Breast Cancer

Histopathologic image from ductal cell carcinoma in situ (DCIS) of breast. Hematoxylin-eosin stain.

Typical macroscopic (gross) appearance of the cut surface of a mastectomy specimen containing a cancer (in this case, an invasive ductal carcinoma of the breast, pale area at the center).

Mastectomy specimen containing a very large cancer of the breast (in this case, an invasive ductal carcinoma).

Breast cancer is a cancer that starts in the cells of the breast. Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted) and the fifth most common cause of cancer death. However, among women worldwide, breast cancer is by far the most common cause of cancer, both in incidence and death. In 2005, breast cancer caused 502,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.

Breast cancer incidence is much higher in the Western world, whether in Europe or North America, than in third world countries. North American women have the highest incidence of breast cancer in the world. Among women in the U.S., breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer). Women in the U.S. 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. In 2007, breast cancer was expected to cause 40,910 deaths in the U.S. (7% of cancer deaths; almost 2% of all deaths). In the U.S., both incidence and death rates for breast cancer have been declining in the last few years. Nevertheless, a U.S. study conducted in 2005 by the Society for Women's Health Research indicated that breast cancer remains the most feared disease, 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.


Time line of breast cancer suggesting probable heterogeneity. Primary breast cancers begin as single (or more) cells which have lost normal regulation of differentiation and proliferation but remain confined within the basement membrane of the duct or lobule. As these cells go through several doublings, at some point they invade through the basement membrane of the duct or lobule and ultimately metastasize to distant organs.

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 tumour - The currently accepted staging scheme for breast cancer is the TNM classification : o Tumor - 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). o 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. o 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).

Pathologic types
The latest (2003) World Health Organization (WHO) classification of tumors of the breast recommends the following pathological types: Invasive breast carcinomas
• Invasive ductal carcinoma o Most are "not otherwise specified" o The remainder are given subtypes:  Mixed type carcinoma  Pleomorphic carcinoma

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 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

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Angiosarcoma Liposarcoma Rhabdomyosarcoma Osteosarcoma Leiomyoma


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

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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

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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

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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. 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).

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. 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. Lumps found in lymph nodes located in the armpits 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. 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. 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. 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. 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.

Epidemiology and Etiology:
Epidemiological risk factors for a disease can provide important clues as to the etiology, or cause, of a disease. 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. Beyond the contribution of estrogen, research has implicated viral

oncogenesis and the contribution of ionizing radiation in causing genetic mutations. 2. Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout ones life. 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 and p53. 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, age, childbearing, hormones, a high-fat diet, alcohol intake, obesity, and environmental factors such as tobacco use and radiation. No etiology is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes. 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.

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. 2. Plant estrogen intake later in life is not likely to influence breast cancer incidence either positively or negatively.

Folic acid (folate)
Studies have found that "folate intake counteracts breast cancer risk associated with alcohol consumption" and "women who drink alcohol and have a high folate intake are not at increased risk of cancer." A prospective study of over 17,000 women found that those who consume 40 grams of alcohol (about 3-4 drinks) per day have a higher risk of breast cancer. However, in women who take 200 micrograms of folate (folic acid or Vitamin B9) every day, the risk of breast cancer drops below that of alcohol abstainers.

Folate is involved in the synthesis, repair, and functioning of DNA, the body’s genetic map, and a deficiency of folate may result in damage to DNA that may lead to cancer. In addition to breast cancer, studies have also associated diets low in folate with increased risk of pancreatic, and colon cancer. Foods rich in folate include citrus fruits, citrus juices, dark green leafy vegetables (such as spinach), dried beans, and peas. Vitamin B9 can also be taken in a multivitamin pill.

Avoiding exposure to secondhand tobacco smoke
Breathing secondhand smoke increases breast cancer risk by 70% in younger, primarily premenopausal women. The California Environmental Protection Agency has concluded that passive smoking causes breast cancer and the US Surgeon General has concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problemmatic 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.

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%.

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.

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)

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%. 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. 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. 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.

