Mammography Screening: Truth, lies and controversy
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The fourth edition of the European guidelines for quality assurance in breast cancer screening and diagnosis was published by the European Commission in 2006. The present supplements to the fourth edition have been produced by the same groups of experts originally established under the Europe Against Cancer programme that have developed and updated the guidelines since the early 1990s. Over the years, the scope and the depth of the multidisciplinary guidelines have expanded, and recommendations and protocols have been updated to keep pace with developments in the field. The present supplements lay a cornerstone for a new, completely revised fifth edition of the guidelines
We review our work over the past 14 years that began when we were first confronted with bimodal relapse patterns in two breast cancer databases from different countries. These data were unexplainable with the accepted continuous tumor growth paradigm. To explain these data, we proposed that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell phase and the avascular micrometastasis phase. We also suggested that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. These iatrogenic events are apparently very common in that over half of all metastatic relapses progress in that manner. Assuming this is true, there should be ample and clear evidence in clinical data. We review here the breast cancer paradigm from a variety of historical, clinical, and scientific perspectives and consider how dormancy and surgery-driven escape from dormancy would be observed and what this would mean. Dormancy can be identified in these diverse data but most conspicuous is the sudden synchronized escape from dormancy following primary surgery. On the basis of our findings, we suggest a new paradigm for early stage breast cancer. We also suggest a new treatment that is meant to stabilize and preserve dormancy rather than attempt to kill all cancer cells as is the present strategy.
Context
Patients with prostate cancer and their physicians need knowledge of
treatment options and their potential complications, but limited data on complications
are available in unselected population-based cohorts of patients.Objective
To measure changes in urinary and sexual function in men who have undergone
radical prostatectomy for clinically localized prostate cancer.Design
The Prostate Cancer Outcomes Study, a population-based longitudinal
cohort study with up to 24 months of follow-up.Setting
Population-based cancer registries in 6 geographic regions of the United
States.Participants
A total of 1291 black, white, and Hispanic men aged 39 to 79 years who
were diagnosed as having primary prostate cancer between October 1, 1994,
and October 31, 1995, and who underwent radical prostatectomy within 6 months
of diagnosis for clinically localized disease.Main Outcome Measures
Distribution of and change in urinary and sexual function measures reported
by patients at baseline and 6, 12, and 24 months after diagnosis.Results
At 18 or more months following radical prostatectomy, 8.4% of men were
incontinent and 59.9% were impotent. Among men who were potent before surgery,
the proportion of men reporting impotence at 18 or more months after surgery
varied according to whether the procedure was nerve sparing (65.6% of non–nerve-sparing,
58.6% of unilateral, and 56.0% of bilateral nerve–sparing). At 18 or
more months after surgery, 41.9% reported that their sexual performance was
a moderate-to-large problem. Both sexual and urinary function varied by age
(39.0% of men aged <60 years vs 15.3%-21.7% of older men were potent at ≥18
months [P<.001]; 13.8% of men aged 75-79 years
vs 0.7%-3.6% of younger men experienced the highest level of incontinence
at ≥18 months [P = .03]), and sexual function
also varied by race (38.4% of black men reported firm erections at ≥18
months vs 25.9% of Hispanic and 21.3% of white men; P
= .001).Conclusions
Our study suggests that radical prostatectomy is associated with significant
erectile dysfunction and some decline in urinary function. These results may
be particularly helpful to community-based physicians and their patients with
prostate cancer who face difficult treatment decisions.
Prostate cancer is the most frequently diagnosed solid tumor in US men.
An estimated 179,300 men will be diagnosed as having the disease in 1999,1 and in more than 70% of these patients, the disease
will be clinically localized.2 Treatment options
for men with tumors confined to the prostate who have at least a 10-year life
expectancy include radical prostatectomy, external beam radiation, brachytherapy,
or expectant management. Each of these approaches is associated with a different
spectrum of morbidity and effects on quality of life, which may be short-term
or long-term.
