Breast Cancer

Breast cancer is cancer of breast tissue. Worldwide, it is the most common form of cancer in females, affecting approximately 1 out of 11-12 women at some stage of their life in the Western world. Although significant efforts are made to achieve early detection and effective treatment, about 20% of all women with breast cancer will die from the disease, and it is the second most common cause of cancer deaths in women.

Epidemiologic risk factors
It is important to have a model of causation of a disease in order to distinguish epidemiological risk factors or associations with disease, from the biological etiology and primary cause, secondary co-factors, and simple promoters of the disease given the underlying cause. By analogy in peptic ulcer disease, the cause is Helicobacter pylori, a co-factor is stomach acidity, a promoter may be aspirin which altogether produce a stomach ulcer. Each is a risk factor associated with disease, and one is the primary cause. The cause of breast cancer is not known.

Age
The risk of getting breast cancer increases with age. For a woman who lives to the age of 90 the chances of getting breast cancer her entire lifetime is about 12.5% or 1 in 8. Men can also develop breast cancer, but their risk is less than 1 in 1000 (see sex and illness). This risk is modified by many different factors. In a very small (~ 5%) proportion of breast cancer cases, there is a strong inherited familial risk. [1] Some racial groups have a higher risk of developing breast cancer - notably, women of European and African descent have been noted to have a higher rate of breast cancer than women of Asian origin. (figures from breastcancer.org) However, these apparent racial differences diminish when geography is altered, as Asian women migrating to the western world, gradually acquire risk approaching that of western women.

The probability of breast cancer rises with age but breast cancer tends to be more aggressive when it occurs in younger women. One type of breast cancer that is especially aggressive and disproportionately occurs in younger women is inflammatory breast cancer. It is initially staged as Stage IIIb or Stage IV. It also is unique because it often does not present with a lump so that it often is not detected by mammography or ultrasound. It presents with the signs and symptoms of a breast infection like mastitis.

Genes
Two genes, BRCA1 and BRCA2, have been linked to the rare familial form of breast cancer. Women in families expressing mutations in these genes have a much higher risk of developing breast cancer than women who do not. Not all people who inherit mutations in these genes will develop breast cancer. Together with Li-Fraumeni syndrome (p53 mutations), these genetic aberrations determine around 5% of all breast cancer cases, suggesting that the remainder is sporadic. Genetic counseling and genetic testing should be considered for families who may carry a hereditary form of cancer.

Alcohol
Alcohol is another risk factor for the development of breast cancer. Women who drink half a glass of wine every day have 6% increased risk of developing breast /lead/8-2005/even-half-a-glass-of-wine-a-day-can-increase-the-risk-of-breast-cancer.html 1]

Hormones
The International Agency for Research on Cancer (IARC) in Lyon, France invited 21 scientists from eight countries in June 2005, to evaluate the risk of cancer for humans of combined estrogen-progesterone contraceptives and combined estrogen-progesterone menopausal therapy. The working group found that there is a small increase in the relative risk of breast cancer in current and recent users of combined oral contraceptives.

The risk decreases to that of those who have never used such combined therapy ten years after cessation of use. The scientists described combined oral estrogen-progesterone contraceptives as "carcinogenic to humans." [2] They also found an increased risk of breast cancer in women under treatment with combined menopausal therapy, which is confined mostly to current or recent users, increases with duration of use and exceeds that in women taking estrogen-only therapy.

Other
Other established risk factors include not having children, delaying first childbirth, not breastfeeding, early menarche (the first menstrual period), late menopause, obesity and taking hormone replacement therapy.

Screening
Due to the high incidence of breast cancer among older women, screening is now recommended in many countries. Screening methods suggested include breast self-examination and mammography. Only mammography has been proven to reduce mortality from breast cancer. In some countries routine (annual) mammography of older women is encouraged as a screening method to diagnose early breast cancer.

Mammography is still the modality of choice for screening of early breast cancer. Magnetic resonance imaging (MRI) has been shown to detect cancers that are not visible on mammograms, but it has several disadvantages. For example, although it is more sensitive, it is less specific than mammography. It is also a relatively expensive procedure, and one which requires the injection of a chemical agent to be effective. It may be valuable for younger women, whose breasts contain less fat and more connective tissue, making it harder to spot cancers on mammograms. Ultrasound alone is not adequate as a screening tool but it is a useful additional investigation, especially for the characterisation of benign tumours.

The U.S. National Cancer Institute recommends screening mammography with a baseline mammogram at age 35, mammograms every two years beginning at age 40, and then annual mammograms beginning at age 50. In the UK women are invited to attend for screening once every three years beginning at age 50. Women with a family history of breast cancer should start screening mammography at an earlier age, and it is usually suggested to start screening at an age that is 10 years less than the age at which a relative was diagnosed with breast cancer.

Breast cancers detected by mammography are usually smaller than those detected clinically, and women who undergo mammography are more likely to be eligible for breast-conserving therapy.

Diagnosis
Many breast cancers are diagnosed now by mammography before they are large enough to be palpated, but despite screening efforts, many women are diagnosed with breast cancer after they notice a lump or when experiencing symptoms due to metastatic disease.

Breast cancer can be suspected after a cautious clinical history, physical examination and imaging (either mammography or ultrasound). The diagnosis can only be established when a suspicious lump is biopsied for histological confirmation of whether it is malignant or not. The biopsy is usually performed either with a fine needle guided by ultrasound or with a larger "core" needle. Some cases require an open biopsy after wire localization under x-ray.

A pathology report will usually contain a description of cell type and grade. Other useful information derived from the pathology laboratory include estrogen receptor and progesterone receptors status and HER2/neu status; these can help to guide treatment.

The most common invasive breast cancer cell type is infiltrating ductal carcinoma (M8500/3). Other types include:

(M8500/2): the noninvasive ductal carcinoma in situ (DCIS)
(M8520/2): lobular carcinoma in situ (LCIS)
infiltrating lobular carcinoma
(M8510/3): medullary carcinoma
After diagnosis, the next phase is tumour staging - this aims to assess the extent of the tumour and whether it has metastasized (spread to distant sites).

Treatment
The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor), chemotherapy, and/or radiotherapy.

Surgery
Depending on the staging and type of the tumour, just a lumpectomy (removal of the lump only) may be all that is necessary or removal of larger amounts of breast tissue may be necessary. Surgical removal of the entire breast is called mastectomy.

Standard practice requires that the surgeon must establish that the tissue removed in the operation has margins clear of cancer, indicating that the cancer has been completely excised. If the tissue removed does not have clear margins, then further operations to remove more tissue may be necessary. This may sometimes require removal of part of the pectoralis major muscle which is the main muscle of the anterior chest wall.

During the operation, the lymph nodes in the axilla are also considered for removal. In the past, large axillary operations took out 10-40 nodes to establish whether cancer had spread - this had the unfortunate side effect of frequently causing lymphedema of the arm on the same side as the removal of this many lymph nodes affected lymphatic drainage. More recently the technique of sentinel lymph node dissection has become popular as it requires the removal of far fewer lymph nodes, resulting in fewer side effects.