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. 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 to be effective. Proposed indications for using MRI for screening include:

Strong family history of breast cancer

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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

Breast self-examination
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. 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. Breast self-examination (BSE) is an easy but unreliable method for finding possible breast cancer. If performed appropriately and regularly BSE may help in early detection of some types of breast cancers, although it should not substitute for screening methods (such as mammography) that have been proven to be effective. The method involves feeling breasts for possible distortions or swelling. How to perform BSE The steps involved in self exam are:
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Stand in front of a mirror with top exposed. Place hands on hips. Look for signs of dimpling, swelling, soreness, or redness in all parts of your breasts in the mirror. Repeat with arms raised above your head. While still standing, palpate your breasts with your fingers, feeling for lumps. Try to use a larger area of your fingers rather than prodding. Feel both for the area just beneath the skin and for the tissue deeper within. Go over the entire breast while examining. One method is to divide the breast into quadrants and palpate each quadrant carefully. Also examine the "axillary tail" of each breast that extends toward the axilla (armpit). Repeat palpation while lying down.

Check the nipples and the area just beneath them. Gently squeeze each nipple to check for any discharge.

The Seven P's method A similar method of self-examination is known as the Seven P's of BSE: 1. Position: Inspect breasts visually and palpate in the mirror with arms at various positions. Then perform the examination lying down, first with a pillow under one shoulder, then with a pillow under the other shoulder, and finally lying flat. 2. Perimeter: Examine the entire breast, including the nipple, the axillary tail that extends into the armpit, and nearby lymph nodes. 3. Palpation: Palpate with the pads of the fingers, without lifting the fingers as they move across the breast. 4. Pressure: First palpate with light pressure, then palpate with moderate pressure, and finally palpate with firm pressure. 5. Pattern: There are several examination patterns, and each woman should use the one which is most comfortable for her. The vertical strip pattern involves moving the fingers up and down over the breast. The pie-wedge pattern starts at the nipple and moves outward. The circular pattern involves moving the fingers in concentric circles from the nipple outward. Don't forget to palpate into the axilla. 6. Practice: Practice the breast self-exam and become familiar with the feel of the breast tissue, so you can recognize changes. A health care practitioner can provide feedback on your method. 7. Plan: Know what to do if you suspect a change in your breast tissue. Know your family history of breast cancer. Have mammography done as often as your health care provider recommends. For premenopausal women, BSE is best done at the same stage of their period every month to minimize changes due to the menstrual cycle. The recommended time is just after the end of the last period when the breasts are least likely to be swollen and tender. Older, menopausal women should do BSE once a month, perhaps on the first or last day of every month. About eight in ten lumps discovered by BSE are harmless. Nevertheless, any abnormality thus detected should immediately be reported to a doctor. Though most breast cancers are detected by women, BSE should be combined with an annual examination by a doctor for better chances of detection. Women can easily miss a breast lump that an expert can find. For the same reasons it is better to learn BSE from an expert. It is not a replacement for more trustworthy techniques like mammography or an examination using MRI.

A woman examines her breast.

Genetic testing
A clinical practice guideline by the US Preventive Services Task Force :

"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. "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.

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"

"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 diagnosed by the examination of surgically removed breast tissue. A number of procedures can obtain tissue or cells prior to definitive treatment for histological or cytological examination. Such procedures include fine-needle aspiration, nipple aspirates, ductal lavage, core needle biopsy, and local surgical excision. These diagnostic steps, when coupled with radiographic imaging, are usually accurate in diagnosing a breast lesion as cancer. Occasionally, pre-surgical procedures such as fine needle aspirate may not yield enough tissue to make a diagnosis, or may miss the cancer entirely. Imaging tests are sometimes used to detect metastasis and include chest X-ray, bone scan, Cat scan, MRI, and PET scanning. While imaging studies are useful in determining the presence of metastatic disease, they are not in and of themselves diagnostic of cancer. Only microscopic evaluation of a biopsy specimen can yield a cancer diagnosis. Ca 15.3 (carbohydrate antigen 15.3, epithelial mucin) is a tumor marker determined in blood which can be used to follow disease activity over time after definitive treatment. Blood tumor marker testing is not routinely performed for the screening of breast cancer, and has poor performance characteristics for this purpose.

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

Summary of stages:
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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)

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+). Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ERnegative tumors, are sensitive to hormonal therapy. 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.

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 earlystage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.

