Login | Register

Breast Cancer



Breast Cancer

Breast Cancer

Breast cancer refers to cancers originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; while those originating from lobules are known as lobular carcinomas. There are many different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup; survival varies greatly depending on those factors. Computerized models are available to predict survival (see CancerMath.net)

With best treatment, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs (hormonal therapy and chemotherapy), and radiation.

Breast cancer is about 100 times more common in women than in men, but survival rates are equal in both sexes.

Some breast cancers require the hormones estrogen and progesterone to grow, and have receptors for those hormones. After surgery those cancers are treated with drugs that interfere with those hormones (see tamoxifen), and with drugs that shut off the production of estrogen in the ovaries or elsewhere; this may damage the ovaries and end fertility. After surgery, 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 characteristics, are higher-risk, and are treated more aggressively.

Contents

Signs and Symptoms
Causes
Diagnosis
Pathogenesis/Pathophysiology
Prevention
Treatment
Complications
References

Signs and Symptoms

Back to Top

Mammograms showing a normal breast (left) and a breast cancer (right).

Mammograms showing a normal breast (left) and a breast cancer (right).

Early breast cancer can, in some cases, present as breast pain (mastodynia) or a painful lump. Since the advent of breast mammography, breast cancer is most frequently discovered as an asymptomatic nodule on a mammogram, before any symptoms are present. A lump under the arm or above the collarbone that does not go away may be present.

When breast cancer has invaded the dermal lymphatics – small lymph vessels of the skin, its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer. In inflammatory breast cancer, the breast cancer is blocking lymphatic vessels and this can cause pain, swelling, warmth, and redness throughout the breast, as well as an orange peel texture to the skin referred to as peau d’orange. Although there may have been no previous signs of breast cancer and the cancer might be missed in screening mammograms, Inflammatory Breast Cancer is at least locally advanced at presentation (LABC) and Stage IIIB. Immediate staging tests are required to rule out distant metastes which might already be present making it Stage IV.

Changes in the appearance or shape of the breast can raise suspicions of breast cancer.

Another reported symptom complex of breast cancer is Paget’s disease of the breast. This syndrome presents as eczematoid skin changes at the nipple, and is a late manifestation of an underlying breast cancer.

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

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. Pleural effusions are not uncommon with metastatic breast cancer. Obviously, these symptoms are “non-specific,” meaning they can also be manifestations of many other illnesses.

Causes

Back to Top

Risk Factors

Many women who develop breast cancer have no risk factors other than age and sex.

  • Gender is the biggest risk because breast cancer occurs mostly in women.
  • Age is another critical factor. Breast cancer may occur at any age, though the risk of breast cancer increases with age. The average woman at age 30 years has one chance in 280 of developing breast cancer in the next 10 years. This chance increases to one in 70 for a woman aged 40 years, and to one in 40 at age 50 years. A 60-year-old woman has a one in 30 chance of developing breast cancer in the next 10 years.
  • White women are slightly more likely to develop breast cancer than African American women in the U.S.
  • A woman with a personal history of cancer in one breast has a three- to fourfold greater risk of developing a new cancer in the other breast or in another part of the same breast. This refers to the risk for developing a new tumor and not a recurrence (return) of the first cancer.

Genetic Causes

Family history has long been known to be a risk factor for breast cancer. Both maternal and paternal relatives are important. The risk is highest if the affected relative developed breast cancer at a young age, had cancer in both breasts, or if she is a close relative. First-degree relatives, (mother, sister, daughter) are most important in estimating risk. Several second-degree relatives (grandmother, aunt) with breast cancer may also increase risk. Breast cancer in a male increases the risk for all his close female relatives. Having relatives with both breast and ovarian cancer also increases a woman’s risk of developing breast cancer.

There is great interest in genes linked to breast cancer. About 5-10% of breast cancers are believed to be hereditary, as a result of mutations, or changes, in certain genes that are passed along in families.

BRCA1 and BRCA2 are abnormal genes that, when inherited, markedly increase the risk of breast cancer to a lifetime risk estimated between 40 and 85%. Women with these abnormal genes also have an increased likelihood of developing ovarian cancer. Women who have the BRCA1 gene tend to develop breast cancer at an early age.

Hormonal Causes

Hormonal influences play a role in the development of breast cancer.

