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1.  Screening Mammography for Women Aged 40 to 49 Years at Average Risk for Breast Cancer 
Executive Summary
Objective
The aim of this review was to determine the effectiveness of screening mammography in women aged 40 to 49 years at average risk for breast cancer.
Clinical Need
The effectiveness of screening mammography in women aged over 50 years has been established, yet the issue of screening in women aged 40 to 49 years is still unsettled. The Canadian Task Force of Preventive Services, which sets guidelines for screening mammography for all provinces, supports neither the inclusion nor the exclusion of this screening procedure for 40- to 49-year-old women from the periodic health examination. In addition to this, 2 separate reviews, one conducted in Quebec in 2005 and the other in Alberta in 2000, each concluded that there is an absence of convincing evidence on the effectiveness of screening mammography for women in this age group who are at average risk for breast cancer.
In the United States, there is disagreement among organizations on whether population-based mammography should begin at the age of 40 or 50 years. The National Institutes of Health, the American Association for Cancer Research, and the American Academy of Family Physicians recommend against screening women in their 40s, whereas the United States Preventive Services Task Force, the National Cancer Institute, the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists recommend screening mammograms for women aged 40 to 49 years. Furthermore, in comparing screening guidelines between Canada and the United States, it is also important to recognize that “standard care” within a socialized medical system such as Canada’s differs from that of the United States. The National Breast Screening Study (NBSS-1), a randomized screening trial conducted in multiple centres across Canada, has shown there is no benefit in mortality from breast cancer from annual mammograms in women randomized between the ages of 40 and 49, relative to standard care (i.e. physical exam and teaching of breast-self examination on entry to the study, with usual community care thereafter).
At present, organized screening programs in Canada systematically screen women starting at 50 years of age, although with a physician’s referral, a screening mammogram is an insured service in Ontario for women under 50 years of age.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined, whereas mortality is decreasing, though at a slower rate. These decreasing mortality rates may be attributed to screening and advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the SEER cancer registry in the United States indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20-year period (from 2.7 to 25 per 100,000).
The incidence of breast cancer is lower in women aged 40 to 49 years than in women aged 50 to 69 years (about 140 per 100,000 versus 500 per 100,000 women, respectively), as is the sensitivity (about 75% versus 85% for women aged under and over 50, respectively) and specificity of mammography (about 80% versus 90% for women aged under and over 50, respectively). The increased density of breast tissue in younger women is mainly responsible for the lower accuracy of this procedure in this age group. In addition, as the proportion of breast cancers that occur before the age of 50 are more likely to be associated with genetic predisposition as compared with those diagnosed in women after the age of 50, mammography may not be an optimal screening method for younger women.
Treatment options vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy, and/or radiotherapy.
Surgery is the first-line intervention for biopsy confirmed tumours. The subsequent use of radiation, chemotherapy, or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is noninvasive.
With such controversy as to the effectiveness of mammography and the potential risk associated with women being overtreated or actual cancers being missed, and the increased risk of breast cancer associated with exposure to annual mammograms over a 10-year period, the Ontario Health Technology Advisory Committee requested this review of screening mammography in women aged 40 to 49 years at average risk for breast cancer. This review is the first of 2 parts and concentrates on the effectiveness of screening mammography (i.e., film mammography, FM) for women at average risk aged 40 to 49 years. The second part will be an evaluation of screening by either magnetic resonance imaging or digital mammography, with the objective of determining the optimal screening modality in these younger women.
Review Strategy
The following questions were asked:
Does screening mammography for women aged 40 to 49 years who are at average risk for breast cancer reduce breast cancer mortality?
What is the sensitivity and specificity of mammography for this age group?
What are the risks associated with annual screening from ages 40 to 49?
What are the risks associated with false positive and false negative mammography results?
What are the economic considerations if evidence for effectiveness is established?
The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the International Network of Agencies for Health Technology Assessment.
Keywords used in the search were breast cancer, breast neoplasms, mass screening, and mammography.
In total, the search yielded 6,359 articles specific to breast cancer screening and mammography. This did not include reports on diagnostic mammograms. The search was further restricted to English-language randomized controlled trials (RCTs), systematic reviews, and meta-analyses published between 1995 and 2005. Excluded were case reports, comments, editorials, and letters, which narrowed the results to 516 articles and previous health technology policy assessments.
These were examined against the criteria outlined below. This resulted in the inclusion of 5 health technology assessments, the Canadian Preventive Services Task Force report, the United States Preventive Services Task Force report, 1 Cochrane review, and 8 RCTs.
