Impact of extending screening mammography to older women: Information to support informed choices.

From 2013 through 2017, the Australian national breast cancer screening programme is gradually inviting women aged 70-74 years to attend screening, following a policy decision to extend invitations to older women. We estimate the benefits and harms of the new package of biennial screening from age 50-74 compared with the previous programme of screening from age 50-69. Using a Markov model, we applied estimates of the relative risk reduction for breast cancer mortality and the risk of overdiagnosis from the Independent UK Panel on Breast Cancer Screening review to Australian breast cancer incidence and mortality data. We estimated screening specific outcomes (recalls for further imaging, biopsies, false positives, and interval cancer rates) from data published by BreastScreen Australia. When compared with stopping at age 69, screening 1,000 women to age 74 is likely to avert one more breast cancer death, with an additional 78 women receiving a false positive result and another 28 women diagnosed with breast cancer, of whom eight will be overdiagnosed and overtreated. The extra 5 years of screening results in approximately 7 more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. Supporting informed decision making for this age group should be a public health priority.

Trends in stage-specific breast cancer incidence in New South Wales, Australia: insights into the effects of 25 years of screening mammography.

PURPOSE: Screening mammography aims to improve breast cancer (BC) prognosis by increasing the incidence of early-stage tumours in order to decrease the incidence of late-stage cancer, but no reports have investigated these potential effects in an Australian population. Therefore we aimed to identify temporal trends in stage-specific BC in New South Wales (NSW), Australia, between 1972 and 2012. METHODS: An observational study of women who received a diagnosis of BC from 1972-2012 as recorded in the NSW Cancer Registry, a population-based registry with almost complete coverage and high rates of histological verification. We analysed trends in stage-specific incidence before screening and compared them to periods after screening began. Our primary group of interest was women in the target age range of 50-69 years, though trends in women outside the target age were also assessed. RESULTS: Screening was not associated with lower incidence of late-stage BC at diagnosis. Incidence for all stages remained higher than prescreening levels. In women aged 50-69 years, the incidence of carcinoma in situ (CIS), localised and regional BC has more than doubled compared to the prescreening era, with incidence rate ratios ranging from 2.0 for regional (95% CI 1.95-2.13) to 121.8 for CIS (95% CI 82.58-179.72). Before the introduction of screening, there was a downward trend in distant metastatic BC incidence, and after the introduction of screening there was an increase (IRR 1.8; 95% CI 1.62-2.00). In women too young to screen the incidence of late-stage BC at diagnosis also increased, whereas localised disease was stable. CONCLUSIONS: The incidence of all stages of BC has increased over the past 40 years, with the greatest rise seen during the established screening period for women aged 50-69 years. Our findings suggest that some of the expected benefits of screening may not have been realised and are consistent with overdiagnosis.

Meta-analysis of breast cancer mortality benefit and overdiagnosis adjusted for adherence: improving information on the effects of attending screening mammography.

BACKGROUND: Women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. To provide this information we aimed to meta-analyse randomised controlled trials adjusted for adherence to the trial protocol. METHODS: Nine screening mammography trials used in the Independent UK Breast Screening Report were selected. Extending an existing approach to adjust intention-to-treat (ITT) estimates for less than 100% adherence rates, we conducted a random-effects meta-analysis. This produced a combined deattenuated prevented fraction and a combined deattenuated percentage risk of overdiagnosis. RESULTS: In women aged 39-75 years invited to screen, the prevented fraction of breast cancer mortality at 13-year follow-up was 0.22 (95% CI 0.15-0.28) and it increased to 0.30 (95% CI 0.18-0.42) with deattenuation. In women aged 40-69 years invited to screen, the ITT percentage risk of overdiagnosis during the screening period was 19.0% (95% CI 15.2-22.7%), deattenuation increased this to 29.7% (95% CI 17.8-41.5%). CONCLUSIONS: Adjustment for nonadherence increased the size of the mortality benefit and risk of overdiagnosis by up to 50%. These estimates are more appropriate when developing quantitative information to support individual decisions about attending screening mammography.

Use of a decision aid including information on overdetection to support informed choice about breast cancer screening: a randomised controlled trial.

