Breast Cancer

Breast Cancer is the most common female cancer with approximately 194,000 new cases diagnosed each year in the United States. More than 70% of breast cancers occur in women who are 50 years of age and older. The incidence of breast cancer increases with age, beginning slowly between ages of 45 and 50 years of age, and steadily rises each year thereafter. Breast cancers is the leading cause of cancer deaths for women between 20 and 59 years of age.

There is no single cause of breast cancer. This type of cancer is a heterogeneous disease, resulting from many causes. The following are the most common suspected factors that may increase the probability of a woman having breast cancer:

• Gender: 99% of the cases occur in women, with only 1% occurring in the male population
• Age: risk increases with age
• Personal History of breast cancer: threefold to fourfold increased risk of a second primary cancer
• Family History of breast cancer: the risk is greater if the affected relative is on the maternal side of the family, two first-degree relatives are affected, the related has bilateral breast cancer, or the relative’s breast cancer was diagnosed before the age of 50 years
• Hormonal Factors: postmenopausal obesity, early menarche (before the age of 12) and late menopause (after the age of 50), nulliparity, first term pregnancy after 30 or 35 years of age, use of oral contraceptives before the age of 20, lasting 6 or more years, hormone replacement therapy with estrogen plus progestin
• History of ionizing radiation
• Genetic influences: BRCAl, BRCA2, CHEK2 thought to activate BRCAl, TP53 germ line mutations, EMSY thought to interact with BRCA2
• Ingestion of 15g of alcohol daily or 2 drinks per day

Anatomy of the Breast:
The breast is made up of lobules, ducts, fatty tissue, blood vessels, lymph vessels, muscles and nerves. The lobules are tiny sacs that make milk during breast feeding. There are approximately one million lobules in each breast. The ducts are tubes that carry the milk from the lobules to the nipple. The fatty tissue surrounds the lobules and ducts to provide support. The lymph vessels carry lymph to lymph nodes in the underarm, above the collarbone, and in the chest. The billions of cells that form not only the breast, but also other tissues and organs are made and replaced on a regular basis. During the process of making new cells, the old cells die and are replaced by new cells. Occasionally, cells are replaced by abnormal cells that grow in an uncontrolled way. This abnormal growth process produces an abnormal growth or lump that forms a tumor. These tumors can be either benign (non-cancerous) or malignant (cancerous). The benign tumors have cells that do not spread to other parts of the body. The malignant tumors have cells that do spread from breast tissue to other parts or organs of the body.

Types of Brest Cancer:
There are 24 distinct histological types of breast cancer that can be divided into two categories:

1. Non-invasive Breast Cancer: Approximately 85% of these are DCIS (dutal carcinoma in situ) where the cancer cells are found only in the ducts. If the DCIS is not treated, then it may progress to invasive cancer. In LCIS (lobular carcinoma in situ) the cancer cells are found only in the lobules of the breast. It is a warning sign of having an increased risk of getting an invasive breast cancer in the same or opposite breast.
2. Invasive Breast Cancer: Invasive breast cancer can penetrate through normal breast tissue such as the ducts and lobules and invade surrounding areas. Having invasive breast cancer is more serious than the non-invasive cancers because they can spread to other parts of the body. There are several types of invasive cancers, including invasive ductal carcinoma that accounts for about 80% of all breast cancer cases.
3. Inflammatory Breast Cancer: this is an aggressive type of breast cancer that has different symptoms than other types of breast cancer. There is redness, warmth, and swelling which is caused by the blockage of lymph vessels by cancer cells. Unfortunately in 1/3 of the cases, the cancer has already spread to the lymph nodes at the time of diagnosis. IBC is less common. The risk factors are poorly understood, but we do know that IBC tends to occur in younger women, and is more common in African American women.

Prognostic Factors:
There are factors that are critical in determining the appropriate treatment of a women’s breast cancer.

1. Tumor size: increase risk of recurrence with increasing size.
2. Hormone status:  Estrogen receptor (ER) and Progesterone receptor (PR) negative tumors are associated with a worse prognosis than if a woman has a ER+ / PR+ status.
3. DNA aneuploid tumors or those with abnormal amount of DNA have a poorer prognosis
4. Axillary lymph node status: prognosis worsens with increased involvement
5. High S-phase fraction predicts poorer outcome
6. Molecular and biological factors that may be associated with loss of functioning of tumor suppression genes, p53 ,nm23, or overexpression of oncogenes like HER-2/neu and epidermal growth factor receptor (EGFR)

Clinical Staging:
Clinical staging is based on the characteristics of the primary tumor, the physical examination of the axilla and distant metastasis. These three factors determine the four stages of breast cancer.