A prognosis is the medical team's "best guess" in how cancer will affect a patient. There are many prognostic factors associated with breast cancer: staging, tumour size and location, grade, whether disease is systemic (has metastasized, or traveled to other parts of the body), recurrence of the disease, and age of patient. Stage is the most important, as it takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. Larger tumours, invasiveness of disease to lymph nodes, chest wall, skin or beyond, and aggressiveness of the cancer cells raise the stage, while smaller tumours, cancer-free zones, and close to normal cell behaviour (grading) lower it. Grading is based on how cultured biopsied cells behave. The closer to normal cancer cells are, the slower their growth and a better prognosis. If cells are not well differentiated, they appear immature, divide more rapidly, and tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used). Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. The presence of estrogen and progesterone receptors in the cancer cell, while not prognostic, is important in guiding treatment. Those who do not test positive for these specific receptors will not respond to hormone therapy.

Likewise, HER2/neu status directs the course of treatment. Patients whose cancer cells are positive for HER2/neu have more aggressive disease and may be treated with trastuzumab, a monoclonal antibody that targets this protein.

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. 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.

Most people understand breast cancer as something that happens in the breast. However it can metastasise (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. 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.

Breast cancer may be one of the oldest known forms of cancer tumors in humans. The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization.The writing says about the disease, "There is no treatment." For centuries, physicians described similar cases in their practises, with the same sad conclusion. It wasn't until doctors achieved greater understanding of the circulatory system in the 17th century that they could establish a link between breast cancer and the lymph nodes in the armpit. The French surgeon Jean Louis Petit (1674-1750) and later the Scottish surgeon Benjamin Bell (1749-1806) were the first to remove the lymph nodes, breast tissue, and underlying chest muscle. Their successful work was carried on by William Stewart Halsted who started performing mastectomies in 1882. He became known for his Halsted radical mastectomy, a surgical procedure that remained popular up to the 1970s.

In medicine, mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. Mastectomy is usually done to treat breast cancer; in some cases, women and some men believed to be at high risk of breast cancer have the operation prophylactically, that is, to prevent cancer rather than treat it. It is also the medical procedure carried out to remove breast cancer (tissue) in males. Alternatively, certain patients can choose to have a wide local excision (also called a lumpectomy), an operation in which a small volume of breast tissue containing the tumor and some surrounding healthy tissue is removed to conserve the breast. Both mastectomy and lumpectomy are what are referred to as "local therapies" for breast cancer, targeting the area of the tumor, as opposed to systemic therapies such as chemotherapy, hormonal therapy, or immunotherapy. Traditionally, in the case of breast cancer, the whole breast was removed. Currently the decision to do the mastectomy is based on various factors including breast size, number of lesions, biologic aggressiveness of a breast cancer, the availability of adjuvant radiation, and the willingness of the patient to accept higher rates of tumor recurrences after lumpectomy and radiation. Outcome studies comparing mastectomy to lumpectomy with radiation have suggested that routine radical mastectomy surgeries will not always prevent later distant

secondary tumors arising from micro-metastases prior to discovery, diagnosis, and operation.

Mastectomy indications:
Despite the increased ability to offer breast-conservation techniques to patients with breast cancer, there exist certain groups who may be better served by traditional mastectomy procedures including:
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women who have already had radiation therapy to the affected breast women with 2 or more areas of cancer in the same breast that are too far apart to be removed through 1 surgical incision, while keeping the appearance of the breast satisfactory women whose initial lumpectomy along with (one or more) re-excisions has not completely removed the cancer women with certain serious connective tissue diseases such as scleroderma, which make them especially sensitive to the side effects of radiation therapy pregnant women who would require radiation while still pregnant (risking harm to the fetus) women with a tumor larger than 5 cm (2 inches) that doesn't shrink very much with neoadjuvant chemotherapy women with a cancer that is large relative to her breast size male breast cancer patients

Types of mastectomy:
There are a variety of types of mastectomy in use, and the type that a patient decides to undergo (or whether he or she will decide instead to have a lumpectomy) depends on factors such as size, location, and behavior of the tumor (if there is one), whether or not the surgery is prophylactic, and whether or not the patient intends to undergo reconstructive surgery.