BACKGROUND: Mammography screening can reduce breast cancer mortality. However, most women are unaware that inconsequential disease can also be detected by screening, leading to overdiagnosis and overtreatment. We aimed to investigate whether including information about overdetection of breast cancer in a decision aid would help women aged around 50 years to make an informed choice about breast screening. METHODS: We did a community-based, parallel-group, randomised controlled trial in New South Wales, Australia, using a random cohort of women aged 48-50 years. Recruitment to the study was done by telephone; women were eligible if they had not had mammography in the past 2 years and did not have a personal or strong family history of breast cancer. With a computer program, we randomly assigned 879 participants to either the intervention decision aid (comprising evidence-based explanatory and quantitative information on overdetection, breast cancer mortality reduction, and false positives) or a control decision aid (including information on breast cancer mortality reduction and false positives). Participants and interviewers were masked to group assignment. The primary outcome was informed choice (defined as adequate knowledge and consistency between attitudes and screening intentions), which we assessed by telephone interview about 3 weeks after random allocation. The primary outcome was analysed in all women who completed the relevant follow-up interview questions fully. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001035718. FINDINGS: Between January, 2014, and July, 2014, 440 women were allocated to the intervention group and 439 were assigned to the control group. 21 women in the intervention group and 20 controls were lost to follow-up; a further ten women assigned to the intervention and 11 controls did not answer all questions on attitudes. Therefore, 409 women in the intervention group and 408 controls were analysed for the primary outcome. 99 (24%) of 409 women in the intervention group made an informed choice compared with 63 (15%) of 408 in the control group (difference 9%, 95% CI 3-14; p=0·0017). Compared with controls, more women in the intervention group met the threshold for adequate overall knowledge (122/419 [29%] vs 71/419 [17%]; difference 12%, 95% CI 6-18; p<0·0001), fewer women expressed positive attitudes towards screening (282/409 [69%] vs 340/408 [83%]; 14%, 9-20; p<0·0001), and fewer women intended to be screened (308/419 [74%] vs 363/419 [87%]; 13%, 8-19; p<0·0001). When conceptual knowledge alone was considered, 203 (50%) of 409 women in the intervention group made an informed choice compared with 79 (19%) of 408 in the control group (p<0·0001). INTERPRETATION: Information on overdetection of breast cancer provided within a decision aid increased the number of women making an informed choice about breast screening. Becoming better informed might mean women are less likely to choose screening. FUNDING: Australian National Health and Medical Research Council.

The management of women with ductal carcinoma in situ of the breast in Australia and New Zealand between 2007 and 2016.

BACKGROUND: The incidence of detected ductal carcinoma in situ (DCIS) continues to increase and now accounts for 14% of all breast cancer, and 20%-25% of screen-detected cases. Treatment trends of DCIS are important in order to inform the ongoing debate about possible overdiagnosis and overtreatment, but have not been investigated for over a decade in Australia and New Zealand. Against this background, we aimed to describe the temporal trends in management of DCIS in Australian and New Zealander women. METHODS: Using the BreastSurgANZ Quality Audit (BQA) database, we conducted a descriptive study of the trends of management of DCIS in Australia and New Zealand from 2007 to 2016. We assessed the frequency of surgical treatments, adjuvant therapies, and axillary surgery conducted in women with pure DCIS. RESULTS: There were 17 883 cases of pure DCIS in 2007-2016 in Australia and New Zealand recorded in the BQA database. The treatment patterns were consistent with no changes over time. The most common surgical treatment was breast-conserving surgery (66%), followed by mastectomy (37%), and 36% of women with DCIS received sentinel node biopsy (SNB). CONCLUSION: The clinical management of women diagnosed with DCIS in Australia and New Zealand, appears stable over time. A substantial proportion of women with DCIS receive SNB and this aspect of surgical care warrants further exploration to determine whether it represents appropriate care. These results, alongside the outcomes of the ongoing clinical trials on the management of DCIS, will help inform if any changes to best practice treatment are required.

Informing Women About Overdetection in Breast Cancer Screening: Two-Year Outcomes From a Randomized Trial.

