A recent study by Dr. Ayman Linjawi of the Royal Victoria Hospital in Montreal, Quebec, Canada reveals that the expression of the mutant bcl-2 gene and p53 tumor suppressor in women with early stage breast cancer may lead to treatment with tamoxifen and chemotherapy, preventing more invasive surgical procedures such as lumpectomy or mastectomy.
Dr. Linjawi and colleagues analyzed the frequency of mutant bcl-2 and p53 in 75 women with Stage I breast cancer (cancer that has not spread to the lymph nodes) and found a significant correlation between the expression of bcl-2 and the status of the hormone receptors of the breast cancer cells. Breast cancer cells contain several receptors that attract hormones such as estrogen. Estrogen binds to the cells’ receptors and causes the cells to grow and multiply quickly. The study also found that the expression of the mutant p53 tumor suppressor predicts a poor prognosis for women with early breast cancer.
Dr. Linjawi suggests that patients who express mutant bcl-2 are good candidates for treatment with tamoxifen. Tamoxifen is an "anti-estrogen" and works by binding to estrogen receptors. Tamoxifen is formally known as a selective estrogen receptor modulator (SERM). Anti-estrogens compete with estrogen to bind to estrogen receptors. SERMs have estrogen-like affects on bone (they help increase bone density ), but SERMs are estrogen antagonists (anti-estrogens) that block or inhibit estrogen affects in the breast and uterus. By blocking estrogen in the breast, anti-estrogen agents slow the growth and reproduction of breast cancer cells. Tamoxifen has been used for over twenty years in patients with advanced breast cancer and has recently been granted FDA approval for use in patients with earlier stages of the disease or in women at high risk for breast cancer.
Additionally, Dr. Linjawi and colleagues found the Stage I breast cancer patients who had the mutant p53 tumor suppressor had an average survival rate of 74% after five years compared with a survival rate of 83% who did not have the mutant p53. Dr. Meterissian, a colleague of Dr. Linjawi, commented that early-stage breast cancer patients with the mutant p53 tumor suppressor should be considered for chemotherapy to increase breast cancer survival. Chemotherapy is treatment with a combination of anticancer drugs injected intravenously (into the vein) or orally (by mouth).
Presently, many women with Stage 0 or Stage I breast cancer undergo lumpectomy (removal of a breast lump and margin of surrounding tissue) with radiation therapy or mastectomy (removal of the affected breast). Less invasive procedures, such as chemotherapy or tamoxifen may prove to be as effective if more women are tested for mutations of bcl-2 and p53 as soon as the cancer is detected. Presently, women with early stage breast cancer are usually only tested for mutations of BRCA1 and BRCA2 genes.
Researchers are currently trying to further determine if tamoxifen is effective in preventing breast cancer in women at high risk for the disease. At its annual meeting in May 1999, held in Atlanta, the American Society of Clinical Oncology (ASCO) reported the results of a large study sponsored by the National Cancer Institute. The study analyzed 13,388 breast cancer patients given either tamoxifen or a placebo (an inactive substance given as if it were a real drug). In the subset of more than 2,000 women with lobular carcinoma in situ or atypical hyperplasia, those who took tamoxifen were 66% to 86% less likely to develop breast cancer within five years, compared with those who took the placebo. Typically, women with either condition are at a 6% increased risk of developing breast cancer. Click here for more information on the ASCO report .
The new STAR clinical trial (Study of Tamoxifen And Raloxifene) is being run to compare the long-term safety of raloxifene (a SERM similar to tamoxifen) and tamoxifen in women at increased risk for breast cancer.
The National Cancer Institute (NCI) has developed a software program called the Breast Cancer Gail Model Risk Assessment Tool to help women and their doctors calculate their risk of breast cancer. The formal Breast Cancer Gail Model Risk Assessment Tool incorporates statistical methods that were utilized by the National Surgical Adjuvant Breast and Bowel Project to screen patients for the groundbreaking Breast Cancer Prevention Trial. This tool is available as a slide rule or computer software package but is intended for physician use only. However, a version of this software has been prepared for public use and is available online at http://www.nolvadex.com/prescreen.cfm.
Other risk factors for developing breast cancer include:
- Age
- Family history
- Previous breast biopsy showing benign conditions
- Menstruation beginning at an early age
- Menstruation continuing past age 50
- Not having children
- Having a first child after age 30
- High fat diets
- Obesity
- Mutations of the genes, BRCA1 and BRCA2
- Long term hormone replacement therapy
Women with early stage breast cancer are encouraged to discuss bcl-2 and p53 genetic testing with their physicians, as well as treatment with tamoxifen or chemotherapy.
- This article references the October 19, 1999 Reuters Health report, "Tumor Genetics Can Help to Direct Therapy in Breast Cancer Patients" available at http://www.reutershealth.com.
- The American Cancer Society provides information on genetic risk factors for breast cancer at http://www3.cancer.org/cancerinfo/main_cont.asp?st=pr&ct=5 and on tamoxifen at http://www2.cancer.org/bcn/info/tamoxifin_qa.asp.
- Zeneca Pharmaceuticals maintains a website about tamoxifen (product name Nolvadex) at http://www.nolvadex.com.
- Visit the Susan G. Komen Cancer Foundation/Breast Help website at www.breastcancerinfo.com/bhealth/html/tamoxifen.asp or the ACS/Breast Cancer Network at http://www2.cancer.org/bcn/info/tamoxifin_qa.asp to learn more about using tamoxifen to treat breast cancer.
