Frequently Asked Questions about Estrogen plus Progestin and Breast Cancer
These questions and answers supplement the June 25, 2003 JAMA publication on E+P and breast cancer.
- What were the main findings from the estrogen plus progestin and breast cancer analyses?
- What is the increased risk for women taking E+P for breast cancer?
- What were the main findings about E+P and mammography?
- What are the conclusions from these findings?
- What is breast cancer?
- What is in situ breast cancer?
- What is invasive breast cancer?
- What is a mammogram?
- What is an abnormal mammogram?
- What happens to breast cancer risk and the frequency of abnormal mammograms after E+P use is discontinued?
- Was the effect of E+P on breast cancer different in women who had taken menopausal hormone therapy before entering the WHI study?
- What type of hormone treatment did women in the E+P study take?
- Is there an increased risk of breast cancer and abnormal mammograms in women taking estrogen alone (without progestin) or other E+P formulas?
- Should I discuss this information with my healthcare provider?
- If I have an abnormal mammogram now, and have taken (or I still take) E+P, what should I do?
- Was the effect of E+P on breast cancer different in women who had used oral contraceptives in the past?
- I am taking prescription hormones. What should I do?
1. What were the main findings from the estrogen plus progestin and breast cancer analyses?
Answer: More women who took estrogen plus progestin (E+P) developed breast cancer than women taking placebo (inactive pills). The cancer cases found in women taking E+P had similar characteristics (looked the same under the microscope), but the tumors were larger and had spread more throughout the body than those in the placebo group.
2. What is the increased risk for women taking E+P for breast cancer?
Answer: A woman is more likely to develop breast cancer if she is taking E+P. For every 10,000 women taking estrogen plus progestin, 41 women each year will develop breast cancer as compared to 33 women per year who would develop breast cancer while taking placebo. While this difference in risk is important, the overall risk to an individual woman remains small.
The breast cancer cases which developed in women taking E+P were larger and more advanced; about 25% had spread to lymph nodes or elsewhere in the body, compared to 16% of women on placebo.
3. What were the main findings about E+P and mammography?
Answer: After just one year of taking E+P, a woman was much more likely to have an abnormal mammogram compared to a woman taking placebo. In the E+P group, 9.4% of women had an abnormal mammogram after one year, compared with 5.4% in the placebo group. The increased rate of abnormal mammograms continued until the study ended.
A woman’s chance of having an abnormal mammogram resulting from E+P use was about 1 in 25 for one year’s use, and about 1 in 10 after 5½ years of use.
4. What are the conclusions from these findings?
Answer: Use of E+P increases the rate of more advanced breast cancer compared with placebo and substantially increases the rate of abnormal mammograms. As a result, abnormal mammograms in women receiving menopausal hormone therapy need closer attention. The increased frequency of abnormal mammograms is a newly found negative effect of even short-term E+P use. These findings should be considered in the discussion of risks and benefits for women considering E+P use for any amount of time.
5. What is breast cancer?
Answer: Breast cancer is a disease in which abnormal breast cells divide without control and can spread to other parts of the body.
6. What is in situ breast cancer?
Answer: In situ is an early cancer where abnormal breast cells are confined to the ducts or lobules in the breast. There are two forms, ductal carcinoma (DCIS) and lobular carcinoma in situ (LCIS).
7. What is invasive breast cancer?
Answer: Invasive breast cancer involves abnormal breast cells which have spread outside the breast duct or lobule where they began. This type of cancer accounts for 80% of breast cancer cases. When the term "breast cancer" is used, it generally means invasive breast cancer.
8. What is a mammogram?
Answer: A mammogram is an X-ray of the breast.
9. What is an abnormal mammogram?
Answer: An abnormal mammogram is a breast X-ray with characteristics leading the radiologist to recommend some additional testing, either another mammogram within 6 months, or occasionally other procedures. A recommendation to have a repeat mammogram seldom results in a cancer diagnosis. Some characteristics seen on a mammogram are suspicious enough to indicate that additional tests (like a biopsy) are needed. These tests are more likely to result in a cancer diagnosis.
