Clinical review

Advice about mammography for a young woman with a family history of breast cancer

Anneke Lucassen, consultant ^a, Eila Watson, senior research officer ^b, Diana Eccles, consultant ^a. 

^a Wessex Regional Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, ^b CRC Primary Care Education Research Group, Department of Primary Health Care, University of Oxford Institute of Health Sciences, Oxford OX3 7LG

Correspondence to: A Lucassen annekel{at}soton.ac.uk

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.

	An area of confusion

Top An area of confusion Searching for evidence Evidenceor the lack of... The limitations of mammography The patient's risk Advice to the patient References

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

Top An area of confusion Searching for evidence Evidenceor the lack of... The limitations of mammography The patient's risk Advice to the patient References

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.

	Evidenceor the lack of it

Top An area of confusion Searching for evidence Evidenceor the lack of... The limitations of mammography The patient's risk Advice to the patient References

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.

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	The limitations of mammography

Top An area of confusion Searching for evidence Evidenceor the lack of... The limitations of mammography The patient's risk Advice to the patient References

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 specificityThe 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 riskRegular 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 women ^{15 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

Top An area of confusion Searching for evidence Evidenceor the lack of... The limitations of mammography The patient's risk Advice to the patient References

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

Top An area of confusion Searching for evidence Evidenceor the lack of... The limitations of mammography The patient's risk Advice to the patient References

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.

	Acknowledgments

We thank Jon Emery and Peter Rose for their comments on an earlier draft.

Contributors: AL identified the subject for the case report, participated in the literature search and assimilation of evidence, and wrote the paper; she will act as guarantor. EW participated in the literature search and in discussing and assimilating the evidence and contributed to the writing of the paper. DE contributed to the literature search and commented on the paper.

	Footnotes

Competing interests: None declared.

	References

Top An area of confusion Searching for evidence Evidenceor the lack of... The limitations of mammography The patient's risk Advice to the patient References

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