Breast cancer overview

# Overview
Breast cancer was first described in Egyptian literature. In 1976, mammography became officially recommended by the American cancer society for screening breast cancer. Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. Genes involved in the pathogenesis of breast cancer include  BRCA1, BRCA2 and p53. On microscopic histopathological analysis, minimal tubule formation marked pleomorphism, and numerous mitotic figures are characteristic findings of breast cancer. Breast cancer must be differentiated from other diseases that cause mass in the breast such as fibroadenoma, fibrocystic disease of the breast, mastitis, galactocele, traumatic fat necrosis, intraductal papilloma, and lipoma. The prevalence of breast cancer is approximately 124.8 per 100,000 women per year. The number of deaths was 21.9 per 100,000 women per year, based on 2010-2012 data. Common risk factors in the development of breast cancer are family history, dense breast, obesity, radiation therapy, older age at first birth or never having given birth, hormone replacement therapy, and alcohol. Symptoms of breast cancer include a lump in the breast, discharge from the nipple, and thickening of the skin. A breast biopsy may be helpful in the diagnosis of breast cancer. Breast cancer chemotherapy refers to the use of cytotoxic drugs (chemotherapy) in the treatment of breast cancer. The aim of chemotherapy is to prevent the growth of micrometastatic disease that is responsible for systemic disease recurrence. Surgery is the mainstay of treatment for breast cancer.

# Historical Perspective
Breast cancer was first described in Egyptian literature. In 1976, mammography became officially recommended by the American cancer society for screening the breast cancer.

# Classification
Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. There are also other methods of classification such as classification based on gene expression, and classification based on hormone receptors present. In practice, a combination of all above-mentioned classification is combined with the surgical characteristics of tumors and radiologic findings is being applied for patient management, treatment planning, and prognosis determination.

# Pathophysiology
Genes involved in the pathogenesis of breast cancer include BRCA1, BRCA2 and p53. On microscopic histopathological analysis, minimal tubule formation, marked pleomorphism, and numerous mitotic figures are characteristic findings of breast cancer.

# Causes
The cause of breast cancer is not yet known exactly, though many risk factors can increase the chance of developing breast cancer.

# Differentiating Epithelioid sarcoma from other Diseases
Breast cancer must be differentiated from other diseases such as malignancy, cysts, inflammation and non-inflammatory solid lumps. Breast symptoms such as nipple discharge and mastalgia require assessment as well. Differentiating breast cancer different types of breast lumps are based on imaging findings and breast clinical exam results.

# Epidemiology and Demographics
The prevalence of breast cancer is approximately 124.8 per 100,000 women per year. The number of deaths was 21.9 per 100,000 women per year, based on 2010-2012 data. About 1 out of 8 women in United states will develop invasive breast cancer. Annually (i . e in 2019) around 268,600 and 62,930 new cases of invasive and non-invasive (in situ) breast cancer are expected to be diagnosed respectively. In men, life time likelihood of developing breast cancer is about 1 in 883. Annually 2,670 new cases of invasive breast cancer are expected to be diagnosed in males. Breast cancer increasing pattern of incidence rates began decreasing after year 2000 in US.

# Risk Factors
Common risk factors in the development of breast cancer are family history, dense breast, obesity, radiation therapy, older age at first birth or never having given birth, hormone replacement therapy, and alcohol.

# Screening
According to the U.S. Preventive Service Task Force (USPSTF), screening for breast cancer by a mammogram is recommended for women aged 50-74 years, twice a year.

# Natural history, Complications and Prognosis
If left untreated, 22% of patients with breast cancer may regress. Common complications of breast cancer include metastasis. Prognosis is generally good with treatment.
Breast cancer used to be staged according to the TNM system. Recently, the American Joint Committee on Cancer (AJCC) Staging Manual (8th edition, last updated 1/25/2018) extensively revised their staging system. The 8th edition of the AJCC TNM breast cancer staging system delivers a flexible platform for prognostic classification based on traditional anatomic factors, which may be modified and enhanced with respect to patient biomarkers and other prognostic panel data. Nevertheless, in order to maintain worldwide value, AJCC tumor staging system remained based on classic TNM anatomic factors. Prognosis is closely linked to results of staging, and staging is also used to allocate patients to treatments both in clinical trials and clinical practice.

# Diagnostic study of choice
Biopsy is the gold standard test for the diagnosis of breast cancer. Meanwhile, the diagnostic study of choice for breast cancer screening is mammography. Magnetic resonance imaging (MRI) is also recommended in selected patients. Compared to the Mammography, MRIhas higher sensitivity and lower specificity.

# Biopsy
Breast biopsy the only definite way to diagnose breast cancer. Hence, every patient with a suspicious lesion in her/his breast needs a biopsy to evaluate the nature of the mass precisely. Nevertheless, a large number of biopsy samples taken from breast lumps are found to be benign.