Simple mastectomy (or "total mastectomy"): In this procedure, the entire breast tissue is removed, but axillary contents are undisturbed. Sometimes the "sentinel lymph node"--that is, the first axillary lymph node that the would be expected to drain into--is removed. This surgery is sometimes done bilaterally (on both breasts) on patients who wish to undergo mastectomy as a cancer-preventative measure. Patients who undergo simple mastectomy can usually leave the hospital after a brief stay. Frequently, a drainage tube is inserted during surgery in their chest and attached to a small suction device to remove subcutaneous fluid. These are usually removed several days after surgery as drainage decrease to less than 20-30 ml per day. illustration

Modified radical mastectomy: The entire breast tissue is removed along with the axillary contents (fatty tissue and lymph nodes). illustration Radical mastectomy (or "Halsted mastectomy"): First performed in 1882, this procedure involves removing the entire breast, the axillary lymph nodes, and the pectoral tissue behind the breast. This procedure is more disfiguring than a modified radical mastectomy and provides no survival benefit for most tumors. This operation is now reserved for tumors involving the pectoralis major muscle or recurrent breast cancer involving the chest wall. illustration Skin-sparing mastectomy: In this surgery, the breast tissue is removed through a conservative incision made around the areola (the dark part surrounding the nipple). The increased amount of skin preserved as compared to traditional mastecomy resections serves to facilitate breast reconstruction procedures. Patients with cancers that involve the skin, such as inflammatory cancer, are not candidates for skin-sparing mastectomy. illustration Quadrantectomy, or partial mastectomy: Like a lumpectomy, this is considered a form of breast conservation therapy. However, a quadrantectomy involves removal of more breast tissue than a lumpectomy--up to a quarter of the breast may be removed, whereas a lumpectomy removes only the tumor and a margin of surrounding tissue. Subcutaneous mastectomy: Breast tissue is removed, but the nippleareola complex is preserved. This procedure was historically done only prophylactically or with mastecomy for benign disease over fear of increased cancer development in retained areolar ductal tissue. Recent series suggest that it may be an oncologically sound procedure for tumors not in the subareolar position.

Breast Reconstruction
Breast reconstruction is the rebuilding of a breast, usually in women. It involves using autologous tissue or prosthetic material to construct a natural-looking breast. Often this includes the reformation of a natural-looking areola and nipple. This procedure involves the use of implants or relocated flaps of the patient's own tissue.

There are many methods for breast reconstruction. The two most common are:

Tissue Expander - Breast implants This is the most common technique used in worldwide. The surgeon inserts a tissue expander, a temporary silastic implant, beneath a pocket under the pectoralis major and serratus anterior muscles of the chest wall. The pectoral muscles may be released along its inferior edge to allow a larger, more supple pocket for the expander at the expense of thinner lower pole soft tissue coverage. The use of acellular human or animal dermal grafts have been described as an onlay patch to increase coverage of the implant when the pectoral muscle is released, which purports to improve both functional and aesthtic outcomes of implant-expander breast reconstruction. [1] [2] o In a process that can take weeks or months, saline solution is percutaneously injected to progressively expand the overlaying tissue. Once the expander has reached an acceptable size, it may be removed and replaced with a more permanent implant. Reconstruction of the areola and nipple are performed in a separate operation after the skin has stretched to its final size. Flap reconstruction The second most common procedure uses tissue from other parts of the patient's body, such as the back, buttocks, thigh or abdomen. This procedure may be performed by leaving the donor tissue connected to the original site to retain its blood supply (the vessels are tunnelled beneath the skin surface to the new site) or it may be cut off and new blood supply may be connected. o The latissimus dorsi muscle flap is the donor tissue available on the back. It is a large flat muscle which can be employed without significant loss of function. It can be moved into the breast defect still attached to its blood supply under the arm pit (axilla). A latissimus flap is usually used to recruit soft-tissue coverage over an underlying implant. Enough volume can be recruited occasionally to reconstruct small breasts without an implant. o Abdominal flaps The abdominal flap for breast reconstruction is the TRAM flap or its technically distinct variants the DIEP/SIEP flaps. Both use the abdominal tissue between the umbilicus and the pubis. The DIEP and free-TRAM flaps require advanced microsurgical technique and are less common as a result. Both can provide enough tissue to reconstruct large breasts. The contour of the lower abdomen is reliably improved by these procedures which remove the same tissue as an abdominoplasty (tummy tuck.) TRAM flap procedures may weaken the abdominal muscles, but are usually tolerated well in most patients. To prevent muscle weakness and incisional hernias, the portion of abdominal wall exposed by reflection of the rectus abdominis muscle may be strengthened by a piece of surgical mesh placed over the defect and sutured in place. The DIEP (deep inferior epigastric perforator flap) and SIEA (superficial inferior epigastric artery flap) require precise dissection of small perforating vessels through the rectus muscle, and purport the advantage of less weakening of the

abdominal wall. Other total autologous tissue breast reconstruction donor sites include the buttocks (superior or inferior gluteal artery perforator flaps (SGAP or IGAP)). The purpose of perforator flaps (DIEP, SIEA, SGAP, IGAP) is to provide sufficient skin and fat for an aesthetic reconstruction while minimizing deficit in the underlying muscles. The TRAM Flap Procedure

