A 35 year old woman with a family history of breast cancer was in need of advice. Her two sisters, aged 34 and 38, were healthy and not affected, but her mother had developed breast cancer at the age of 48, and her mother's paternal aunt had developed it at 39 (figure). The sisters lived in different parts of the United Kingdom. Her elder sister had been told that this family history was not important and that she would not need any screening until she was eligible for the national screening programme, whereas her younger sister had already had a mammogram and been told that she should have these yearly from the age of 35. The patient was confused and asked her general practitioner whether she should have mammography. The general practitioner wrote to the local genetics service for advice.
Summary points
There have been no randomised controlled trials of mammography in women under 50 with a family history of breast cancer
The sensitivity and specificity of mammography are lower in women aged under 50 than in those over 50
There is no NHS funding for mammographic screening of women under 50 with a family history of breast cancer, although such screening is performed regularly
The current consensus view is that mammography for women under 50 is appropriate if there is a certain degree of family history of breast cancer
Guidelines for such screening are available locally through most clinical genetics departments
An area of confusion
Our experience with such enquiries suggested that the patient and her doctor were not alone in their confusion. Nationally and internationally, recommendations for screening women under 50 with a family history of breast cancer vary enormously. When family members are separated geographically they often receive different advice in both primary and secondary care. There is a plethora of local guidelines in the United Kingdom, which list varying degrees of family history needed before women under the age of 50 should be referred for mammography, but these are largely based on the opinions of local experts.
Breast screening in the general population has been shown to reduce mortality in women aged 50-64.1,2 However, screening women in the general population below the age of 50 is much more controversial. Some trials have reported a reduction in mortality in this age group, but this reduction, if real, is much smaller and takes longer to appear than for women aged over 50, and the adverse consequences of screening have been shown to be greater.1,3 We wanted to know what evidence exists to suggest that mammography is worth while in women aged under 50 with a family history of breast cancer.
Searching for evidence
We started searching for evidence with the easy option: typing “detection breast cancer in women with a family history” and “diagnosis” into the PubMed clinical query site (www.ncbi.nlm.nih.gov/pubmed/clinical.html). This gave 55 hits. Excluding reviews and non-English publications, there were five papers examining mammography in women with a family history.4–6,8,9 We tried the alternative phrase “management women with family history breast cancer.” This gave 50 hits, which did not include any of the above five but did identify a further relevant paper.10 We next searched Medline for the period January 1995 to December 2000, combining free text words “mammography” or “breast screening” and “family history.” This search yielded 114 papers in English, including all but the most recent of the six papers found using the clinical query and one additional study.11 We also searched the Cochrane Database of Systematic Reviews and Best Evidence but found no relevant studies.
Evidence—or the lack of it
There have been no randomised controlled trials looking at the effectiveness of mammography for women under 50 with a family history of breast cancer. Six of the seven studies listed in the table are small studies (European and Canadian), and all have slightly different comparison groups. The only large study was an American study in 2000 comparing cancer detection rates in screened women with and without a family history. Four of the studies reported that the rate of detection of cancer in women under 50 with a family history is comparable to that seen in women over 50 in a screening programme, and one study found more cancers in higher risk groups than lower risk groups. Most of these studies combined mammographic screening with clinical breast examination and one combined it with breast self examination, which is not the case with the British national screening programme, and two papers commented on the importance of using a combination of screening modalities. Furthermore, not all the papers gave full details of the type of mammography (for example, one or two views, dosage of radiation) used.
From the studies that investigated the pathological features of the detected tumours, it seemed that screening young women with a family history will detect cancers at an earlier stage than if they presented with symptoms, suggesting that a survival benefit may be expected. However, importantly, no evidence yet exists to show that mortality from breast cancer in this group of women will decrease as a result of early mammography.
The limitations of mammography
The potential benefits of offering mammography to this group have to be weighed against the potential harms, and most of the papers we examined listed potential problems with screening women under 50 with a family history by mammography that need to be considered. Searching Medline with the MeSH heading “mammography” and subheading “adverse effects” and limiting the search to publications in English for 1995-2000, we found studies on the limitations of mammography. We also examined some of the references cited in the papers in the table. The studies could be divided into two broad categories.
