WASHINGTONThere is really no reason to doubt that
mammography screening works for women in their 40s, and saves
lives, said Stephen A. Feig, MD, director of the Breast Imaging
Center at Thomas Jefferson Hospital and professor of radiology at the
Jefferson Medical College, both in Philadelphia.
Addressing a plenary session of the 28th National Conference on
Breast Cancer of the American College of Radiology, he cited
scientific proof from randomized trials that mammographic
screening cuts breast cancer deaths in younger women, and made a
strong case for annual rather than less frequent screening of women
in their 40s.
Randomized trials, he said, are easier said than done.
However, most randomized trials have shown benefits for screening
women in their 40s, he said, and the few that have not are marred by
substantial flaws in their design and implementation.
The very influential HIP study done in New York in the 1960s
established a significant reduction in breast cancer mortality with
mammographic screening in a study population aged 40 to 64, Dr. Feig
said. When broken down by decade, the results showed a 23% mortality
reduction in women aged 40 to 49 with screening, but this was not
statistically significant. Yet, he explained, some of the other
older decade groups did not reach statistical significance either.
He finds it amazing that this was overlooked, and
emphasized that no one has ever said, dont screen women
in their 50s, because of this studys findings. In fact,
he stated, the study enrolled too few women in their 40s to establish
statistical significance.
The Great Guidelines Controversy
In 1993, the National Cancer Institute rescinded a guideline
recommending mammography screening for women in their 40s, a decision
made, in part, because of the findings of the National Breast Cancer
Screening Study of Canada, a trial marred by many serious flaws, Dr.
Feig said. Poor quality mammography and faulty randomization render
this studys results worthless, he maintains.
Only a third of the mammograms in the Canadian study met acceptable
technical standards, he said. Further, a decision to do clinical
exams before randomization encouraged coding clerks to place the bulk
of those with palpable masses, including late-stage breast cancers,
in the experimental group that would receive mammographic screening,
in hopes that these womens cancers would be found and treated.
This rendered the results invalid, he explained.
Because breast cancer occurs less commonly in younger than in older
women, studies of younger women need more subjects in order to find
sufficient cases for statistical significance, he said. Younger
womens denser breasts also make good mammography technique more
important. Furthermore, because many cancers in younger women grow
faster than those in older women, the screening intervals must
actually be shorter to avoid missing interval cancers.
Also influencing the NCIs 1993 decision, Dr. Feig said, was the
fact that metaanalyses done at that time showed no benefit for women
in their 40s, although subsequent metaanalyses with longer term
follow-up have shown a statistically significant benefit, with the
mortality differences increasing and the confidence limits narrowing
with each study.
In addition, metaanalyses of five trials done in Sweden found a
statistically significant mortality drop of 29%. Several of the
Swedish trials by themselves have now attained statistical
significance and have shown 35% and 45% reductions in breast cancer
deaths for women in their 40s, Dr. Feig observed.
The NCI had set statistical significance as the goal for recommending
mammo-grams for women in their 40s, but when that evidence emerged,
they pulled the goal post back, he said. The 1993
conclusion was obsolete even when made and is all the
more so now.
We were really incredulous at the decision, he said,
adding that Richard Klausner, MD, director of the National Cancer
Institute, expressed surprise and disappointment, and referred the
question to the National Cancer Advisory Board, which came back with
a decision opposite that of the NCI.
The guideline was changed in 1997, Dr. Feig noted, and a number of
leading bodies in addition to the NCI now recommend mammography
screening for women in their 40s. Even two of the experts who served
on the initial NCI panel now also advise annual screening for this
age group, he said.
Dr. Feig also said that women in their 40s need to be screened every
year rather than less frequently. Although none of the trials
compared different screening intervals, he said there is compelling
evidence that annual mammographic screening will save more lives than
biennial screening.
Since breast cancers grow at different rates, some can reach the
clinical threshold between biennial screenings, and the lead
time to the clinical stage will be shorter in younger
women, he said. Therefore, we may have to screen younger
women much more frequently than every 2 years. The incremental
benefit of more frequent screening is greater in younger women
because the cancer is growing faster.
Indeed, he said, its more than coincidental that the two
trials with the shortest screening intervals showed the greatest
impact on death rate. In the Swedish Two County trial, younger
women had proportionately twice as many interval cancers as older
women. Interval cancers have lower survival rates than
screen-detected cancers at all ages, he added.
Clearly, Dr. Feig concluded, younger women need more frequent
mammography screening than they received in most trials in order to
reduce the number of interval cancers.