Controversial Findings on the Value of Mammography to be 'Dissected†at Miami Breast Cancer Conference

March 20, 2014
Beth Fand Incollingo

Evidence-Based Oncology, November/December 2013, Volume 19, Issue SP13

A large Canadian study that has

caused a stir by indicating that

mammograms are of no use in

women aged 40 to 59 years, and in fact

can lead to over-diagnosis of breast cancer,

is flawed and misleading, according

to the program chairman of the Miami

Breast Cancer Conference.

The Canadian National Breast Screening

Study1—whose results were published

in mid-February in the British

Medical Journal and reported widely in

newspapers and on television—will also

be the subject of discussion during the

conference, the chairman, Patrick Borgen,

MD, said.

“The Canadian study is probably the

single most flawed, confounded trial in

the history of trials—certainly in trials

of mammography,” Borgen said. “This is

a trial from 34 years ago using ancient

technology and a very flawed randomization

technique which put women

with breast lumps into the mammography

arm and normal-exam women into

the control arm—and, of course, after 30

years, it showed no difference. Applying

that to today is simply outrageous.”

“We’ll be spending a lot of time at the

Miami Breast Cancer Conference dissecting

this trial, talking about it, and, frankly,

developing a group strategy for how

to overcome it,” he said. “Mammograms

save lives, and we’ll be getting that message

out loud and clear at Miami.”

In the study, Anthony B. Miller, professor

emeritus at the University of Toronto,

and 5 colleagues compared 25-year

cancer outcomes in 89,835 women aged

40 to 59 who were randomly assigned

to either receive or not receive annual

mammography screening. The trial was

launched in 1980, and the recruitment

period continued through 1985.

In women who received mammography,

screening took place over 5 years

at 15 centers in 6 Canadian provinces.

Two-view film screen mammography

was used, with craniocaudal and mediolateral

views taken until 1985; after that,

in accordance with updated guidelines,

craniocaudal and mediolateral oblique

views were taken.

Women aged 40 to 49 years in the

mammography arm and women aged 50

to 59 years in both arms received annual

physical breast examinations, while

women aged 40 to 49 years in the control

arm received a single physical breast

examination followed by usual care in

the community, the authors wrote. All

women in the study were taught breast

self-examination by trained nurses prior

to randomization.

During the 5-year screening period,

666 invasive breast cancers were diagnosed

in the mammography arm (nearly

three-fourths of them screen-detected),

with 180 of those cancers becoming fatal

within 25 years. In the control arm, 524

invasive breast cancers were diagnosed,

171 of them fatal within 25 years.

The overall hazard ratio (HR) for death

from breast cancers diagnosed during

the screening period by mammography

was 1.05 (95% confidence interval [CI],

0.85-1.30). Age made virtually no difference

in the survival outcomes of these

women, according to the authors.

Over the entire study period, 3250

women in the mammography arm and

3133 in the control arm were diagnosed

with breast cancer, and 500 and 505,

respectively, died of the disease. The

cumulative mortality from breast cancer

did not significantly differ between

women in the mammography arm and

in the control arm (HR 0.99, 95% CI 0.88-

1.12), Miller et al wrote.

Of the cancers found during the

screening period, all those in the control

arm and 68.2% in the mammography

arm were palpable, but rates of nodepositive

cancer in the groups were similar

(32.4% in the control arm and 30.6%

in the mammography arm [P = .53 for

difference]), the investigators found. Palpable

cancers were generally larger than

cancers detected only by mammography

(2.1 cm vs 1.4 cm; P <.001), and were

more likely to be node positive (34.7% vs

16.5%; P <.001), they wrote.

While the cancers detected strictly by

mammography were associated with

better survival outcomes than those

that were palpable upon diagnosis, that

result was not meaningful, the authors

argued. “Although the difference in survival

after a diagnosis of breast cancer

was significant between those cancers

diagnosed by mammography alone and

those diagnosed by physical examination

screening, this is due to lead time,

length time bias, and over-diagnosis,”

they wrote.

After 15 years of follow-up, 106 cancers

detected in the mammography arm

were attributed to over-diagnosis, meaning

they might not have otherwise become

clinically apparent within the patients’

lifetimes.

“Annual mammography in women

aged 40-59 years does not reduce mortality

from breast cancer beyond that

of physical examination or usual care

when adjuvant therapy for breast cancer

is freely available,” the authors concluded.

“Overall, 22% (106/484) of screendetected

invasive breast cancers were

over-diagnosed, representing 1 overdiagnosed

breast cancer for every 424

women who received mammography

screening in the trial.”

The investigators added that “In technically

advanced countries, our results

support the views of some commentators

that the rationale for screening by

mammography should be urgently reassessed

by policy makers.”

In discussing limitations of their findings,

the authors contended that “The

lack of an impact of mammography

screening on mortality from breast cancer

in this study cannot be explained by

design issues, lack of statistical power, or

poor quality mammography. It has been

suggested that women with a positive

physical examination before randomization

were preferentially assigned to the

mammography arm. If this were so, the

bias would only impact on the results

from breast cancers diagnosed during

the first round of screening (women retained

their group assignment throughout

the study). However, after excluding

the prevalent breast cancers from the

mortality analysis, the data do not support

a benefit for mammography screening

(HR 0.90, 95% CI 0.69-1.16).”

In recent findings, contrary to those of

the Canadian National Breast Screening

Study, a different team of investigators

reported that 4 large studies of mammography&#151;

previously thought to have

divergent results&#151;are actually fairly consistent

in demonstrating that mammograms

are associated with reduced breast

cancer mortality. Those results2 were

presented in December during the 2013

San Antonio Breast Cancer Conference

(SABCS) by Robert A. Smith, PhD, senior

director of cancer screening at the American

Cancer Society (ACS) in Atlanta.

Considered in that study were the

Nordic Cochrane review, the UK Independent

Breast Screening Review, the US

Preventive Services Task Force (USPSTF)

review, and the European Screening Network

(EUROSCREEN) review. Each review

had generated different findings regarding

how many women must be screened

with mammography in order to prevent

1 breast cancer death, with estimates

ranging from 90 to 2000, about a 20-fold

difference, Smith said.

“We wanted to understand why these

estimates differ so much,” he added in

Controversial Findings on the Value of Mammography to be 'Dissected†at Miami Breast Cancer Conference