breast cancer

Breast cancer is a cancer that starts in the cells of the breast in men and women.[1] Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted)[2] and the fifth most common cause of cancer death.[3] Worldwide, breast cancer is by far the most common cancer amongst women, with an incidence rate more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer. However breast cancer mortality worldwide is just 25% greater than that of lung cancer in women.[2] In 2005, breast cancer caused 502,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).[3] The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.

The incidence of breast cancer varies greatly around the world, being lower in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.[6]

Women in the United States have the highest incidence rates of breast cancer in the world; 141 among white women and 122 among African American women.[7][8] Among women in the US, breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer). Women in the US have a 1 in 8 (12.5%) lifetime chance of developing invasive breast cancer and a 1 in 35 (3%) chance of breast cancer causing their death.[8] In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths).

In the US, both incidence and death rates for breast cancer have been declining in the last few years. Nevertheless, a US study conducted in 2005 by the Society for Women's Health Research indicated that breast cancer remains the most feared disease,[11] even though heart disease is a much more common cause of death among women.

Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males.Incidences of breast cancer in men are approximately 100 times less common than in women, but men with breast cancer are considered to have the same statistical survival rates as women.

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Breast cancers are described along four different classification schemes, or groups, each based on different criteria and serving a different purpose:

* Pathology - A pathologist will categorize each tumor based on its histological (microscopic anatomy) appearance and other criteria. The most common pathologic types of breast cancer are invasive ductal carcinoma, malignant cancer in the breast's ducts, and invasive lobular carcinoma, malignant cancer in the breast's lobules.
* Grade of tumor - The histological grade of a tumor is determined by a pathologist under a microscope. A well-differentiated (low grade) tumor resembles normal tissue. A poorly differentiated (high grade) tumor is composed of disorganized cells and, therefore, does not look like normal tissue. Moderately differentiated (intermediate grade) tumors are somewhere in between.
* Protein & gene expression status - Currently, all breast cancers should be tested for expression, or detectable effect, of the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins. These tests are usually done by immunohistochemistry and are presented in a pathologist's report. The profile of expression of a given tumor helps predict its prognosis, or outlook, and helps an oncologist choose the most appropriate treatment. More genes and/or proteins may be tested in the future.
* Stage of a tumor - The currently accepted staging scheme for breast cancer is the TNM classification.

There are five tumor classification values (Tis, T1, T2, T3 or T4) which depend on the presence or absence of invasive cancer, the dimensions of the invasive cancer, and the presence or absence of invasion outside of the breast (e.g. to the skin of the breast, to the muscle or to the rib cage underneath):

* Tx - Primary tumor cannot be assessed.
* T0 - No evidence of primary tumor.
* Tis - Carcinoma in situ.
o Tis(DCIS) - Intraductal Carcinoma in situ.
o Tis(LCIS) - Lobular Carcinoma in situ.
o Tis(Paget's) - Paget's disease of the nipple with no tumor.
* T1 - Tumor 2cm or less in its greatest dimension.
o T1mic - Microinvasion 0.1cm or less in greatest dimension.
o T1a - Tumor more then 0.1cm but not more than 0.5cm in its greatest dimension.
o T1b - Tumor more than 0.5cm but not more than 1.0cm in its greatest dimension.
o T1c - Tumor more than 1.0cm but not more than 2.0cm in its greatest dimension.
* T2 - Tumor more than 2.0cm but not more than 5.0cm in its greatest dimension.
* T3 - Tumor more than 5cm in its greatest dimension.
* T4 - Tumor of any size with direct extension to (a) chest wall or (b) skin as described below:
o T4a - Extension to chest wall.
o T4b - Edema (including peau d'orange) or ulceration of the breast skin, or satellite skin nodules confined to the same breast.
o T4c - Both T4a and T4b.
o T4d - Inflammatory breast cancer.

Lymph Node - There are four lymph node classification values (N0, N1, N2 or N3) which depend on the number, size and location of breast cancer cell deposits in lymph nodes.

* Nx - regional lymph nodes cannot be assessed. Perhaps due to previous removal.
* N0 - no regional lymph node metastasis.
* N1 - metastasis to movable regional axillary lymph nodes on the same side as the affected breast.
* N2 - metastasis to fixed regional axillary lymph nodes, or metastasis to the internal mammary lymph nodes, on the same side as the affected breast.
* N3 - metastasis to supraclavicular lymph nodes or infraclavicular lymph nodes or metastasis to the internal mammary lymph nodes with metastasis to the axillary lymph nodes.

