The influence of breast screening on breast cancer incidence in England: observational study based on cancer registries and bulletins of the NHS Breast Screening Programme.

BACKGROUND: To assess the amount of breast cancer overdiagnosis associated with the National Health Service Breast Screening Programme (NHSBSP) that started in 1988 in England. METHODS: First, numbers of breast cancers in women eligible for breast screening not attending screening were estimated for the period 1995-2019, which were extrapolated to all women. A second method was based on ratios of incidence rates of breast cancers in women aged 50-69 to women aged 70 years or more in 1971-1985. The ratio was used for estimating expected numbers of cancers in 1988-2019, and 1995-2019. RESULTS: From 1995 to 2019, 506,607 non-invasive and invasive breast cancers were diagnosed among women aged 50-64 years (1995-2001) and 50-70 years (2002-2019). A first method estimated that 95,297 cancers were in excess to the number of cancers that would be expected had the NHSBSP not existed. 42,567 screen-detected non-invasive and micro-invasive cancers represented 45.8% of the total excess cancer. 18.8% of all cancers diagnosed among women invited to screening, 25.1% of cancers found in women attending screening, and 35.1% of cancers detected by screening would represent overdiagnosis. A second method estimated that, 18.0% of all cancers diagnosed in 1988-2019, and 18.2% of all cancers diagnosed in 1995-2019 among women invited to screening would represent overdiagnosis. CONCLUSION: The two independent methods obtained similar estimates of overdiagnosis. The NHS Breast Screening Programme in England is associated with substantial amount of overdiagnosis.

Change in effectiveness of mammography screening with decreasing breast cancer mortality: a population-based study.

BACKGROUND: Reductions in breast cancer mortality observed over the last three decades are partly due to improved patient management, which may erode the benefit-harm balance of mammography screening. METHODS: We estimated the numbers of women needed to invite (NNI) to prevent one breast cancer death within 10 years. Four scenarios of screening effectiveness (5-20% mortality reduction) were applied on 10,580 breast cancer deaths among Norwegian women aged 50-75 years from 1986 to 2016. We used three scenarios of overdiagnosis (10-40% excess breast cancers during screening period) for estimating ratios of numbers of overdiagnosed breast cancers for each breast cancer death prevented. RESULTS: Under the base case scenario of 20% breast cancer mortality reduction and 20% overdiagnosis, the NNI rose from 731 (95% CI: 644-830) women in 1996 to 1364 (95% CI: 1181-1577) women in 2016, while the number of women with overdiagnosed cancer for each breast cancer death prevented rose from 3.2 in 1996 to 5.4 in 2016. For a mortality reduction of 8.7%, the ratio of overdiagnosed breast cancers per breast cancer death prevented rose from 7.4 in 1996 to 14.0 in 2016. For a mortality reduction of 5%, the ratio rose from 12.8 in 1996 to 25.2 in 2016. CONCLUSIONS: Due to increasingly potent therapeutic modalities, the benefit in terms of reduced breast cancer mortality declines while the harms, including overdiagnosis, are unaffected. Future improvements in breast cancer patient management will further deteriorate the benefit-harm ratio of screening.

Efforts needed for preventing breast and colorectal cancer through changes in dietary patterns.

BACKGROUND: Prospective cohort studies on diet and cancer report risk associations as hazard ratios. But hazard ratios do not inform on the number of people who need to alter their dietary behaviours for preventing cancer. The objective of this study is to estimate the number of people that need to alter their diet for preventing one additional case of female breast or colorectal cancer. METHODS: Based on the largest prospective studies done in the USA and in Europe, we computed the number of subjects who need to alter their diet. RESULTS: For preventing one case of breast cancer, European women should increase their fruit consumption by 100 g/day during 33 000 person-years, and US women by 60 g/day during 10 600 person-years. For vegetables, European women should increase their consumption by 160 g/day during 26 900 person-years and US women by 100 g/day during 19 000 person-years. For preventing one case of colorectal cancer, European subjects should decrease their red meat consumption by 20 g/day during 26 100 person-years, and US subjects by 30 g/day during 8170 person-years. For processed meat, European subjects should decrease their consumption by 20 g/day during 17 400 person-years, and US subjects by 10 g/day during 7940 person-years. CONCLUSIONS: Large number of subjects would need to alter their intake of fruits, vegetables, red and processed meat during many years in order to prevent one additional breast or colorectal cancer.

AI for reading screening mammograms: the need for circumspection.

