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Should We Recommend Screening Mammography for Women Aged 40 to 49?

Should We Recommend Screening Mammography for Women Aged 40 to 49?

ABSTRACT: In clinical trials, screening mammography has been shown to reduce mortality from breast cancer by about 25% to 30% among women aged 50 years and older after only 5 to 6 years from the initiation of screening. Among women 40 to 49 years old, the evidence supporting the efficacy of screening mammography is less convincing. Eight randomized controlled trials have reported no statistically significant reduction in breast cancer mortality among women age 40 to 49 years after 7 to 9 years from the initiation of screening. After 10 to 12 years from the initiation of screening, there is a trend toward a reduction in breast cancer mortality that appears to be smaller than that observed in women age 50 and older. Even if there is a small delayed reduction in breast cancer mortality among women age 40 to 49 years, the potential absolute benefit of screening women in this age group is likely to be small, given that the incidence of breast cancer is low. Since there is strong scientific evidence that mammography reduces breast cancer mortality among women age 50 and older, our national focus should be on screening these women who have the most to benefit. [ONCOLOGY 10(3):357-376, 1996]

Introduction

In evaluating the controversy over regular screening mammography
for women 40 to 49 years old, it is important to remember that
the goal of screening is to reduce mortality from breast cancer.
As we will discuss below, the benefit of screening is clear for
women age 50 years and over, but evidence is less compelling for
women 40 to 49 years old. If screening is beneficial for women
over 50 years old, why would it not confer the same benefit for
women 40 to 49 years of age?

In this article, we review the efficacy of screening mammography
by age, based on evidence from randomized controlled trials, and
discuss possible explanations for the differential effect of screening
mammography in younger vs older women. We also explore the potential
risks of performing widespread screening mammography among a population
of young women when the incidence of disease is low.

Basis of the Dispute

In 1987, the National Cancer Institute (NCI), along with the American
Cancer Society, recommended screening mammography for women in
their 40s despite the lack of evidence showing that such screening
reduces breast cancer mortality in this age group. At the same
time, several prominent organizations (the American College of
Physicians, American Academy of Family Medicine, US Preventive
Task Force, Canadian Task Force) did not recommend screening mammography
for women in their 40s because of the lack of evidence showing
that mammography lowers breast cancer mortality among these women.

In February 1993, the NCI convened an international workshop to
reassess whether more recent screening mammography trials demonstrated
the efficacy of mammography among women 40 to 49 years old. Based
on this workshop, the NCI withdrew its recommendation for screening
women in their 40s since there was still no scientific evidence
that screening mammography decreases breast cancer mortality among
these women [1]. Instead, the NCI advised women in their 40s to
discuss with their physician the risks and potential benefits
of screening mammography.

At present, many scientific organizations and most countries in
the world who conduct screening mammography do not recommend screening
mammography for younger women, but there are still groups in the
United States that advocate such screening (Table 1). This disagreement
among organizations may be due, in part, to differences in requirements
for recommending screening. Organizations that do not recommend
screening mammography among women in their 40s maintain that the
goal of screening mammography is to reduce the number of deaths
from breast cancer. They further argue that proof that mammography
can detect small breast tumors is insufficient grounds for recommending
routine screening in this age group. Rather, there must be scientific
evidence to show that detection of breast cancer by mammography
reduces breast cancer mortality before making such a recommendation.

Data From Randomized Controlled Trials

Randomized controlled trials are the most unbiased means to assess
whether a screening test reduces the likelihood of death in a
person who has the disease, and thus, are considered the gold
standard when evaluating the efficacy of a screening test. Table
2 summarizes data from eight randomized screening mammography
trials. Among women 40 to 49 years old, four of the eight trials
reported a nonsignificant increase in breast cancer mortality
after 7 to 9 years from the initiation of screening, whereas four
found a nonsignificant decrease, indicating a lack of statistically
significant benefit or harm from screening mammography. This is
in contrast to the data for women age 50 and older, which showed
a reduction in breast cancer mortality among all studies (Table
3).

Several meta-analyses have combined data from the randomized controlled
trials in order to quantify the overall impact of screening mammography
among women 40 to 49 years old. The first meta-analysis by Elwood
et al of published data from six of the randomized controlled
trials of screening mammography found no reduction in breast cancer
mortality in women 40 to 49 years old after 7 years from the initiation
of screening [2].

