Breast cancer is the second most lethal cancer in women. (Lung cancer is the leading cancer killer in women.) The good news is that early detection and new treatments have improved survival rates. Unfortunately, women in lower social and economic groups still have significantly lower survival rates than women in higher groups.
Several factors are used to determine the risk for recurrence and the likelihood of successful treatment. They include:
- Location of the tumor and how far it has spread
- Whether the tumor is hormone receptor-positive or -negative
- Tumor markers
- Gene expression
- Tumor size and shape
- Rate of cell division
Women are now living longer with breast cancer. Breast cancer mortality rates have declined by about 25% since 1990. This decline may be due to better screening and better treatment options. However, survivors must live with the uncertainties of possible recurrent cancer and some risk for complications from the treatment itself.
Recurrences of cancer usually develop within 5 years of treatment. About 25% of recurrences and half of new cancers in the opposite breast occur after 5 years.
Location of the Tumor
The location of the tumor is a major factor in outlook:
- If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (node negative), the 5-year survival rates with treatment are up to 98%.
- If the cancer has spread to the lymph nodes or beyond the primary tumor site (node positive), the 5-year survival rate is about 84%.
- If the cancer has spread (metastasized) to other sites (most often the lung, liver, and bone), the average 5-year survival rate is 23%. New drug therapies, particularly aromatase inhibitors, have helped prolong survival for women with metastatic (stage IV) cancer.
The location of the tumor within the breast is an important predictor. Tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.
Hormone Receptor-Positive or -Negative
Breast cancer cells may contain receptors, or binding sites, for the hormones estrogen and progesterone. Cells containing these binding sites are known as hormone receptor-positive cells. If cells lack these connectors, they are called hormone receptor-negative cells. About 75% of breast cancers are estrogen receptor-positive (ER-positive, or ER+). About 65% of ER-positive breast cancers are also progesterone receptor-positive (PR-positive, or PR+). Cells that have receptors for one of these hormones, or both of them, are considered hormone receptor-positive.
Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to hormone therapy such as tamoxifen or aromatase inhibitors. Hormone receptor-negative tumors are referred to as "hormone insensitive" or "hormone resistant."
Women have a better prognosis if their tumors are hormone receptor-positive because these cells grow more slowly than receptor-negative cells. In addition, women with hormone receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors can be treated only with chemotherapy.) Recent declines in breast cancer mortality rates have been most significant among women with estrogen receptor-positive tumors, due in part to the widespread use of post-surgical hormone-blocking therapy.
Tumor markers are proteins found in blood or urine when cancer is present. Although they are not used to diagnose cancer, the presence of certain markers can help predict how aggressive a patient’s cancer may be and how well the cancer may respond to certain types of drugs.
Tumor markers relevant for breast cancer prognosis include:
HER2. The American Cancer Society recommends that all women newly diagnosed with breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2-positive cancer usually occurs in younger women and is more quickly-growing and aggressive than other types of breast cancer. The HER2 marker is present in about 20% of cases of invasive breast cancer. Two types of tests are used to detect HER2:
- Immunohistochemistry (IHC)
- Fluorescence in-situ hybridization (FISH)
Either test may be used as long as it is performed by an accredited laboratory. Tests that are not clearly positive or negative should be repeated.
Treatment with trastuzumab (Herceptin) or lapatinib (Tykerb) may help women who test positive for HER2. In 2008, the FDA approved a new genetic test (Spot-Light) that can help determine which patients with HER2-positive breast cancer may be good candidates for trastuzumab treatment.
Other Markers. Other markers that may be evaluated include CA 15-3, CA 27.29, CEA, ER, PgR, uPA, and PAI-1.
Gene Expression Profiling
Gene expression profiling tests (Oncotype DX, MammaPrint) examine a set of genes in tumor tissue to determine the likelihood of breast cancer recurrence. These tests are also used to help determine whether adjuvant (following surgery) drug treatments should be given. The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend that gene expression profiling tests be administered to newly diagnosed patients with node-negative, estrogen-receptor-positive breast cancer (only Oncotype DX is approved for this use). Based on the results, a doctor can decide whether a patient who has had surgery may benefit from chemotherapy.
Other Factors for Predicting Outlook
Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.
Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide. The higher the MI, the more aggressive the cancer. Other tests measure cells at a certain phase of their division.
Effect of Emotions and Psychological Support
Recent evidence has not supported early reports of survival benefits for women with metastatic breast cancer who engage in support groups. However, some studies have suggested that psychotherapy, group support, or both may relieve pain and reduce stress, particularly in women who are suffering emotionally.
Stress has been ruled out as a risk factor either for breast cancer itself or for its recurrence.