Drop in hormone replacement therapy use explains part of decline in breast cancer rates
Last updated: April 5, 2010
- News type:
- Breast cancer study
- Conference:
- American Association for Cancer Research Int'l Conference on Frontiers in Cancer Prevention Research, December 2009
- Topic:
- Declining incidence of breast cancer since 2002 in the United States: How much is explained by the decrease in postmenopausal hormone use?
A new study presented at the 2009 American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research has found that only some of the estimated 7% decline in breast cancer incidence since 2002 can be attributed to a decline in combined hormone replacement therapy (HRT) use. The decline in breast cancer incidence since 2002 has been widely attributed to discontinuation of HRT use following the Women’s Health Initiative randomized trial. However, very little analysis has been conducted to quantify the relationship. Using an estimated 46% decline in HRT use and a relative risk for current use of 1.5, the authors estimate that 42% of the decline in breast cancer incidence is attributable to cessation of hormone use. The authors conclude that cessation of postmenopausal hormone use following the 2002 announcement of an association between HRT use and breast cancer is unlikely to account for more than half of the observed decline in breast cancer incidence among women aged 40-79 years old. The potential contributions of other factors should be examined in future studies, especially the role of the recent plateau in use of breast cancer screening.
HRT use dropped after link with breast cancer was reported
Some of the benefits once thought to be associated with HRT, such as reductions in heart disease and dementia, have been found to be non-existent. In addition, HRT has been found to be associated with increased risk of breast cancer, especially estrogen receptor positive (
ER+/PR+ and
ER+/PR-) and
lobular breast cancer. Strong evidence that HRT (conjugated equine estrogen combined with progestin) use could increase the risk of breast cancer was first published in 2002, when it was reported that participants in the Women’s Health Initiative (WHI) randomized trial who were taking HRT had higher rates of breast cancer than those who did not. Subsequent studies have confirmed the finding that HRT promotes breast cancer. While HRT is effective in reducing menopausal symptoms such as hot flashes, women are advised to use HRT for the shortest possible period for the relief of severe menopause-related symptoms.
For women who need to take HRT
Women with severe menopausal symptoms who use HRT should be aware of the following study findings:
- Use of HRT appears to increase risk of breast cancer by at least 25%. This might not be an acceptable increase for women who are already at high risk
- Women who develop breast tenderness as a result of using HRT have been found to have a higher risk of breast cancer than those who don't
- The immediate reduction in breast cancer incidence after a decline in HRT usage suggests that HRT is a strong promoter of tiny, mammographically and clinically undetectable cancers, suggesting that HRT use is especially dangerous for breast cancer survivors who may have micrometastases that otherwise might not develop into deadly recurrences.
Generally speaking, the increase in breast cancer risk from HRT increases with years of use and disappears within five years of cessation of treatment.
Bioidentical hormones
Bioidentical hormone formulations, which have been described by some health practitioners as more natural and safer than conventional HRT, have been welcomed by many women who seek relief from menopause-related symptoms. Bioidentical hormones are plant-derived hormones that are biochemically identical or similar to those produced in the body, especially those produced by the ovaries. Some prescription products that contain bioidentical hormones are FDA approved. However, bioidentical hormones that are custom-compounded have not been tested for purity, potency, efficacy, and safety. Although many people think of bioidentical as natural hormones, they are often derived from some of the same precursors as HRT, namely soy or wild yam, and a great deal of processing is required to extract them.
Unfortunately, large-scale and carefully designed population studies comparing HRT with bioidentical hormone treatments are simply not available. There is some evidence that hormone replacement formulations different from the estrogen plus progestin combinations normally used in the U.S. may result in smaller increases in breast cancer risk. There are some responsible physicians who are taking this approach using FDA-approved bioidentical hormones to treat women with menopausal symptoms.
However, the term "bioidentical hormone treatment" is also used by some nontraditional health care providers in ways that might be unsafe for any women, but especially those who are breast cancer survivors or are at high risk for breast cancer. The hallmarks of such practices are the use of saliva tests to determine dosage, the use of compounded products, and the sale of hormonal formulations directly to patients.
Estriol is commonly used in compounded products. It is promoted as a preferential form of estrogen that may produce fewer risks commonly associated with estrogens. However, it still carries risks associated with estrogen, and has been found to stimulate the growth of hormone receptor breast cancer cells. In addition, it is not known how estriol and other hormones are absorbed from compounded gels and creams. Again, while estriol is a weak estrogen, there is no evidence that, if given at a dosage high enough to relieve symptoms, it is any safer than other estrogens.
