filed in Healthcare on Aug.18, 2010
Scientists reported updated results on the number and characteristics of breast cancer, as well as the frequency of abnormal mammograms, in the estrogen and progestin (E+P) arm of the Women’s Health Initiative Study (WHI). When comparing patients who developed invasive breast cancer to those on placebo, tumors in the E+P group were larger (mean 1.7 cm vs 1.5 cm for placebo [0.2 cm larger]); associated more often with positive lymph nodes (25.9% vs 15.8% in the placebo group); were more likely to present at an advanced stage of disease (regional or metastatic disease was observed in 25.4% of patients vs 16.0% of those on placebo; regional spread only was observed in 24.4% of patients vs 14.0% of placebo; metastatic spread was observed in 1% of patients vs 2% of placebo). Thus, the major difference between the E+P and placebo users is the increased number of patients with node-positive disease (nearly a 10% increase) in the hormone therapy (HT) group.
The findings of slightly larger and more advanced node-positive tumors is in sharp contrast to prior observational studies which had found smaller breast cancers, with less node positivity and better survival in women on HT. Survival data from the WHI is mostly unknown at this early time, but with no significant difference to date. Conclusive data about whether HT will be more harmful (because of larger tumors with greater incidence of lymph node spread) will require longer follow-up and analysis of survival data.
Information regarding the 4% increase in abnormal mammograms seen at year 1 and continuing throughout the study needs to be relayed to patients. There were 9.4% (716/7656) abnormal mammograms in the E+P group vs 5.4% (398/7310) in the placebo group. It is well known that E+P increases breast density, which can make mammography more difficult to interpret; the discontinuation of E+P therapy for a 2-week period will allow resolution of 75% of the abnormalities seen. However, the need for repeat mammogram, spot compressions, or extra views significantly increases patient anxiety. The use of digital mammography rather than standard mammography may lesson this problem to some extent. In addition, in women who initiate hormone therapy close to the time of the menopause, breast density tends to be maintained rather than increased. Based on these findings, it seems likely that tumors in patients on E+P may be more difficult to find, partly because of the increase in breast density. The WHI investigators will be evaluating the mammograms in more detail to determine whether there is a correlation between hormone-induced breast density and the risk of later developing a breast cancer.
It is important to remember that the estrogen-only arm of the WHI is continuing, and that as of May 2003, no increase in adverse events significant enough to stop the study has been found. Thus, this increased risk of breast cancer so far appears to be only in the E+P group, and not in the estrogen-only arm.