Metastases - There are two metastatic classification values (M0 or M1) which depend on the presence or absence of breast cancer cells in locations other than the breast and lymph nodes (so-called distant metastases, e.g. to bone, brain, lung).

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Pathologic types

Note: The following table includes benign tumours (non cancers) as well as malignant tumours (cancers)

The latest (2003) World Health Organization (WHO) classification of tumors of the breast[16] recommends the following pathological types:

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Invasive breast carcinomas

* Invasive ductal carcinoma
o Most are "not otherwise specified"
o The remainder are given subtypes:
+ Mixed type carcinoma
+ Pleomorphic carcinoma
+ Carcinoma with osteoclastic giant cells
+ Carcinoma with choriocarcinomatous features
+ Carcinoma with melanotic features
* Invasive lobular carcinoma
* Tubular carcinoma
* Invasive cribriform carcinoma
* Medullary carcinoma
* Mucinous carcinoma and other tumours with abundant mucin
o Mucinous carcinoma
o Cystadenocarcinoma and columnar cell mucinous carcinoma
o Signet ring cell carcinoma
* Neuroendocrine tumours
o Solid neuroendocrine carcinoma (carcinoid of the breast)
o Atypical carcinoid tumour
o Small cell / oat cell carcinoma
o Large cell neuroendocrine carcioma
* Invasive papillary carcinoma
* Invasive micropapillary carcinoma
* Apocrine carcinoma
* Metaplastic carcinomas
o Pure epithelial metaplastic carciomas
+ Squamous cell carcinoma
+ Adenocarcinoma with spindle cell metaplasia
+ Adenosquamous carcinoma
+ Mucoepidermoid carcinoma
o Mixed epithelial/mesenchymal metaplastic carcinomas
* Lipid-rich carcinoma
* Secretory carcinoma
* Oncocytic carcinoma
* Adenoid cystic carcinoma
* Acinic cell carcinoma
* Glycogen-rich clear cell carcinoma
* Sebaceous carcinoma
* Inflammatory carcinoma
* Bilateral breast carcinoma

Mesenchymal tumors (including sarcoma)

* Haemangioma
* Angiomatosis
* Haemangiopericytoma
* Pseudoangiomatous stromal hyperplasia
* Myofibroblastoma
* Fibromatosis (aggressive)
* Inflammatory myofibroblastic tumour
* Lipoma
o Angiolipoma
* Granular cell tumour
* Neurofibroma
* Schwannoma
* Angiosarcoma
* Liposarcoma
* Rhabdomyosarcoma
* Osteosarcoma
* Leiomyoma
* Leiomysarcoma



Precursor lesions

* Lobular neoplasia
o lobular carcinoma in situ
* Intraductal proliferative lesions
o Usual ductal hyperplasia
o Flat epithelial hyperplasia
o Atypical ductal hyperplasia
o Ductal carcinoma in situ
* Microinvasive carcinoma
* Intraductal papillary neoplasms
o Central papilloma
o Peripheral papilloma
o Atypical papilloma
o Intraductal papillary carcinoma
o Intracystic papillary carcinoma

Benign epithelial lesions

* Adenosis, includin variants
o Sclerosing adenosis
o Apocrine adenosis
o Blunt duct adenosis
o Microglandular adenosis
o Adenomyoepithelial adenosis
* Radial scar / complex sclerosing lesion
* Adenomas
o Tubular adenoma
o Lactating adenoma
o Apocrine adenoma
o Pleomorphic adenoma
o Ductal adenoma

Myoepithelial lesions

* Myoepitheliosis
* Adenomyoepithelial adenosis
* Adenomyoepithelioma
* Malignant myoepithelioma

Fibroepithelial tumours

* Fibroadenoma
* Phyllodes tumour
o Benign
o Borderline
o Malignant
* Periductal stromal sarcoma, low grade
* Mammary hamartoma

Tumours of the nipple

* Nipple adenoma
* Syringomatous adenoma
* Paget's disease of the nipple

Malignant lymphoma

Metastatic tumours

Tumours of the male breast

* Gynecomastia
* Carcinoma
o In situ
o Invasive

The classifications above show that breast cancer is usually, but not always, classified by its histological appearance. Rare variants are defined on the basis of physical exam findings. For example, Inflammatory breast cancer (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other carcinomas by the inflamed appearance of the affected breast.[17] In the future, some pathologic classifications may be changed. For example, a subset of ductal carcinomas may be re-named basal-like carcinoma (part of the "triple-negative" tumors).[citation needed]

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Signs and symptoms

The first symptom, or subjective sign, of breast cancer is typically a lump that feels different than the surrounding breast tissue. According to the Merck Manual, greater than 80% of breast cancer cases are discovered as a lump by the woman herself.[18] According to the American Cancer Society (ACS), the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram.[9] Lumps found in lymph nodes located in the armpits[18] and/or collarbone[citation needed] can also indicate breast cancer.

Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain is an unreliable tool in determining the presence of breast cancer, but may be indicative of other breast-related health issues such as mastodynia.[9][18][19]

When breast cancer cells invade the dermal lymphatics, small lymph vessels in the skin of the breast, its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange peel texture to the skin referred to as peau d'orange.[18]

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.[20]

Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. More common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific," meaning they can also be manifestations of many other illnesses.[21]

Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.[22]

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Epidemiology and etiology



Epidemiological risk factors for a disease can provide important clues as to the etiology, or cause, of a disease. The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.

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Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors. Some of these factors include:

1. Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.[25] Beyond the contribution of estrogen, research has implicated viral oncogenesis and the contribution of ionizing radiation in causing genetic mutations.[citation needed]
2. Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout one's life.[26]
3. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth. For example, tumors can induce blood vessel growth (angiogenesis) by secreting various growth factors further facilitating cancer growth.
4. Inherited defects in DNA repair genes, such as BRCA1, BRCA2[27] and p53.[citation needed]

Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is often unknowable. In other words, epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. The primary risk factors that have been identified are sex,[28] age,[29] childbearing, hormones,[30] a high-fat diet,[31] alcohol intake,[32][33] obesity,[34] and environmental factors such as tobacco use, radiation[27] and shiftwork.[35]

No etiology is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes.[36] In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occurs.[37]

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Prevention

Lower age of first childbirth (less than 24 years maternal age), having more children (about 7% lowered risk per child), and breastfeeding (4% per breastfeeding year, with an average relative risk around 0.7[38][39]) have all been correlated to lowered breast cancer risk in large studies.[40] In addition, exercising three times a week for one hour each has been found to lower breast cancer by up to 40%.[citation needed]

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Phytoestrogens and soy

Phytoestrogens such as found in soybeans have been extensively studied in animal and human in-vitro and epidemiological studies. The literature support the following conclusions:

1. Plant estrogen intake, such as from soy products, in early adolescence may protect against breast cancer later in life.[41]
2. Plant estrogen intake later in life is not likely to influence breast cancer incidence either positively or negatively.[42]
Avoiding exposure to secondhand tobacco smoke

Breathing secondhand smoke increases breast cancer risk by 70% in younger, primarily pre-menopausal women. The California Environmental Protection Agency has concluded that passive smoking causes breast cancer[51] and the US Surgeon General[52] has concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problematic between puberty and first childbirth. The reason that breast tissue appears most sensitive to chemical carcinogens in this phase is that breast cells are not fully differentiated until lactation.[53]

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Oophorectomy and mastectomy

Prophylactic oophorectomy (removal of ovaries), in high-risk individuals, when child-bearing is complete, reduces the risk of developing breast cancer by 60%, as well as reducing the risk of developing ovarian cancer by 96%.[54]

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Medications

Hormonal therapy has been used for chemoprevention in individuals at high risk for breast cancer. In 2002, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) recommended that "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.[55][verification needed][56][57]

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Selective estrogen receptor modulators (SERMs)

The guidelines[clarify] were based on studies of SERMs from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the relative risk reduction for raloxifene was 76%.[58] The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of finasteride on the prevention of prostate cancer, in which only low-grade prostate cancers were prevented).[59][60] The Italian trial showed benefit from tamoxifen.[61]

Additional randomized controlled trials have been published since the guidelines. The IBIS trial found benefit from tamoxifen.[62] In 2006, the NSABP STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene.[63] The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke".[64] On September 14, 2007, the US Food and Drug Administration approved raloxifene (Evista) to prevent invasive breast cancer in postmenopausal women.[65]

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Screening



Breast cancer screening is an attempt to find unsuspected cancers. The most common screening methods are self and clinical breast exams, x-ray mammography, and breast Magnetic resonance imaging (MRI)

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X-ray mammography

Mammography is still the modality of choice for screening of early breast cancer, since it is relatively fast, reasonably accurate, and widely available in developed countries.