Inclusion Criteria
English-language articles, and English and French-language health technology policy assessments, conducted by other organizations, from 1995 to 2005
Articles specific to RCTs of screening mammography of women at average risk for breast cancer that included results for women randomized to studies between the ages of 40 and 49 years
Studies in which women were randomized to screening with or without mammography, although women may have had clinical breast examinations and/or may have been conducting breast self-examination.
UK Age Trial results published in December 2006.
Exclusion Criteria
Observational studies, including those nested within RCTs
RCTs that do not include results on women between the ages of 40 and 49 at randomization
Studies in which mammography was compared with other radiologic screening modalities, for example, digital mammography, magnetic resonance imaging or ultrasound.
Studies in which women randomized had a personal history of breast cancer.
Intervention
Film mammography
Comparators
Within RCTs, the comparison group would have been women randomized to not undergo screening mammography, although they may have had clinical breast examinations and/or have been conducting breast self-examination.
Outcomes of Interest
Breast cancer mortality
Summary of Findings
There is Level 1 Canadian evidence that screening women between the ages of 40 and 49 years who are at average risk for breast cancer is not effective, and that the absence of a benefit is sustained over a maximum follow-up period of 16 years.
All remaining studies that reported on women aged under 50 years were based on subset analyses. They provide additional evidence that, when all these RCTs are taken into account, there is no significant reduction in breast cancer mortality associated with screening mammography in women aged 40 to 49 years.
Conclusions
There is Level 1 evidence that screening mammography in women aged 40 to 49 years at average risk for breast cancer is not effective in reducing mortality.
Moreover, risks associated with exposure to mammographic radiation, the increased risk of missed cancers due to lower mammographic sensitivity, and the psychological impact of false positives, are not inconsequential.
The UK Age Trial results published in December 2006 did not change these conclusions.
PMCID: PMC3377515  PMID: 23074501
2.  Cancer Screening with Digital Mammography for Women at Average Risk for Breast Cancer, Magnetic Resonance Imaging (MRI) for Women at High Risk 
Executive Summary
Objective
The purpose of this review is to determine the effectiveness of 2 separate modalities, digital mammography (DM) and magnetic resonance imaging (MRI), relative to film mammography (FM), in the screening of women asymptomatic for breast cancer. A third analysis assesses the effectiveness and safety of the combination of MRI plus mammography (MRI plus FM) in screening of women at high risk. An economic analysis was also conducted.
Research Questions
How does the sensitivity and specificity of DM compare to FM?
How does the sensitivity and specificity of MRI compare to FM?
How do the recall rates compare among these screening modalities, and what effect might this have on radiation exposure? What are the risks associated with radiation exposure?
How does the sensitivity and specificity of the combination of MRI plus FM compare to either MRI or FM alone?
What are the economic considerations?
Clinical Need
The effectiveness of FM with respect to breast cancer mortality in the screening of asymptomatic average- risk women over the age of 50 has been established. However, based on a Medical Advisory Secretariat review completed in March 2006, screening is not recommended for women between the ages of 40 and 49 years. Guidelines published by the Canadian Task Force on Preventive Care recommend mammography screening every 1 to 2 years for women aged 50 years and over, hence, the inclusion of such women in organized breast cancer screening programs. In addition to the uncertainty of the effectiveness of mammography screening from the age of 40 years, there is concern over the risks associated with mammographic screening for the 10 years between the ages of 40 and 49 years.
The lack of effectiveness of mammography screening starting at the age of 40 years (with respect to breast cancer mortality) is based on the assumption that the ability to detect cancer decreases with increased breast tissue density. As breast density is highest in the premenopausal years (approximately 23% of postmenopausal and 53% of premenopausal women having at least 50% of the breast occupied by high density), mammography screening is not promoted in Canada nor in many other countries for women under the age of 50 at average risk for breast cancer. It is important to note, however, that screening of premenopausal women (i.e., younger than 50 years of age) at high risk for breast cancer by virtue of a family history of cancer or a known genetic predisposition (e.g., having tested positive for the breast cancer genes BRCA1 and/or BRCA2) is appropriate. Thus, this review will assess the effectiveness of breast cancer screening with modalities other than film mammography, specifically DM and MRI, for both pre/perimenopausal and postmenopausal age groups.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined whereas mortality is decreasing, though at a slower rate. The observed decreases in mortality rates may be attributable to screening, in addition to advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the Surveillance, Epidemiology and End Results (better known as SEER) cancer registry in the United States, indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20 year period, from 2.7 to 25 per 100,000.