BACKGROUND: Supporting well-informed decisions about breast cancer screening requires communicating that inconsequential disease may be detected, leading to overdiagnosis and overtreatment. Having previously shown that telling women about overdetection improved informed choice, we investigated effects on screening knowledge and participation over 2 years. METHODS: We conducted a community-based, parallel-group, randomized controlled trial in Australia. Participants were women aged 48-50 years, without personal or strong family history of breast cancer, who had not undergone mammography in the past 2 years. We randomly assigned 879 women to receive the intervention decision aid (evidence-based information on overdetection, breast cancer mortality reduction, and false-positives) or control decision aid (identical but without overdetection information). We interviewed 838 women postintervention and recontacted them for follow-up at 6 months and 1 and 2 years. Main outcomes for this report are screening knowledge and participation. RESULTS: We interviewed 790, 746, and 712 participants at 6 months, 1, and 2 years, respectively. The intervention group demonstrated superior knowledge throughout follow-up. After 2 years, conceptual knowledge was adequate in 123 (34.4%) of 358 women in the intervention group compared with 71 (20.1%) of 354 control participants(odds ratio = 2.04, 95% confidence interval = 1.46 to 2.85). Groups were similar in total screening participation (200 [55.1%] vs 204 [56.0%]; = 0.97, 95% confidence interval = 0.73 to 1.29). CONCLUSIONS: A brief decision aid produced lasting improvement in women's understanding of potential consequences of screening, including overdetection, without changing participation rates. These findings support the use of decision aids for breast cancer screening.

Impact of Full-Field Digital Mammography Versus Film-Screen Mammography in Population Screening: A Meta-Analysis.

BACKGROUND: Breast screening programs replaced film mammography with digital mammography, and the effects of this practice shift in population screening on health outcomes can be measured through examination of cancer detection and interval cancer rates. METHODS: A systematic review and random effects meta-analysis were undertaken. Seven databases were searched for publications that compared film with digital mammography within the same population of asymptomatic women and reported cancer detection and/or interval cancer rates. RESULTS: The analysis included 24 studies with 16 583 743 screening examinations (10 968 843 film and 5 614 900 digital). The pooled difference in the cancer detection rate showed an increase of 0.51 per 1000 screens (95% confidence interval [CI] = 0.19 to 0.83), greater relative increase for ductal carcinoma in situ (25.2%, 95% CI = 17.4% to 33.5%) than invasive (4%, 95% CI = -3% to 13%), and a recall rate increase of 6.95 (95% CI = 3.47 to 10.42) per 1000 screens after the transition from film to digital mammography. Seven studies (80.8% of screens) reported interval cancers: the pooled difference showed no change in the interval cancer rate with -0.02 per 1000 screens (95% CI = -0.06 to 0.03). Restricting analysis to studies at low risk of bias resulted in findings consistent with the overall pooled results for all outcomes. CONCLUSIONS: The increase in cancer detection following the practice shift to digital mammography did not translate into a reduction in the interval cancer rate. Recall rates were increased. These results suggest the transition from film to digital mammography did not result in health benefits for screened women. This analysis reinforces the need to carefully evaluate effects of future changes in technology, such as tomosynthesis, to ensure new technology leads to improved health outcomes and beyond technical gains.

Women's Acceptance of Overdetection in Breast Cancer Screening: Can We Assess Harm-Benefit Tradeoffs?

Background. Breast cancer screening has been presented to women as mostly positive for decades, despite voices raising issues related to harms since its introduction. Public communications about breast cancer screening tended to use persuasive techniques aimed at maximizing uptake. Concern about the harm of overdetection is more recent, and awareness of overdetection among the public is limited. We aimed to assess the impact of extensive information on treatment following overdetection in breast screening on women's acceptance of screening, and to assess correlates of acceptance. Methods. We performed an online survey among women aged 45-75 from the general public in the Netherlands and Australia, asking women their maximum acceptable ratio of overdetection, per breast cancer death avoided, for four treatment scenarios (randomized order): mastectomy; lumpectomy; lumpectomy plus radiotherapy; lumpectomy plus radiotherapy and hormone therapy. The effect of treatment was assessed using General Linear Models, controlling for socio-demographics, experience, and psychological characteristics. Results. Four-hundred Australian and 403 Dutch women responded. Around half of the women would always screen, even at a 6:1 overdetection-to-death-avoided ratio. Acceptance was highest for the lumpectomy scenario, decreasing with more invasive treatment. In multivariate analyses the effect of treatment remained (p<0.001). Higher acceptance was seen for women with children (p=0.04), screening experience (p<0.001), and less understanding of overdetection (p<0.001). A learning effect was seen: acceptance was highest for the first scenario shown. Conclusions. Acceptance of overdetection was high, but decreased after the first scenario and with invasiveness of treatment. This provides a first indication that with more knowledge and understanding, women may move from uncritical acceptance of screening towards a more informed decision that involves a trade-off of the benefits and harms.

Carcinoma in situ of the breast in New South Wales, Australia: Current status and trends over the last 40 year.

