breast cancer

Breast Cancer: Introduction
Breast cancer ranks as one of the leading cancer types in the number of new cases diagnosed and is second only to lung cancer as the the most prevalent cause of cancer death in women. In 2010 the American Cancer Society estimates approximately 209,060 new cases of breast cancer will be diagnosed and 40,230 deaths due to breast cancer will occur in the United States. It is important to note that men also develop breast cancer. Approximately 390 of the estimated deaths due to breast cancer in 2010 will be men.(1)
Below is a list of the information found within this section:
Anatomy of the Breast
Types of Breast Cancer
Risk Factors
Symptoms
Detection and Diagnosis
Pathology Report & Staging
Breast Cancer Tumor Biology
Treatment
Prophylactic Mastectomy, BCO and Mastectomy
Axillary Lymph Node Dissection
Breast Cancer in Men
Triple Negative Breast Cancer
Breast Cancer Resources
FAQs about Breast Reconstruction
Section Summary
References for this page:
Cancer Facts and Figures 2010. American Cancer Society. [http://www.cancerquest.org/multimedia/pdf/facts&figures2010.pdf]

Anatomy of the Breast
In women, the breasts are made up of milk-producing glands (lobules), milk ducts, and connective tissue (stroma). Milk is produced by cells in the lobules and moves from these sacs, through the mammary ducts, to the nipple. Most breast cancers originate in mammary ducts.(1)

Blood and lymphatic vessels are found within the stroma surrounding the lobules and ducts:
Blood vessels are part of the circulatory system. They supply oxygen and nutrients to and remove waste from the cells of the breast.
Lymphatic vessels are part of a large network termed the lymphatic system. These vessels collect and carry fluid and cells from the tissues of the body. Smaller lymphatic vessels merge with larger ones, as streams merge into a river. Large vessels empty into grape-like clusters of lymphatic tissue called lymph nodes. The lymphatic vessels in the breast carry lymphatic fluid to a mass of lymph nodes located near the underarm.
References for this page:
What is Breast Cancer? American Cancer Society (accessed October 2010). [http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_breast_cancer_5.asp]
Breast Cancer: Types
There are several different kinds of breast cancer. However, the majority of breast cancer cases are classified as either in situ or invasive. Both cancer types are described below.

Carcinoma In Situ
Lobular Carcinoma In Situ (LCIS)
Lobular carcinoma in situ describes breast cancer that is confined to the milk-producing glands (lobules) of the breast. Tumors classified as LCIS are made up of small uniform cells that are similar to cells found in breast lobules. LCIS will not progress to invasive breast cancer; therefore it is considered a risk factor for the development of invasive cancer rather than a true precursor. It is also referred to as lobular neoplasia (LN), a more inclusive description that also includes atypical lobular hyperplasia (ALH), another abnormal breast finding (1).
Lobular carcinoma in situ is most commonly found in pre-menopausal women between the ages 40 and 50 (1). It is not usually found on a mammogram and generally does not produce a lump (1). These tumors are usually HER2 negative (-) and ER/PR positive (+) and therefore may be treated with hormone therapy (tamoxifen). Overall LCIS is highly treatable and in many cases continued observation is enough.
Ductal Carcinoma In Situ (DCIS)
Ductal carcinoma in situ describes breast cancer that is confined to the milk ducts of the breast. Tumors classified as DCIS are made up of irregular cells that resemble cells found in the ductal system of the breast. Unlike LCIS, DCIS can be detected on a mammogram and usually does produce a lump. DCIS accounts for 20% of all breast cancers detected with mammography and about 85% of in situ cancers diagnosed each year in the United States. Most cases of DCIS (~98%) will not become metastatic, but around 50% progress to invasive breast cancer (IBC). The progression of DCIS to IBC is not completely understood and because of this treatment recommendations vary. The most common treatment plan for DCIS is breast-conserving surgery with or without radiation.
Recurrence of DCIS is a possibility; therefore prognostic factors are calculated based on nuclear grade (most important factor), cell necrosis, and cell and tumor architecture. 50-75% of DCIS lesions are ER/PR positive and 30-50% of the time (more often in high-grade lesions) HER2 is over-expressed. DCIS that over express HER-2 are associated with a negative prognosis.(2)However, these biological markers cannot fully predict recurrence risk, but may be helpful in follow up observation and treatment planning.
Invasive Breast Carcinoma (IBC)

Left: Pathology slide image of cancerous breast tissue, Right: Tumor (white area) in fatty breast tissue.
Images courtesy: C. Whitaker Sewell, MD - Professor of Pathology, Emory University School of Medicine
Invasive Lobular Carcinoma (ILC)
Invasive lobular carcinoma develops in the milk-producing glands (lobules)of the breast. ILC has the ability to spread to other parts of the body, (most commonly bone, brain, liver, and lungs) either through the bloodstream or the lymphatic system. ILC usually presents as an abnormal feeling breast (most often a thickening) and not as a hard mass that can be felt. ILC is less likely to show up on a mammogram.
Women over the age of 40 have an increased risk of developing invasive lobular carcinoma, with most cases occurring in women between the ages 45-56.