To make informed choices about treatment alternatives, patients with
prostate cancer and their physicians need accurate information to assess the
potential and pattern of complications associated with each option. Numerous
investigators have assessed urinary and sexual function 1 or more years after
radical prostatectomy, with rates of incontinence ranging from 4% to 40% and
impotence from 29% to 75%.3- 12
These findings reflect the experiences of patients from selected clinical
practices,3- 5,7- 9,12
a health maintenance organization,10 and Medicare
recipients.6,11 Differences in
patient mix, study size, and data collection methods may explain the wide
range of results.
Limited data are available to describe the outcome experiences of unselected
population-based patients. We report results from the multicenter Prostate
Cancer Outcomes Study (PCOS), which has completed longitudinal assessments
of functional status in a large community-based cohort of patients with prostate
cancer treated with radical prostatectomy for clinically localized disease.
Screening mammography differs between the United States and the United Kingdom; a direct comparison may suggest methods to improve the practice.
To compare screening mammography performance between the United States and the United Kingdom among similar-aged women.
Women aged 50 years or older were identified who underwent 5.5 million mammograms from January 1, 1996, to December 31, 1999, within 3 large-scale mammography registries or screening programs: the Breast Cancer Surveillance Consortium (BCSC, n = 978 591) and National Breast and Cervical Cancer Early Detection Program (NBCCEDP, n = 613 388) in the United States; and the National Health Service Breast Screening Program (NHSBSP, n = 3.94 million) in the United Kingdom. A total of 27 612 women were diagnosed with breast cancer (invasive or ductal carcinoma in situ) within 12 months of screening among the 3 groups.
Recall rates (recommendation for further evaluation including diagnostic imaging, ultrasound, clinical examination, or biopsy) and cancer detection rates were calculated for first and subsequent mammograms, and within 5-year age groups.
Recall rates were approximately twice as high in the United States than in the United Kingdom for all age groups; however, cancer rates were similar. Among women aged 50 to 54 years who underwent a first screening mammogram, 14.4% in the BCSC and 12.5% in the NBCCEDP were recalled for further evaluation vs only 7.6% in the NHSBSP. Cancer detection rates per 1000 mammogram screens were 5.8, 5.9, and 6.3, in the BCSC, NBCCEDP, and NHSBSP, respectively. Recall rates were lower for subsequent examinations in all 3 settings but remained twice as high in the United States. A similar percentage of women underwent biopsy in each setting, but rates of percutaneous biopsy were lower and open surgical biopsy higher in the United States. Open surgical biopsies not resulting in a diagnosis of cancer (negative biopsies) were twice as high in the United States than in the United Kingdom. Based on a 10-year period of screening 1000 women aged 50 to 59 years, 477, 433, and 175 women in the BCSC, NBCCEDP, and NHSBSP, respectively, would be recalled; and for women aged 60 to 69 years, 396, 334, and 133 women, respectively. The estimated cancer detection rates per 1000 women aged 50 to 59 years were 24.5, 23.8, and 19.4, respectively, and for women aged 60 to 69 years, 31.5, 26.6, and 27.9, respectively.
Recall and negative open surgical biopsy rates are twice as high in US settings than in the United Kingdom but cancer detection rates are similar. Efforts to improve US mammographic screening should target lowering the recall rate without reducing the cancer detection rate.
Twenty-five years after its first description the p53 protein has been shown to play a key role in both cancer and ageing. The p53 protein is activated by many different stress pathways, including oncogene action and DNA damage. The elucidation of the p53 response, which is aberrant in most cancers (including breast, lung, stomach and colorectal cancer), has provided many new targets for drug development and p53 gene therapy is now approved in China. In tumours where p53 is mutant small molecules may be able to restore its function. In many tumours the wild-type p53 gene remains intact but its function is compromised by loss of upstream signalling pathways or downstream effectors. A key regulator is Mdm2, an E3 ubiquitin ligase, that binds and ubiquitinates p53 and directs its degradation via the proteosome. Small potent peptides that can block the p53 Mdm2 interaction and activate the p53 response have been described. Growing selections of lead small molecules that mimic the action of these peptides have also been recently discovered. Cell-based screens have revealed that inhibitors of nuclear export and inhibitors of transcription (one of which is in clinical trial) can also activate the p53 response therapeutically. The pharmaceutical regulation of the p53 pathway offers great hope for improved treatment of human cancer.
