Breast cancer screening

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There have been at least seven randomized controlled trials of mammographic screening over the last 30 years. The HIP study of New York and the Two Counties Study from Sweden both showed a 30% reduction in mortality in the >50-year-old age group who were screened with mammography. Meta-analysis of all the published trials confirms a significant benefit for the over-50s.

None of the trials published so far have shown a mortality benefit for women under the age of 50 years, although two meta-analyses report a 14% but non-significant reduction in mortality. Screening the under-50 age group remains a controversial area and in the UK a current trial is recruiting over 200 000 women to address this question.

Imaging modality

The aim of screening for this disease is to identify pre-invasive disease or invasive disease before dissemination (through the lymphatics or blood). There is no evidence that simple breast self-examination is an effective means of screening for breast cancer. X-ray mammography is the most sensitive technique for detecting breast cancer and is also the most specific. Mammography is most sensitive once involution of the breast tissue has occurred (i.e. once the menopause has taken place). The test is less sensitive in women with dense breasts—that is those with predominantly glandular tissue or residual stromal tissue.

Breast ultrasound, useful for focal abnormalities, is also useful in detecting impalpable lesions. Telediaphanography (infrared scanning of the breast tissue) has both low sensitivity and specificity. Magnetic resonance imaging with dynamic intravenous contrast is a very sensitive technique but variable specificity has been reported.

Mammographic technique

The breast is compressed to flatten the breast tissue to reduce movement, overlapping shadows, and radiation dose. The uniform thickness of the tissue improves image quality and contrast. Low-energy radiation is passed through the breast, resulting in a high-contrast image. The image is recorded on X-ray film presently, but in the future will be digitally recorded, with display on a high-resolution computer screen.

Two views of each breast are performed—one in the lateral oblique position diagonally across the chest, the other in the cranio-caudal position. Some 7% of women find the examination very painful, and a large proportion find it uncomfortable. The compression of the breast tissue lasts only a few seconds.

Table 17.3 Indications for referral to breast clinic

♦ Screen-detected breast cancer

— any new discrete lump

— new lump in pre-existing nodularity

— asymmetrical nodularity persisting after menstruation

— abscess/inflammation which does not settle after one course of antibiotics

— persistent or recurrent cyst

—associated with a lump

— intractable pain which interferes with the patients life and fails to respond to simple measures (well-supporting bra, simple analgesics, abstention from caffeine, evening primrose oil)

— unilateral persistent pain in post-menopausal women

♦ Nipple discharge

— in younger women if blood-stained, persistent single duct or bilateral, sufficient to stain clothes

♦ Nipple retraction, distortion, or eczema

♦ Change in breast skin contour

Radiation dose

A low radiation dose of approximately 2 mGy per examination is used. The radiation risk is 1-2 excess cancers per million women screened after a latent period of 10 years in the post-menopausal age group but is higher in women under 30 years. The dose to the breast is approximately five times that of a chest X-ray.

Organization of the UK Breast Screening Programme

In the UK, women aged 50-64 years are invited through their GP, to attend either a breast screening centre or a mobile van for mammog-raphy every three years. Women aged over 64 years can self-refer every three years. It was thought that the over 64-year-old age group would be less likely to take up screening, but this has not been substantiated in European screening programmes. The 65-69-year-old age group will in the future be formally invited for screening as there is a higher yield of cancers in this older age group. The under-50 age group will not be invited until the UK CCCR age trial, screening 40-49-year-olds, is completed.

The mammograms are read by a consultant radiologist. If an abnormality is seen which is thought to be suspicious, the woman is recalled to an assessment clinic at the breast screening centre. A clinical examination is performed at the recall visit with further X-rays, an ultrasound examination, and a needle test for cytology or core biopsy if appropriate. Women thought to have cancer are referred promptly to a breast surgeon who will arrange appropriate treatment.

An average of 72% of women accept the invitation to be screened and approximately 5% of women are recalled for further tests; 5 cancers per 1000 women screened are found.

The quality of the UK programme is monitored rigorously, with regular checks on all aspects of screening. Performance data on breast screening centres, as well as individuals within the centre, are monitored annually.

Interval cancers

These are cancers that occur in the interval between two screening episodes. They fall into five categories:

♦ True interval cancer: where a cancer appears in the 3-year interval and was not present on the previous screening mammogram.

♦ False negative: where the lesion was present on the previous screening mammogram.

♦ Technical: where the cancer was not on the film due to its position.

♦ Mamographically occult: where the cancer is not visualized on either the screening mammogram or at the time of diagnosis.

♦ Unclassifiable: no mammogram taken at the time of diagnosis. There are approximately 12 interval cancers per 10 000 women screened in the first two years after screening and 13 interval cancers appear in the third year.

One- or two-view screening

The UK NHS Breast Screening Programme was initially funded for one X-ray (lateral oblique view) of each breast. A large trial comparing one-view with two-view mammography has shown that the second view results in a 24% increase in detection rate compared with singleview mammography.

All women attending screening for the first time have two views performed and screening centres are encouraged to perform two-view mammography on all women. The additional radiation dose for the second view is very low.

Frequency of mammography

Many European countries offer screening every two years, whereas the UK service is currently funded to perform screening every three years. There is a large ongoing UK trial looking at the question of frequency of screening. Although there is almost certainly increased detection of cancers when screening every two years, it may be that the large costs associated with more frequent screening will outweigh the benefit.

Screening for high-risk groups

Women thought to have strong family history of breast cancer are recommended to have genetic counselling and not assessment. If they are found to be at more than 16% risk, then mammographic screening is recommended. Meta-analysis of screening data of 40-50-year-olds suggests there is a non-significant benefit of mammography. At present, annual mammography is performed, with data being systematically collected. The MRC have funded a multi-centre trial to determine the place ofmagnetic resonance imaging in the detection of asymptomatic breast cancer. Women who are BRCA1, BRCA2, or p53 gene carriers, or at 50% risk of being a gene carrier, are being recruited into this study of annual MRI and mammography.

Features of screen-detected breast cancer

The expected outcome of breast cancer screening is a reduction in breast cancer deaths. Other useful measures are the pathological features of screen-detected tumours, which should reflect earlier disease compared with symptomatic women. This has been confirmed in a number of studies that show:

♦ 10-20% screen-detected disease is non-invasive

♦ >30% invasive cancers are less than 10 mm diameter

♦ 70-80% of patients are node negative

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