Raising the flap and Identification of the target The result of the transposing it to the target and donor sites reconstruction site

Other considerations:
Nipple reconstruction is usually delayed until after the breast mound reconstruction is completed so that the positioning can be planned precisely. There are several methods of reconstructing the nipple-areolar complex, including:

Nipple-Areolar Composite Graft (Sharing) - if the contralateral breast has not been reconstructed and the nipple and areolar are sufficiently large, tissue may be harvested and used to recreate the nipple-areolar complex on the reconstructed side. Local Tissue Flaps - a nipple may be created by raising a small flap in the target area and producing a raised mound of skin. To create an areola, a circular incision may be made around the new nipple and sutured back again. The nipple and areolar region may then be tattooed to produce a realistic colour match with the contralateral breast.

Local Tissue Flaps With Use of AlloDerm - as above, a nipple may be created by raising a small flap in the target area and producing a raised mound of skin. AlloDerm (cadaveric dermis) can then be inserted into the core of the new nipple acting like a "strut" which may help maintain the projection of the nipple for a longer period of time. The nipple and areolar region may then be tattooed later.

One of the challenges in breast reconstruction is to match the reconstructed breast to the mature breast on the other side (often fairly 'ptotic' - droopy.) This often requires a lift (mastopexy), reduction, or augmentation of the other breast.

Follow-up and Recovery:
Recovery from implant-based reconstruction is generally faster than with flapbased reconstructions, but both take at least three to six weeks to recover and both require follow-up surgeries in order to construct a new areola and nipple. All recipients of these operations should refrain from strenuous sports, overhead lifting and sexual activity during the recovery period (three to six weeks). TRAM flap patients can show abdominal muscle weakness on EMG studies, but clinically most patients return to normal activities after recovery. There is little information about upper body exercise post-mastectomy. Issues such as simple mastectomy, mastectomy with reconstruction, mastectomy with lymph node excision and reconstruction all factor into limitations to amount and extent of upper body exercise. Generally, cardiac exercise (treadmill, walking, etc.) are approved for rehabilitation post-surgery and for weight control. Women who have undergone breast reconstruction must still be followed for local or regional recurrence of their cancer with manual exams of the breast/chest wall and axilla.

Breast Implant / Prosthesis
A breast implant is a prosthesis used to enlarge the size of a woman's breasts (known as breast augmentation, breast enlargement, mammoplasty enlargement, augmentation mammoplasty or the common slang term boob job) for cosmetic reasons; to reconstruct the breast (e.g. after a mastectomy; or to correct genetic deformities), or as an aspect of male-to-female sex reassignment surgery. According to the American Society of Plastic Surgeons, breast augmentation is the most commonly performed cosmetic surgical procedure in the United States. In 2006, 329,000 breast augmentation procedures were performed in the U.S. There are two primary types of breast implants: saline-filled and silicone-gel-filled implants. Saline implants have a silicone elastomer shell filled with sterile saline liquid. Silicone gel implants have a silicone shell filled with a viscous silicone gel.

There have been several alternative types of breast implants developed, such as polypropylene string or soy oil, but these are uncommon and not recommended.

Breast implants are used for:
• • •

primary augmentation (to increase breast size for cosmetic reasons) revision-augmentation (revision surgery to correct or improve the result of an original breast augmentation surgery) primary reconstruction (to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality) revision-reconstruction (revision surgery to correct or improve the result of an original breast reconstruction surgery)

The surgical procedure for breast augmentation takes approximately one to two hours. Variations in the procedure include the incision type, implant material, and implant pocket placement.