A more recent meta-analysis, which combined data from all eight
randomized controlled screening mammography trials, revealed a
nonsignificant, 2% increase in breast cancer mortality after 7
to 9 years from the initiation of screening [3]. After 10 to 12
years from the initiation of screening, combined results showed
a nonsignificant, 17% (95% confidence interval, -35% to +6% reduction
in breast cancer mortality [3].

Pooled data from the five Swedish trials and results from the
HIP trial have also suggested a benefit from screening mammography
in younger women that does not occur until after 10 years from
the initiation of screening [4-6]. A meta-analysis by Smart et
al [7] eliminated the Canadian data [8] and included unpublished
results from the Gothenborg and two-county Swedish trials. This
meta-analysis contained several errors [9];when these errors were
taken into account, the meta-analysis yielded results similar
to those previously published [5], that is, that there is a delayed
benefit, although statistically not significant, of screening
mammography in younger women.

What Accounts for the Discrepancy in Screening Efficacy by
Age?

It is unclear why the efficacy of screening mammography in women
age 40 to 49 years varies with the length of time from the initiation
of screening. The findings are most consistent with two possible
explanations:

  1. The reduction in breast cancer mortality noted after 10 to
    12 years from the initiation of screening occurs because, in women
    who start screening between 40 and 49 years old, breast cancer
    is diagnosed when the women are 50 years or older, an age at which
    mammography is known to be efficacious.
  2. A proportion of indolent tumors, if detected early among women
    in their 40s, will result in a delayed reduction in breast cancer
    mortality.

Continuation of Screening After Age 50--In the HIP study,85% of breast cancers in women who started screening between
40 and 49 years old were diagnosed between ages 45 and 54, when
most women would have become menopausal [10]. Likewise, the majority
of women in the Edinburgh and Malmo trials, which also showed
a trend toward a delayed benefit of mammography after 10 to 12
years from the initiation of screening, were also probably age
50 or older and postmenopausal when their breast cancer was diagnosed,
since the youngest age of women at the start of screening was
45 years old [11,12]. Computer modeling of the Swedish breast
cancer screening trial data estimated that most (70%) of the small
observed decrease in breast cancer mortality for women 40 to 49
years old at trial entry may be attributable to the continuation
of screening after women reach 50 years of age [13].

Differences in Tumor "Aggressiveness"--An alternative
explanation for the variation in efficacy of screening mammography
with the length of time from the initiation of screening is possible
if one accepts the premise that breast cancer is a heterogeneous
disease with two basic forms: a "less aggressive" form
that mammography detects in time for treatment to be effective
and a second form that is more rapidly fatal regardless of early
mammographic detection. In women 40 to 49 years old, mammography
may detect some less aggressive tumors that are more curable than
similar tumors detected clinically, but because they are less
aggressive, a reduction in breast cancer mortality among screened
women is delayed for up to 10 to 12 years. If this is true, the
reduction in mortality among screened women age 50 and older,
who tend to have slower tumor growth rates [14], should also be
delayed for 10 to 12 years. Yet, mammography reduces breast cancer
mortality by about 25% after only 5 to 6 years from the initiation
of screening in older women.

This finding suggests that, in women age 50 and older, mammography
is able to detect "more aggressive" tumors, since a
significant reduction in breast cancer mortality among screened
women occurs after only 5 to 6 years from the initiation of screening.
It further suggests that mammography detects a substantial proportion
of less aggressive tumors, since the cumulative reduction in breast
cancer mortality increases over time. However, among women 40
to 49 years of age, the proportion of less aggressive tumors detected
by mammography is small, which may account for the marginal, delayed
reduction in breast cancer mortality among screened women. This
hypothesis is supported by the observation that a greater proportion
of small, screening-detected tumors are associated with positive
lymph nodes among women 40 to 49 years old when compared to similar
screening-detected tumors in older women [15].

Summary of Meta-analysis Results--In summary, based on
the results of meta-analyses, there is no reduction in breast
cancer mortality among women 40 to 49 years old who undergo screening
mammography for 7 to 9 years. It is important to emphasize that
if screening mammography is effective in reducing breast cancer
deaths among women age 40 to 49 years, the reduction in deaths
does not occur for at least a decade following the initiation
of screening and appears to be smaller than the reduction observed
in women age 50 and older. Furthermore, since it is appears that,
among women who start screening in their 40s, the majority of
breast cancers are detected by mammography after they reach age
50 or older or become menopausal, it may be possible to wait to
begin screening then and achieve the same mortality benefit as
would occur if screening were started at age 40.

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