Women taking combination hormone replacement therapy (HRT) are not only at increased risk of developing breast cancer, they are also more likely to have the worry of mammogram abnormalities and otherwise avoidable breast biopsies, a new study suggests.

US researchers also found that breast cancer was less likely to detected by these methods in women using combination HRT. Post-menopausal women considering HRT “should take the results of this study into consideration and consult with their physicians before undergoing even short-term hormone therapy”, commented lead author Dr Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in California.

The research team examined the effect of combined oestrogen and progesterone on breast cancer detection in the trial of 16,608 healthy menopausal women conducted in the US as part of the Women’s Health Initiative (WHI). That study was famously halted early in 2002, due to an increased risk of breast cancer in the oestrogen-progesterone group as well as evidence that overall health risks (including coronary heart disease, stroke and pulmonary embolism) outweighed any benefits of therapy.

Women participating in the WHI study were given mammograms and breast examinations at baseline and subsequently once a year. Breast biopsies were performed based on the clinical judgment of physicians. The results were reported in the 25 February issue of Archives of Internal Medicine.

During the 5.6 years of the study, 199 women in the combination HRT group (total = 8,506 women) developed breast cancer, compared with 150 women taking placebo (total = 8,102). The cumulative frequency of mammograms with abnormal results was also higher in the HRT (35.0%) than in the placebo (23.0%) group. Women taking hormones had a 4% greater risk of mammogram abnormalities after one year of therapy and an 11% greater risk after five years.

These abnormal mammograms were less sensitive in detecting breast cancer and were more likely to result in breast biopsies, the researchers found. On a cumulative basis, 10.0% of the women on combination HRT had breast biopsies compared with 6.1% on placebo. And although breast cancer was diagnosed at more advanced stages in the HRT group, biopsies detected cancer in only 14.8% of those women versus 19.6% in the placebo group.

Sustained effect
Once women came off hormone therapy, the adverse effect on mammograms “modulated but remained significantly different from that of placebo for at least 12 months”, the authors noted. Moreover, Dr Chlebowski added, the adverse effects on mammogram and breast biopsy performance after discontinuation of HRT “were seen even in younger women in the fifth decade of life, so the finding may impact women just entering menopause as well”.

Overall, the researchers concluded that use of oestrogen plus progesterone over roughly five years resulted in more than one in 10 and one in 25 women, respectively, having otherwise avoidable mammogram abnormalities and breast biopsies. Taking HRT “also compromised the diagnostic performance of both”.

One suggested explanation for this latter effect is that HRT increases breast density, which can make it harder to detect cancers.

The findings were downplayed by Wyeth, which markets the hormone replacement therapies Prempro and Premarin and was badly affected by the original WHI study results.

While use of combined oestrogen and progesterone increased the need for repeat mammograms in the study, nearly one in four women in the placebo group also required repeat mammograms due to abnormalities, it pointed out, adding: “The findings in this report do not change what we already know about the benefits and risks of hormone therapy”.

Current labelling for all hormone therapy products provides information about breast cancer risks and abnormal mammograms as well as guidance on having annual breast examinations performed by a healthcare professional, Wyeth noted.