We analysed the relation between tumour sizes and stages and the reported effects on breast cancer mortality with and without screening in trials and observational studies. The average tumour sizes in all the trials suggest only a 12% reduction in breast cancer mortality, which agrees with the 10% reported in the most reliable trials. Recent studies of tumour sizes and tumour stages show that screening has not lowered the rate of advanced cancers. In agreement with this, recent observational studies of breast cancer mortality have failed to find an effect of screening. In contrast, screening leads to serious harms in healthy women through overdiagnosis with subsequent overtreatment and false-positive mammograms. We suggest that the rationale for breast screening be urgently reassessed by policy-makers. The observed decline in breast cancer mortality in many countries seems to be caused by improved adjuvant therapy and breast cancer awareness, not screening. We also believe it is more important to reduce the incidence of cancer than to detect it 'early.' Avoiding getting screening mammograms reduces the risk of becoming a breast cancer patient by one-third.
The BMJ has published several articles over the past few years raising concerns about the accuracy and transparency of information provided to women about the benefits and harms of mammography screening for breast cancer ( BMJ 2006;332:538, doi:10.1136/bmj.332.7540.538; 2009;338:b86, doi:10.1136/bmj.b86; 2010;340:c3106, doi:10.1136/bmj.c3106). Last month the professor of complex obstetrics Susan Bewley sent us for publication an open letter to England’s cancer tsar. Here we publish the letter and Mike Richards’s response ( BMJ 2011;343:d6843, doi:10.1136/bmj.d6843)
Dear Mike
Personal reasons propelled me into the debate on breast cancer screening. As a house officer (in the early 1980s) working for two surgeons—one still performing “frozen section, query proceed to radical (Halsted) mastectomy” and the other promulgating the perceived heretical practice of breast conservation by lumpectomy—we dealt with what seemed an inevitably fatal disease. After my sister’s discovery in 2006 of a malignant lump when in her mid-40s I was impressed by the intervening improvements in diagnosis, treatment, care, and prognosis, which were based on a continuing programme of research evidence.
Approaching 50, with a family history of the cancer (grandmother, aunt, and sister) and risk factors (late childbearing, low parity, obesity), I had to consider …
To the Editor: I am enclosing a short research paper, which I would appreciate your considering for publication in the Journal. Introduction: I subscribe to The New England Journal of Medicine. Materials and Methods. I took the eight original articles in the September 30 and October 14, 1976, issues of the Journal and studied them. Results: My analysis of these eight original articles reveals the following facts: there are 46 authors (range, two to 12 authors per article, and mean, 5.75 authors per article); the length of these articles, excluding references, is 33 pages. . . No extract is available for articles shorter than 400 words.
Objectives
To estimate the degree of overdiagnosis of breast cancer in a mammographic screening programme.
Setting
A mammography service screening programme in Florence, Italy.
Methods
We studied the incidence of breast cancer in Florence between 1990 and 1999, following the introduction of screening in 1990. Incidence of breast cancer in this period was compared with incidence between 1985 and 1989, before the introduction of screening. It was necessary to estimate the number of cancers that would have arisen in the absence of screening, but after the end of followup (31 December 1999), so that these were not misclassified as overdiagnosed tumours. Around 60,000 women aged 50–69 were invited for screening during the period of study.
Results
There were 2780 breast cancers diagnosed during the period of study (2626 were invasive). There was no significant evidence of overdiagnosis of invasive cancers. When invasive and in situ cancers were considered together, around 5% of cases were overdiagnosed.
Conclusions
There is a small amount of overdiagnosis of ductal carcinoma in situ in mammography screening; however, this should not deter women from being screened. Training and practice in mammographic screening should emphasise detection of small, invasive lesions. Research into the natural history and treatment of the disease should aim at minimising overtreatment of those in situ lesions that are less likely to progress to invasive disease.
