Full Text Review
Screening for Breast Cancer
Prepared by Brenda J. Morrison, PhD, Professor,
Department of Health Care and Epidemiology, University of British
Columbia, Vancouver, BC
These recommendations were finalized by the Task Force in January 1994
Contents
Overview
Screening by clinical examination and mammography
is recommended for women age 50 to 69; the basis for this recommendation
is that seven randomized controlled trials (RCTs), using one or both of
these modalities, have shown a survival benefit in this age group.<
1>
However, although more than 150,000
women between the ages of 40 and 49 were enrolled in these trials no significant
decrease in breast cancer mortality was demonstrated for them. As a consequence
it is now recommended that women younger than 50 not be screened, whereas
in 1986 the
Task Force found insufficient evidence to make a recommendation for this
age group.<2>
Some cohort studies<3-6> suggest a decreased
mortality for women who practice breast self-examination (BSE), but the
biases implicit in this type of study make it impossible to make a positive
recommendation with regard to the teaching and practice of BSE. This recommendation
remains unchanged from that made in 1986.<2>
Burden
of Suffering
Breast cancer is the third most common cause of death
in women in Canada and excluding skin cancer is the most common cancer
in women in Canada.<7> There were an estimated 16,300
new cases of breast cancer in Canada in 1993
and an estimated 5,400 deaths. Over the last 20 years the incidence rate
has increased by about 15%
whereas the mortality has remained relatively stable.<8>
Within Canada, there is an east-west gradient with
lower rates in the east. Risk factors for breast cancer include hormonal,
dietary and hereditary factors. Early menarche, late menopause and delayed
first pregnancy are associated with higher risk. There is some evidence
linking high intake of dietary fat to risk of breast cancer; family history,
obesity, alcohol use, ionizing radiation and post-menopausal estrogen replacement
therapy (see Chapter 52) have also been associated with increased risk,
while the evidence for oral contraceptives is more controversial.
Maneuver
There are three maneuvers to be considered. They are
clinical examination of the breasts, mammography, and self-examination
of the breasts. Some of the seven RCTs carried out these screening maneuvers
in combination, and some separately; the prescribed frequencies of the
mammographic screenings varied from 12
to 33 months. The sensitivities and specificities of detection varied widely
between the trials<1>
depending on the maneuver(s) that were employed, the length of the interval
between screenings, the underlying incidence of the disease and the method
of calculating estimates of the screening proficiency. For sensitivity
the range was 46-88%; for specificity, it was 82-99.9%. In the Canadian
trial the sensitivity, using the ratio of screen-detected cases to all
cases, of annual mammography plus clinical examination was 88% in women
50-59 and 81%
in the women 40-49. Specificity, using surgical biopsy as the definition
of a positive case, ranged from 96.5% to 99.9%. For the younger women,
the ratio of benign biopsy to malignant biopsy was about 9:1
on
the first screen, dropping to 6:1
on
later screens.<9> For women 50 and over, it was about 5:1
on
the initial screen, dropping to 3:1
for
later screens.<10>
Effectiveness
of Prevention and Treatment
Clinical Examination
and Mammography
The seven screening trials enrolled women whose age
at entry ranged from 40 to 74. In three of the trials individuals were
the unit of randomization; in the the other four the units were neighbourhood
or practice clusters. The four trials which were located in Sweden investigated
only the benefits of mammography.
Clinical Examination
and Mammography forWomen Aged Over 50 years
The original trial, that of the Health Insurance Plan
(HIP) of New York,<11>
demonstrated a significant mortality reduction with a relative risk (RR)
of 0.45 five years after entry in women aged 50 to 59.<12>
After nine years this rose to 0.67.<13>
The combined Swedish trials,<14>
after 7 to 12
years of follow-up,<1>
also showed a significant benefit extending to the age of 69 (RR=0.71).
The Edinburgh trial<15>
at 10 years
of follow-up produced a non-significant benefit (RR=0.85). Compliance in
this trial was poor though and the study and control groups were found
to differ on factors that could have affected survival. The Canadian trial,<10>
which in the 50-59 year old age group looked only at the benefits of mammography
over and above that of annual clinical examination, found an improved survival
rate (RR=0.97), but at 7 years of follow-up the improvement was not statistically
significant.
Clinical Examination
and Mammography for Women Aged 40-49 years
Most interest in breast screening has centered about
benefit for the 40-49-year-old women. In this age group the HIP showed
a non-None significant
decrease in mortality (RR=0.95) five years after entry.<12>
At nine years this had dropped to 0.81
but
it was still not significant.<13>
However, the number of women in the group was not large and consequently
the power of the test was low. Because of these two factors the Task Force
in its 1986
report gave a C Recommendation for the 40-49 year olds.<2> Now with
seven trials reporting, and two of them, the Swedish Two County trial and
the Canadian trial,<9> having large numbers of compliant enrollees,
there is now a considerable amount of evidence. None of the trials showed
a significant benefit. The relative risks ranged from 0.51
to
1.36.
In the five trials that had reported early age-specific follow-up, increased
mortality occurred in this younger age group in all of the studies (in
the Malmo trial the younger age group was composed of women 45-54). In
the HIP the excess of deaths disappeared after 3 years but in the other
trials it lasted for seven or eight years. Of all the trials, the Canadian
study showed the greatest excess, RR=1.36
(95% confidence interval: 0.84-2.21);
this was after seven years of follow-up. This is not really surprising
since the Canadian trial was the only one of the seven which was an efficacy
trial and the results of efficacy trials are expected to be more extreme
than those of effectiveness trials.
