Breast Cancer

Abnormal (uncontrolled) growth of cells originating from the breast tissue is termed as breast cancer. The abnormal growth in the breast can be felt as a lump. Most of the cancerous tumours (malignant tumours) develop in the ducts and the lobules of the breast, whereas, a few others develop in the breast tissue (stroma). Malignant tumours are those that spread to other body parts beyond the site of origin while benign tumours are those abnormal growths that are not life-threatening and do not spread. Malignant cells can invade the tissues, which surround the breasts. Sometimes, the cancerous cells can even travel away from the breast to distant organs. An extremely small percentage of men may also develop breast cancer.  In India, breast cancer ranks first amongst all cancer types with an incidence rate of 25.8 per 100,000 women. In India, breast cancer-related mortality or deaths is also high.

Breast cancer can be broadly classified based on the histologic, molecular, and functional aspects of the disease. Each of the three categories further has several subtypes. 

Histological subtypes

This classification is based on the site of development of the cancer cells in the breast. Carcinoma in-situ is a group of cancerous cells that remain at the site of origin, are non-invasive in nature and do not invade the surrounding or distant tissues. The other subtype is invasive in nature. These cells break through (invade) the walls of the ducts and the lobules entering the surrounding tissues and proliferating there.

• Carcinoma in-situ 
  • Ductal (in the milk ducts)
  • Lobular (in the lobules)
• Invasive carcinoma 
  • Tubular (tube-shaped cancerous growth in the milk ducts)
  • Ductal
  • Lobular
  • Invasive ductal (that invades tissues surrounding the ducts)
  • Infiltrating lobular (that pushes through the surrounding breast tissue)
  • Mucinous (cancer cells invade beyond the tissues beyond the milk ducts and are found to be surrounded with a slimy fluid called mucin)
  • Medullary (ductal cancer that is soft and fleshy, resembling the medulla in the brain)
  • Infiltrating lobular

Molecular subtypes

These subtypes are based on the molecular analysis of the tumours. These subtypes are related to the expression of a particular gene in people. This classification is helpful to design treatment strategies for people with breast cancer.

• Claudin-low
• Basal-like
• HER- 2 enriched
• Normal- like
• Luminal A
• Luminal B

Functional subtypes

This classification is based on the type of cells that cancer develops from.  

Stem cells in the breast. Stem cells are mother cells from which all other cells are formed. They help in regeneration of tissues and can lead to tumours too when they grow uncontrollably. These can be:

• Mammary stem cells
• Cancer stem cells

Apart from these, there are also some rare forms of breast cancer such as inflammatory breast cancer, Paget’s disease of the nipple, and Phylloides tumour.

Breast cancer can be divided into four stages from stage 0 to stage IV. Stage 0 indicates the presence of localized cancer, while stage IV suggests an advanced form of cancer that has spread to other parts of the body. 

• Stage 0 
  Tumour is confined to the milk-producing tube (duct) or gland and has not invaded any other tissue.
• Stage I 
  Tumour is limited to the breast tissue and measures around 0.75 inches.
• Stage II A 
  Tumour has spread to the lymph nodes near the breastbone and measures larger than 0.75 inches but less than 2 inches or it is less than 0.75 inches but has spread to one of the three lymph nodes in the armpit.
• Stage II B 
  Tumour has spread to the lymph nodes in the armpit but measures more than 0.75 inches and less than 2 inches or measures more than 2 inches but has not spread to the armpit.
• Stage III A 
  Tumour is smaller than 2 inches and has spread to 4 to 9 lymph nodes in the armpit and has enlarged in at least one of it or it is more than 2 inches and has spread till the 9th lymph node in the armpit and near the breastbone.
• Stage III B 
  Tumour has affected the chest wall causing inflammation (Inflammatory breast cancer).
• Stage III C 
  Tumour has affected the armpit, chest wall, and the breast and collar bones.
• Stage IV 
  Tumour has spread to organs distant from the breast like lungs, bones (metastatic cancer).