There is a 4-fold lower incidence of breast cancer in the 40 to 49 year age group than in the 50 to 69 year age group (approximately 140 per 100,000 versus 500 per 100,000 women, respectively). The sensitivity of FM is also lower among younger women (approximately 75%) than for women aged over 50 years (approximately 85%). Specificity is approximately 80% for younger women versus 90% for women over 50 years. The increased density of breast tissue in younger women is likely responsible for the decreased accuracy of FM.
Treatment options for breast cancer vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy and/or radiotherapy. Surgery is the first-line intervention for biopsy-confirmed tumors. The subsequent use of radiation, chemotherapy or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is considered a noninvasive tumour.
Women at high risk for breast cancer are defined as genetic carriers of the more commonly known breast cancer genes (BRCA1, BRCA2 TP53), first degree relatives of carriers, women with varying degrees of high risk family histories, and/or women with greater than 20% lifetime risk for breast cancer based on existing risk models. Genetic carriers for this disease, primarily women with BRCA1 or BRCA2 mutations, have a lifetime probability of approximately 85% of developing breast cancer. Preventive options for these women include surgical interventions such as prophylactic mastectomy and/or oophorectomy, i.e., removal of the breasts and/or ovaries. Therefore, it is important to evaluate the benefits and risks of different screening modalities, to identify additional options for these women.
This Medical Advisory Secretariat review is the second of 2 parts on breast cancer screening, and concentrates on the evaluation of both DM and MRI relative to FM, the standard of care. Part I of this review (March 2006) addressed the effectiveness of screening mammography in 40 to 49 year old average-risk women. The overall objective of the present review is to determine the optimal screening modality based on the evidence.
Evidence Review Strategy
The Medical Advisory Secretariat followed its standard procedures and searched the following electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment database. The subject headings and keywords searched included breast cancer, breast neoplasms, mass screening, digital mammography, magnetic resonance imaging. The detailed search strategies can be viewed in Appendix 1.
Included in this review are articles specific to screening and do not include evidence on diagnostic mammography. The search was further restricted to English-language articles published between January 1996 and April 2006. Excluded were case reports, comments, editorials, nonsystematic reviews, and letters.
Digital Mammography: In total, 224 articles specific to DM screening were identified. These were examined against the inclusion/exclusion criteria described below, resulting in the selection and review of 5 health technology assessments (HTAs) (plus 1 update) and 4 articles specific to screening with DM.
Magnetic Resonance Imaging: In total, 193 articles specific to MRI were identified. These were examined against the inclusion/exclusion criteria described below, resulting in the selection and review of 2 HTAs and 7 articles specific to screening with MRI.
The evaluation of the addition of FM to MRI in the screening of women at high risk for breast cancer was also conducted within the context of standard search procedures of the Medical Advisory Secretariat. as outlined above. The subject headings and keywords searched included the concepts of breast cancer, magnetic resonance imaging, mass screening, and high risk/predisposition to breast cancer. The search was further restricted to English-language articles published between September 2007 and January 15, 2010. Case reports, comments, editorials, nonsystematic reviews, and letters were not excluded.
MRI plus mammography: In total, 243 articles specific to MRI plus FM screening were identified. These were examined against the inclusion/exclusion criteria described below, resulting in the selection and review of 2 previous HTAs, and 1 systematic review of 11 paired design studies.
Inclusion Criteria
English-language articles, and English or French-language HTAs published from January 1996 to April 2006, inclusive.
Articles specific to screening of women with no personal history of breast cancer.
Studies in which DM or MRI were compared with FM, and where the specific outcomes of interest were reported.
Randomized controlled trials (RCTs) or paired studies only for assessment of DM.
Prospective, paired studies only for assessment of MRI.
Exclusion Criteria
Studies in which outcomes were not specific to those of interest in this report.
Studies in which women had been previously diagnosed with breast cancer.
Studies in which the intervention (DM or MRI) was not compared with FM.
Studies assessing DM with a sample size of less than 500.
Intervention
Digital mammography.
Magnetic resonance imaging.
Comparator
Screening with film mammography.
Outcomes of Interest
Breast cancer mortality (although no studies were found with such long follow-up).
Sensitivity.
Specificity.
Recall rates.
Summary of Findings
Digital Mammography
There is moderate quality evidence that DM is significantly more sensitive than FM in the screening of asymptomatic women aged less than 50 years, those who are premenopausal or perimenopausal, and those with heterogeneously or extremely dense breast tissue (regardless of age).
