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Dr. RISHIKESH MAJUMDER

SONGSOPTOK THE WRITERS BLOG | 12/10/2014 |





What is breast cancer? Breast cancers are malignant tumors that arise from the uncontrolled growth of cells in the breast. They occur primarily in the ducts that transport milk to the nipple during breast feeding (lactation) and secondarily in the lobules, the glands that produce milk. Thumbnail diagram of the breast. Each breast cancer will have its own characteristics. Some are slow-growing; others can be aggressive. Some are sensitive to the hormones estrogen and progesterone, while others can over-express certain proteins. The cancer's characteristics can affect treatment choices and the potential for the cancer to recur. Each year, more women in the United States are diagnosed with breast cancer than with any other cancer, with the exception of skin cancer. The American Cancer Society (ACS) estimates that 230,480 new cases of invasive breast cancer will be diagnosed in women in the U.S. in 2011 and that about 39,520 women will die from the disease. Men can also develop the disease. ACS estimates that about 2,140 men will be diagnosed with breast cancer in 2011, and about 450 men will die. The rest of this article will focus on breast cancer in women. It is recommended that men who have been diagnosed with breast cancer speak to their doctor for information specific to them and see the ACS's web site All About Breast Cancer in Men.


RISK IN BREAST CANCER


Breast cancer can develop at any age, but the risk of developing it increases as women get older. While 5% to 10% of breast cancers are related to an inherited defect in one of two breast cancer genes (BRCA1 or BRCA2), the majority of cases develop for reasons we do not yet understand. As a general rule, some of those at higher risk of developing breast cancer include women: With close relatives (mother, sister, aunt) who have had the disease. Who have had a cancer in the other breast.
Who have not had children. Who had their first child after the age of-30. A healthy lifestyle that includes regular exercise, maintaining a healthy body weight, and avoiding alcohol may help to minimize the risk of developing breast cancer. Research studies continue to identify factors that are associated with an increased or decreased risk of developing the disease, but there is no single set of actions that will cause or prevent breast cancer. The most important factors in breast cancer risk are family history (genetics) and exposure to estrogen. Women should work with their doctor to determine their personal risk factors and how to best address them. For example, a woman may choose to avoid long-term use of hormone replacement therapy (HRT). Women who are at high risk of developing breast cancer may be able to take the drug tamoxifen to reduce their risk. However, tamoxifen can increase the risk of developing blood clots, endometrial (uterine) cancer, and possibly cardiovascular disease, so the decision to take the medication needs to be weighed carefully. A doctor can help assess the risks and benefits of such treatment.


For those women who have the gene mutation (BRCA1 and BRCA2) frequently associated with breast cancer, prophylactic mastectomy is an option. Women electing this option choose to have both breasts removed before developing cancer rather than run the high risk of developing the disease later in their lifetime. Studies have shown that such surgery can reduce the risk of developing breast cancer by approximately 90%. Other women elect to have a prophylactic mastectomy on their cancer-free breast after developing cancer in the other breast. A doctor can help advise and work with a woman who is considering prophylactic mastectomy.

SIGNS AND SYMPTOMS


It is important to remember that most lumps found in the breast are not cancerous but are benign and that the symptoms and signs associated with breast cancer may be due to other causes. Some signs and symptoms include:

Mass or lump in the breast
Breast skin dimpling, reddening, or thickening
Nipple retraction
Breast swelling or pain
Nipple pain and/or discharge
Swelling or lumps in adjacent underarm lymph node
A rare form of breast cancer, inflammatory breast cancer (IBC), does not form a lump. Some of the symptoms of this condition can be similar to those of a breast infection, with warmth, tenderness, breast swelling, itching, and ridged thickened skin.


EARLY DETECTION

Breast cancer that is detected and treated in its earliest stages can be cured over 90% of the time. The primary early detection tools are breast self-exams, clinical breast exams, and mammograms. The American Cancer Society (ACS) recommends that: Women age 20 and older consider doing a breast self-exam every month. Women in their 20s and 30s should have a clinical breast exam by a health care professional as part of their regular physical at least every three years. Women age 40 and over should have a yearly mammogram. The medical community recognizes the value of mammography in breast cancer screening, but there is not universal consensus on how often it should be done or when it should be started. The U.S. Preventive Services Task Force updated its recommendations on the use of these screening methods in November of 2009. Based on their scientific review, they no longer recommend screening mammograms for women under the age of 50 and they recommend routine mammography every 2 years for women ages 50-74.


In July 2011, The American College of Obstetricians and Gynecologists (ACOG) issued new breast cancer screening guidelines that recommend mammography screening be offered annually to women starting at age 40. This replaces their previous recommendations for mammograms every one to two years starting at age 40 and annually beginning at age 50. Women should work with their doctors to assess their risk of developing breast cancer and to determine how often screening should be done. Women with certain risk factors may be advised to begin screening at an earlier age and may be advised to be screened more frequently, with additional testing such as imaging scans. For more information on self breast exams, go to the American Cancer Society web site.

LABORATORY TESTS

Laboratory tests for breast cancer can be broken down into groups, based on the purpose of testing: To determine genetic risk in high risk women: blood testing for mutations that may be present in the BRCA1 and BRCA2 genes. To diagnose: cytology - a microscopic examination of tumor cells obtained through fine needle aspiration and surgical pathology - a microscopic examination of tissue sampling via biopsy
To determine treatment options: evaluation of the tumor's HER2/neu gene amplification status and estrogen and progesterone receptor status
To monitor treatment and for recurrence: measurement of CA 15-3 or CA 27.29 in the blood. Some tests for breast cancer are performed on the woman's blood; others are done on a sample of cells or the tumor tissue.