References for this page:
1. Simpson PT, Gale T, Fulford LG, Reis-Filho JS, Lakhani SR. "The diagnosis and management of pre-invasive breast disease: pathology of atypical lobular hyperplasia and lobular carcinoma in situ." Breast Cancer Research (July 2003). 5(5):258-62. [PUBMED]
2. Wiechmann L, Kuerer HM. "The molecular journey from ductal carcinoma in situ to invasive breast cancer." Cancer. 2008 May 15;112(10):2130-42. [PUBMED]

Breast Cancer: Risk Factors
Factors that influence risk of developing breast cancer include:
-Prior History of Breast Disease
-Family History of Breast Disease
-Age
-Race
-Reproductive and Menstrual History
-Radiation Exposure
-Dietary Factors

The relative effects of these and other risk factors in any given case of cancer is variable and very difficult to determine with accuracy at this time. Some of these and other risk factors are discussed on the following pages.
Prior History of Breast Disease
History of breast cancer, regardless of the type, greatly increases an individual's risk for future development of breast cancer. The second occurrence is most likely to be classified as invasive and ductal, rather than a lobular breast cancer.(1) Such women are strongly advised to carefully monitor themselves and receive mammograms on a regular basis.
Family History of Breast Disease
It is possible to inherit defective genes that lead to the development of a familial form of a particular cancer type. Individuals with a family history of breast cancer are therefore at an increased risk of developing the disease. The degree of risk depends upon the type of relative affected. For example, risk is higher if an immediate family member has been diagnosed with breast cancer. The more closely related an individual is to someone with breast cancer, the more likely they will share the same genes that increased the risk of the affected individual. Risk also increases with the number of relatives affected.(1)

Age
Breast cancer risk is low before age 30 and increases with age, leveling off at the age of 80.(1) More information about the relationship between cancer and age can be found in the Cancer Biology section.

Race
African American women are more likely to be diagnosed with early-onset (before age 45) breast cancer compared to white American women. This trend in incidence shifts, however, for women in their fifties. When comparing overall lifetime risk, African American women have a lower risk of developing breast cancer compared to white American women.(2)
Cancer survival rates are greatly affected by the stage at which a cancer is detected. Early-onset cancers are generally more aggressive than cancers that develop later in life. Studies show that African American women have a greater chance of being diagnosed with high-grade and estrogen receptor (ER)-negative tumors. Regardless of their lower overall lifetime risk of developing the disease, African American women have a significantly higher chance of dying from breast cancer than any other ethnic group in the United States.(3)
Reasons for these differences in cancer occurrence and death rate are still unclear. One explanation for the disparity is the socioeconomic differences that exist between ethnic groups. In this view, limited access to health care and clinical trials and the high cost of treatments may account for the higher African American breast cancer death rate. New investigations focused on biological differences, however, suggest that African Americans may develop tumors that are harder to treat. Current research seems to suggest that the disparity in cancer death rate is due to a combination of socioeconomic and genetic factors.(3) Clearly, more work needs to be done in this area.

Reproductive and Menstrual History
Exposure to estrogen is associated with increased breast cancer risk. For this reason, women who experience menarche (begin their menstrual cycle) before age 12 and the onset of menopause at age 55 or older are at an increased risk of developing breast cancer.(1)
On the other hand, women who carry pregnancy to full term at a young age have a decreased risk of developing breast cancer. During pregnancy, maternal hormone levels change drastically. Studies show that some of these hormones may provide anti-estrogen effects, protecting individuals from the negative effects of estrogen. Examples of proteins thought to impact cancer risk include:
Alpha-fetoprotein: Alpha-fetoprotein is a glycoprotein produced by the liver of a developing fetus. Since the protein is at its highest level during the third trimester, a pregnancy that is not carried to full term may not provide a protective effect.(4)
Human Chorionic Gonadotropin (hCG): Human chorionic gonadotropin is a hormone produced by the placenta during pregnancy. The protein is elevated during the first trimester of pregnancy. Experiments with breast cancer cells suggest that the effects of hCG may partially explain the higher rate of breast cancer among nulliparous (non-child bearing) women.(5)

Hormone Replacement Therapy
Hormone replacement therapy (HRT) is often prescribed to control menopausal symptoms that include decreased bone density, sexual dysfunction, fatigue, and mood swings. HRT may include treatment with estrogen alone or a combination of both estrogen and progesterone. Studies indicate that use of menopausal hormone therapy, currently or within the past five years, is associated with an increased risk of developing breast cancer.(6) Several studies have shown that individuals who have stopped using HRT for more than five years are not at a significantly greater risk.(1) Much of the information regarding HRT and breast cancer risks has come from population studies that may be difficult to compare with each other. The actual impact of HRT on breast cancer risk is still under investigation.