"Why do life-saving prescription drugs cost so much? Drug companies insist that prices reflect the millions they invest in research and development. In this gripping exposé, Merrill Goozner contends that American taxpayers are in fact footing the bill twice: once by supporting government-funded research and again by paying astronomically high prices for prescription drugs. Goozner demonstrates that almost all the important new drugs of the past quarter-century actually originated from research at taxpayer-funded universities and at the National Institutes of Health. He reports that once the innovative work is over, the pharmaceutical industry often steps in to reap the profit. Goozner shows how drug innovation is driven by dedicated scientists intent on finding cures for diseases, not by pharmaceutical firms whose bottom line often takes precedence over the advance of medicine. A university biochemist who spent twenty years searching for a single blood protein that later became the best-selling biotech drug in the world, a government employee who discovered the causes for dozens of crippling genetic disorders, and the Department of Energy-funded research that made the Human Genome Project possible--these engrossing accounts illustrate how medical breakthroughs actually take place. The $800 Million Pill suggests ways that the government's role in testing new medicines could be expanded to eliminate the private sector waste driving up the cost of existing drugs. Pharmaceutical firms should be compelled to refocus their human and financial resources on true medical innovation, Goozner insists. This book is essential reading for everyone concerned about the politically charged topics of drug pricing, Medicare coverage, national health care, and the role of pharmaceutical companies in developing countries."
Objective: To compare breast cancer mortality in 40- to 49-year-old women who received either 1) screening with annual mammography, breast physical examination, and instruction on breast self-examination on 4 or 5 occasions or 2) community care after a single breast physical examination and instruction on breast self-examination. Design: Individually randomized, controlled trial. Setting: 15 Canadian centers. Participants: 50 430 volunteers age 40 to 49 years, recruited from January 1980 to March 1985, who were not pregnant, had no previous breast cancer diagnosis, and had not had mammography in the preceding 12 months. Interventions: Breast physical examination and instruction on breast self-examination preceded random assignment of 25 214 women to receive mammography and annual mammography, breast physical examination, and breast self-examination and 25 216 women to receive usual community care with annual follow-up. Measurements: verified breast cancer incidence and cohort mortality through 31 December 1993 and deaths from breast cancer through 30 June 1996. Results: The 105 breast cancer deaths in the mammography group and 108 breast cancer deaths in the usual care group yielded a cumulative rate ratio, adjusted for mammography done outside the study, of 1.06 (95% CI, 0.80 to 1.40). A total of 592 cases of invasive breast cancer and 71 cases of in situ breast cancer were diagnosed by 31 December 1993 in the mammography group compared with 552 and 29 cases, respectively, in the usual care group. The expected proportions of nonpalpable and small invasive tumors were detected on mammography. Conclusion: After 11 to 16 years of follow-up, four or five annual screenings with mammography, breast physical examination, and breast self-examination had not reduced breast cancer mortality compared with usual community care after a single breast physical examination and instruction on breast self-examination. The study data show that true effects of 20% or greater are unlikely.
It would be fair to say that the BMJ tends towards less rather than more medicine. We’ve published a lot over the years on the risks of overtreatment and the problems of medicalisation. It’s not a bad default to have in times of economic hardship, although I hope we also do our bit to highlight evidence of undertreatment where it exists. In a recent letter David Oliver warned that, although ageing should not be routinely medicalised, there is a risk of “socialising” treatable problems in older people such as incontinence and falls ( BMJ 2009;338:b1200).
With that proviso, I’m drawn to several articles this week that …
This book presents a wealth of experience derived from improvements in UK screening over recent years and it covers all aspects of screening. The first four chapters of the book deal with concepts, methods, and evidence, explaining what screening is and how it is evaluated. Chapters five to eight describe practical aspects, for example how to make policy, and how to deliver screening to a high standard. The book includes many examples and real-life case histories, a glossary of medical terms, and each chapter concludes with a summary and self-test questions. Reference is made to the UK National Health Service, a leader in screening, but the book is internationally relevant because the principles of good screening apply in any setting. The controversies, paradoxes, uncertainties, and ethical dilemmas of screening are explained in a balanced way.