  • Women who start their periods at an early age (11 or younger) or experience a late menopause (55 or older) have a slightly higher risk of developing breast cancer. Conversely, being older at the time of the first menstrual period and early menopause tend to protect one from breast cancer.
  • Having a child before age 30 years may provide some protection, and having no children may increase the risk for developing breast cancer.
  • Oral contraceptives have not been shown to definitively increase or decrease a woman’s lifetime risk of breast cancer.
  • A large study conducted by the Women’s Health Initiative showed an increased risk of breast cancer in postmenopausal women who were on a combination of estrogen and progesterone for several years. Therefore, women who are considering hormone therapy for menopausal symptoms need to discuss the risk versus the benefit with their health-care providers.

Lifestyle and Dietary Causes

Breast cancer seems to occur more frequently in countries with high dietary intake of fat, and being overweight or obese is a known risk factor for breast cancer, particularly in postmenopausal women.

  • This link is thought to be an environmental influence rather than genetic. For example, Japanese women, at low risk for breast cancer while in Japan, increase their risk of developing breast cancer after coming to the United States.
  • Several studies comparing groups of women with high- and low-fat diets, however, have failed to show a difference in breast cancer rates.

The use of alcohol is also an established risk factor for the development of breast cancer. The risk increases with the amount of alcohol consumed. Women who consume two to five alcoholic beverages per day have a risk about one and a half times that of nondrinkers for the development of breast cancer. Consumption of one alcoholic drink per day results in a slightly elevated risk.

Studies are also showing that regular exercise may actually reduce a woman’s risk of developing breast cancer. Studies have not definitively established how much activity is needed for a significant reduction in risk. One study from the Women’s Health Initiative (WHI) showed that as little as one and a quarter to two and a half hours per week of brisk walking reduced a woman’s breast cancer risk by 18%.

Benign Breast Disease

Fibrocystic breast changes are very common. Fibrocystic breasts are lumpy with some thickened tissue and are frequently associated with breast discomfort, especially right before the menstrual period. This condition does not lead to breast cancer. However, certain other types of benign breast changes, such as those diagnosed on biopsy as proliferative or hyperplastic, do predispose women to the later development of breast cancer.

Environmental Causes

Radiation treatment increases the likelihood of developing breast cancer but only after a long delay. For example, women who received radiation therapy to the upper body for treatment of Hodgkin’s disease before 30 years of age have a significantly higher rate of breast cancer than the general population.

Diagnosis

Back to Top

Digital tomosynthesis

Digital tomosynthesis

An abnormal area on a mammogram, a lump, or other changes in the breast can be caused by cancer or by other, less serious problems. To find out the cause of any of these signs or symptoms, a woman’s doctor does a careful physical exam and asks about her personal and family medical history. In addition to checking general signs of health, the doctor may do one or more of the breast exams described below.

  • Palpation. The doctor can tell a lot about a lump—its size, its texture, and whether it moves easily—by palpation, carefully feeling the lump and the tissue around it. Benign lumps often feel different from cancerous ones.
  • Mammography. X-rays of the breast can give the doctor important information about a breast lump. If an area on the mammogram looks suspicious or is not clear, additional x-rays may be needed.
  • Ultrasonography. Using high-frequency sound waves, ultrasonography can often show whether a lump is solid or filled with fluid. This exam may be used along with mammography.

Based on these exams, the doctor may decide that no further tests are needed and no treatment is necessary. In such cases, the doctor may need to check the woman regularly to watch for any changes. Often, however, the doctor must remove fluid or tissue from the breast to make a diagnosis.

Aspiration or needle biopsy. The doctor uses a needle to remove fluid or a small amount of tissue from a breast lump. This procedure may show whether a lump is a fluid-filled cyst (not cancer) or a solid mass (which may or may not be cancer). Using special techniques, tissue can be removed with a needle from an area that is suspicious on a mammogram but cannot be felt.

If tissue is removed in a needle biopsy, it goes to a lab to be checked for cancer cells. Clear fluid removed from a cyst may not need to be checked by a lab.

Surgical biopsy. The surgeon cuts out part or all of a lump or suspicious area. A pathologist examines the tissue under a microscope to check for cancer cells.

Pathogenesis/Pathophysiology

Back to Top

In a normal state, cells proliferate in response to external proliferation-promoting signals to fulfill a function such as replacing lost cells or repairing injured tissues. Once the goal has been reached, a set of proliferation-repressing signals is activated. These signals allow the cells to exit the proliferation cycle (cell cycle) by returning to the dormant state (G0), by differentiating, or by dying (apoptosis). Each of these functions is carried out by a complex system of interacting proteins. Constitutive expression by mutation or another genetic change of any component of the proliferation-promoting system may result in uncontrolled proliferation. The constitutively expressed component is called an oncogene.