It is not known what effect these differences in sensitivity will have on the more important effectiveness outcome measure of breast cancer mortality, as there was no evidence of such an assessment.
Other factors have been set out to promote DM, for example, issues of recall rates and reading and examination times. Our analysis did not show that recall rates were necessarily improved in DM, though examination times were lower than for FM. Other factors including storage and retrieval of screens were not the subject of this analysis.
Magnetic Resonance Imaging
There is moderate quality evidence that the sensitivity of MRI is significantly higher than that of FM in the screening of women at high risk for breast cancer based on genetic or familial factors, regardless of age.
Radiation Risk Review
Cancer Care Ontario conducted a review of the evidence on radiation risk in screening with mammography women at high risk for breast cancer. From this review of recent literature and risk assessment that considered the potential impact of screening mammography in cohorts of women who start screening at an earlier age or who are at increased risk of developing breast cancer due to genetic susceptibility, the following conclusions can be drawn:
For women over 50 years of age, the benefits of mammography greatly outweigh the risk of radiation-induced breast cancer irrespective of the level of a woman’s inherent breast cancer risk.
Annual mammography for women aged 30 – 39 years who carry a breast cancer susceptibility gene or who have a strong family breast cancer history (defined as a first degree relative diagnosed in their thirties) has a favourable benefit:risk ratio. Mammography is estimated to detect 16 to 18 breast cancer cases for every one induced by radiation (Table 1). Initiation of screening at age 35 for this same group would increase the benefit:risk ratio to an even more favourable level of 34-50 cases detected for each one potentially induced.
Mammography for women under 30 years of age has an unfavourable benefit:risk ratio due to the challenges of detecting cancer in younger breasts, the aggressiveness of cancers at this age, the potential for radiation susceptibility at younger ages and a greater cumulative radiation exposure.
Mammography when used in combination with MRI for women who carry a strong breast cancer susceptibility (e.g., BRCA1/2 carriers), which if begun at age 35 and continued for 35 years, may confer greatly improved benefit:risk ratios which were estimated to be about 220 to one.
While there is considerable uncertainty in the risk of radiation-induced breast cancer, the risk expressed in published studies is almost certainly conservative as the radiation dose absorbed by women receiving mammography recently has been substantially reduced by newer technology.
A CCO update of the mammography radiation risk literature for 2008 and 2009 gave rise to one article by Barrington de Gonzales et al. published in 2009 (Barrington de Gonzales et al., 2009, JNCI, vol. 101: 205-209). This article focuses on estimating the risk of radiation-induced breast cancer for mammographic screening of young women at high risk for breast cancer (with BRCA gene mutations). Based on an assumption of a 15% to 25% or less reduction in mortality from mammography in these high risk women, the authors conclude that such a reduction is not substantially greater than the risk of radiation-induced breast cancer mortality when screening before the age of 34 years. That is, there would be no net benefit from annual mammographic screening of BRCA mutation carriers at ages 25-29 years; the net benefit would be zero or small if screening occurs in 30-34 year olds, and there would be some net benefit at age 35 years or older.
The Addition of Mammography to Magnetic Resonance Imaging
The effects of the addition of FM to MRI screening of high risk women was also assessed, with inclusion and exclusion criteria as follows:
Inclusion Criteria
English-language articles and English or French-language HTAs published from September 2007 to January 15, 2010.
Articles specific to screening of women at high risk for breast cancer, regardless of the definition of high risk.
Studies in which accuracy data for the combination of MRI plus FM are available to be compared to that of MRI and FM alone.
RCTs or prospective, paired studies only.
Studies in which women were previously diagnosed with breast cancer were also included.
Exclusion Criteria
Studies in which outcomes were not specific to those of interest in this report.
Studies in which there was insufficient data on the accuracy of MRI plus FM.
Intervention
Both MRI and FM.
Comparators
Screening with MRI alone and FM alone.
Outcomes of Interest
Sensitivity.
Specificity.
Summary of Findings
Magnetic Resonance Imaging Plus Mammography
Moderate GRADE Level Evidence that the sensitivity of MRI plus mammography is significantly higher than that of MRI or FM alone, although the specificity remains either unchanged or decreases in the screening of women at high risk for breast cancer based on genetic/familial factors, regardless of age.
These studies include women at high risk defined as BRCA1/2 or TP53 carriers, first degree relatives of carriers, women with varying degrees of high risk family histories, and/or >20% lifetime risk based on existing risk models. This definition of high risk accounts for approximately 2% of the female adult population in Ontario.