The earliest sign of breast cancer is typically a lump felt in the breast, however, there can be other symptoms too, which may indicate the development of breast cancer. The symptoms can be classified as breast lump symptoms, non-lump symptoms, and non-breast symptoms. 

Breast Lump Symptoms

• Hard growth with prominent edges.
• Soft and round growth.
• Small sized lumps detected as abnormal growths.

Non-Lump Symptoms

• Swelling in the entire or a part of the breast.
• Nipples turning inwards.
• Secretions from the nipple other than milk and without a recent history of pregnancy.
• Redness, scaling or peeling on the breast.

Non-Breast Symptoms

• Fatigue.
• Breathlessness.
• Lump in the neck.
• Unexplained loss of appetite and weight.

Causes

Breast cancer is the most prevalent cancer in Indian women. Let us have a look at the causative agents of breast cancer. The exact causes of breast cancer are not known, however, there are certain factors, which have been found to be associated with breast cancer. These include:

• A history of breast cancer
  A woman who already has suffered from breast cancer has higher chances of its recurrence.
• Presence of abnormal genes
  Women with abnormal genes inherited from family members can develop breast cancer at a young age. The common genes, which have been identified in relation to breast cancer are BRCA1 and BRCA 2.

Risk Factors

Following conditions can put a woman at a greater risk of developing breast cancer:

• Family history
  A strong family history of breast cancer is the most common cause.
• Age
  The most common factor is age. Women aged above 50 are more prone to developing breast cancer than women of other age groups Those who are in the post-menopausal phase are even more susceptible to develop breast cancer.
• Hormonal factors
  Women who have been on hormonal pills for menstrual problems or contraception are at risk of developing breast cancer.
• High intake of fat and alcohol
  Obesity, sedentary life, and regular consumption of alcohol can be a reason for developing breast cancer in some women.
• Exposure to harmful radiations
  Women involved in contact with low-doses of radiations are prone to developing breast cancer.
• Exposure to chemicals
  Chemicals like Bisphenol A, a component in manufacturing plastic also increases the risk of breast cancer in women working in the plastics industry. 

Breast cancer risk can be reduced by taking some preventive measures. In the case of inherited factors, though prevention is not an option.

• Changes in lifestyle
  Some lifestyle changes, such as weight management, drinking less alcohol, and daily exercise could prove beneficial in reducing the risk of acquiring breast cancer.
• Breastfeeding
  Breastfeeding up to one year can help prevent the chances of developing breast cancer at a later age. Some studies have shown that it is possible to reduce the risks of recurrence of breast cancer if a woman breastfeeds the baby. 
• Chemoprevention
  Most of the breast cancers are oestrogen receptor (ER receptor) positive cancers and hence, two major classes of drugs ER modulators (SERMs) and aromatase inhibitors (AIs) are commonly used in women who are prone to breast cancer. Studies have shown that in ER + ve breast cancer, these medicines can be used as a preventive measure.
• Biological Prevention
  Treatment with monoclonal antibodies can prove helpful in ER –ve women. After the first incidence of breast cancer, the recurrence of the disease can be prevented by this treatment.

Self-examination

Self-examination of breasts can detect a breast cancer in the early stages. It is important to examine your breasts every month to know how they feel. This helps in recognizing any abnormal changes in the breasts. Along with the breasts, the examination of armpits should also be done. The examination should be done in sitting or standing and lying down position by raising one arm above the head and examining the breast on the same side by the opposite hand. Small circular motions should be used to examine the breasts.

Diagnostic tests

There are many tests and methods available to clinically diagnose breast cancer. These are:

• Diagnostic mammography
  Digital X-ray screening of the breasts is recommended for women over the age of 45 to check for breast cancer.
• MRI
  Screening of the breasts by an injected contrast dye in the bloodstream and scanning the breast area with an MRI machine is one of the best ways to diagnose breast cancer.
• Molecular Breast Imaging
  This is a procedure in which the breast tissue is examined by injecting a radioactive molecule tracer and scanning the breast area.
• Breast biopsy
  Testing of a sample tissue collected from the involved breast is the gold-standard to confirm breast cancer and its type.
• Needle biopsy
  Examination of the liquid that is aspirated from the site of cancer using a fine needle.
• Immunohistochemistry Assay
  Use of antibodies to detect the expression of specific proteins related to breast cancer.
• Blood-based assay
  Use of biomarkers to detect proteins in metastasized (invasive) tumours. 

