Combo HRT tied to delayed detection of breast cancers: expert urges caution in applying these findings to younger women

Combo HRT tied to delayed detection of breast cancers: expert urges caution in applying these findings to younger women – Elevated Breast CA Risk

Kate Johnson

Invasive breast cancer is detected at a more advanced stage in women who are on estrogen-progestin therapy, compared with those who develop the disease while taking a placebo, according to a new analysis of data from the Women’s Health Initiative.

The analysis also showed that women taking combination therapy were significantly more likely to have an abnormal mammogram requiring further follow-up, even after just 1 year of use.

Women in the combination therapy group were found to have a significant 24% increase in their relative risk of breast cancer when evaluated an average of 5.6 years after initiating hormone use, an increase similar to that seen in last year’s results reported after an average of 5.2 years. In terms of absolute risk, the excess risk per 10,000 women on combination therapy was eight additional breast cancers per year (JAMA 289[24]:3243-53, 2003).

“The ability of combined hormone therapy to decrease mammographic sensitivity creates an almost unique situation in which an agent increases the risk of developing a disease while simultaneously delaying its detection,” according to Dr. Peter H. Gann and Dr. Monica Morrow of Northwestern University, Chicago, commenting in an accompanying editorial (JAMA 289[24]:3304-06, 2003).

Still, clinicians must be careful not to extrapolate these findings to all menopausal women, Dr. Lee Shulman, professor of obstetrics and gynecology and head of reproductive genetics at Northwestern, said in an interview.

The WHI trial included women between the ages of 50 and 79 years, with a mean age of 63 years. “The population base studied in the WHI trial is not the population that we typically discuss hormone therapy with, which is a younger population who are just entering menopause and who desire hormone therapy primarily for osteoporosis prevention and symptom relief,” explained Dr. Shulman, who is on the speakers’ bureau for Solvay, which markets hormone therapies.

Natalie de Vane, a spokesperson for Wyeth Pharmaceuticals, which makes the Prempro formulation used in the WHI (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), noted in an interview that “it’s important that women understand that hormone therapy is not a lifetime commitment. It’s a short-term treatment for menopausal symptoms.”

After an average follow-up at 5.6 years, 245 of the 8,506 women in the combination group developed breast cancer, compared with 185 of the 8,102 women in the placebo group, said Dr. Rowan T. Chlebowski of Harbor-UCLA Research and Education Institute, Torrance, Calif., and his associates.

Invasive disease was diagnosed in 199 women in the combination group and 150 in the placebo group. The invasive cancers in the combination group were similar in histology and grade to those in the placebo group but were larger (1.7 cm vs. 1.5 cm), more advanced (regional/metastatic cancer 25.4% vs. 16%), and more likely to be node positive (25.9% vs. 15.8%).

After 1 year of treatment, the percentage of women with abnormal mammograms was substantially greater in the combination therapy group (9.4% vs. 5.4%). Overall by the end of the study, 31.5% of treated women had at least one abnormal mammogram, compared with 21.2% of those in the placebo group.

In first-time users, invasive breast cancer rates were lower than the placebo group for the first 2 years of the study, similar in the third, and higher in the fourth year and beyond. In previous users, rates were higher than the placebo group by the third year.

The early development of more breast cancers in the combination group was unexpected; most recent reviews of observational studies suggest that breast cancer risk would be increased mainly with longer-term (>5 years) hormone use. “This discrepancy could be related to estrogen plus progestin hindering mammographic identification of breast cancers,” the investigators said. But Ms. de Vane countered that “this study doesn’t actually tell us that.”

In an interview, Dr. Robert Reid urged caution in interpreting the results.

“Women without prior hormone use, which amounted to 75% of the women in the WHI, showed no statistically significant increase in breast cancer at any annual evaluation, although the trend for an increased risk over time was statistically significant. Women with prior hormone exposure showed a statistically significant increased risk only in year 5, based on annual evaluation and a significant trend for increasing risk over time,” said Dr. Reid, professor of obstetrics and gynecology and head of reproductive endocrinology at Queen’s University in Kingston, Ont.

“Accordingly, the concern that short-term hormone therapy may be causing cancers needs to be viewed with caution. … It is equally possible that the older women in WHI had preexisting cancers that were unmasked by hormone therapy and that prior hormone users had a cumulative exposure to hormones longer than that reflected by the years reported in the WHI study.”

A second study in the same issue found that women who take combined HRT have a 1.7-fold increased risk of breast cancer, compared with women who have either never used menopausal hormones or who used estrogen replacement with no progestin (JAMA 289[24]:3254-63, 2003).

The population-based, case-control study of 975 breast cancer patients between ages 65 and 79 years found that hormone users had a 2.7-fold increased risk of invasive lobular carcinoma, a 1.5-fold increased risk of invasive ductal carcinoma, and a 2-fold increased risk of estrogen receptor +/ progesterone receptor+ breast cancers. Risks generally increased with increasing duration of hormone use and were associated with sequential and continuous combined estrogen / progestin regimens. “Women using unopposed estrogen replacement therapy, even for 25 years or longer, had no appreciable increase in risk of breast cancer,” said Dr. Christopher I. Li and associates at the Fred Hutchinson Cancer Research Center and the University of Washington, Seattle.

COPYRIGHT 2003 International Medical News Group

COPYRIGHT 2003 Gale Group