One of the more newsworthy items of late, has been the decline of breast cancer seen in 2003. The rate of breast cancer in women in the U.S. fell significantly by 6.7% in 2003, according to data from the National Cancer Institute (NCI) registries. Data from 2004, showed a leveling off, with no real additional decrease. The decrease, starting in mid- 2003, was only in women who were 50 years of age or older, and was more evident in estrogen-receptor-positive cancers (14.7%; 95% CI, 11.6 to 17.4) The decreases were similar for localized disease, more advanced disease, and were more evident in primary breast cancers but not in contralateral second primary or later breast cancers.
Comparing the incidence rates in 2001 with the rates in 2004, but not including this rapidly changing period from mid-2002 to mid- 2003, showed that the annual decrease in breast cancer incidence was only present in women who were 50 or older. During that time period, there was an increase of 1.3% in breast cancer incidence in women under age 50 (95% CI, -3.1 to 5.8), a decrease of 11.8% for women between 50 and 69 (95% CI, 9.2 to 14.5) , and a decrease of 11.1% for women 70 and older (95% CI 7.9 to 14.2). The compelling question is, why this sharp drop, followed by a stabilization at a lower rate in women 50 and older?
As best I can tell, there are potentially, several explanations: 1. A decline in hormone use since the first report of the Women’s Health Initiative (WHI). 2. A decrease in the rate of screening mammograms. 3. A possible decrease in the rates of annual exams in women 50 and older due to discontinuing HRT 4. An error in the NCI Surveilance, Epidemiology, and End Results (SEER) data. 5. A possible general decrease in the rates of cancers in general 6. Some possible positive influence on the rates of breast cancer. A little closer examination of each of these is important.
One possible explanation that has been posed, is a reporting flaw in the SEER data. This is considered to be unlikely due to there being no significant change in the incidence of any other cancer other than breast cancer during this period. In addition, all nine SEER registries showed the same trend.
A feasible explanation might be related to a major decrease in the rate of screening mammography. For 2003, there was a decrease of 3.2% in the rate of screening mammograms between the ages of 50 and 65, compared with the year 2000. Another aspect of this influence, might be that there could be a change in the frequency and pattern of screening mammograms in women who formerly used hormone replacement therapy (HRT), and now do not. Women who receive HRT, are likely to also receive annual mammograms. Once they discontinue HRT, might they also discontinue doing annual mammograms, as well as go to the doctor less frequently for breast exams? Basically, breast cancers going undetected. Although I do think that in fact, women who discontinue HRT, do initially delay their annual screening mammograms and visits to the doctors, we have no published data showing a decrease in mammographic screening in women who discontinue HRT. In addition, women who discontinue HRT, who are 50 and older, are also disinclined to receive annual exams, especially now since they are being told they do not need an annual pap smear.
The decrease in breast cancer incidence began in mid-2002, and occurred shortly after the publication of the first report of the Women’s Health Initiative in July of 2002, which demonstrated a slight increase in the risk of breast cancer after 4 years of use. By the end of 2002, the use of conventional HRT, declined by approximately 38% in the U.S. and there were 20 million fewer prescriptions written in 2003 than in 2002. , The total number of prescriptions for Premarin and PremPro, the two most common forms of HRT, saw a steep decline starting in 2002, and especially in 2003. 62 million prescriptions were written in 2000, 61 million in 2001, 47 million in 2002, 27 million in 2003, 21 million in 2004, and 18 million in 2005. The periods of sharpest decline appeared to start in 2002 and then also in 2003.
What about some positive influence on the rates of breast cancer? Could there have been something that emerged starting in 2003? Drugs such as tamoxifen, raloxifene, nonsteroidal antiinflammatories and statins have certainly increased dramatically, and there is some evidence for the beneficial effects of these medications on the overall risk of breast cancer. However, it appears that none of these medications had a significant increased change in use during the period from 2000 to 2004. Increased utilization of vitamin D or green tea or soy products might also deserve some thought. While there is some data as to the potential positive influence of these on breast health and even reducing the risk of breast cancer, we do not have any data on increased utilization of these products distinctly in this period of 2002 to 2003.
Women who were in the Women’s Health Initiative PremPro arm when the study was discontinued, are being followed for clinical outcomes, and a report of this will likely be published later in 2007. This report will shed additional evidence related to the influence of discontinuation of HRT on the incidence of breast cancer.
Experts on the topic of HRT and breast cancer are hesitating to render any final opinion on this report while also admitting that “the ultimate understanding of the effect of cessation of hormone-replacement therapy will be complex; it will probably depend on more than one mechanism and will be affected in different ways by various forms of postmenopausal hormone-replacement therapy.â€
Additional time will reveal another interesting aspect of this: will the appearance of clinically detectable tumors by mammography only be delayed, rather than an actual long term reduction in breast cancer incidence. Removing HRT may only slightly or temporarily slow the growth of tumors that already exist. If this is the case, then as the use of HRT stabilizes at a certain utilization rate, then the incidence of breast cancer would rise again.
It is my humble opinion that since the WHI and many other studies demonstrate only a slight increase in the rates of breast cancer after combined conjugated equine estrogens and progestins for 5 years or more, that any decrease in the rates of breast cancer seen in 2003, immediately post WHI, is associated with withdrawal of an agent that can slightly increase the growth of an already pre-existing tumor.
- Ravdin P, Cronin K, Howlander N, Chlebowski R, Berry D. A sharp decrease in breast ancer incidence in the United States in 2003. Breast Cancer Res Treat 2006; 100: Suppl: S2, a abstract.
- Ravdin P, Cronin K, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. NEJM 2007;365;16:1670-1674.
- Rossouw J, Anderson G, Prentice R, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288: 321-333.
- Buist D, Newton K, Miglioretti D, et al. Hormone therapy prescribing patterns in the United States. Obstet Bynecol 2004; 104:1042-1050.
- Hersh A, Stefanick M, Stafford R. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA 2004;291:47-53.
- Drug Topics. Drugs by units in the United States ion specific years. (Accessed March 29, 2007, at http://www.drugtopics.com/drugtopics/.)