Breast cancer is treatable and with early diagnosis and proper regimen, complications can be drastically reduced. The death-incidence ratio is very high in rural India as compared to urban Indian cities, hence, better health awareness and early diagnosis can help to reduce mortality or death rates. 

Conventional treatment

Conventional treatment for breast cancer includes breast conservation surgery, radiation therapy, chemotherapy, and hormonal therapy.

• Breast conservation surgery
  It involves the removal of only a part of the breast affected by cancer to avoid further spread of the cancer cells. It is done in the case of a localized tumour, which hasn’t spread to the surrounding tissues. Thus, surgical removal of the involved area of the breast is the best alternative to avoid further spread of cancer growth. In this type of surgery, the healthy breast tissue is not removed and the breast is conserved. In cases with extensive spread of cancer, complete removal of the breast may be necessary. In such cases, a second surgery called breast reconstructive surgery may be performed using a breast implant to restore the physical appearance.
• Radiation therapy
  After the surgery, the area is treated with radiations from that help destroy the cancerous cells. However, it is associated with certain side-effects and can leave the site sensitive, red, moist, and weepy.
• Chemotherapy
  It involves systemic administration of various anticancer drugs either orally or through injections. The duration of treatment depends upon the severity and stage of breast cancer.

Adjuvant therapy

It involves endocrinal treatment that balances or blocks hormones, which might be aggravating the growth of cancer.

Novel strategies in breast cancer treatment

• Nanotechnology has proven to be a successful method that involves the use of nano-sized delivery of the suitable drug, thereby, targeting the cancer cells with immense precision.
• Nucleic acid technologies is another method in which the expression of the cancer-causing genes can be silenced using specific drugs.

Immunomodulation

This approach involves the use of cytokines (chemicals released by the immune system) to enhance immunity against cancer cells.

Use of natural medicines

Certain phytoconstituents (naturally occurring substances found in plants) like curcumin, gallates, lycopene, obtained from certain vegetables have proven to be beneficial in the treatment of breast cancer. 

Lifestyle management

Almost 45% of the cases in India are reported at the metastatic stage of breast cancer. Certain changes in lifestyle can prove useful in the management of breast cancer. These include:

• Weight management.
• Avoiding eating fatty food items.
• Regular exercise.
• Avoiding alcohol intake.
• Breastfeeding the child until one year after delivery.
• Regular breast examination.
• Eating a healthy and balanced diet rich in antioxidants.

Prognosis

The outcomes of breast cancer depend upon the way the disease might progress. Several factors like the stage of breast cancer, type and size of a breast tumour, type of genes expressed, the presence of specific proteins in samples, and menopausal status of the woman affect the outcomes. If detected early at stage 0, there is 100% chance of survival. If not detected early, then the breast cancer can progress to advanced stages and invade the surrounding tissues. In metastasised stage, the treatment can be challenging. There are chances of recurrence in women who have already suffered from breast cancer.

Complications

Complications of breast cancer generally arise when cancer is in its advanced stage. The complications can be roughly classified as those due to the advancement of the disease and due to treatment. 

• Complications due to the advancement of the disease include: 
  • Metastasis to bone causing destruction.
  • Swelling of the lymph nodes.
  • Impairment in the lungs due to an invasion of the pulmonary tissue.
• Complications due to treatment:
  • Cognitive impairment.
  • Chemotherapy-induced peripheral nerve damage.
  • Nerve pain.
  • Encephalopathy (impairment of brain functions).
  • Stroke.
  • Aplastic anaemia.
  • Difficulty in breathing.
  • Lowered immunity.
  • Skin redness.
• Complications after reconstructive breast surgery:
  • Inability to move the arm.
  • Infection in the implant and surrounding tissue.