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
Morrison BJ. Screening for breast cancer. In:
Canadian Task Force on the Periodic Health Examination. Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994; 788-95.