In fact, the main danger of unregulated bioidentical hormone treatments is that women may be exposed to high levels of estrogen (potentially higher than HRT) that could promote breast cancer. The sense of well being that some women report while using bioidentical hormones may in fact be the result of dangerous levels of estrogen and other hormones. The promises that were once made for HRT, including various aspects of youthfulness in addition to the relief of symptoms such as hot flashes and vaginal dryness, are now being made for compounded bioidentical hormone treatments. Neither are safe for women at high risk for breast cancer or its recurrence.
,
ER+/PR+,
ER+/PR-,
HRT,
breastCancerRisk,
hormoneReplacementTherapy,
hotFlashes,
lobularBreastCancer,
micrometastases
Selected studies
Declining incidence of breast cancer since 2002 in the United States: How much is explained by the decrease in postmenopausal hormone use?
American Association for Cancer Research (AACR) Int'l Conference on Frontiers in Cancer Prevention Research, December 2009
The present study was designed to investigate the extent to which the recent decline in U.S. breast cancer incidence is attributable to the reduction in hormone replacement (HRT) use since 2002. The 7% decline in breast cancer incidence since 2002 has been widely attributed to discontinuation of HRT use following the Women’s Health Initiative randomized trial. However, very little analysis has been conducted to quantify the relationship. The authors used literature-based estimates of the change in HRT use and the relative risk associated with hormone use to estimate the impact of reduced HRT use on breast cancer incidence between 2002 and 2003 among women aged 40 to 79 years old. Using an estimated 46% decline in HRT use and a relative risk for current use of 1.5, the authors estimate that 42% of the decline in breast cancer incidence is attributable to cessation of hormone use. Based on further analyses using a range of parameter values, it was found that unrealistically high values of relative breast cancer risk (namely, greater than 2.25) or percent decline in hormone use (at least 75%) would be required to account for all of the observed decrease in breast cancer incidence. The authors conclude that cessation of postmenopausal hormone use following the 2002 announcement of an association between HRT use and breast cancer is unlikely to account for more than half of the observed decline in breast cancer incidence among women aged 40-79 years old. The potential contributions of other factors should be examined in future studies, especially the role of the recent plateau in use of breast cancer screening.
New-Onset Breast Tenderness After Initiation of Estrogen Plus Progestin Therapy and Breast Cancer Risk
Archives of Internal Medicine, October 2009
The present study was designed to examine the question of whether breast tenderness which develops during estrogen plus progestin hormone replacement therapy (HRT) is associated with increased risk of breast cancer. HRT has been found to increase breast cancer incidence and it also increases breast tenderness in some women. The study used data from the Women's Health Initiative Estrogen Plus Progestin Trial. This trial was halted in July 2002 before completion when it was discovered that women on the combination therapy had an elevated risk for breast cancer. In this trial, 16,608 postmenopausal women who had not had hysterectomies were randomly assigned to receive either daily conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) or a placebo. The women underwent mammography and clinical breast examination at the outset of the study (baseline) and annually thereafter. Self-reported breast tenderness was recorded at baseline and at the end of one year. New cases of invasive breast cancer were confirmed by medical record review. The average follow-up period was 5.6-years. Of the 14,538 women who did not have breast tenderness at baseline, significantly more in the HRT group compared to the placebo group experienced new-onset breast tenderness as of the end of one year (36.1% versus 11.8%, P < .001). Of the 8,506 women in the HRT group, the risk of breast cancer was found to be significantly higher in those with new-onset breast tenderness compared with those without (hazard ratio (HR) = 1.48; 95% confidence interval (CI) = 1.08-2.03; P = .02). Breast cancer risk was not significantly associated with new-onset breast tenderness in the placebo group. The authors conclude that new-onset breast tenderness during conjugated equine estrogens plus medroxyprogesterone therapy is associated with increased breast cancer risk. The explanation for the association between breast tenderness and breast cancer was not uncovered during the study. The sensitivity and specificity of the association between breast tenderness and breast cancer were similar in magnitude to those of the Gail model.
Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks?
