February 5, 2009

Breast Cancer Overview – January 2008


Breast cancer is a common malignancy, with ~180,000 new cases diagnosed in the United States each year.1 The disease occurs most frequently in women and rarely, in men. The breasts are glands that produce and release milk in women in association with pregnancy. Breast cancer develops from cells in the breast.

The normal breast has 6 to 9 overlapping sections called lobes and within each lobe are several smaller lobules that contain the cells that produce milk. The lobes and lobules are linked by thin tubes called ducts, which lead to the nipple in the center of the breast. The spaces around the lobules and ducts are filled with fat. Lymph vessels carry colorless fluid called lymph, which contains important immune cells. The lymph vessels lead to small bean-shaped structures called lymph nodes. Clusters of lymph nodes are found in the axilla (under the arm), above the collarbone, and in the chest.

The suspicion of breast cancer first arises when a lump is detected in the breast during breast examination or a suspicious area is identified during screening mammography. In order to diagnose the cause of the suspicious area or lump in the breast, a physician will perform a biopsy. A biopsy can be performed on an outpatient basis. During a biopsy, a physician removes cells for examination in the laboratory to determine whether cancer is present. Other information obtained from the biopsy sample will play an important role in treatment decisions. If the biopsy indicates that cancer is present, additional surgery may be performed after the patient and doctor select a course of treatment.

There are many types of breast tumors. Some breast tumors are benign (not cancerous). Benign breast tumors such as fibroadenomas or papillomas do not spread outside of the breast and are not life threatening. Other breast tumors are malignant (cancerous). The most common type of breast cancer is called ductal carcinoma and begins in the lining of the ducts. Another type of cancer is called lobular carcinoma, which arises in the lobules.

Personalized Cancer Care Center

When cancer is identified in the biopsy specimen, several other tests may be performed on the specimen in order to further classify the cancer and determine the optimal treatment strategy. Based on the stage of the cancer and the results of these tests, treatment of breast cancer is personalized for each individual. Treatment may involve surgery, radiation therapy, chemotherapy, targeted therapy, and/or hormonal therapy.


: Stage is a measure of the extent of the cancer, and is based on the size of the tumor and the presence or absence of lymph node metastases and distant metastases. Determining the stage of the cancer may require a number of procedures, such as blood tests, chest x-rays, mammography, computed tomography (CT), or magnetic resonance imaging (MRI). For patients with early-stage cancer, the spread of the cancer to the axillary (under the arm) lymph nodes may be assessed through either sentinel lymph node biopsy or axillary lymph node dissection. Axillary lymph node dissection involves the removal of many axillary lymph nodes; the procedure can be associated with chronic side effects such as pain, limited shoulder motion, numbness, and swelling. Sentinel lymph node biopsy is a more recent procedure that involves the removal of only a small number of nodes, or even a single node. If the sentinel lymph nodes are negative (show no evidence of cancer), then no further lymph node surgery is required. Sentinel lymph node biopsy is becoming more widely adopted in the clinical setting for determining whether cancer has spread to the lymph nodes in women with localized breast cancer.

HER2 status:

Twenty to thirty percent of breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells. Fortunately, the development of treatments that specifically target HER2-positive cells – such as Herceptin® (trastuzumab) and Tykerb® (lapatinib) -- has improved outcomes among women with HER2-positive breast cancer. For this reason, HER2 status should be accurately measured on all breast cancers.

Hormone receptor status

: Some breast cancer cells express an abundance of receptors for the female hormones estrogen and/or progesterone.  These cancers-- called hormone receptor-positive --are typically associated with a better prognosis and are treated differently from breast cancers that are hormone receptor-negative.  Patients with hormone receptor-positive breast cancer often receive treatment with hormonal therapy, such as tamoxifen or an aromatase inhibitor. For more information, go to Hormonal Therapy.

Predicting the need for chemotherapy

: Among women with early-stage breast cancer, the expression, or activity, of certain genes has been linked with the likelihood of cancer recurrence and chemotherapy benefit; testing tumor tissue for the expression of these genes can provide important information about prognosis and likely response to treatment.