At present plans are being made to organize and carry
out a RCT in Europe and the U.S. of 1.5
million women age 40-42, who will be followed for 10
years.<16>
Breast Self-Examination
(BSE)
Before the introduction of mass screening programs,
the vast majority of tumours were reputed to have been detected by the
women themselves. As a consequence of this, breast self-examination was
and is advocated by various bodies and organizations in the hopeful expectation
that early detection will result in improved survival. Five studies<2,17-20>
have shown an association between the practice of BSE and factors associated
with better survival, such as stage, tumour size or axillary node involvement,
but other studies have shown no benefit.<21-23>
Four studies compared the survival rates from breast
cancer in women who had been taught or practiced BSE and in those who had
not been instructed or did not practice it. Foster looked at those who
had performed it regularly with those who had not. At five years the respective
rates were 75% and 57% (p<0.0002). Locker compared all those invited
to attend an instructive course in BSE with an historical group of cases.
The latter had slightly better survival despite having poorer prognostic
indicators. However, after seven years of follow-up those in the instructed
group who attended had a significantly lower mortality in contrast with
those who did not attend (p<0.001).
Le Geyte compared those who practiced BSE with those who had never been
taught it. After 6 years of follow-up the respective survival rates were
73.1% and
66.1% (p=0.07).
Kuroishi compared those who had found their cancer by self-examination
with those who had found theirs by chance. After five year the follow-up
rates were significantly different (p<0.001)
but at ten years the difference was no longer significant, suggesting that
the apparent improvement was due to lead-time bias. The results of all
of these studies could have been distorted by lead-time, length-time and
self-selection bias.
Recommendations
of Others
In 1992
the U.S. Preventive Services Task Force (USPSTF) called for annual clinical
breast examinations after age 40, mammography every 1
to
2 years beginning at age 50 and early screening of women at increased risk
for breast cancer.<24> These recommendations are currently under review.
The differences between our recommendations and the USPSTF could be accounted
for by the recent publication of longer follow-up results from several
of the trials.
Conclusions
and Recommendations
Since all of the trials demonstrated a mortality reduction
in the 50-69 age group, the Task Force recommends breast screening for
women of this age (A
Recommendation). Because the relative contributions of mammography
and clinical examination have not yet been fully ascertained, both manuevers
are recommended. Also, since from the limited data available it is not
possible to deduce confidently if biennial screening is as effective as
annual screening, the Task Force advises that annual screening be maintained.
Wherever possible, screening should be done at centers dedicated to this
purpose.
In view of the absence of a significant benefit and
the possibility that screening and intervention might be causing harm,
the Task Force recommends that until further evidence is available, women
age 40-49 not be screened (D
Recommendation).*Note: This recommendation has been
updated.
Link to Recommendation Table of
2001 Update: Screening mammography among women aged 40-49 years at average risk
of breast cancer
The evidence is not strong enough to make a clear
recommendation on teaching breast self-examination; there is insufficient
evidence to either include or exclude such teaching in periodic health
examinations for women (C
Recommendation). *Note:
This recommendation has been updated.
Link to Recommendation Table of
2001 Update: Should women be routinely taught breast self-examination to screen
for breast cancer?
Unanswered
Questions (Research Agenda)
In 1990
a gene responsible for a sizeable proportion of familial breast cancer,
possibly 45%, and 80% of familial ovarian cancer,<25> was localized
by genetic linkage on the long arm of chromosome 17.<26>
The gene, BRCA1,
has not yet been isolated but some screening, by means of linkage, is being
performed on high risk women.<27-29> Two other genes relating to breast
cancer have also been localized<30> ESR and p53 (associated with the
Li-Fraumeni syndrome). It is estimated that inherited susceptibility occurs
in 1 in 200
women in the U.S. and may be responsible for about 10-15%
of premenopausal breast cancer. BRCA1
and
p53 appear to be autosomal dominants and relate most strongly to premenopausal
breast cancer. The penetrance of the BRCA1
gene
has been estimated to be at least 50% by age 50 and 80% by age 80, and
that for the p53 gene, slightly higher. At present identification requires
blood samples from many members of a family, including those who have developed
the disease, but in the near future these genes will be isolated and cloned.
Then individuals carrying the genes will be able to be identified by a
simple blood test. This scientific breakthrough is a mixed blessing for
those found to have the gene, but for those who are found to be negative
the knowledge will bring substantial relief. Centres presently carrying
out this screening have set up intensive counselling programs for sessions
prior and subsequent to testing and disclosure.
Unlike the situation with Huntington’s Chorea, "preventive"
strategies (preventive in terms of breast and ovarian cancer) are presently
available. They are bilateral mastectomy and oophorectomy, or medication
with tamoxifen. These are radical measures; nevertheless, many women who
consider themselves at high risk are prepared to undergo these treatments.
No randomized trials of the efficacy of prophylactic mastectomy or oophorectomy
have been carried out specifically in the women carrying these genes, but
there is some evidence that both of these measures have reduced the risk
in women who have undergone them. A large RCT is being carried out on tamoxifen
at present.<31>
Screening for these breast cancer genes will probably be the first widespread
presymptomatic genetic test for adults in general medical practice.<25>
Evidence
The evidence reviewed was identified from the collection
of the author and using a MEDLINE search in November 1993
using the key words: breast neoplasms, mass screening, guideline, familial
or genetic markers.
This review was initiated in March 1993
and recommendations were finalized by the Task Force in January 1994.
Full Citation
Link to Structured Abstract of
this review
Link to Summary Table of this
review
Link to Selected References list of this review
Link to 2001 Update: Screening
mammography among women aged 40-49 years at average risk of breast cancer
Link to 1999 Update: Follow-up
after breast cancer
Link to 1998 rewording of
recommendation for screening women aged 50-59 for breast cancer
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