Increasing numbers of women in their 50s and 60s are using hormone replacement therapy to alleviate menopausal symptoms.  The effect of long term use of these agents in women aged over 50 on the breast is only now becoming apparent.  Hormone replacement therapy given to perimenopausal women increases breast pain and nodularity, increases the frequency of benign cysts and fibroadenomas in the breast, and results in the growth of some already established benign lesions.

Breast density increases in 17% to 73% of women who use hormone replacement therapy depending on how breast density is assessed..<snip>....[leading to]...  a significant reduction in specificity in women taking hormone replacement therapy...<snip>...In countries where hormone replacement therapy is widely used this reduction in the sensitivity of mammography could undermine the capacity of population based mammographic screening programmes to reduce mortality due to breast cancer.

The combined analysis of studies of early hormone replacement therapy reported an increased risk of breast cancer of 1.023 for each year of use.....1. 35 (1.21 to1.49) for women who took hormone replacement therapy for five or more years.....recent studies have reported significantly higher levels of risk of breast cancer in women taking combined oestrogen and progestogen preparations compared with women taking oestrogen alone....Continuous combined preparations containing a testosterone derived progestogen also appear to be associated with a significantly greater risk than the use of sequential oestrogen and progestogen.

The evidence that hormone replacement therapy reduces the effectiveness of breast screening and causes breast cancer in women over the age of 50 is clear; the challenge for clinicians is to control menopausal symptoms while limiting these unwanted effects.

http://www.medscape.com/reuters/prof/2001/09/09.03/20010831epid004.html

Hormone Replacement Therapy Tied to Lower Mortality From Breast Cancer 

WESTPORT, CT (Reuters Health) Aug 31 - Women who use hormone replacement therapy (HRT) are less likely to die from breast cancer than nonusers, according to the results of a meta-analysis conducted by researchers at the University of Maryland School of Medicine in Baltimore. 
<snip>

However, Dr. Eugenia Calle, director of analytic epidemiology at the American Cancer Society in Atlanta, disagrees with some of the conclusions drawn by Dr. Flaws' group. She referred to a 1997 Lancet report by the Collaborative Group on Hormonal factors in Breast Cancer <snip> [which] "established a definite association between HRT and recent and current use of HRT of long duration. I don't think that issue is open to debate anymore," she added. 

"Most of a few studies have shown slightly better survival in women treated with HRT. Is it real? I don't know," she said. "It is an important question that remains to be resolved through further epidemiological study." 

" ...lead author Dr. Holly L. Howe told Reuters Health. ' We think this is associated with increased mammography screening in this population. In such cases we often see an increase in incidence but eventually a decline in mortality.' "

No mention was made in either case of the increase in breast cancer risk from HRT use

"Hormone Replacement Therapy Has No Adverse Effect on Cancer Recurrence and Mortality in Women with Breast Cancer." So says the memo sent to reporters about a study published in the May 16, 2001, Journal of the National Cancer Institute. And so say many of the newsstories that followed this memo’s release. This headline, though, doesn’t come close to telling the whole story. And here’s why. [see URL above]

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Incidence of breast cancer was increased in post-menopausal women who used HRT at baseline. Among HRT users, there was over-representation of tumours that, with regard to stage, type and grade, are associated with a favourable prognosis.

Postmenopausal use of estrogen therapy, particularly when it includes progestin, significantly increases the risk that a woman will develop breast cancer by age 70, according to researchers at Harvard University, Boston, Massachusetts.

.....In women who used unopposed postmenopausal estrogen from ages 50 to 60, the cumulative risk increased by 23% compared with women who had never used hormones. The risk was increased by 67% in those who used estrogen plus progestin.....

The researchers found that women taking combination hormone replacement therapy experienced a 40% greater risk of breast cancer than those taking no therapy; women taking oestrogen alone had a 20% greater risk. Moreover, the relative risk increased with duration of therapy, increasing by 0.01 for each year of oestrogen only use and by 0.08 a year for those taking oestrogen plus progesterone. 

The results were found to be significant only in lean women, those with a body mass index (weight(kg)/(height(m)2)) of 24.2 or less, and those who were either currently taking hormone replacement or had taken it within four years. 

Commenting on the report, Dr Schairer said that the research suggests that combination replacement may increase the risk of breast cancer but admitted that the mode of replacement continuous versus cyclic was not controlled for and that further studies will need to be done. 

Although this and some other studies, such as the nurses' health study, show increased risk, the data are still murky. 

