Breast cancer is not a single disease.
Rather it is any of up to 15 different types of breast disease all of which
behave in different ways. Hence, many frustrating questions arise when dealing
with breast cancer concerning our lack of knowledge of the cause, natural
history and biological behaviour of these cancers, including DCIS (ductal
carcinoma in situ). It is these issues that should receive maximum research
funding if we are to beat breast cancer. However, they are currently
overshadowed by ongoing controversies regarding screening efficacy, and in
particular the age at which screening should be commenced. I continue to see
scientific evidence that screening of women under 50 years of age is effective
and therefore support Tim and Debbie Short’s submission.
There are a number of objections to extending breast cancer screening to this age group. Perhaps the only irrefutable one is that this option would be costly, not only due to the large number of women in this age group (baby-boomers bulging the 40s) but also to the fact that cancer is less common in this age group than it is in older women, thus increasing the cost per cancer found ratio. This economic argument overshadows the scientific literature, which is extensive.
It has been argued that mammography in women under 50 does not work because breast tissue is too dense. This has been refuted. Advances in screening equipment have rendered this objection obsolete1. Furthermore, there is no significant difference in mammographic denseness between the two decades (40-50s and 50-60s)2. It is true there are some types of cancers which are very difficult to see on mammogram – at times completely invisible. This is particularly true of lobular breast cancer, but the problems of detection are similar in the under- and over-50s. In both age groups approximately 10% of breast cancer is not visible on mammography.
Thirdly it has been argued that the low rate of breast cancer in this age group does not justify exposing the vast majority of healthy women to the radiation of mammography. Dr Blue has comprehensively answered this point in her submission, pointing out, for example, that the radiation dose received by the breast during a mammographic screening is equivalent to that received every three months from normal ambient radiation. Further data can be found in a review by Feig3.
Another major argument against screening mammography has been the over-diagnosis of DCIS. A recent paper by Yen4 shows that 37% of DCIS was estimated to be non-progressive (would not have progressed to invasive disease if left untreated) in the prevalence screen (women who have not had a previous mammogram). In the subsequent incidence screen (women who have had a mammogram within the previous five years) the non-progressive DCIS was estimated to be 4%. Therefore in subsequent mammograms DCIS is not over-diagnosed.
Finally, it has been suggested that screening women for a disease which, in their age group, will occur in only four about of 1000 women subjects the rest to unnecessary psychological, physical and social stress. However, the desire for reassurance is paramount in most women aged 40-495, and is in fact the main reason why most women who participate in mammographic screening studies do so.
There is also undoubtedly a perception that radiologists such as myself advocate screening in the 40-49 year-old group to increase our workload and hence our income. Speaking for myself, my workload is more than enough as it is, and breast screening is neither the most lucrative nor the most satisfying aspect of it. Looking at thousands of normal mammograms is very demanding, and telling the few women whose results are abnormal that they may have a cancer, and subsequently performing breast biopsies is emotionally draining. Furthermore, breast imaging is now the most litigatious area of radiology, which when combined with its low rate of remuneration is a factor in the decreasing interest among radiology trainees in specialising in this area. In the USA, this trend has now reached crisis stage. I am making this submission only because after 16 years of breast screening, I feel I am in a position of some expertise and continue to be deeply committed to women’s health.
The rationale for mammographic screening is to detect breast cancer at a smaller size and earlier stage than would otherwise be the case, thus interrupting the natural history of the disease. Many studies have shown that the prognosis for breast cancer is improved in direct proportion to the size of the cancer when first detected. The average size of a breast cancer detected by screening mammography is 10-15mm compared to 20-25mm when found clinically as a palpable lump. That this results in a reduction in mortality has been confirmed by Swedish studies that show that the mortality from breast cancer between 1961 and 1992 was reduced by 43% in the screened community compared to the rest of Sweden where the reduction was 17%6.
Merely showing that women whose cancer is detected earlier live longer is not sufficient to claim a true benefit. But this can be shown conclusively using randomised control trials (RCT) in which a large group is randomly divided and one half is offered screening while the other half acts as a control group. RCTs overcome all biases such as lead-time bias and length time bias.
There is almost complete agreement that RCTs of breast screening have demonstrated that screening is efficacious. These trials were not specifically designed to examine the subject of 40-49-year-olds. The combined (meta-analysis) data from RCTs suggest a reduction of 35% in mortality. This is considered to be an under-estimate for women who actually have a mammogram. In RCT analysis, all women invited to have a mammogram are considered to have actually had a mammogram. The non-attenders dilute the result. Therefore the actual benefit for an individual woman is calculated to be a 45% reduction in mortality7.
