Male Breast Cancer

Breast cancer

Breast cancer is a cancer that starts in the breast, usually in the inner lining of the milk ducts or lobules. There are different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup. With best treatment, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs (hormone therapy and chemotherapy), and radiation.[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] In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).[3]

Breast cancer is about 100 times as frequent among women as among men, but survival rates are equal in both sexes.[4][5][6]

Some breast cancers require the hormones estrogen and progesterone to grow, and have receptors for those hormones. Those cancers are treated with drugs that interfere with those hormones, usually tamoxifen, and with drugs that shut off the production of estrogen in the ovaries or elsewhere; this may damage the ovaries and end fertility. Low-risk, hormone-sensitive breast cancers may be treated with hormone therapy and radiation alone. Breast cancers without hormone receptors, or which have spread to the lymph nodes in the armpits, or which express certain genetic characeristics, are higher-risk, and are treated more aggressively. One standard regimen, popular in the U.S., is cycophosphamide plus doxorubicin (Adriomycin), known as CA; these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. An equivalent treatment, popular in Europe, is cyclophosphamide, methotrexate, and fluorouracil (CMF).[7] Monoclonal antibodies, such as trastuzumab, are used for cancer cells that have the HER2 mutation. Radiation is usually added to the surgical bed to control cancer cells that were missed by the surgery, which usually extends survival, although radiation exposure to the heart may cause damage and heart failure in the following years.[8]

Classification

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

  • Pathology - Each tumor is classified by its histological (microscopic anatomy) appearance and other criteria.[9]
  • 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. This considers the Tumor itself, whether it has spread to lymph Nodes, and whether there are any Metastases to locations other than the breast and lymph nodes.

Breast cancer is usually, but not always, primarily 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.[10] In the future, some pathologic classifications may be changed.

Breast cancer  Signs and symptoms

The first symptom, or subjective sign, of breast cancer is typically a lump that feels different from the rest of the breast tissue. According to the The Merck Manual, more than 80% of breast cancer cases are discovered when the woman feels a lump.[11] According to the American Cancer Society, the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram.[12] Lumps found in lymph nodes located in the armpits[11] 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 ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.[11][12][13]

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.[11]

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.[14]

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. Common sites of metastasis include bone, liver, lung and brain.[15] 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.[16]

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.[17]

Breast cancer  Risk factors

The primary risk factors that have been identified are sex,[18] age,[19] childbearing, hormones,[20] a high-fat diet,[21] alcohol intake,[22][23] obesity,[24] and environmental factors such as tobacco use, radiation[25], endocrine disruptors and shiftwork.[26] However, studies of environmental and lifestyle factors only attribute a small increase in breast cancer to each factor. Furthermore, these studies are not randomized, controlled trials, and so they may associate breast cancer with factors that don't actually cause breast cancer.[original research?]

No cause is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes.[27] 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.[28]

  • Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast.
  • Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk.
  • Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia and lobular carcinoma in situ [LCIS]) increases the risk of breast cancer.
  • Race: Breast cancer is diagnosed more often in Caucasian women than Latina, Asian, or African American women.
  • No physical activity: Women who are physically inactive throughout life may have an increased risk of breast cancer. Being active may help decrease risk.
  • Tamoxifen may interact unfavorably with certain antidepressants when used for prevention of breast cancer recurrence.[29]
  • Abortion-breast cancer hypothesis: Mainstream organizations such as the American Cancer Society and National Cancer Institute have concluded there is no link between induced abortion and breast cancer, although a minority of doctors continue to disagree.

Breast cancer  Diagnosis

While screening techniques discussed above are useful in determining the possibility of cancer, a further testing is necessary to confirm whether a lump detected on screening is cancer, as opposed to a benign alternative such as a simple cyst.

In a clinical setting, breast cancer is commonly diagnosed using a "triple test" of clinical breast examination (breast examination by a trained medical practitioner), mammography, and fine needle aspiration cytology. Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also identify any other lesions. Fine Needle Aspiration and Cytology (FNAC), which may be done in a GP's office using local anaesthetic if required, involves attempting to extract a small portion of fluid from the lump. Clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, these three tools can be used to diagnose breast cancer with a good degree of accuracy.

Other options for biopsy include core biopsy, where a section of the breast lump is removed, and an excisional biopsy, where the entire lump is removed.

Breast cancer  Treatment

The mainstay of breast cancer treatment is surgery. Adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor) is given when the tumor expresses estrogen receptors or progesterone receptors. Chemotherapy is given for more advanced stages of disease. Monoclonal antibodies are sometimes used, especially for HER2-positive tumors. Radiotherapy is given after surgery to the region of the tumor bed, to destroy microscopic tumors that may have escaped surgery. Treatments are constantly being evaluated in randomized, controlled trials, to evaluate and compare individual drugs, combinations of drugs, and surgical and radiation techniques. The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology and St. Gallen, Switzerland.[citation needed] These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests that predict breast cancer recurrence risk based on gene expression. In February 2007, the first breast cancer predictor test won 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.[35]

Radiation therapy 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. [36]

In 2008, the American College of Surgeons Oncology Group began a National Cancer Institute funded study to explore the success of cryoablation therapy in the treatment of Invasive Breast Carcinoma. The Visica 2TM Treatment System from Sanarus Technologies was chosen as the exclusive cryoablation treatment technology for the study, which is currently in Phase 2. [37]