PMCID: PMC3377503  PMID: 23074406
3.  Modern mammography screening and breast cancer mortality: population study 
Objective To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes.
Design Prospective cohort study of Norwegian women who were followed between 1986 and 2009. Within that period (1995-2005), a national mammography screening programme was gradually implemented, with biennial invitations sent to women aged 50-69 years.
Participants All Norwegian women aged 50-79 between 1986 and 2009.
Main outcome measures Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening (intention to screen) with women who were not invited, with a clear distinction between cases of breast cancer diagnosed before (without potential for screening effect) and after (with potential for screening effect) the first invitation for screening. We took competing causes of death into account by censoring women from further follow-up who died from other causes. Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009, we used the CISNET (Cancer Intervention and Surveillance Modeling Network) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50-69 years to prevent one breast cancer death during their lifetime.
Results During 15 193 034 person years of observation (1986-2009), deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis. After adjustment for age, birth cohort, county of residence, and national trends in deaths from breast cancer, the mortality rate ratio associated with being invited to mammography screening was 0.72 (95% confidence interval 0.64 to 0.79). To prevent one death from breast cancer, 368 (95% confidence interval 266 to 508) women would need to be invited to screening.
Conclusion Invitation to modern mammography screening may reduce deaths from breast cancer by about 28%.
doi:10.1136/bmj.g3701
PMCID: PMC4061379  PMID: 24951459
4.  Cervical Screening at Age 50–64 Years and the Risk of Cervical Cancer at Age 65 Years and Older: Population-Based Case Control Study 
PLoS Medicine  2014;11(1):e1001585.
Peter Sasieni and colleagues use a population-based case control study to assess the risk of cervical cancer in screened women aged over 65 years to help inform policy on the upper age of cervical cancer screening.
Please see later in the article for the Editors' Summary
Background
There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50–64 y and cervical cancer at age 65–83 y.
Methods and Findings
Cases were women (n = 1,341) diagnosed with cervical cancer at age 65–83 y between 1 April 2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646) were randomly selected from population registers. Screening details from 1988 onwards were extracted from national databases. We calculated the odds ratios (OR) for different screening histories and subsequent cervical cancer. Women with adequate negative screening at age 65 y (288 cases, 1,395 controls) were at lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared with those (532 cases, 429 controls) not screened at age 50–64 y (20-y risk: 49 cancers per 10,000 women, with OR = 0.16, 95% CI 0.13–0.19). ORs depended on the age mix of women because of the weakening association with time since last screen: OR = 0.11, 95% CI 0.08–0.14 at 2.5 to 7.5 y since last screen; OR = 0.27, 95% CI 0.20–0.36 at 12.5 to 17.5 y since last screen. Screening at least every 5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21–0.30), and the attributable risk was such that in the absence of screening, cervical cancer rates in women aged 65+ would have been 2.4 (95% CI 2.1–2.7) times higher. In women aged 80–83 y the association was weaker (OR = 0.49, 95% CI 0.28–0.83) than in those aged 65–69 y (OR = 0.12, 95% CI 0.09–0.17). This study was limited by an absence of data on confounding factors; additionally, findings based on cytology may not generalise to human papillomavirus testing.
Conclusions
Women with adequate negative screening at age 50–64 y had one-sixth of the risk of cervical cancer at age 65–83 y compared with women who were not screened. Stopping screening between ages 60 and 69 y in women with adequate negative screening seems sensible, but further screening may be justifiable as life expectancy increases.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Nearly one in ten cancers diagnosed in women occur in the cervix, the structure that connects the womb to the vagina. Every year, more than a quarter of a million women (mostly in developing countries) die because of cervical cancer, which occurs only after the cervix has been infected with human papillomavirus (HPV) through sexual intercourse. In the earliest stages of cervical cancer, abnormal cells begin to grow in the cervix. Cells with low-grade abnormalities (changes that often revert to normal), cells with high-grade abnormalities (which are more likely to become cancerous), and cancer cells can all be detected by collecting a few cells from the cervix and examining them under a microscope. This test forms the basis of cervical screening, which has greatly reduced cervical cancer deaths in countries with a national screening program by ensuring that cervical abnormalities are detected at an early, treatable stage. In the UK, for example, since the start of a cervical screening program in 1988 in which women aged 25–64 years are called for testing every 3–5 years, the incidence of cervical cancer (the number of new cases per year) has almost halved at a time when sexually transmitted diseases have more than doubled.