The first issue is whether hormone use is needed at all; reducing risks of fractures and coronary heart disease rarely will provide sufficient justification because avoidance of smoking, performance of regular exercise, and consuming a good diet are effective preventive measures.
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The commonly held belief that aging routinely requires pharmacological management has unfortunately led to neglect of diet and lifestyle as the primary means to achieve healthy aging. Now is an appropriate time to reassess this emphasis.

Jane Brody in NYTimes:
http://www.nytimes.com/library/national/science/health/020100hth-breast-cancer.html

WESTPORT, Feb 04 (Reuters Health) - The addition of progestin to a woman's hormone replacement therapy (HRT) regimen substantially increases her risk of developing breast cancer relative to the use of estrogen alone, according to a report to be published in the February 16th Journal of the National Cancer Institute. 
<snip>
 Five years of combination therapy increased a woman's risk of breast cancer by 24%, four times as much as ERT. Though the differences were not statistically significant, sequential combination HRT appeared slightly riskier than continuous combination HRT, the investigators note. 

The excess risk of ERT was limited to in situ disease, while the risk associated with combination HRT was comparable for all pathologic stages of breast cancer.

We found no difference in type, size, or grade of tumour in users compared with non-users (table). Twenty four per cent of users developed well differentiated tumours (tubular, mucoid, and invasive ductal grade 1 cancers) compared with 22% of non-users. This equates to an odds ratio of 0.98 (95% confidence interval 0.63 to 1.50). Seventy seven per cent of users were node negative compared with 67% of non-users. There was no difference in mean tumour size (mean difference 0.25 mm (-2.02 mm to 2.53 mm) in users compared with non-users. No difference was seen in the distribution of the Nottingham prognostic index5 between the two groups. Eight per cent of women using hormone replacement developed ductal carcinoma in situ compared with 15% of non-users. When screen detected cancers were analysed alone, no differences were found between the type, grade, size, or nodal status in users compared with non-users.

Purpose:
Hormone replacement therapy (HRT) has been associated with an increased risk for breast cancer. Cancers in women who use HRT are often less advanced, and lower mortality has been reported in those who use HRT than in nonusers. We sought to explain this by a comparison of indicators of tumor aggressiveness in patients who received HRT with those in patients who did not. 

Women making decisions about hormone replacement therapy (HRT) will find it helpful to have the information from the thorough reanalysis reported in today's Lancet of accumulated epidemiological data on the very salient question of whether use of HRT for many years increases the risk of breast cancer.

• ...This analysis reveals an increased relative risk of breast cancer among current or recent users of HRT for more than 5 years and shows that risk is associated with duration of use. 
• ....only 12% of hormone users had been exposed to progestagens. Thus, HRT in this report refers predominantly to the use of oestrogen with or without progestagen, and there remains too little information on the use of progestagens with oestrogen for long periods to draw firm conclusions on the combination. (Tishy's emphasis)
• ...The results of this meta-analysis may underestimate the true magnitude of breast cancer risk associated with HRT. Osteoporotic women, who are also more likely than others to be on HRT, are at considerably lower risk of breast cancer than other women
• ...may also overestimate the true magnitude of breast-cancer risk associated with long-term HRT.
• ...The results of this well-conducted meta-analysis should serve to over-ride debate about the relative merits and plausibility of individual studies and focus attention appropriately on the totality of the epidemiological evidence so far. These findings create an ethical responsibility for physicians and other health-care providers to advise women that the accumulated epidemiological data show an increased risk of breast cancer among those on HRT for 5 or more years.
• ...Because the data are based on observation of women rather than controlled experimental trials, the excess risk should be viewed as a possibility but not a certainty.
• ...There is the danger that new preventive agents marketed as alternatives to hormone replacement (eg, selective oestrogen-receptor modulators, biphosphonates) will be assumed to be effective and safer, when in fact there is no information on their long-term risks and benefits

Nurses' Health Study
This is a US study involving nearly 122,000 female nurses aged 30 to 55 years in 1976. 
Breast cancer diagnosis (or death) was one outcome, and details about newly diagnosed cancers were obtained, with permission, from hospital records and reviewed for over 93% of cases identified. Data from women with carcinoma in situ, who reported breast cancer in 1976, or who were premenopausal were omitted [2]. 

This left some 24,000 women who were postmenopausal in 1976, rising to nearly 70,000 by 1990. Follow up of index cases was over 95% for breast cancer diagnosis and 98% for fatal breast cancer.