A genomic test that is included in guidelines from both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) is Oncotype DX®. Based on the expression of 21 genes, this test provides information about recurrence risk and likely chemotherapy benefit among women with newly diagnosed breast cancer that has not spread to the lymph nodes (node-negative) and is hormone receptor-positive. Oncotype DX has also shown promising results in women with node-positive breast cancer.2

For more information about OncotypeDX, visit http://www.mytreatmentdecision.com/

Predicting drug metabolism

: Another type of test that may prove important is the assessment of inherited genetic variation that influences drug metabolism (the processing of drugs by the body). In the case of tamoxifen, for example, differences in effectiveness may be explained at least in part by inherited differences in a gene known as CYP2D6.3 Most people have two functional versions of this gene and are able to effectively process tamoxifen. Some people, however, have versions of this gene that are less effective at processing tamoxifen. Testing patients for these gene variants could help doctors identify patients who are less likely to respond to tamoxifen. A currently available test is AmpliChip®, which assseses CYP2D6 as well as CYP2C19 (another gene involved in drug metabolism). Additional data are required, however, before formal recommendations can be developed about this type of testing.4

For more information about AmpliChip, visit http://www.amplichip.us/.

Learn More

Patients who have already undergone surgery and lymph node evaluation and know their stage of cancer may select from the options below. In order to learn more about surgery and sentinel lymph node dissection, go to Surgical Management of Breast Cancer.

Carcinoma In Situ: Approximately 15-20% of breast cancers are very early in their development. These are sometimes referred to as carcinoma in situ and consist of two types: ductal carcinoma in situ (DCIS), which originates in the ducts and lobular carcinoma in situ (LCIS), which originates in the lobules. DCIS is the precursor to invasive cancer and LCIS is a risk factor for developing cancer.

Stage I: Cancer is confined to a single site in the breast, is less than 2 centimeters (3/4 inch) in size and has not spread outside the breast.

Stage IIA: Cancer has spread to involve underarm lymph nodes and is less than 2 centimeters (3/4 inch) in size or the primary cancer itself is 2-5 centimeters (3/4-2 inches) and has not spread to the lymph nodes.

Stage IIB: Cancer has spread to involve underarm lymph nodes and/or the primary cancer is greater than 5 centimeters (2 inches) in size and does not involve any lymph nodes.

Stage IIIA: Cancer is smaller than 5 centimeters (2 inches) and has spread to the lymph nodes under the arm or the lymph nodes are attached to each other or to other structures or the primary cancer is larger than 5 centimeters (2 inches) and has spread to the lymph nodes under the arm.

Stage IIIB: Cancer directly involves the chest wall or has spread to internal lymph nodes on the same side of the chest.

Inflammatory: Inflammatory breast cancer is a special class of breast cancer that is rare. The breast looks as if it is inflamed because of its red appearance and warmth. The skin may show signs of ridges and wheals or it may have a pitted appearance. Inflammatory breast cancer tends to spread quickly.

Stage IV: Cancer has spread to distant locations in the body, which may include the liver, lungs, bones or other sites.

Recurrent/Relapsed: The breast cancer has progressed or returned (recurred/relapsed) following an initial treatment.


1. American Cancer Society. Cancer Facts & Figures 2007. Available at: http://www.cancer.org/docroot/stt/stt_0.asp (Accessed December 10, 2007).

2. Albain K, Barlow W, Shak S et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal, node-positive, ER-positive breast cancer (S8814,INT0100). Presented at the 30th Annual San Antonio Breast Cancer Symposium. San Antonio, TX, December 13-16, 2007. Abstract #10.

3. Schroth W, Antoniadou L, Fritz P et al. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. Journal of Clinical Oncology. 2007;25:5187-5193.

4. Desta Z, Flockhart DA. Germline pharmacogenetics of tamoxifen response: have we learned enough? Journal of Clinical Oncology. 2007;5147-5149.

Tags: Breast Cancer, Uncategorized