Why Was This Study Done?
Currently, there is little consensus about the age at which cervical screening should stop, and minimal evidence about the impact of cervical screening on the incidence of cervical cancer in older women. In this population-based case control study (a study that compares the characteristics of all the cases of a disease in a population with the characteristics of matched individuals without the disease), the researchers examine the association between screening in women aged 50–64 years and cervical cancer in women aged 65–83 years. They ask whether well-screened women with a history of negative results and no evidence of high-grade abnormalities are at sufficiently low risk of cervical cancer that screening can be stopped at age 65 years, and whether women who are regularly screened (at least once every 5.5 years) between the ages of 50 and 64 years are subsequently at reduced risk of cervical cancer.
What Did the Researchers Do and Find?
The researchers randomly selected two age-matched controls for every woman aged 65–83 years who was diagnosed with cervical cancer between 2007 and 2012 in England and Wales. The researchers included 1,341 women with cervical cancer and 2,646 controls. They extracted each woman's cervical screening details from national databases and calculated the association between screening history and subsequent cervical cancer. Women with adequate negative screening at age 65 years (at least three tests at age 50–64 years with the last one over age 60, the last three of which were negative, and no evidence of high-grade abnormalities) were at the lowest risk of cervical cancer (20-year risk of eight cancers per 10,000 women) compared with unscreened women (20-year risk of 49 cancers per 10,000 women). That is, women who were not screened at age 50–64 years were six times more likely to develop cervical cancer between the ages of 65 and 83 years than women who were screened. The risk of developing cervical cancer among adequately negatively screened women increased with age and with time since the last screen. Finally, the researchers estimate that in the absence of any cervical screening, the rate of cervical cancer among women aged 65–79 years would be 23 cases per 100,000 woman-years, 2.4 times higher than the current rate.
What Do These Findings Mean?
These findings show that women who exited the screening program in England and Wales with a history of adequate negative screening between the ages of 50 and 64 years were at a very low risk of being diagnosed with cervical cancer at the age of 65 years or older. The “protection” provided by screening was greatest for women aged 65–69 years and decreased steadily with increasing age and with time since the last negative screen. Because the researchers did not have any information on other characteristics that might have affected cervical cancer risk (for example, number of sexual partners), the women who were screened may have shared other characteristics that reduced their risk of developing cervical cancer. Moreover, these findings, which are based on microscopic examination of cells, may not generalise to the HPV-based screening programs that many countries are considering. Despite these limitations, the researchers conclude that, for now, it seems sensible to continue screening at least until age 60 years and not beyond age 69 years in women with adequate negative screening, but that given increasing life expectancy, screening in older women might be justified in the future.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001585.
This study is further discussed in a PLOS Medicine Perspective by Anne Rositch and colleagues
The US National Cancer Institute provides information about cervical cancer for patients and for health professionals, including information on cervical screening (in English and Spanish)
The US Centers for Disease Control and Prevention also has information about cervical cancer and about cervical screening
The UK National Health Service Cervical Screening Programme website has detailed information and statistics on cervical screening in England
The UK National Health Service Choices website has pages on cervical cancer (including a personal story about cervical cancer) and on cervical screening (including personal comments about screening)
Cancer Research UK provides detailed information about all aspects of cervical cancer
More information about cervical cancer and screening is available from the Macmillan cancer charity
MedlinePlus provides links to additional resources about cervical cancer and screening (in English and Spanish)
Personal stories about cervical cancer and about cervical screening are available through the charity Healthtalkonline
doi:10.1371/journal.pmed.1001585
PMCID: PMC3891624  PMID: 24453946
5.  A pilot telephone intervention to increase uptake of breast cancer screening in socially deprived areas in Scotland (TELBRECS): study protocol for a randomised controlled trial 
BMC Public Health  2014;14(1):824.
Background
Breast cancer accounts for almost 30% of all cancers and is the second leading cause of cancer deaths in women in Scotland. Screening is key to early detection. The Scottish Breast Screening Programme is a nationwide, free at point of delivery screening service, to which all women aged between 50 and 70 years are invited to attend every 3 years. Currently over three-quarters of invited women regularly attend screening. However, women from more deprived areas are much less likely to attend: for example in the 3 years from 2010–2012 only 63% of women in the most deprived area attended the East of Scotland Breast Screening programme versus 81% in the least deprived. Research has suggested that reminders (telephone or letter) and brief, personalised interventions addressing barriers to attendance may be helpful in increasing uptake in low-income women.