KEY POINTS: • The studies on AI reading of screening mammograms have methodological limitations that undermine the conclusion that AI could do better than radiologists. • These studies do not informon numbers of extra breast cancers found by AI that could represent overdiagnosis. • The ability of AI to detect breast cancers is overestimated because there are no result on biopsy procedures that should be performed when mammograms are positive at AI reading but not at radiology reading.

Relation between Breast Cancer and High Glycemic Index or Glycemic Load: A Meta-analysis of Prospective Cohort Studies.

Breast cancer is the commonest form of cancer in women worldwide. It has been suggested that chronic hyperinsulinemia associated with insulin resistance plays a role in breast cancer etiology. To test the hyperinsulinemia hypothesis, a dietary pattern associated with a high glycemic index and glycemic load, both proxies for chronic hyperinsulinemia, should be associated with an increased risk of breast cancer. A meta-analysis restricted to prospective cohort studies was undertaken using a random effects model with tests for statistical significance, publication bias and heterogeneity. The metric for analysis was the risk of breast cancer in the highest relative to the lowest glycemic index and glycemic load dietary pattern. A dietary pattern with a high glycemic index was associated with a summary relative risk (SRR) of 1.05 (95% CI: 1.00, 1.11), and a high glycemic load with a SRR of 1.06 (95% CI: 1.00, 1.13). Adjustments for body mass index [BMI], physical activity and other lifestyle factors did not influence the SRR, nor did menopausal status and estrogen receptor status of the tumor. In conclusion, the current evidence supports a modest association between a dietary pattern with high glycemic index or glycemic load and the risk of breast cancer.

Daily milk consumption and all-cause mortality, coronary heart disease and stroke: a systematic review and meta-analysis of observational cohort studies.

BACKGROUND: Observational studies and meta-analyses relating milk consumption by adults to all-cause mortality, coronary heart disease and stroke have obtained contradictory results. Some studies found a protective effect of milk consumption, whilst other found an increased risk. METHODS: We performed a systematic literature search until June 2015 on prospective studies that looked at milk consumption, all-cause mortality, coronary heart disease and stroke. Random-effect meta-analyses were performed with dose-response. RESULTS: Twenty-one studies involving 19 cohorts were included in this meta-analysis, 11 on all-cause mortality, 9 on coronary heart disease, and 10 on stroke. Milk intake ranged from 0 to 850 mL/d. The summary relative risk (SRR) for 200 mL/d milk consumption was 1.01 (95% CI: 0.96-1.06) for all-cause mortality, 1.01 (95% CI: 0.98-1.05) for fatal and non fatal coronary heart disease, and 0.91 (95% CI: 0.82-1.02) for fatal and non fatal stroke. Stratified analyses by age, Body Mass Index, total energy intake and physical acitivity did not alter the SRR estimates. The possibility of publication bias was found for all cause mortality and for stroke, indicating a gap in data that could have suggested a higher risk of these conditions with increased milk consumption. CONCLUSIONS: We found no evidence for a decreased or increased risk of all-cause mortality, coronary heart disease, and stroke associated with adult milk consumption. However, the possibility cannot be dismissed that risks associated with milk consumption could be underestimated because of publication bias.

Global cancer surgery: delivering safe, affordable, and timely cancer surgery.

Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, affordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and financing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US $6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis identified substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.

MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project.

The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects.

Active and passive smoking and risk of breast cancer: a meta-analysis.

Studies on active and passive tobacco smoking and breast cancer have found inconsistent results. A meta-analysis of observational studies on tobacco smoking and breast cancer occurrence was conducted based on systematic searches for studies with retrospective (case-control) and prospective (cohort) designs. Eligible studies were identified, and relative risk measurements were extracted for active and passive tobacco exposures. Random-effects meta-analyses were used to compute summary relative risks (SRR). Heterogeneity of results between studies was evaluated using the (I (2)) statistics. For ever active smoking, in 27 prospective studies, the SRR for breast cancer was 1.10 (95 % CI [1.09-1.12]) with no heterogeneity (I (2) = 0 %). In 44 retrospective studies, the SRR was 1.08 (95 % CI [1.02-1.14]) with high heterogeneity (I (2) = 59 %). SRRs for current active smoking were 1.13 (95 % CI [1.09-1.17]) in 27 prospective studies and 1.08 (95 % CI [0.97-1.20]) in 22 retrospective studies. The results were stable across different subgroup analyses, notably pre/post-menopause, alcohol consumption adjustments, including/excluding passive smokers from the referent group. For ever passive smoking, in 11 prospective studies, the SRR for breast cancer was 1.07 (95 % CI [1.02-1.13]) with no heterogeneity (I (2) = 1 %). In 20 retrospective studies, the SRR was 1.30 (95 % CI [1.10-1.54]) with high heterogeneity (I (2) = 74 %). Too few prospective studies were available for meaningful subgroup analyses. There is consistent evidence for a moderate increase in the risk of breast cancer in women who smoke tobacco. The evidence for a moderate increase in risk with passive smoking is more substantial than a few years ago.

Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients.

OBJECTIVE: To quantify the incremental detection rate (DR) of a targeted biopsy in addition to a randomized 10-core biopsy. PATIENTS AND METHODS: This retrospective study analysed 1024 patients who consecutively underwent a four-core real-time elastography (RTE) targeted biopsies in addition to a randomized 10-core transrectal ultrasonography (TRUS)-guided biopsy in a primary or rebiopsy setting. The overall DR, the DR of a 10-core randomized, RTE targeted biopsy and the incremental DR were calculated. RESULTS: Overall, randomized and RTE targeted biopsy DRs (for the combination, the 10-core and the four-core RTE biopsy scheme) were 46.2% (n = 473), 39.1% (n = 400) and 29.0% (n = 297), respectively. Four-core RTE targeted biopsies detected an additional 73 patients not detected by the 10-core randomized biopsies (increase in the overall DR of 7.1%). This represented a relative increase in DR of 18.3%. The incremental DR was better in rebiopsy patients (24.8%) than in patients having their first biopsy (14.7%). Within all patients diagnosed by RTE targeted biopsy only, 34 patients harboured significant Gleason 4 or 5 prostate cancer (PCa), diagnosed by four-core RTE biopsy only. Moreover, PCa with a Gleason grade of 4 or 5 was detected by four-core RTE biopsies in 30 patients, who showed low-grade PCa ≤ Gleason 3 only in the systematic 10-core biopsy. CONCLUSIONS: Real-time elastography targeted biopsy seems to be an appropriate method for increasing the DR of PCa. Nevertheless, RTE targeted biopsies missed a high proportion of patients with PCa and should therefore be considered as an addition to randomized biopsies.

Radiotherapy capacity in European countries: an analysis of the Directory of Radiotherapy Centres (DIRAC) database.

Radiotherapy is used for cure or palliation in around half of patients with cancer. We analysed data on radiotherapy equipment in 33 European countries registered in the Directory of Radiotherapy Centres (DIRAC) database, managed by the International Atomic Energy Agency. As of July, 2012, Europe had 1286 active radiotherapy centres. The average number of teletherapy machines per radiotherapy centre ranged from 1·2 to 7·0 in different countries. Nordic countries, the UK, the Netherlands, and Slovenia all have large centres with four to ten teletherapy machines. Most western and southern European countries have several small centres with one or two machines, with few larger centres. The fragmentation in radiotherapy services that prevails in many European countries might affect the economic burden of radiotherapy and its quality. Eastern and southeastern European countries need to expand and modernise their radiotherapy equipment.

Effect of screening mammography on the risk of breast cancer death and of all-cause death: A systematic review with meta-analysis of cohort studies.

OBJECTIVE: Observational cohort studies are used to evaluate the effectiveness of screening mammography in women offered screening. Because screening mammography has no effect on causes of death other than breast cancer, cohort studies should show reductions in the risk of breast cancer death substantially greater than possible reductions in the risk of all cause death. We assessed the risk of breast cancer death and of all-cause (or of non-breast cancer) death associated with screening mammography attendance reported in cohort studies. STUDY DESIGN AND SETTING: Cohort studies published from 2002 to 2022 on women invited to screening mammography were searched in PubMed, Web of Sciences, Scopus and in review articles. Random effect meta-analyses were performed using relative risks of death between women who attended screening compared to women who did not attend screening. RESULTS: Eighteen cohort studies were identified, nine that reported relative risks of breast cancer death only, five that reported relative risks of all cause death only, and four that reported relative risks for both breast cancer death and all cause death. The latter four cohort studies reported 12 to 76 times more all-cause deaths than breast cancer deaths. The random-effect summary relative risk for breast cancer mortality in screening attenders vs. nonattenders was 0.55 (95% CI: 0.50-0.60) in 13 cohort studies. The summary relative risk for all-cause mortality was 0.54 (0.50-0.58) in 10 cohort studies. In the four cohort studies that evaluated both outcomes, the summary relative risks were 0.63 (0.43-0.83) for breast cancer mortality and of 0.54 (0.44-0.64) for all-cause mortality. CONCLUSION: The similar relative reductions in breast- and all-cause (or non-breast cancer) mortality indicates that screening mammography attendance is an indicator of characteristics associated with a lower risk of dying from any cause, including from breast cancer, which observational studies have falsely interpreted as a screening effect.

Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.