Due to the high incidence of breast cancer among older women, screening is now recommended in many countries. Recommended screening methods include breast self-examination and mammography. Mammography has been estimated to reduce breast cancer-related mortality by 20-30%.[66] Routine (annual) mammography of women older than age 40 or 50 is recommended by numerous organizations as a screening method to diagnose early breast cancer and has demonstrated a protective effect in multiple clinical trials.[67] The evidence in favor of mammographic screening comes from eight randomized clinical trials from the 1960s through 1980s. Many of these trials have been criticised for methodological errors, and the results were summarized in a review article published in 1993.[68]

Improvements in mortality due to screening are hard to measure; similar difficulty exists in measuring the impact of Pap smear testing on cervical cancer, though worldwide, the impact of that test is likely enormous. Nationwide mortality due to cancer before and after the institution of a screening test is a surrogate indicator about the effectiveness of screening, and results of mammography are favorable.
Normal (left) versus cancerous (right) mammography image.
Normal (left) versus cancerous (right) mammography image.

The U.S. National Cancer Institute recommends screening mammography every one to two years beginning at age 40.[69] In the UK, women are invited for screening once every three years beginning at age 50. Women with one or more first-degree relatives (mother, sister, daughter) with premenopausal breast cancer should begin screening at an earlier age. It is usually suggested to start screening at an age that is 10 years less than the age at which the relative was diagnosed with breast cancer.

A clinical practice guideline by the US Preventive Services Task Force recommended "screening mammography, with or without clinical breast examination (CBE), every 1 to 2 years for women aged 40 and older."[70] The Task Force gave a grade B recommendation.[55][verification needed]

In 2005, 67.9% of all U.S. women age 40–64 had a mammogram in the past two years (74.5% of women with private health insurance, 56.1% of women with Medicaid insurance, 38.1% of currently uninsured women, and 32.9% of women uninsured for > 12 months).[71]

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Criticisms of screening mammography

Several scientific groups however have expressed concern about the public's perceptions of the benefits of breast screening.[72] In 2001, a controversial review published in The Lancet claimed that "there is no reliable evidence that screening for breast cancer reduces mortality".[73][74]The Cochrane Collaboration concluded, "for every 2000 women invited for screening throughout 10 years, one will have her life prolonged. In addition, 10 healthy women, who would not have been diagnosed if there had not been screening, will be diagnosed as breast cancer patients and will be treated unnecessarily. It is thus not clear whether screening does more good than harm."[75]

False positives are a major problem of mammographic breast cancer screening. Data reported in the UK Million Woman Study indicates that if 134 mammograms are performed, 20 women will be called back for suspicious findings, and four biopsies will be necessary, to diagnose one cancer. Recall rates are higher in the U.S. than in the UK.[76] The contribution of mammography to the early diagnosis of cancer is controversial, and for those found with benign lesions, mammography can create a high psychological and financial cost.

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Mammography in women less than 50 years old

Part of the difficulty in interpreting mammograms in younger women stems from the problem of breast density. Radiographically, a dense breast has a preponderance of glandular tissue, and younger age or estrogen hormone replacement therapy contribute to mammographic breast density. After menopause, the breast glandular tissue gradually is replaced by fatty tissue, making mammographic interpretation much more accurate. Some authors speculate that part of the contribution of estrogen hormone replacement therapy to breast cancer mortality arises from the issue of increased mammographic breast density. Breast density is an independent adverse prognostic factor on breast cancer prognosis.

A systematic review by the American College of Physicians concluded "Although few women 50 years of age or older have risks from mammography that outweigh the benefits, the evidence suggests that more women 40 to 49 years of age have such risks".[77].

A report released November 27, 2007 by the Journal of the National Cancer Institute showed that the formula doctors use to calculate a woman's risk of breast cancer underestimates the danger for black women most of the time and especially for those age 50 and older — the age when they are most likely to benefit from screening tests and protective drugs, according to the first major reassessment of the widely used tool.[78]

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Enhancements to mammography

CAD is especially established in US and the Netherlands. It is used in addition to the human evaluation of the diagnostician.