Methods/Design
We will employ a brief telephone reminder and support intervention, whose purpose is to elicit and address any mistaken beliefs women have about breast screening, with the aim that the perceived benefits of screening come to outweigh any perceived barriers for individuals. We will test whether this intervention, plus a simple anticipated regret manipulation, will lead to an increase in the uptake of breast cancer screening amongst low-income women who have failed to attend a first appointment, in a randomised controlled trial with 600 women. Participants will be randomly allocated to one of four treatment arms i.e. 1) Letter reminder (i.e. Treatment as usual: CONTROL); 2) Telephone reminder (TEL), 3) Telephone reminder plus telephone support (TEL-SUPP) and 4) Telephone reminder plus support plus AR (TEL-SUPP-AR). The primary outcome will be attendance at breast screening within 3 months of the reminder letter.
Discussion
If this simple telephone support intervention (with or without AR intervention) leads to a significant increase in breast screening attendance, this would represent a rare example of a theoretically-driven, relatively simple psychological intervention that could result in earlier detection of breast cancer amongst an under-served group of lower socio-economic women.
Trial registration
Current Controlled trials: ISRCTN06039270. Registered 16th January 2014.
doi:10.1186/1471-2458-14-824
PMCID: PMC4143584  PMID: 25106506
Breast cancer; Screening; Anticipated regret; Telephone reminder; Barriers to breast screening
6.  Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial 
Objective To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening.
Design Follow-up of randomised screening trial by centre coordinators, the study’s central office, and linkage to cancer registries and vital statistics databases.
Setting 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia).
Participants 89 835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography).
Interventions Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community.
Main outcome measure Deaths from breast cancer.
Results During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44 925 participants) and 524 in the controls (n=44 910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis.
Conclusion Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.
doi:10.1136/bmj.g366
PMCID: PMC3921437  PMID: 24519768
7.  Factors Associated with Breast Cancer Screening Decision Stage among Women in Tehran, Iran 
Background:
Early detection through screening is the best method to reduce death due to breast cancer. It has been shown, having knowledge and generating positive attitudes, influences the decision of women to participate in the screening programs. The aim of this study was to identify the factors associated with breast cancer screening (BCS) and with an intention to have screening among women in Tehran, Iran.
Methods:
A cross-sectional study was carried out from January to July 2011, among women who had attended to primary health-care centers in West Tehran using multi-stage sampling method. We invited 1,240 women sequentially to complete a self-administered survey questionnaire at the beginning of their visit; and 1,012 (82%) completed the survey. The questionnaire included, items drawn from the Preventive Health Model that assess socio-demographic background and perceptions about BCS. Multiple logistic regression analysis was performed to identify factors associated with screening and intention to do screening in the future.
Results:
The mean age of subjects was 38.2 years. Women who perceived more screening efficacy (odd ratio [OR] =1.63; confidence interval [CI] 95%: 1.12-2.37) and fewer performance barriers (OR = 0.82; CI 95%: 0.68-0.97) were more likely to perform clinical breast exam in the future. The women who reported higher clinical breast exam self-efficacy (OR = 1.82; CI 95%: 1.39-2.37), mammography self-efficacy (OR = 1.31; CI 95%: 1.04-1.65), screening efficacy (OR = 1.53; CI 95%: 1.18-1.97), and family influence (OR = 1.27; CI 95%: 1.05-1.54), and those who reported fewer screening performance barriers (OR = 0.56; CI 95%: 0.48-0.67) were more likely to decide for carried out mammography in the future. Most respondents indicated that they intended to do clinical breast exam and mammography in the future (75.8% and 72.1% respectively). About 65% of women reported they would do both.
Conclusions:
We found that women's intention to do BCS was very high and a comprehensive national program is needed to guide their intention. Among different demographic factors, the impact of education level on doing BCS was significant.
PMCID: PMC3950743  PMID: 24627747
Attitude; breast cancer screening; decision making; knowledge
8.  Breast cancer screening in France: results of the EDIFICE survey 
Background: The EDIFICE survey aimed to investigate the compliance of the general population to the screening tests available in France for the 4 most common cancers: breast, colorectal, prostate and lung. Implementation of breast cancer screening has been generalized in France since 2003: women aged between 50 and 74 years are systematically invited to perform a mammography every second year. Results pertaining to breast cancer are reported hereafter.
Methods: This nationwide observational survey was carried out in France from 18 January to 2 February 2005 among representative samples of 773 women aged between 40 and 75 years and 600 general practitioners (GPs). Information collected included socio-demographic characteristics, attitude towards cancer screening and actual experience of cancer screening, as well as GPs' practice regarding screening. The precision of the results is ± 4.3% for a 95% confidence interval.