# History and Symptoms
Symptoms of breast cancer include a lump in the breast, discharge from the nipple, and thickening of the skin.

# Physical Examination
Patients with breast cancer usually are generally well appearing. Physical examination of patients with breast cancer is usually remarkable for a lump in the breast, peau d'orange, an inverted nipple.

# Laboratory Findings
Laboratory studies play a crucial role in prevention, diagnosis, staging, treatment planning, management, determining prognosis and follow up of patients with breast cancer. Among them are single gene studies (i. e. BRCA1, BRCA2, and HER2), multiple gene panels (i.e. Oncotype DX), tumor markers (Ki67), and metastatic markers such as serum alkaline phosphatase as a marker of bone metastasis. A variety of other blood chemistry tests are also used in the management process of patients with breast cancer, among them are liver function tests (alanine aminotransferase (ALT), aspartate transaminase (AST) , bilirubin, alkaline phosphatase) and markers of kidney function (BUN, creatinine).

# Electrocardiogram
There are no ECG findings associated with breast cancer

# X Ray
There are no x-ray findings associated with breast cancer. However, an x-ray may be helpful in the diagnosis of complications of breast cancer, which include:
- Bone and lung metastasis.
- Nevertheless, more accurate and sensitive imaging techniques are available and are widely used, among them are CT scan, MRI, PET scan, PET- CT scan.

# CT scan
There are no CT scan findings associated with breast cancer. However, a CT scan may be helpful in staging and the diagnosis of complications of breast cancer, which include brain, bone, liver, lung, and peritoneal metastasis. A combination of CT scan with other imaging techniques such as PET scan increases its

# MRI
Although a number of breast MRI indications remained controversial, breast MRI has been recommended for a variety of conditions such as studying a probable occult primary breast cancers, evaluation of disease extension, watching up the response to neoadjuvant chemotherapy, studying disease recurrence, as an adjuvant method to clarify inconclusive clinical or imaging findings, and as the recommended method of screening for high-risk patients another indication of breast MRI is assessment of silicone implant integrity

# Ultrasound
Breast ultrasound may be helpful in the diagnosis of breast cancer, especially, to further evaluate an abnormal mammogram and to distinguish between solid and cystic lesions. Ultrasonography is the first-line imaging method in pregnant women and women less than 30 years old with focal breast sign and symptoms. AlthoughUltrasonography might be used as an adjunct to mammography in women with increased breast density, it has not been shown to decrease mortality from breast cancer. Nevertheless, using ultrasound may increase the risk for false-positive findings, unnecessary breast biopsy, and follow-up imaging.
It has been shown that heart failure is prevalent in women being treated with this novel treatment. As a potentially serious side effect of this novel treatment, serial Echocardiography is recommended in all patients treated with trastuzumab.

# Other Imaging Studies
Other diagnostic studies for breast cancer include modified MRI utilities (high-field strength MRI, magnetic resonance spectroscopy, and diffusion weighted imaging, breast-specific gamma imaging, positron emissionmammography, scintimammography, thermography and bone scan.

# Mammography
Mammography has been proven to reduce mortality from breast cancer. No other imaging technique has been shown to reduce risk. In some countries, routine (annual to five-yearly) mammography of older women is encouraged as a screening method to diagnose early breast cancer.

# Other Diagnostic Studies
Other diagnostic studies for breast cancer is hormone receptor testing.

# Medical Therapy
Breast cancer chemotherapy is a combination of cytotoxic drugs (chemotherapy), hormonal therapy, hormonal receptor modulators, aromatase inhibitors, monoclonal antibodies, and growth factor receptor tyrosine kinase inhibitors

# Surgery
Surgery is the mainstay of treatment for breast cancer.

# Bone Metastasis
Bone is the most common site of breast cancer distant spread. Bone metastases due to the breast cancer cause major morbidity, decrease survival and reduce the quality of life of many patients. Rather than systemic chemotherapy, bisphosphonates like Pamidronate, Alendronate, Ibandronate, Risedronate, and Zoledronic acid , RANKL-RANK inhibitors like Denosumab, also has been recommended and studied for the treatment of bone metastases..Additionally, External beam radiotherapy (EBRT) has been, and continues to be, the mainstay for the treatment of painful, uncomplicated bone metastases.

# Primary Prevention
Avoiding risk factors and increasing protective factors may help prevent cancer.

# Future or Investigational Therapies
Medical investigational therapies are a wide range of new generations of targeted therapy, cancer vaccines, oncolytic virotherapy, gene therapy, and immunotherapy. Novel surgical and radiation techniques are also under investigation. A new generation of clinical trials (adaptive trials) are already being used in the war against breast cancer (i.e. I-SPY 2).