BACKGROUND: The incidence of non-invasive breast cancer has increased substantially over time. We aim to describe temporal trends in the incidence of carcinoma in situ of the breast in New South Wales (NSW), Australia. METHODS: Descriptive study of trends in the incidence of ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) in women who received a diagnosis from 1972 to 2012, recorded in the NSW Cancer Registry. RESULTS: Carcinoma in situ as a proportion of all breast cancer was 0.4% during the prescreening period 1972 to 1987 and is currently 14.1% (2006 to 2012). Among 10,810 women diagnosed with DCIS, incidence across all ages rose from 0.15 per 100,000 during 1972 to 1983 to 16.81 per 100,000 over 2006 to 2012, representing a 100-fold increase (IRR 113.10; 95% CI 81.94 to 156.08). Among women in the target age group for screening (50-69 years) incidence rose from 0.27 per 100,000 to 51.96 over the same period (IRR 195.50; 95% CI 117.26 to 325.89). DCIS incidence peaks in women aged 60-69 years. DCIS incidence has not stabilized despite screening being well established for over 20 years, and participation rates in the target age range remaining stable. CONCLUSIONS: Our findings raise questions about the value of the increasing detection of DCIS and aggressive treatment of these lesions, especially among older women, and support trials of de-escalated treatment.

Assessing the efficacy of cancer screening.

BACKGROUND: Population-based cancer screening has been established for several types of cancer in Australia and internationally. Screening may perform differently in practice from randomised controlled trials, which makes evaluating programs complex. MATERIALS AND METHODS: We discuss how to assess the evidence of benefits and harms of cancer screening, including the main biases that can mislead clinicians and policy makers (such as volunteer, lead-time, length-time and overdiagnosis bias). We also discuss ways in which communication of risks can inform or mislead the community. RESULTS: The evaluation of cancer screening programs should involve balancing the benefits and harms. When considering the overall worth of an intervention and allocation of scarce health resources, decisions should focus on the net benefits and be informed by systematic reviews. Communication of screening outcomes can be misleading. Many messages highlight the benefits while downplaying the harms, and often use relative risks and 5-year survival to persuade people to screen rather than support informed choice. LESSONS LEARNED: An evidence based approach is essential when evaluating and communicating the benefits and harms of cancer screening, to minimise misleading biases and the reliance on intuition.

How information about overdetection changes breast cancer screening decisions: a mediation analysis within a randomised controlled trial.

OBJECTIVES: In a randomised controlled trial, we found that informing women about overdetection changed their breast screening decisions. We now present a mediation analysis exploring the psychological pathways through which study participants who received the intervention processed information about overdetection and how this influenced their decision-making. We examined a series of potential mediators in the causal chain between exposure to overdetection information and women's subsequently reported breast screening intentions. DESIGN: Serial multiple mediation analysis within a randomised controlled trial. SETTING: New South Wales, Australia. PARTICIPANTS: 811 women aged 48-50 years with no personal history of breast cancer. INTERVENTIONS: Two versions of a decision aid giving women information about breast cancer deaths averted and false positives from mammography screening, either with (intervention) or without (control) information on overdetection. MAIN OUTCOME: Intentions to undergo breast cancer screening in the next 2-3 years. MEDIATORS: Knowledge about overdetection, worry about breast cancer, attitudes towards breast screening and anticipated regret. RESULTS: The effect of information about overdetection on women's breast screening intentions was mediated through multiple cognitive and affective processes. In particular, the information led to substantial improvements in women's understanding of overdetection, and it influenced-both directly and indirectly via its effect on knowledge-their attitudes towards having screening. Mediation analysis showed that the mechanisms involving knowledge and attitudes were particularly important in determining women's intentions about screening participation. CONCLUSIONS: Even in this emotive context, new information influenced women's decision-making by changing their understanding of possible consequences of screening and their attitudes towards undergoing it. These findings emphasise the need to provide good-quality information on screening outcomes and to communicate this information effectively, so that women can make well-informed decisions. TRIAL REGISTRATION NUMBER: This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613001035718) on 17 September 2013.

Screening for Cervical, Prostate, and Breast Cancer: Interpreting the Evidence.