GENETIC RISK: BRCA1 or BRCA2 gene mutation - Women who are at high risk because of a personal or strong family history of early onset breast cancer or ovarian cancer can find out if they have a BRCA gene mutation. A mutation in either gene indicates that the person is at significantly higher lifetime risk (up to 80%) for developing the disease. It is important to remember, however, that only about 5% to 10% of breast cancer cases occur in women with a BRCA gene mutation. Genetic counseling should be considered both before testing takes place and after receiving positive test results. Diangosis: cytology and surgical pathology.When a radiologist detects a suspicious area, such as hardened tissue (calcifications) or a non-palpable mass on a mammogram, or if a lump has been found during a clinical or self-exam (see Non-Laboratory Tests below), a doctor will frequently order a needle or surgical biopsy or a fine needle aspiration. In each case, a small sample of tissue is taken from the suspicious area of the breast so that a pathologist can examine the cells microscopically for signs of cancer. This pathological examination is done to determine whether the lesion is benign or malignant. Malignant cells show changes or deviations from normal cells. Signs include changes in the size, shape, and appearance of cell nuclei and evidence of increased cell division. Malignant cells can also distory the normal arrangement of cells within breast tissue. Pathologists can diagnose cancer based upon the observed changes, determine how abnormal the cells appear, and see whether there is a single type of change or a mixture of changes. These results help guide breast cancer treatment. Needle aspiration evaluations are limited due to the small sample that is obtained. A tissue biopsy is needed to determine if a cancer is early stage or invasive. When a breast cancer is surgically removed (see Treatment), cells from the tumor and sometimes from adjacent tissue and lymph nodes are examined by the pathologist to help determine how far the cancer has spread.

TREATMENT OPTIONS:

If the pathologist's diagnosis is breast cancer, there are several tests that may be performed on the tissue cancer cells. The results of these tests provide a prognosis and help the oncologist (cancer specialist) guide the woman's treatment. The most useful of these are HER-2/neu and estrogen and progesterone receptors. HER2/neu is an oncogene associated with cell growth. Normal epithelial cells contain two copies of the HER2/neu gene and produce low levels of the HER2 protein on the surface of their cells. In about 20-30% of invasive breast cancers, the HER2/neu gene is amplified and its protein is over-expressed. These tumors are susceptible to treatment that specifically binds to this over-expressed protein. The chemotherapeutic agent Herceptin® (tastuzumab) blocks the protein receptors, inhibiting continued replication and tumor growth. Women with amplified HER2/neu gene respond well to Herceptin® and have a good prognosis. Estrogen and progesterone receptor (ER and PR) status are important prognostic markers. Breast cancer cells that have estrogen and/or progesterone receptors can bind estrogen and progesterone. These female hormones promote cell growth and can "feed" ER- and PR-positive cancers. The higher the percentage of cancer cells that are positive, as well as the greater the intensity (the number of receptors per cell), the better the prognosis. This is because hormone-dependant cancers frequently respond well to hormonal therapy.


MONITOR TREATMENT:

Blood tests may be used to help determine whether or not the tumor is responding to therapy or if it has recurred. Some may be ordered on women who are at a high risk of developing breast cancer to determine whether their risk has a genetic component. CA15-3 (or CA 27.29) is a tumor marker that may be ordered at intervals after treatment to help monitor a person for breast cancer recurrence. It is not used as a screen for breast cancer but can be used to follow it in some women once it has been diagnosed.


OTHER TESTS:

There are several tests available, and many others being researched, that evaluate large numbers of genetic patterns in breast cancer tumor tissue. These tests are being investigated as predictive tests for the recurrence of breast cancer and therapy outcome. The American Society of Clinical Oncology (ASCO) mentioned several of them in its recent "2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer" and some have been included in the National Comprehensive Cancer Network's 2011 Breast Cancer Treatment Guidelines. In most cases, the tests were deemed promising, but data to support their routine clinical use were still thought to be insufficient. Examples of tests being ordered by some doctors include: Oncotype DX® - ASCO indicates that this test, which measures 21 genes, can be used to predict risk of cancer recurrence in those who have been newly diagnosed with early breast cancer, have cancer-negative lymph nodes, have estrogen receptor positive tumors, and are taking the drug tamoxifen. MammaPrint® test - in use in Europe and recently cleared by the FDA for use in the U.S. This test evaluates gene activity patterns in 70 tumor genes. It may be used to help predict whether a breast cancer will recur and/or metastasize in women who have early stage cancer, are under the age of 61, and have cancer-negative lymph nodes. There are additional tests that may be used in some breast cancer cases, such as DNA ploidy, Ki-67, or other proliferation markers. However, most authorities believe that HER2/neu, estrogen and progesterone receptor status are the most important to evaluate first. The other tests do not have therapeutic implications and, when compared with grade and stage of the disease, are not independently significant with respect to prognosis. Some medical centers use these tests for additional information in evaluating patients, making it important to discuss the value of these tests with your cancer management team.

NON-LABORATORY TESTS

In addition to laboratory tests, there are non-laboratory tests that are equally important. These include:

Mammography is widely recommended as a screening tool. A screening mammogram uses X-ray technology to produce an image of the breasts and can reveal breast cancer up to two years before a lump is large enough to be felt during a clinical or self-exam. Newer technologies, such as digital mammography and computer-aided detection, may yield a clearer image than a mammography in some cases. In particular, younger women, whose breast tissue is often too dense to show tumors clearly on the X-ray film used for a standard mammogram, may benefit from ultrasound exams or magnetic resonance imaging (MRI).

[Dr. RISHIKESH MAJUMDER]





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