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Breast MRI

Magnetic resonance imaging (MRI) has been shown to detect cancers not visible on mammograms, but has long been regarded to have disadvantages. For example, although it is 27-36% more sensitive, it is less specific than mammography.[79] As a result, MRI studies will have more false positives (up to 5%), which may have undesirable financial and psychological costs. It is also a relatively expensive procedure, and one which requires the intravenous injection of a chemical agent (from which there are side effects, potentially serious in a small number of people) to be effective. Proposed indications for using MRI for screening include:[80]

* Strong family history of breast cancer
* Patients with BRCA-1 or BRCA-2 tumour suppressor gene mutations
* Evaluation of women with breast implants
* History of previous lumpectomy or breast biopsy surgeries
* Axillary metastasis with an unknown primary tumor
* Very dense or scarred breast tissue

However, two studies published in 2007 demonstrated the strengths of MRI-based screening:

* In March 2007, an article published in the New England Journal of Medicine demonstrated that in 3.1% of patients with breast cancer, whose contralateral breast was clinically and mammographically tumor-free, MRI could detect breast cancer. Sensitivity for detection of breast cancer in this study was 91%, specificity 88%.[81]

* In August 2007, an article published in The Lancet compared MRI breast cancer screening to conventional mammographic screening in 7,319 women. MRI screening was highly more sensitive (97% in the MRI group vs. 56% in the mammography group) in recognizing early high-grade Ductal Carcinoma in situ (DCIS), the most important precursor of invasive carcinoma. Despite the high sensitivity, MRI screening had a positive predictive value of 52%, which is totally accepted for cancer screening tests.[82] The author of a comment published in the same issue of The Lancet concludes that "MRI outperforms mammography in tumour detection and diagnosis."[83]

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Breast self-exam

Breast self-examination (BSE) was widely discussed in the 1990s as a useful modality for detecting breast cancer at an earlier stage of presentation. A large clinical trial in China reduced enthusiasm for breast self-exam. In the trial, reported in the Journal of the National Cancer Institute first in 1997 and updated in 2002, 132,979 female Chinese factory workers were taught by nurses at their factories to perform monthly breast self-exam, while 133,085 other workers were not taught self-exam. The women taught self-exam tended to detect more breast nodules, but their breast cancer mortality rate was no different from that of women in the control group. In other words, women taught breast self-exam were mostly likely to detect benign breast disease, but were just as likely to die of breast cancer.[84] In 2003, the American Cancer Society relegated structured BSE to an 'optional' method of detecting breast cancer, citing self awareness as more important than structured self exams based on recent research.[27]

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Genetic testing

A clinical practice guideline by the US Preventive Services Task Force :[70]

* "recommends against routine referral for genetic counseling or routine breast cancer susceptibility gene (BRCA) testing for women whose family history is not associated with an increased risk for deleterious mutations in breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2)" The Task Force gave a grade D recommendation.[verification needed]
* "recommends that women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing." The Task Force gave a grade B recommendation.[55][verification needed]

The Task Force noted that about 2% of women have family histories that indicate increased risk as defined by:

* For non–Ashkenazi Jewish women, any of the following:
o "2 first-degree relatives with breast cancer, 1 of whom received the diagnosis at age 50 years or younger"
o "3 or more first- or second-degree relatives with breast cancer regardless of age at diagnosis"
o "both breast and ovarian cancer among first- and second- degree relatives"
o "a first-degree relative with bilateral breast cancer"
o "a combination of 2 or more first- or second-degree relatives with ovarian cancer regardless of age at diagnosis"
o "a first- or second-degree relative with both breast and ovarian cancer at any age"
o "a history of breast cancer in a male relative."
* "For women of Ashkenazi Jewish heritage, an increased-risk family history includes any first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer


Breast cancer is staged according to the TNM system, updated in the AJCC Staging Manual, now on its sixth edition. 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. The information for staging is as follows:

TX: Primary tumor cannot be assessed. T0: No evidence of tumor. Tis: Carcinoma in situ, no invasion T1: Tumor is 2 cm or less T2: Tumor is more than 2 cm but not more than 5 cm T3: Tumor is more than 5 cm T4: Tumor of any size growing into the chest wall or skin, or inflammatory breast cancer

NX: Nearby lymph nodes cannot be assessed N0: Cancer has not spread to regional lymph nodes. N1: Cancer has spread to 1 to 3 axillary or one internal mammary lymph node N2: Cancer has spread to 4 to 9 axillary lymph nodes or multiple internal mammary lymph nodes N3: One of the following applies:

Cancer has spread to 10 or more axillary lymph nodes, or Cancer has spread to the lymph nodes under the clavicle (collar bone), or Cancer has spread to the lymph nodes above the clavicle, or Cancer involves axillary lymph nodes and has enlarged the internal mammary lymph nodes, or Cancer involves 4 or more axillary lymph nodes, and tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy.