Incision Types:
Breast implants for augmentation may be placed via various types of incisions:

Inframammary - an incision is placed below the breast in the inframammary fold (IMF). This incision is the most common approach and affords maximum access for precise dissection and placement of an implant. It is often the preferred technique for silicone gel implants due to the longer incisions required. This method can leave slightly more visible

scars in smaller breasts which don't drape over the IMF. In addition, the scar may heal thicker. Periareolar - an incision is placed along the areolar border. This incision provides an optimal approach when adjustments to the IMF position or mastopexy (breast lift) procedures are planned. The incision is generally placed around the inferior half, or the medial half of the areola's circumference. Silicone gel implants can be difficult to place via this incision due to the length of incision required (~ 5cm) for access. As the scars from this method occur on the edge of the areola, they are often less visible than scars from inframammary incisions in women with lighter areolar pigment. There is a higher incidence of capsular contracture with this technique. Transaxillary - an incision is placed in the armpit and the dissection tunnels medially. This approach allows implants to be placed with no visible scars on the breast and is more likely to consistently achieve symmetry of the inferior implant position. Revisions of transaxillary-placed implants may require inframammary or periareolar incisions (but not always). Transaxillary procedures can be performed with or without an endoscope. Transumbilical (TUBA) - a less common technique where an incision is placed in the navel and dissection tunnels superiorly. This approach enables implants to be placed with no visible scars on the breast, but makes appropriate dissection and implant placement more difficult. Transumbilical procedures may be performed bluntly or with an endoscope (tiny lighted camera) to assist dissection. This technique is not appropriate for placing silicone gel implants due to potential damage of the implant shell during blunt insertion. Transabdominoplasty (TABA) - procedure similar to TUBA, where the implants are tunneled up from the abdomen into bluntly dissected pockets while a patient is simultaneously undergoing an abdominoplasty procedure.

Types of implants:

 Silicone gel implants  Saline-filled breast implants

 post-operative bleeding (hematoma)

         

fluid collections (seroma) surgical site infection breast pain alterations in nipple sensation interference with breast feeding visible wrinkling asymmetric appearance wound dehiscence (with potential implant exposure) thinning of the breast tissue synmastia (disruption of the natural plane between breasts)

NURSING INTERVENTIONS: For patient undergoing Mastectomy
Preoperative Management:
• General measures
The nurse provides genereal preoperative teaching measures in regard to what the patient can expect after surgery. Instruction for the patient undergoingmastectomy and lymph node dissection should cover information that is specific for this procedure. The nurse reviews the expected incision line and the type of dressing, drains, and drainage collection device anticipated. If breast reconstruction is to be performed immediately, The loction of the donor tissue is indicated(upper back area or lower abdomen). If implant is to be used , the nurse clarifies postion and placement guidelines. The patient should be informed that movement of the arm and shoulder on the affected side will be limited for the first 24hours and that the arm and hand will be elevated on a pillow to facilitate lymphatic and venous drainage. Return demonstration of breathing exercise and turning techniques prepare the patient for a greater understanding of and participation in postoperative recovery.

• Resolution of conflict related to treatment decision
It is important that the physician and the nurse provide unbiased and accurate information on each option.

• Promoting self-esteem
The nurse must assess each patient for indications of potential sexuality concerns and intimate relationship problems in the preoperative time period. Identification of problems and referral for counseling may facilitate a more rapid sexual adjustment and a more positive self concept.

Postoperative Management:

• General postoperative information
Adequate information must be provided so that the patient has full understanding of each intervention and staff expectations regarding her involvement and cooperation throughout hospitalization.

• Promoting comfort/rest/nutrition
 Instructing the patient to get out of the bed from the unaffected side will lessen pain and tension on the operative site.  Numbness, tingling, changes in skin sensitivity of the chest wall and phantom breath sensations, informed the client that these changes are common and expected outcomes after surgery.  The patient is encourage to resume her normal eating patterns as soon as possible.

• • • • • •

Promoting mobility of the arm and shoulder Preventing Infection Assisting with the grief and adaptation process Teaching for effective Home Management Teaching wound Care Instruction for arm/shoulder exercises
     Ball squeezing Pulley motion Hand wall climbing Back Scratcher Elbow pull-in

• Assessment and management of lymphedema • Strategies to prevent trauma and infection

Fibroadenoma of the breast is an encapsulated benign tumor characterized by proliferation of both glandular and stromal elements. A fibroadenoma is usually diagnosed through clinical examination, ultrasound, mammography and often a biopsy sample of the lump. Their incidence declines with increasing age, and they generally appear before the age of 30 years,

probably partly as a result of normal estrogenic hormonal fluctuation. It is found most often in teenagers and the incidence is increased slightly in those taking hormonal contraception. A fibroadenoma is not commonly associated with fibrocystic breast disease and has no known links to cancer. Usually the tumor is solitary, multiple tumors accounting for 10-15% of all fibroadenoma cases. The tumor is not fixed to the adjacent skin, muscle, or lymph nodes, so they are mobile within the breast on palpation. It is commonly found immediately adjacent to the areola, though rarely directly behind the nipple. The tumours are slightly more common on the left breast than on the right, possibly for reasons associated with blood flow or arm and shoulder activity, most people being righthanded. Some malignant breast tumors can be mistaken for a fibroadenoma, so it is important for them to be diagnosed by a doctor. On average, when the diagnostic pathway has been completed, about 5% of these lumps are diagnosed a malignant tumour, and not as a fibroadenoma.