An abnormal mammogram report is not the same as an incomplete mammogram report. Quite often, a woman may be called back after a mammogram to have additional X-rays taken, have an additional non-invasive procedure performed (such as an ultrasound) or be asked to provide earlier mammograms for comparisons. These evaluations are needed to better understand the current mammogram, and by themselves do not signal an abnormal mammogram.
10. What happens to breast cancer risk and the frequency of abnormal mammograms after E+P use is discontinued?
Answer: WHI researchers will be looking at these issues in future analyses, so information is not yet available. Observational studies have suggested that breast cancer risk will diminish over time.
To date, no studies have looked at what effect stopping E+P use has on abnormal mammograms. There have been some studies about breast density change and menopausal hormone therapy use. Increased mammogram density has been linked to E+P use. In observational studies, mammogram density has been shown to decrease when E+P use is stopped. It remains to be seen whether abnormal mammograms will change when E+P use is stopped.
11. Was the effect of E+P on breast cancer different in women who had taken menopausal hormone therapy before entering the WHI study?
Answer: There was a trend for somewhat higher risk in women in the E+P group who reported prior menopausal hormone use. Whenever researchers examine factors like this within a randomized trial, the analyses and interpretation become more complex. Prior hormone use was not randomized and so other factors associated with hormone use must be considered when analyzing this relationship. Though there appears to be some relation between prior hormone use and breast cancer, WHI researchers will be examining this in more detail to gain confidence in their interpretation.
12. What type of hormone treatment did women in the E+P study take?
Answer: Women randomized (assigned by chance) to active hormones were taking one tablet containing conjugated equine estrogens (0.625 mg) and medroxyprogesterone acetate (2.5 mg) each day (Prempro™). When WHI first began, this was the most commonly prescribed menopausal hormonal therapy in the United States for women with a uterus.
13. Is there an increased risk of breast cancer and abnormal mammograms in women taking estrogen alone (without progestin) or other E+P formulas?
Answer: The current report addresses only the issue of E+P use in the form of pills. Final results from the ongoing Estrogen-Alone (E-Alone) study are unknown at this time. Importantly, the WHI investigators have been told that, as of May 31, 2002, no increase in breast cancer has been seen in the E-alone WHI trial.
Participants in the E-Alone study are asked to continue to take their study pills and to come for their regular clinic visits. The National Heart, Lung, and Blood Institute, which oversees WHI, continues to review the study for women receiving E-Alone, and they will provide investigators and participants with any new information about the study that might affect their participation
This information has been superceded by the 2004 Hormone Program Update.
14. Should I discuss this information with my healthcare provider?
Answer: Yes. Your healthcare provider may read the scientific paper in the June 25, 2003 issue of JAMA, or you may direct your provider to this web site. Your provider may also want to speak with your local WHI Principal Investigator about these results.
15. If I have an abnormal mammogram now, and have taken (or I still take) E+P, what should I do?
Answer: Talk with your healthcare provider about your individual situation in light of the WHI results.
Additional breast imaging tests may help in evaluating women with abnormal mammograms, such as a nuclear medicine test (scintimammography) or Magnetic Resonance Imaging (MRI); your mammography provider should have information about these tests. However, no approach has been evaluated for women with abnormal mammograms related to E+P use.
16. Was the effect of E+P on breast cancer different in women who had used oral contraceptives in the past?
Answer: The analyses done so far do not suggest that use of oral contraceptives had any important influence on the breast cancer findings. Less than half of the women in this study had ever used oral contraceptives and the length of use was often relatively short (less than 5 years). With the small number of breast cancer cases that occurred in these women, these data do not provide a very clear answer to this question.
17. I am taking prescription hormones. What should I do?
Answer: Talk with your healthcare provider about your individual risk profile and the hormones you are currently taking in light of the WHI results.