined screenings detect cancer 97 percent of the time,” says Cappello.

Ultrasound can indeed help. So can MRIs.

But I believe there’s even a better approach, one that solves the dense breast detection problem completely—and makes it possible to spot signs of precancerous changes up to eight years before a tumor would show up on a mammogram or an ultrasound.

To explain this approach, which I think is a major medical advance, let me tell the story of another pioneer, a Greek-born doctor named Georgios Nikolaou Papanikolaou. In the 1920s, Papanikolaou discovered that he could take cells from women’s vaginal fluid, smear them on a slide and spot cancerous cells. The now famous Pap smear was born.

Papanikolaou also showed that a normal