Cancer screening is an important component of prevention and early detection in public health and clinical medicine. The evidence for cancer screening, however, is often contentious. A description and explanation of disagreements over the evidence for cervical, breast, and prostate screening may assist physicians, policymakers, and citizens faced with screening decisions and suggest directions for future screening research. There are particular issues to be aware of in the evidence base for each form of screening, which are summarized in this paper. Five tensions explain existing conflicts over the evidence: (1) data from differing contexts may not be comparable; (2) screening technologies affect evidence quality, and thus evidence must evolve with changing technologies; (3) the quality of evidence of benefit varies, and the implications are contested; (4) evidence about harm is relatively new, there are gaps in that evidence, and there is disagreement over what it means; and (5) evidence about outcomes is often poorly communicated. The following principles will assist people to evaluate and use the evidence: (1) attend closely to transferability; (2) consider the influence of technologies on the evidence base; (3) query the design of meta-analyses; (4) ensure harms are defined and measured; and (5) improve risk communication practices. More fundamentally, there is a need to question the purpose of cancer screening and the values that inform that purpose, recognizing that different stakeholders may value different things. If implemented, these strategies will improve the production and interpretation of the methodologically challenging and always-growing evidence for and against cancer screening.

The effect of information about overdetection of breast cancer on women's decision-making about mammography screening: study protocol for a randomised controlled trial.

INTRODUCTION: Women are largely unaware that mammography screening can cause overdetection of inconsequential disease, leading to overdiagnosis and overtreatment of breast cancer. Evidence is lacking about how information on overdetection affects women's breast screening decisions and experiences. This study investigates the consequences of providing information about overdetection of breast cancer to women approaching the age of invitation to mammography screening. METHODS AND ANALYSIS: This is a randomised controlled trial with an embedded longitudinal qualitative substudy. Participants are a community sample of women aged 48-50 in New South Wales, Australia, recruited in 2014. Women are randomly allocated to either quantitative only follow-up (n=904) or additional qualitative follow-up (n=66). Women in each stream are then randomised to receive either the intervention (evidence-based information booklet including overdetection, breast cancer mortality reduction and false positives) or a control information booklet (including mortality reduction and false positives only). The primary outcome is informed choice about breast screening (adequate knowledge, and consistency between attitudes and intentions) assessed via telephone interview at 2 weeks postintervention. Secondary outcomes measured at this time include decision process (decisional conflict and confidence) and psychosocial outcomes (anticipated regret, anxiety, breast cancer worry and perceived risk). Women are further followed up at 6 months, 1 and 2 years to assess self-reported screening behaviour and long-term psychosocial outcomes (decision regret, quality of life). Participants in the qualitative stream undergo additional in-depth interviews at each time point to explore the views and experiences of women who do and do not choose to have screening. ETHICS AND DISSEMINATION: The study has ethical approval, and results will be published in peer-reviewed journals. This research will help ensure that information about overdetection may be communicated clearly and effectively, using an evidence-based approach, to women considering breast cancer screening. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12613001035718.

Overdetection in breast cancer screening: development and preliminary evaluation of a decision aid.

OBJECTIVE: To develop, pilot and refine a decision aid (ahead of a randomised trial evaluation) for women around age 50 facing their initial decision about whether to undergo mammography screening. DESIGN: Two-stage mixed-method pilot study including qualitative interviews (n=15) and a randomised comparison using a quantitative survey (n=34). SETTING: New South Wales, Australia. PARTICIPANTS: Women aged 43-59 years with no personal history of breast cancer. INTERVENTIONS: The decision aid provides evidence-based information about important outcomes of mammography screening over 20 years (breast cancer mortality reduction, overdetection and false positives) compared with no screening. The information is presented in a short booklet for women, combining text and visual formats. A control version produced for the purposes of comparison omits the overdetection-related content. OUTCOMES: Comprehension of key decision aid content and acceptability of the materials. RESULTS: Most women considered the decision aid clear and helpful and would recommend it to others. Nonetheless, the piloting process raised important issues that we tried to address in iterative revisions. Some participants found it hard to understand overdetection and why it is of concern, while there was often confusion about the distinction between overdetection and false positives. In a screening context, encountering balanced information rather than persuasion appears to be contrary to people's expectations, but women appreciated the opportunity to become better informed. CONCLUSIONS: The concept of overdetection is complex and new to the public. This study highlights some key challenges for communicating about this issue. It is important to clarify that overdetection differs from false positives in terms of its more serious consequences (overtreatment and associated harms). Screening decision aids also must clearly explain their purpose of facilitating informed choice. A staged approach to development and piloting of decision aids is recommended to further improve understanding of overdetection and support informed decision-making about screening.