Exposure to Diethylstilbestrol

Diethylstilbestrol (DES) is a man-made estrogen that was prescribed between 1947 and 1971 to treat complications associated with pregnancy. Women who ingested this chemical during their pregnancy are at a slightly increased risk of developing breast cancer. Female offspring of women who were exposed to DES have a higher incidence of reproductive problems and cancers of the vagina and cervix.(7)

Radiation Exposure
Exposure to radiation, such as radiation therapy used to treat Hodgkin lymphoma, increases risk of breast cancer throughout the remainder of a woman's lifetime.(1)Relative risk depends on the age at which irradiation occurred, time since treatment, and radiation dose received. Women irradiated at a young age (before age of 30) are at an increased risk of developing breast cancer later in life compared to older women. Advances in therapeutic radiation techniques have resulted in the use of lower doses of radiation and exposure of smaller regions of the body. Such advances will hopefully reduce breast cancer risk due to irradiation therapy in years to come.(8)
Dietary Factors
It is very difficult to identify dietary items that cause a particular cancer. Factors that may increase breast cancer risk include high fat intake, high alcohol consumption, and a diet rich in overcooked meats.
Alcohol: While studies indicate that consumption of one drink per day or less does not increase risk of breast cancer, there is evidence that heavy consumption of alcohol is associated with an increased risk. Findings show that women who consume an average of 4 or more drinks per day, regardless of the type of alcohol, may be at a 50% higher risk of breast cancer than those who do not drink alcohol.(9)
Overcooked Meats: Heterocyclic amines are chemicals formed in the cooking process of meat products such as fish, beef, pork, and chicken. Exposure to high amounts of these chemicals, caused by a diet rich in broiled, grilled, or fried meat, has been correlated with increased risk of breast cancer in women.(10)
References for this page:
--Singletary SE. "Rating the risk factors for breast cancer." Ann Surg (2003); 237(4):474-82. [PUBMED]
--Newman LA, Griffith KA, Jatoi I, Simon MS, Crowe JP, Colditz GA. "Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status." Journal of Clinical Oncology (2006); 24:1342-1349 [PUBMED]
--Whitworth A. "New research suggests access, genetic differences play role in high minority cancer death rate." Journal of the National Cancer Institute (2006); 98(10):669 [PUBMED]
--Lambe M, Trichopoulos D, Hsieh CC, Wuu J, Adami HO, Wide L. "Ethnic differences in breast cancer risk: a possible role for pregnancy levels of alpha-fetoprotein?" Epidemiology (2003);14(1):85-9. [PUBMED]
--Rao CV, Li X, Manna SK, Lei AM, Aggarwal BB. "Human Chorionic Gonadotropin Decreases Proliferation and Invasion of Breast Cancer MCF-7 Cells by Inhibiting NF-kB and AP-1 Activation." J Biol Chem (2004), Vol. 279, Issue 24, 25503-25510. [PUBMED]

Breast Cancer: Symptoms
Symptoms
The American Cancer Society lists the following symptoms associated with breast cancer:
Presence of a lump or thickening in the breast;
Swelling, dimpling, redness, or soreness of skin;
Change in shape or appearance of the nipple; and
Nipple discharge.
References for this page:
American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010. [http://www.cancerquest.org/multimedia/pdf/facts&figures2010.pdf]

Breast Cancer: Treatment
The treatment of breast cancer can be broken down into two categories: early stage and advanced stage. Early stage treatment involves tumors that are confined to the breast. Advanced stage treatment involves tumors that have spread beyond the breast to other regions of the body. Treatment options are dependent upon size of tumor, location, physical condition of patient, and stage of cancer.
As our focus is on the biology of the cancers and their treatments, we do not give detailed treatment guidelines. Instead, we link to organizations in the U.S. that generate the treatment guidelines.
The National Comprehensive Cancer Network (NCCN) lists the following treatments for breast cancer:
Surgery
Radiation Therapy
Chemotherapy
Hormone Therapy
SERMs
Monoclonal Antibody Therapy
Herceptin®