The conventional wisdom about breast cancer screening is coming under sharp attack in Britain, and health officials there are taking notice. They have promised to rewrite informational fliers about mammography after advocates and experts complained in a letter to The Times of London that none of the handouts "comes close to telling the truth" — overstating the benefits of screening and leaving out critical information about the harms. What women are not told, the letter said, is that for every woman whose life is saved by breast cancer screening, up to 10 healthy women are given diagnoses — and, often, surgery — for a cancer that is so slow-growing it would never have threatened a woman's life. "The culture is just that mammography is such a very sensible thing to do, so you chug along and have it done," said one of the signers, Hazel Thornton, in a telephone interview. Mrs. Thornton, 75, said she became disenchanted with routine screening more than 15 years ago, after a mammogram identified ductal carcinoma in situ, a noninvasive breast cancer that often does not progress. She had a lumpectomy, but was offered such a confusing array of treatment options that she realized doctors knew little about how aggressively to treat this kind of cancer. "You don't know about all the uncertainty until you're one of the unlucky ones, and it happens to you," she said. The idea that mammography may do more harm than good may be alien to many American women. The prevention message has emphasized that screening protects women from breast cancer, and one survey of 479 women found that only 7 percent were aware that some cancers grow so slowly that even without treatment they will not affect a woman's health. A 2006 analysis by the Nordic Cochrane Center collaborative, an independent research and information center based in Copenhagen, found that for every 2,000 women age 50 to 70 who are screened for 10 years, one woman will be saved from dying of breast cancer, while 10 will have their lives disrupted unnecessarily by overtreatment. The figures were cited in the letter to The Times.
Background The long term effect of mammographic service screening is not well established. We aimed to assess the long-term effect of mammographic screening on death from breast cancer, taking into account potential biases from self-selection, changes in breast cancer incidence, and classification of cause of death.
Letter to the Editor. Comments to the letters by Per-Henrik Zahl and Jan Maehlen and by Peter C Gotzsche concerning our article: : Increased incidence of invasive breast cancer after the introduction of service screening with mammography in Sweden
This article describes the background, implementation, organization, and outcomes of the nationwide mammography breast cancer screening program in the Netherlands. Since 1998, all Dutch women aged 50 to 75 years get a personal invitation for a mammography every 2 years. The main objective of the program that started in 1990 for women aged 50 to 69 is the reduction of breast cancer mortality by detecting and treating breast cancer in an early stage. Eighty percent of the invited women participate in the program. Some 1% of the screened women are referred for additional clinical assessment of suspect mammography lesions; in almost half of them, breast cancer eventually is confirmed. Breast cancer screening resulted in a temporary strong increase in in situ and small lymph node-negative invasive breast cancers and a concomitant decrease of advanced disease rates. In the same period, the proportion of mastectomies decreased in favor of a rise of breast conserving surgical treatment. Since 1997, breast cancer mortality has decreased significantly and has reached a 25% lower level 15 years after the start of the nationwide screening program. Undoubtedly, the screening program contributed to this decline, together with improved breast cancer treatment.
There are plenty of substantive disputes in the controversy over mammography screening for women in their forties. But one
individual has raised the level of acrimony even further, say his colleagues. This screening advocate has repeatedly charged
his opponents with fraud and deception, an approach some of his colleagues consider intemperate.