MX: Presence of distant spread (metastasis) cannot be assessed. M0: No distant spread. M1: Spread to distant organs, not including the supraclavicular lymph node, has occurred

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Summary of stages:

* Stage 0 - Carcinoma in situ
* Stage I - Tumor (T) does not involve axillary lymph nodes (N).
* Stage IIA – T 2-5 cm, N negative, or T <2 cm and N positive.
* Stage IIB – T > 5 cm, N negative, or T 2-5 cm and N positive (< 4 axillary nodes).
* Stage IIIA – T > 5 cm, N positive, or T 2-5 cm with 4 or more axillary nodes
* Stage IIIB – T has penetrated chest wall or skin, and may have spread to < 10 axillary N
* Stage IIIC – T has > 10 axillary N, 1 or more supraclavicular or infraclavicular N, or internal mammary N.
* Stage IV – Distant metastasis (M)

Approximately 90% of new breast cancer cases in the US will be classified as a "Stage I" cases, due to early detection and prevention techniques. Early-stage treatment options are different from late-stage options.[85] Breast lesions are examined for certain markers, notably sex steroid hormone receptors. About two thirds of postmenopausal breast cancers are estrogen receptor positive (ER+) and progesterone receptor positive (PR+).[86] Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal therapy.

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Human epidermal growth factor two (HER2)

The breast cancer is also usually tested for the presence of human epidermal growth factor receptor 2, a protein also known as HER2, neu or erbB2. HER2 is a cell-surface protein involved in cell development. In normal cells, HER2 controls aspects of cell growth and division. When activated in cancer cells, HER2 accelerates tumor formation. About 20-30% of breast cancers overexpress HER2. Those patients may be candidates for the drug trastuzumab, both in the postsurgical setting (so-called "adjuvant" therapy), and in the metastatic setting.[87]

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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. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern. This pattern is subject to change, as every two years, a worldwide conference takes place in St. Gallen, Switzerland, to discuss the actual results of worldwide multi-center studies. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy.

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests like MammaPrint that predict breast cancer recurrence risk based on gene expression. In February 2007, the MammaPrint test became the first breast cancer predictor to win formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.[88]

Interstitial laser thermotherapy (ILT) is an innovative method of treating breast cancer in a minimally invasive manner and without the need for surgical removal, and with the absence of any adverse effect on the health and survival of the patient during intermediate followup [89].

Radiation treatment is also used to help destroy cancer cells that may linger after surgery. Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose. [90]

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Early-stage research

In mice, flaxseed oil reduced the growth and metastasis of breast cancer tumors that were cultured in the laboratory and implanted in mice. In humans, flaxseed oil reduced markers that are associated with cancer growth.

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Psychological aspects of diagnosis and treatment

The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which can help patients cope with the many issues that come up in a supportive environment with other people with experience with similar issues. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. For example, a recent study conducted by researchers at the College of Public Health of the University of Georgia showed that older women may face a more difficult recovery from breast cancer than their younger counterparts.[95] As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.

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Metastasis

Most people understand breast cancer as something that happens in the breast. However it can metastasize (spread) via lymphatics to nearby lymph nodes, usually those under the arm. That is why surgery for breast cancer always involves some type of surgery for the glands under the arm — either axillary clearance, sampling, or sentinel node biopsy.

Breast cancer can also spread to other parts of the body via blood vessels or the lymphatic system. So it can spread to the lungs, pleura (the lining of the lungs), liver, brain, and most commonly to the bones.[102] Seventy percent of the time that breast cancer spreads to other locations, it spreads to bone, especially the vertebrae and the long bones of the arms, legs, and ribs. Breast cancer cells "set up house" in the bones and form tumors. Usually when breast cancer spreads to bone, it eats away healthy bone, causing weak spots, where the bones can break easily. That is why breast cancer patients are often seen wearing braces or using a wheelchair, and have aching bones.

When breast cancer is found in bones, it has usually spread to more than one site. At this stage, it is treatable, often for many years, but it is not curable. Like normal breast cells, these tumors in the bone often thrive on female hormones, especially estrogen. Therefore treatment with medicines that lower estrogen levels may be prescribed.

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Cultural references

In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease. A pink ribbon is worn to recognize the struggle that sufferers face when battling the cancer.

Pink for October is an initiative started by Matthew Oliphant, which asks that any sites willing to help make people aware of breast cancer, change their template or layout to include the color pink, so that when visitors view the site, they see that the majority of the site is pink. Then after reading a short amount of information about breast cancer, or being redirected to another site, they are aware of the disease itself.[106]

The patron saint of breast cancer is Saint Agatha of Sicily.