Conversely, the loss by mutation or deletion of a proliferation-repressing gene results in an inability to stop the cell cycle and, thereby, continuous proliferation, possibly leading to cancer. The lost gene is called a tumor suppressor gene. Likewise, constitutive expression of antiapoptotic genes may result in immortalization of the cell, paving the way for further genetic changes and eventually cancer formation. Loss of proapoptotic genes may lead to similar results. Thus, autonomous proliferation and immortality shared by all cancers are the final result of successive genetic changes, which may be different from one cancer to another.

Breast cancer is not an exception in that regard. It is the result of multiple genetic changes that are different from those of other malignancies and that confer to this cancer its characteristic phenotype.

Breast cancer invades locally and spreads initially through the regional lymph nodes, bloodstream, or both. Metastatic breast cancer may affect almost any organ in the body—most commonly, lungs, liver, bone, brain, and skin.

Most skin metastases occur near the site of breast surgery; scalp metastases also are common. Metastatic breast cancer frequently appears years or decades after initial diagnosis and treatment.

Estrogen and progesterone receptors, present in some breast cancers, are nuclear hormone receptors that promote DNA replication and cell division when the appropriate hormones bind to them. Thus, drugs that block these receptors may be useful in treating tumors with the receptors. About 2/3 of postmenopausal patients have an estrogen-receptor positive (ER+) tumor. Incidence of ER+ tumors is lower among premenopausal patients.

Another cellular receptor is human epidermal growth factor receptor 2 (HER2; also, HER2/neu or ErbB2); its presence correlates with a poorer prognosis at any given stage of cancer.

Prevention

Back to Top

The most important risk factors for the development of breast cancer are sex, age, and genetics. Because women can do nothing about these risks, regular screening is recommended in order to allow early detection and thus prevent death from breast cancer.

Regular screening includes breast self-examination, clinical breast examination, and mammography.

Breast self-examination (BSE) is cheap and easy. Routine monthly examination may be helpful. Previously considered critical, more recent studies suggest that self breast exam may be less valuable than previously thought, especially for women who are having routine clinical breast examination and/or mammography.

  • For women who are menstruating, the best time for examination is immediately after the monthly period.
  • For women who are not menstruating or whose periods are extremely irregular, picking a certain date each month seems to work best.
  • Instruction in the technique of breast self-examination can be obtained from your health-care provider or from any one of several organizations interested in breast cancer.

Clinical breast examination: The American Cancer Society recommends a breast examination by a trained health-care provider once every three years starting at age 20 years, and then yearly after age 40 years.

Mammograms are recommended every one to two years starting at age 40 years. For women at high risk for the development of breast cancer, mammogram screening may start earlier, generally 10 years prior to the age at which the youngest close relative developed breast cancer.

Obesity after menopause and excessive alcohol intake may increase the risk of breast cancer slightly. Physically active women may have a lower risk. All women are encouraged to maintain normal body weight, especially after menopause and to limit excess alcohol intake. Hormone replacement should be limited in duration if it is medically required.

Occasionally, a woman at very high risk for development of breast cancer will decide to have a preventive or prophylactic mastectomy to avoid developing breast cancer. Additionally, removal of the ovaries has shown to reduce the risk of developing breast cancer in women who have the BRCA1 mutation and who have their ovaries surgically removed before they reach age 40.

Treatment

Back to Top

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.

Complications

Back to Top

References

Back to Top

1. “Merck Manual Online, Breast Cancer”.

2. CancerMath.net Calculates survival with breast cancer based on prognostic factors and treatment. From the Laboratory for Quantitative Medicine, Massachusetts General Hospital.

3. “Male Breast Cancer Treatment”. National Cancer Institute. 2006. Retrieved 2006-10-16.

4. “Breast Cancer in Men”. Cancer Research UK. 2007. Retrieved 2007-11-06.

5. “What Are the Key Statistics About Breast Cancer in Men?”. American Cancer Society. September 27, 2007. Retrieved 2008-02-03.

6. “eMedicineHealth.com, Breast Cancer”.

, , , , , , , ,

One Response to “Breast Cancer”

Leave a Reply

Your email address will not be published. Required fields are marked *