Why are women told only the benefits of breast screening and none of the possible harms?I have seen enough women die from breast cancer to know very clearly what a terrible disease it can be and to understand the motivation that drives attempts to promote early diagnosis and curative treatment. It is not possible to take this issue lightly, and yet I have cheerfully declined successive NHS invitations to attend for my own screening mammography. My worry is that I have made this decision on the basis of information that is not readily available to my patients.In the United Kingdom each mammography invitation encloses the leaflet Breast Screening: The Facts, a title that in itself seems to deny any sense of the uncertainties permeating the programme. The unforgivable feature of this leaflet is that, despite protests and promises of improvement, it still emphasises only the benefits of screening and makes no mention of the possible harms. Yet every practising clinician knows that screening always produces harms as well as benefits. The reassuring tone of the leaflet conveys a clear expectation that any rational, socially …
The BMJ finds itself in the middle of many spats—academic, clinical, and political. I like to think that’s when the journal is really earning its keep. The BMJ’s rapid responses are its gladiatorial forum; open to all who are willing to engage with the arguments, preferably with references and data, and provided always that they refrain from ad hominem attacks on opponents. Several good clean fights are under way: is the H1N1 vaccine safe in children (www.bmj.com/cgi/eletters/340/jun09_3/c2994) and should homoeopathy be provided on the NHS (www.bmj.com/cgi/eletters/340/jun30_2/c3513), as well as thoughtful discussions on carotid endarterectomy (www.bmj.com/cgi/eletters/341/jul21_1/c3879), assisted suicide (www.bmj.com/cgi/eletters/341/jul20_3/c3943) and Iona Heath’s article on how and when we die (www.bmj.com/cgi/eletters/341/jul21_3/c3883). You can watch or join in.Some fights get into the letters pages, where we also now have a Response section for those who have been written about in the journal and want to put their side of the story. But occasionally a fight is just too difficult to compress into a few hundred words. This was the case with breast cancer screening. A BMJ article—one of several published in the past few years by the Danish team led by Peter Gøtzsche—again questioned the benefits of mammography and highlighted the harms from overdiagnosis (BMJ 2010;340:c1241). Supporters of breast cancer screening howled in alarm at the damage this was doing to the uptake of mammography (www.bmj.com/cgi/eletters/340/mar23_1/c1241). The two sides have thrown data across the divide and the BMJ has been accused of taking sides. I think I can speak for all the editors in saying that the BMJ doesn’t take sides on such matters: we look to the evidence. Unable to see sufficient light amidst the heat of this debate, we asked a highly trusted observer of preventive health strategies, Klim McPherson, to take a look and come to a view. My reading of his helpful article (doi:10.1136/bmj.c3106) is that those who argue that screening may be almost as harmful as it is beneficial could have a point. “There is no doubt that screening for breast cancer has limited benefit and some possibility of harm for an individual woman and marginal cost effectiveness for a community,” he writes. He calls for a full and dispassionate examination of individual patient data from all recent studies and, in the meantime, much more honesty from the NHS screening programme about the scientific uncertainties. There is also a sense of measured outrage. How could such an important national programme exist for so long with so many unanswered questions? Could it have done so purely on face validity (“early detection must be good”) plus uncertainty fuelled by polarised debate? If so, he says, that would be “irresponsible.” Heated discussion is also bubbling around the proposed reorganisation of the NHS and we now have a sizeable collection of related articles, discussion threads, blogs, podcasts, and BMJ learning modules at doc2doc.bmj.com/whitepaper. In the journal we have Martin Roland’s editorial (doi:10.1136/bmj.c3985) and Nigel Hawkes’s commentary (doi:10.1136/bmj.c4035), and we have asked a range of other commentators to share their thoughts (doi:10.1136/bmj.c3977). One of them is John Appleby, who notices that opinions seem unconventionally split, with ex-Labour advisers supporting the proposals and right of centre think tanks opposing them. We would welcome your own views via rapid responses on bmj.com.NotesCite this as: BMJ 2010;341:c4096FootnotesFollow BMJ Editor Fiona Godlee on Twitter at twitter.com/fgodlee and the BMJ at twitter.com/bmj_latest
BACKGROUND
The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screening outside of research settings (so-called “service screening“) faces unique methodologic and conceptual challenges. The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties.METHODS In the group of subjects ages 20–69 years, there were 6807 women diagnosed with breast carcinoma over a 29-year period in 2 counties in Sweden and 1863 breast carcinoma deaths. All patients were classified from patient charts based on their screening status (i.e., whether they had been invited to undergo screening and whether they actually had undergone screening). The number of women who lived in the 2 counties during the 29-year study period was provided by the Central Bureau of Statistics. Breast carcinoma-specific mortality was compared across three time periods: 1) 1968–1977, when no screening was taking place because mammography had not been introduced; 2) 1978–1987, the approximate period of the Two-County randomized controlled trial of screening in women ages 40–74 years; and 3) 1988–1996, when all women in the 2 counties ages 40–69 years were invited to undergo screening (service screening). When comparing breast carcinoma mortality in screened women with that in women diagnosed before screening was introduced, a correction for self-selection bias was incorporated to prevent overestimation of the benefit of screening.RESULTS The mortality from incident breast carcinoma diagnosed in women ages 40–69 years who actually were screened during the service screening period (1988–1996) declined significantly by 63% (relative risk [RR] = 0.37; 95% CI, 0.30–0.46) compared with breast carcinoma mortality during the time period when no screening was available (1968–1977). The mortality decline was 50% (RR = 0.50; 95% CI, 0.41–0.60) when breast carcinoma mortality among all women who were invited to undergo screening (nonattendees included) was compared with breast cancer mortality during the time period when no screening was available (1968–1977). The reduction in mortality observed during the service screening period, adjusted for selection bias, was 48% (RR = 0.52; 95% CI, 0.43–0.63). No significant change in breast carcinoma mortality was observed over the three time periods in women who did not undergo screening. This group included women ages 20–39 years because these individuals were never invited to undergo screening, and women ages 40–69 years who did not undergo screening (not invited during the randomized trial or invited during the second and third time periods but declined).CONCLUSIONS Regular mammographic screening resulted in a 63% reduction in breast carcinoma death among women who actually underwent screening. The policy of invitation to organized screening with mammography appears to have reduced breast carcinoma mortality by 50% in these 2 counties. Cancer 2001;91:1724–31. © 2001 American Cancer Society.
