MENOPAUSE

In 2004, results of the WHI clinical trial of women with hysterectomy indicated that estrogen was not associated with an increased risk of breast cancer,⁹ consistent with a number of large observational studies conducted in the United States^10,11 and Sweden.¹² Although the British Million Women study found a minimally elevated risk of breast cancer with use of estrogen alone, this risk (RR 1.3) was substantially lower than the risk associated with combination HT (RR 2.0).⁵ Other studies have also found that estrogen-only therapy, compared with combination HT, is associated with either less increased risk or no increased risk.¹³

Confident counseling

Overall, this body of evidence allows us to confidently counsel menopausal patients who have had a hysterectomy and are contemplating use of HT that use of estrogen-only HT is associated with no increased risk or a minimally increased risk of breast cancer.⁴

How does HT affect mammograms?

• Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States.¹⁴
• The overall diagnostic accuracy of digital and film mammography as a means of screening for breast cancer is similar, but digital mammography is more accurate in women younger than 50 years, women with radiographically dense breasts, and premenopausal or perimenopausal women.¹⁵
• Use of estrogen plus progestin is associated with increases in mammographic density.¹⁷

Mammography has contributed much to the detection and treatment of breast cancer, as well as its decline in mortality in the United States since the mid-1970s,¹⁴ reminding us of the importance of this screening test. Increased breast density reduces the sensitivity of mammograms,¹⁵ however, and use of HT (particularly combination HT) increases mammographic breast density.^16,17 In the WHI trial of combination HT, women assigned to HT were more likely to have abnormal mammograms requiring recall.¹⁸

HT may become an indication for digital mammographic technique

In contrast with the findings of many observational studies, the breast tumors found in combination-HT users in the WHI trial were also larger, and disease stage was more advanced at diagnosis.¹⁸ As the WHI authors speculated, these sobering observations suggest that combination HT may have the dual impact of stimulating growth in existing tumors and delaying mammographic diagnosis.¹⁸ Speroff has suggested that the differences between findings of observational studies and the WHI reflect that the WHI participants were older postmenopausal women, who were more likely to have preexisting tumors, and therefore the results may be of less relevance to younger postmenopausal women using HT.¹⁶

For women with dense breast tissue, use of digital as opposed to film mammography enhances accuracy.¹⁵ Accordingly, as digital mammography becomes more available, use of HT may become an indication for use of digital mammographic technique among postmenopausal women.

Use digital if it’s available

In practice settings where digital mammography is available, its use should be considered in preference to film mammography for women using menopausal HT.

Evidence-based answers to 3 top concerns of patients

• Armed with a balanced perspective based on evidence rather than fear, our patients can make sound decisions on use of menopausal HT. We can advise our patients to consider the following evidence-based lines of reasoning:

How does HT affect risk of breast cancer?

• Combination hormone therapy vs estrogen only. Women considering whether to start HT, as well as those deciding whether to continue, need to understand the small but real risk of breast cancer attributable to combination HT, and that this risk is lower (if present at all) with estrogen-only therapy if they have had a hysterectomy.
• It may help to place the risks associated with combination HT in perspective with other breast cancer risk factors and risk factors for other cancers.
• Symptomatic women in their 50s contemplating initiation or ongoing use of HT should also recognize that any increased relative risk of breast cancer associated with use of combination HT translates into an attributable risk substantially lower than that faced by older menopausal women (the WHI population).
• Risk increases with longer duration of combination HT. A consistent finding of recent large studies is that the risk of breast cancer increased with longer durations of combination HT use.⁴ This observation supports clinical strategies that attempt to minimize the duration of combination HT use.

Does HT affect coronary risk?

• Timing of HT initiation in relation to menopause onset or to age might influence coronary risk, with users under age 60 possibly experiencing cardioprotection, concluded a Nurses Health Study report. This study provides reassurance for younger menopausal women (in their 50s) with respect to coronary artery disease risk associated with HT use.¹⁹