Macroscopically The tumor is round or ovoid, elastic, nodular, and has a well demarcated capsule; on cut surface it is grey-white. Microscopically The epithelial proliferation describes duct-like spaces surrounded by a fibroblastic stroma. The proliferated epithelium is typical. Depending on the amount and the relationship between these two components, there are two main histological features: intracanalicular and pericanalicular. Often, both types are found in the same tumor. Intracanalicular fibroadenoma: stromal proliferation predominates and compresses the ducts, which are irregular, reduced to slits. Pericanalicular fibroadenoma: fibrous stroma proliferates around the ductal spaces, so that they remain round or oval, on cross section. The basement membranes is intact.

A fibroadenoma is a benign tumor and sometimes surgery is not needed when the diagnosis is certain especially in a younger woman. When the diagnosis is in doubt, and particularly in older women the tumor is generally surgically removed. Larger fibroadenomas are generally also removed. No medications are used for the treatment of fibroadenoma.


When the woman discovers a breast mass, her primary concern is always a diagnosis of cancer. Reassurance that most breast lesions are not malignant should be avoided. Only the final pathology report will provide this reassurance. Before the surgical removal of the fibroadenoma, the nurse prepares the woman for the type of surgery to be performed, what to expect during the procedure, and how to care for the incision afterward. Practice of BSE should be encouraged, as well as the reporting of any unusual changes found during the examination.

There are two forms of Mastitis: ACUTE and CHRONIC. The acute form is a rare condition almost always found in breast-feeding mothers diuring the first 4 months of lactation. It occurs most frequently from Staphylococcus Aureus or S. epidermidis infection that spread from a break in the skin surface of the nipple to underlying breast tissue. It may confide to quadrant of the breast, Symptoms include a fissured nipple, fever, localized tenderness, and erythema. Purulent drainage may be present. The chronic form of Mastitis can follow acute mastitisor have a slow insidious onset. Both acute and chronic mastitis are caused by the same bacterial agents. The chronic form occurs most often in older wome, and the symptoms can mimic inflammatory breast cancer. The infection usually arises in the sweat or sebaceous glands and spreads to the breast. Symptoms of Chronic mastitis include a painful breast mass that involves the nipple and the areola and that causes a low grade fever.

In both acute and chronic mastitis there are edema and congestion of the periductal and interlobular stromata. The ducts are distended from the accumulation of neutrophils and retained secretions. If an abscess forms, its central core may be necotic and contain creamy, yellow exudat. Fibrosis of the involved tissue can develop after treatmen. Both acute and chronic forms of mastitis can mimic inflammatory breast carcinoma, but recent lactation usually excludes the acute form and the nedd for further evaluation.Fibrosis of the involved tissue can develop after treatment.

Acute mastitis is easy to diagnose in a nursing mother after pregnancy. Treatment with antibiotics will resolve the infectious process. In older women, because the has similarities to inflammatory breast carcinoma, aspiration of the inflammatory exudates should be performed to determine the cause. Antibiotics can then be prescribed.

When acute mastitis is the result of an infestion during lactation, most women will immediately stop breast feeding. Women should be informed that discontinuing

breast-feeding is not always necessary or advisable. It is believed that continued breast-feeding reduces the pain and lessens the volume of milk that can be a source for bacterial growth. If breast feeding is discontinued, however the woman should be instructed to keep her breast empty as possible by pumping.

 is the development of abnormally large mammary glands in males resulting in breast enlargement, which can sometimes cause secretion of milk. The condition can occur physiologically in neonates, in adolescents, and in the elderly. In adolescent boys the condition is often a source of distress, but for the large majority of boys whose pubertal gynecomastia is not due to obesity, the breast development shrinks or disappears within a couple of years. The causes of common gynecomastia remain uncertain, although it has generally been attributed to an imbalance of sex hormones or the tissue responsiveness to them; a root cause is rarely determined for individual cases. Breast prominence can result from hypertrophy of breast tissue, chest adipose tissue and skin, and is typically a combination. Breast prominence due solely to excessive adipose is often termed pseudogynecomastia or sometimes lipomastia.