Reduced sensitivity and specificity—The younger breast is more dense and hence more radio-opaque, and studies have shown that the sensitivity and specificity of mammography are lower for women below the age of 50 and also for women with a family history of breast cancer.12 This results in a greater number of false negatives and false positives,12 which may lead to false reassurance or unnecessary further tests with associated anxiety and adverse psychological consequences.13 One study estimated that over a nine year period of annual mammograms the chance of a false positive mammogram in women aged 40-69 years was 43% (increasing to 100% for those who have a family history together with other risk factors such as benign breast disease or oestrogen use).14
Radiation risk—Regular mammography carries a cumulative risk due to radiation. Dose and age at exposure are the two most important determinants of this risk, and hence the risk is theoretically greater for younger women. In addition, those who have an inherited predisposition to cancer may be more susceptible to environmental carcinogens such as radiation. Several studies have attempted to estimate the number of deaths from breast cancer induced by breast screening in women under 50 compared with the number of deaths prevented. Bearing in mind the uncertainties inherent in modelling studies of this nature, these studies all show that the benefit to risk ratio is considerably less favourable for women under 50 than for older women. Some authors conclude that the benefits of mammography still clearly outweigh the theoretical risks of radiation in younger women15,16; others seem to cautiously support this conclusion.17,18 One British study which specifically considered the issue of family history concluded that there is cause for concern if screening is extended to women aged less than 30, or less than 40 if women with a family history are shown to have increased susceptibility to radiation.19
Some of these concerns may be resolved if the trials of breast screening with magnetic resonance imaging (which carries no radiation risk) for women at high risk prove successful. Early results show higher sensitivity and specificity than mammography, but larger trials are awaited.20
The patient's risk
No randomised controlled trials have looked at the effectiveness of mammography in younger women with a family history of breast cancer, and these may never be conducted because some experts now believe that it would be unethical to randomise women to no mammography. The studies which have been published provide evidence that the detection rate of cancer in women under 50 with a family history of breast cancer is equivalent to that in women over 50 in the general population who are screened. The limited pathology data also suggest that it is reasonable to expect a survival advantage in women with a family history of breast cancer. There does, therefore, seem to be growing evidence to support the widespread pragmatic approach of mammographic screening in women below the age of 50 if a family history is strong enough. But what level of family history is enough?
Standard texts cite family history as one of the strongest risk factors for breast cancer. Risk is increased by the number and type of affected first and second degree relatives, onset of disease before age 50, and the woman being under 50 at the time of risk assessment. Different degrees of family history were used as criteria for screening in the studies listed in the table. Our search thus did not find evidence for a particular risk category for family history above which mammography might be indicated. We infer however that the stronger the family history the better the cancer detection rate.
Advice to the patient
For now, therefore, we have to base the decision on whether to offer mammography to a woman with a family history of breast cancer on much weaker evidence than we would like. A widely adopted pragmatic approach is to offer mammography where the risk due to family history for a woman under 50 years is at least equivalent to the risk for a woman over 50 in the general population. This roughly equates to a threefold increased risk of breast cancer by the age of 50 compared with the general population. With this approach, the patient would be eligible for mammography, which ideally should be part of a quality assured process that can be audited.21,22
We thought the patient should be made aware of the limited evidence and the potential disadvantages of mammography and these were discussed with her in full at the genetic clinic. She had been unaware of these issues and had thought that only cost issues were involved in the decision process. In the end, although aware of the limitations, she decided she would like to have mammography and this was arranged for her.
Table.
Studies examining screening by mammography for women aged under 50 with a family history of breast cancer
| Study | Degree of family history | Frequency of mammographic screening (from age) | Type of breast examination | Number of women | Cancer detection rate | Stage of tumours detected |
|---|---|---|---|---|---|---|
| Kerlikowske et al4 | Any first degree relative | Annual (varied) | None | 389 533 (25 837 aged <50 with family history) | Similar to women a decade older with no family history and higher than women matched for age with no family history | Not examined |
| Macmillan et al5 (includes data from different centres, including data from Lalloo et al6 and Kollias et al8) | Any first degree relative under 50 | Varied | None | 8 783 | Greater than expected figures for general population matched for age; similar to women over 50 in NHSBSP | Screen detected tumours earlier stage than symptomatic age matched population Similar to NHSBSP |
| Lalloo et al6 | At least 1 in 6 lifetime risk (calculated from Claus et al7) | Annual (from 35) | Clinical (annual) | 1 259 | Greater than expected figures for general population matched for age; similar to women over 50 on NHSBSP | |
| Kollias et al8 | At least one first degree relative under 60 or 1 in 9 lifetime risk (calculated from Claus et al7) | Every two years (10 years before earliest onset in family) | Clinical (annual) | 1 371 | Similar to women over 50 in NHSBSP | No differences in tumour size and grade between screened and symptomatic group |
| Chart et al9 | One first degree relative under 45 or prior breast disease or hormonal risk factors without family history (divided into low, medium, and high risk groups) | Annual (10 years before earliest onset in family) | Self (monthly) and clinical (annual) | 986 (all ages; No aged under 50 not given) | Detection rate greater in “high risk” group than in “low risk” group, but need a combination of self examination and clinical examination | |
| Moller et al10 (includes data from seven different European centres, including data from Lalloo et al6) | Genetic risk twice the population risk (calculated from Claus et al7) At least one first degree relative under 40 or first and second degree relatives with average age over 55 | Variable (usually annual from age 35) | Self and clinical ("regularly") | 161 tumours identified prospectively (62 in women aged under 50; total No of women screened not given) | Tumour incidence rates higher than expected rates for age | Greater proportion of tumours detected by screening node negative compared with other tumours |
| Tilanus-Lindthorst et al11 | One first degree relative under 50 or two second degree relatives under 50 | Annual (five years before youngest age of onset in relative) Subset also had magnetic resonance imaging | Clinical (annual) | 678 (all ages; No aged under 50 not given) | More cancers detected at early stage in screened group compared with symptomatic women with a family history |
NHSBSP=UK National Breast Screening Programme.
Figure.
The patient's family history of breast cancer
Acknowledgments
We thank Jon Emery and Peter Rose for their comments on an earlier draft.
Footnotes
Competing interests: None declared.
References
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