There have been eight RCTs. These studies had important differences in recruitment, age group studied and interval between mammograms. There have been recent controversial claims by Gotzsche and Olsen8 that RCT results are not valid because of supposed flaws in the randomisation and ascertainment of cause of death. This has been refuted by numerous scientific papers, summarised by Duffy9. The largest and most robust study to date10 on the benefits of mammography show that screening reduces breast cancer by around 44% in women aged 40 to 69 years. This study is based on a 20-year follow-up; the longest-running programme yet reported.
The authors found a similar reduction in deaths in women between 40 and 49 years as in older women. In the younger age group there was a significant 48% reduction in breast cancer mortality in those women screened, and a 19% reduction in those left unscreened. This latter figure was not statistically significant, and therefore cannot be simply subtracted willy-nilly from the figure of 48%. While its existence may be purely accidental, it is probably worth bearing in mind that the control group were a group of women who, having been made aware of the risks of breast cancer, were left to their own devices. They were not prevented from having mammograms or taking any other precautions they thought necessary. The reduction of 48% is higher than the usually quoted meta-analysis of 35% for two reasons. Most importantly, because this data related to high-quality screening with two views every 18 months, and secondly because there was an 85% compliance rate. It has been calculated that if 100% of the women had had mammographic screening, the reduction in breast cancer deaths would have been 55%. In contrast, programmes where single-view mammography is performed every three years show, not surprisingly, no reduction in mortality.
Here in New Zealand we also perform two-view mammography, but only once every two years. The above results emphasise the need for short-interval (12-18 months) screening for women aged 40-49 years to yield this reduced mortality.
Thirty to forty per cent of breast cancers present in women under the age of 50. But this relatively high proportion is due to the fact that there are a large number of women in this age group – not to the prevalence of the disease. Breast cancer becomes more prevalent with increasing age. In women aged 50-69 there will be seven new cancers per 1000 first attenders in a screening programme. In contrast, for women under 50 there will be four new cancers per 1000 women screened for the first time. To find these four cancers approximately 20 women will be recalled for extra mammographic images and ultrasound and eight needle biopsies will be performed. For 16 of these women these further tests will prove to be negative. This is the ‘false positive’ group, who undeniably are put through considerable anxiety and discomfort. In the majority of cases the negative results of screening are accurate. This is called the true negative and comprises 94% of the screened population. However, for around 0.06% of the screened population the results are falsely negative. These women will be erroneously reassured, and a correct diagnosis will be delayed. On the other hand, the true positive group (0.6%) benefit from early diagnosis and ensuing mortality reduction.
Because of the lower incidence and close interval of required screening (yearly) the cost of cancer detection is significantly higher than in the over 50s. Screening is no less efficacious. Whether it is cost-effective needs to be evaluated not only against the higher screening, treatment and management cost, but also the cost to the community and to the economy of lost productivity. The effect of mammography screening using modern equipment begins to impact upon mortality rates after seven years, and increases steadily after that10. More than 40% of the years of life lost to breast cancer are from women who contracted the disease before the age of 50.
We know that some types of breast cancer have the potential to dedifferentiate (worsening of malignancy grade during tumour growth). Tabar11 has reported extensively on tumour dedifferentiation and states that in the 40-54 year age group 81% of cancers have this potential compared to only 50% in older women. This is a further argument in support of the need for early detection in younger women.
As mentioned above, breast cancer is not a single, uniform disease. In an ideal world we would focus considerable time and resources upon gaining a better understanding of the biological behaviour of the tumour. However, in this country this is currently unfeasible, so we must look instead to the best way of managing the disease after it has occurred – at making sure our ambulance at the bottom of the cliff is at the bottom of the right cliff at the right time! To establish how best we may do so, we must focus on evidence-based medicine, not anecdotes. The RCT trials underestimate the benefit of screening – for an individual woman it is probably more than the 48% reduction in mortality recently shown. As Duffy12 has recently said “The time for repeatedly visiting the trials has gone. The challenge for the future is to evaluate the effects of the service screening programmes which are springing up around the world, and to pinpoint potential improvements where possible. … Arguing the toss about long-completed trials distracts us from making further progress.”
FRACR
Lakeland Health & Lakes Radiology.
Rotorua
Auckland Medical School