An obese teenage male w/ Gynecomastia.

Physiologic gynecomastia occurs in neonates, at or before puberty and with aging. Many cases of gynecomastia are idiopathic, meaning they have no clear

cause. Potential pathologic causes of gynecomastia are: medications including hormones, increased serum estrogen, decreased testosterone production, androgen receptor defects, chronic kidney disease, chronic liver disease, HIV, and other chronic illness. Gynecomastia as a result of spinal cord injury and refeeding after starvation has been reported. In 25% of cases, the cause of the gynecomastia is not known. Medications cause 10-20% of cases of gynecomastia in post-adolescent adults. These include cimetidine, omeprazole, spironolactone, imatinib mesylate, finasteride and certain antipsychotics. Some act directly on the breast tissue, while others lead to increased secretion of prolactin from the pituitary by blocking the actions of dopamine (prolactin-inhibiting factor/PIF) on the lactotrope cell groups in the anterior pituitary. Androstenedione, used as a performance enhancing food supplement, can lead to breast enlargement by excess estrogen activity. Medications used in the treatment of prostate cancer, such as antiandrogens and GnRH analogs can also cause gynecomastia. Marijuana use is also thought by some to be a possible cause; however, published data is contradictory. Increased estrogen levels can also occur in certain testicular tumors, and in hyperthyroidism. Certain adrenal tumors cause elevated levels of androstenedione which is converted by the enzyme aromatase into estrone, a form of estrogen. Other tumors that secrete hCG can increase estrogen. A decrease in estrogen clearance can occur in liver disease, and this may be the mechanism of gynecomastia in liver cirrhosis. Obesity tends to increase estrogen levels. Decreased testosterone production can occur in congenital or acquired testicular failure, for example in genetic disorders such as Klinefelter Syndrome. Diseases of the hypothalamus or pituitary can also lead to low testosterone. Abuse of anabolic androgenic steroids (AAS) has a similar effect. Mutations to androgen receptors, such as those found in Kennedy disease can also cause gynecomastia. Although stopping these medications can lead to regression of the gynecomastia, surgery is sometimes necessary to eliminate the condition. Repeated topical application of products containing lavender and tea tree oils among other unidentified ingredients to three prepubescent males coincided with gynecomastia; it has been theorised that this could be due to their estrogenic and antiandrogenic activity. However, other circumstances around the study are not clear, and the sample size was insignificant so serious scientific conclusions cannot be drawn.

The condition usually can be diagnosed by examination by a physician. Occasionally, imaging by X-rays or ultrasound is needed to confirm the diagnosis. Blood tests are required to see if there is any underlying disease causing the gynecomastia.

Treating the underlying cause of the gynecomastia may lead to improvement in the condition. Patients should talk with their doctor about revising any medications that are found to be causing gynecomastia; often, an alternative medication can be found that avoids gynecomastia side-effects, while still treating the primary condition for which the original medication was found not to be suitable due to causing gynecomastia side-effects (e.g., in place of taking spironolactone the alternative eplerenone can be used.) Selective estrogen receptor modulator medications, such as tamoxifen and clomiphene, or androgens or aromatase inhibitors such as Letrozole are medical treatment options, although they are not universally approved for the treatment of gynecomastia. Endocrinological attention may help during the first 2-3 years. After that window, however, the breast tissue tends to remain and harden, leaving surgery (either liposuction, gland excision, skin sculpture, reduction mammoplasty, or a combination of these surgical techniques) the only treatment option. Many American insurance companies deny coverage for surgery for gynecomastia treatment on the grounds that it is a cosmetic procedure. Radiation therapy is sometimes used to prevent gynecomastia in patients with prostate cancer prior to estrogen therapy. Compression garments can camouflage chest deformity and stabilize bouncing tissue bringing emotional relief to some. There are also those who choose to live with the condition.

The nurse who cares for men with Gynecomastia must offer sympathetic understanding. The nurse should be aware that a variety of drugs, other than hormones, can increase male breast size. These include digitalis, thiazides and spironolactone. Men should be porewarned of this side effect.

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