Journal of Clinical Oncology, September 2009
The current French study was designed to investigate whether the association between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the time that elapses between the onset of menopause and initiation of hormone treatment. Study participants were drawn from the French E3N cohort. During the period 1992-2005, 1,726 cases of invasive breast cancer were identified among 53,310 postmenopausal women in this cohort (average follow-up period = 8.1 years). Cox models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), with never users of menopausal hormone therapy of any type as the reference. Risk of breast cancer was found to vary according to the timing of treatment initiation among recent users of EP-MHT. This variation was limited to those with short durations of use ( 2 years): HR = 1.54 (95% CI = 1.28 - 1.86) for short duration treatments initiated during the first three years following the onset of menopause, whereas HR = 1.00 (95% CI = 0.68 - 1.47) for short duration treatments initiated after the three-year mark. In other words, women who started the therapy at some point during the three years after menopause and took it for two years or less had a 54 percent higher risk of breast cancer than those who never used it. However, this pattern of risks was not observed in users of estrogen-progesterone. Among this group, no significantly increased risk was found associated with short duration of use (HR = 0.87 (95% CI = 0.57 - 1.32) for treatments initiated within three years after menopause, and HR = 0.90 (95% CI = 0.45 - 1.81) for treatments initiated later (suggesting a protective effect for this combination in years further out from menopause). Generally speaking, longer durations of EP-MHT use were associated with increases in the risk of breast cancer, whatever the gap time between menopause and the initiation of EP-MHT. (Note that the regimens typically used in France are different from typical U.S. regimens, and French women often use skin patches rather than pills.) The authors conclude that for some types of menopausal hormone therapy, the timing of treatment initiation temporarily modulates the risk of breast cancer and that, when initiated close to menopause, even short durations of use are associated with an increased breast cancer risk. Estrogen-progesterone combinations might be an exception in this regard, but this finding needs to be confirmed.
A case-control study on hormone therapy as a risk factor for breast cancer in Finland: Intrauterine system carries a risk as well
International Journal of Cancer, July 2009
The present Finnish study was designed to investigate the association between postmenopausal hormone replacement therapy and risk of breast cancer in recently postmenopausal women. The Finnish Cancer Registry was used to identify all Finnish women between the ages of 50 and 62 with new diagnoses of invasive breast cancer during the period 1995-2007 (9,956 women). Three controls of the same age were retrieved from the Finnish Population Register for each breast cancer case. Use of hormone replacement therapy was determined by linkage with the national medical reimbursement register. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer, while adjusting for parity, age at the first birth, and region (health care district). Estradiol-only therapy (991 breast cancer cases) and oral progestagen only (138 cases) were not found to be associated with risk of breast cancer. However, estradiol-progestagen therapy (1,731 cases) was found to be associated with an overall elevated risk (OR = 1.36; 95% CI = 1.27 - 1.46). The increased risk became detectable in less than three years of use. Continuous estradiol-progestagen therapy use tended to be associated with a higher risk of breast cancer than sequential estradiol-progestagen therapy use. The use of tibolone (80 cases) (RR = 1.36; 95% CI = 1.15 - 1.96), a levonorgestrel releasing intrauterine system (LNG-IUS) alone (154 cases) (RR =1.45; 95% CI = 1.97 - 1.77), and LNG-IUS as a complement to estradiol (137 cases) (RR = 2.15; 95% CI = 1.72 - 2.68) were also found to be associated with increased risk of breast cancer. The authors conclude that the association between hormone replacement therapy use and risk of breast cancer varies greatly depending on the form of therapy used.
The Changing Incidence of In situ and Invasive Ductal and Lobular Breast Carcinomas: United States, 1999-2004
Cancer Epidemiology Biomarkers & Prevention, June 2009
The present study provides U.S. rates for both in situ and invasive lobular and ductal breast cancers and examines the changes in their incidence over time. Rates of lobular and ductal breast cancer have not been available previously. The increased risk of breast cancer associated with use of combined hormone replacement therapy has been reported to be higher for invasive lobular breast cancer than for invasive ductal breast cancer. The study comprised data regarding ductal and lobular breast cancer cases diagnosed during the period 1999 to 2004 and included in central cancer registries in 44 states and the District of Columbia. Distinct differences in the change of incidence over time were found for invasive lobular compared to invasive ductal breast cancer. Age-adjusted rates of invasive lobular cancer declined an average of 4.6% per year, whereas invasive ductal cancer declined an average 3.3% per year. Overall, the incidence of invasive lobular cancer dropped 20.5% between 1999 and 2004. The patterns of ductal and lobular in situ cancer incidence were inconsistent over time, and the total change was not significant. The authors conclude that the observed drop in invasive lobular cancer is consistent with a decrease in cancer incidence associated with lower use of combined hormone replacement therapy, however they caution that other factors also could be responsible for this decline.
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