1. Stage I: these patients have a single location of cancer less than 2 cm without any spread to the axillary lymph nodes or distant sites from the breast.
2. Stage II: these patients have a primary cancer that either involves axillary lymph nodes and is less than five cm in size or greater than 2 cm in size and does not involve any axillary lymph nodes.
3. Stage III: these patients have either a primary cancer that measures less than 5 cm in size and causes axillary lymph nodes to be attached to each other or other structures, a primary cancer that is greater than 5cm in size and involves axillary lymph nodes, or a primary cancer that is attached to the chest wall or skin.
4. Stage IV: these patients have a metastatic disease, or a cancer that has spread to the lymph nodes or other parts of the body.

Treatment:

Stage I:
A. Primary treatment is surgery and or radiation
Stage II:
A. Primary treatment is surgery and or radiation
B. Systemic therapy that includes chemotherapy, targeted therapy and hormonal therapy
Stage III:
A. Local therapy is surgery and radiation
B. Systemic therapy is chemotherapy, radiation and hormonal therapy
Stage IV:
A. Hormonal therapy
B. Chemotherapy and targeted therapy
C. Management on bone metastases

Treatment Options:

1. Surgery: the surgical procedures that are utilized in the management of breast cancer are:
   • Biopsy – removal of cells or tissues for further evaluation and to see if the cancer is present.
   • Lumpectomy – Removal of the cancer and a portion of surrounding tissue. Most patients are also treated with radiation to reduce the likelihood of recurrence.
   • Mastectomy – A simple mastectomy is the removal of the entire breast but not the axillary lymph nodes. A partial mastectomy involves the removal of ¼ or more of the breast and the lining of the chest wall. A radical mastectomy is an aggressive therapy that consists of extensive removal of the entire breast, lymph nodes under the arm and the chest wall muscles under the breast. A modified radical mastectomy involves the removal of the entire and lymph nodes in the axilla under the arm.
   • Axillary lymph node evaluation – This dissection has been the standard of care and involves the removal of approximately 10-25 axillary lymph nodes. The removal of these nodes is associated with better outcomes for treatment, but is also commonly associated with complications such as lymph edema (the buildup of lymph fluid in the tissues under the skin), buildup of bacteria in the skin, and inflammation that leads to pain on the side of the surgery. The Sentinel Node biopsy is the newer approach to evaluate the lymph nodes. It involves removing a single lymph node, or the sentinel node which is the first lymph node to collect excess fluid surrounding the cancer. A blue dye is injected near the cancer and the dye will drain from the area containing the cancer to the nearby lymph nodes through the sentinel node.
   • Breast Reconstruction – This involves the artificial creation of a breast by using a breast implant alone, reconstruction of the breast with the patient’s own tissue, or by a combination of both.
2. Radiation: After surgery, breast conserving or not, radiation may be given to achieve local control and to reduce the risk of a local recurrence. There are new operative approaches such as Mammosite or Savy that provide targeted radiation therapy to the tumor bed while reducing radiation exposure to healthy tissue. Radiation is also used in palliative treatment for bone pain with metastatic disease.
3. Chemotherapy: Chemotherapy is a pharmacological approach to destroying the cancer cells. This is akin to an insurance policy to assure that the microscopic cells that we can’t see will be destroyed forever. It also may be given to reduce the size of a tumor before surgery, to eliminate occult tumor cells after primary surgery or for palliation in the patient with metastatic disease. Some of the most commonly known agents used in the adjuvant (after surgery) to the neoadjuvant (prior to surgery) are doxorubicin, epirubicin, paclitaxel, docetaxel, cyclophosphamide, fluorouracil and methotrexate. Research shows that the inclusion of the chemotherapy drug doxorubicin in adjuvant chemotherapy increases the number of women that can expect to survive without evidence of cancer compared to combination chemotherapy without doxorubicin.
4. Adjuvant hormonal therapy: This therapy targets either estrogen or progesterone. Estrogen causes some cancers to grow. The breast is composed of cells that contain estrogen receptors. When the cells that have estrogen receptors become cancerous, exposure to estrogen increases the cancer’s growth. These groups of drugs can inhibit estrogen production or block the receptor. There are now two different hormonal therapies, Tamoxifen, which is given to pre-menopausal women, and aromatase inhibitors that are given to post-menopausal women. If a women expresses the Her-2/neu, there is a biological therapy that selectively targets this gene.

Prevention:
Breast cancer screening includes both clinical and self-evaluations!!

1. Screening mammograms between the ages of35 and 40 years, every 1-2 years between the ages of 40 and 49 years, and then every year after 50 years of age.
2. The ACS (American Cancer Society) recommends a clinical breast exam by a health care professional at least every 3 years between 20 and 39 years of age.
3. The ACS recommends instruction and education about self breast exam (SBE) for women beginning at the age of 20. The Mammosite or BSE pad as improved effectiveness.
4. Prophylactic mastectomy and oophorectomy are appropriate for women with a high genetic risk for development of breast cancer.

The following was adapted from the following resources:
Newton, S., Hickey, M., and Marrs, J. Oncology Nursing Advisor. 2009, Mosby Inc.
AstraZeneca. Understanding Beast Cancer and Treatment Options. 2008 AsraZeneca, Inc.
There were also various other magazine articles referenced.