which com-pared a group of women invited to screening with a control group ofwomen not invited, provided data indicating that there was a signif-icant reduction in mortality during the 10-year period of the scientificstudy. The controlled trial was followed by a 9-year period, when allwomen between the ages of 40–69 years in the same geographic areawere offered mammographic screening. This 9-year period had an85% attendance rate at the offered screenings. Control group contam-ination (women who obtained mammograms anyway) and experi-mental group compliance problems (women who were invited butdid not get mammograms) of the trial were obviated in the mostrecent period by offering the entire age-defined population an invi-tation to screening. Data from these successive periods were com-pared with the 10 years prior to the beginning of the trial, when noscreening was performed, and the results of the comparative analysisof the 3 periods are presented in their report. Tabar and his col-leagues
Using 1,973 breast tumours from women aged 40–69 participating in the Swedish two-county trial of mammographic screening for breast cancer, we examined the effect of histological type on prognosis and sojourn time (the duration of the preclinical screen-detectable phase) by age. The hypothesis of dedifferentiation, according to which a cancer of mixed malignancy grade drifts towards grade 3 as the more poorly differentiated part of the tumour grows faster than the well-differentiated part, was also assessed. Ductal carcinoma in situ, invasive ductal carcinoma of grade 1, mucinous carcinoma and tubular carcinoma were all associated with good survival. Ductal carcinoma of grade 3 was associated with poor survival. Ductal carcinoma of grade 2, lobular and medullary carcinoma were associated with intermediate survival. These patterns were much the same in women aged 40–49 as in women aged 50–69. In women aged 40–49, sojourn time was estimated at about 2 years regardless of histological type. For women aged 50–69, there was a marked association of sojourn time with histological type, the shortest sojourn time being observed for lobular (2 years) and medullary (1.2 years) carcinoma, and the longest for ductal carcinoma grade 1 (7.7 years) and tubular carcinoma (7.1 years). There was strong evidence of a potential to dedifferentiation. A mover-stayer mixture of Markov chain models estimated that, in women aged 40–54, 91% of ductal tumours have the potential to dedifferentiate and, in women aged 55–69, 38% of ductal tumours have such a potential. © 1996 Wiley-Liss, Inc.
For many years, public information about screening has been aimed at achieving high uptake but concerns are now being raised about this approach. There are several problems that have prompted these concerns. By giving information that emphasizes only the positive aspects of screening the autonomy of individuals is ignored, individuals feel angry when they perceive that they are let down by screening, symptoms may be disregarded because of the belief that screening gives full protection, health service staff carry the blame for problems that are in fact inherent in screening, and sound debate about policy and investment in screening is hampered by misunderstanding about the benefits and costs of screening.
Mike Richards and Harpal Kumar, chief executive at Cancer Research UK, were put in charge of the review but neither is independent.
For Richards, this is reflected in the references he chose for his letter.1 The first is used to support his claim of a 35% effect of breast screening in attenders, although they are healthier than non-attenders. The estimate is therefore misleading.
The second …