Results: Among the 507 participating women aged between 50 and 74 years, 92.5% (469/507) had undergone at least one mammography: 54.6% (256/469) underwent this test on their own initiative and 44.6% (209/469) of women performed it in the framework of a systematic screening plan. Most women participating in the systematic screening (89.0% i.e. 186/209) had a mammography within the last dating from less than 2 years versus 73.8% (189/256) of those who performed it outside the screening program (Chi2 test; p<0.01). Interestingly, 422 women (61.9% i.e. 422/682 women aged between 40-75 years with at least one mammography) had performed a mammography before the recommended age for screening. There was a significant correlation (p = 0.009) between the existence of a first mammography before 50 years of age and subsequent screening on women's own initiative (54.6% of 469 screened women). Main reasons for not performing the screening test every second year (77 women aged between 50-74 years) included: feeling unconcerned and/or unmotivated (p = 0.0001), no cancer anxiety (p = 0.020) and no recommendation by the GP (p = 0.015); Of the 600 participating GPs, 68.6% (412/600) systematically recommended a mammography to their patients. GPs' perceptions of the reasons for women's avoidance of the screening test were unwillingness to be aware of mammography results (44.4% - 266/600) and the belief that mammography was painful (52.5% - 315/600).
Conclusion: The main result of the EDIFICE survey is the high rate of women's attendance at mammography screening. The EDIFICE survey pointed out that systematic and organized screening played a major role in the regularity of screening tests for breast cancer every second year. GPs and gynaecologist are key actors in heightening public awareness.
PMCID: PMC2407526  PMID: 18566655
Breast cancer; screening; Survey; mammography
9.  Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England 
Background
Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years.
Methods
Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test.
Results
72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups.
Conclusions
Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes.
doi:10.1186/1472-6963-10-103
PMCID: PMC2867962  PMID: 20423467
10.  Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort 
PLoS Medicine  2014;11(6):e1001660.
Using data from the French E3N prospective cohort, Marina Kvaskoff and colleagues examine the association between number of cutaneous nevi and the risk for breast cancer.
Please see later in the article for the Editors' Summary
Background
While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk.
Methods and Findings
We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with “very many” nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01–1.27 versus “none”; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674–4,649) per 100,000 women with “very many” nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD.
Conclusions
Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2012, nearly 1.7 million women worldwide discovered they had breast cancer, and about half a million women died from the disease. Breast cancer begins when cells in the breast acquire genetic changes that allow them to divide uncontrollably and to move around the body (metastasize). Uncontrolled cell division leads to the formation of a lump that can be detected by mammography (a breast X-ray) or by manual breast examination. Breast cancer is treated by surgical removal of the lump, or, if the cancer has started to spread, by removal of the whole breast (mastectomy). Surgery is usually followed by radiotherapy or chemotherapy to kill any remaining cancer cells. Because the female sex hormones estrogen and progesterone stimulate the growth of some tumors, drugs that block hormone receptors are also used to treat receptor-positive breast cancer. Nowadays, the prognosis (outlook) for women with breast cancer is good, and in developed countries, nearly 90% of affected women are still alive five years after diagnosis.
Why Was This Study Done?
Several hormone-related factors affect a woman's chances of developing breast cancer. For example, women who have no children or who have them late in life have a higher breast cancer risk than women who have several children when they are young because pregnancy alters sex hormone levels. Interestingly, the development of moles (nevi)—dark skin blemishes that are risk factors for the development of melanoma, a type of skin cancer—may also be affected by estrogen and progesterone. Thus, the number of nevi might be a marker of blood hormone levels and might predict breast cancer risk. In this prospective cohort study, the researchers test this hypothesis by investigating the association between how many moles a woman has and her breast cancer risk. A prospective cohort study enrolls a group (cohort) of people, determines their baseline characteristics, and follows them over time to see which characteristics are associated with the development of specific diseases.
What Did the Researchers Do and Find?
In 1990, the E3N prospective cohort study enrolled nearly 100,000 French women (mainly school teachers) aged 40–65 years to investigate cancer risk factors. The women completed a baseline questionnaire about their lifestyle and medical history, and regular follow-up questionnaires that asked about cancer occurrence. In the initial questionnaire, the women indicated whether they had no, a few, many, or very many moles. Between 1990 and 2008, nearly 6,000 women in the cohort developed breast cancer. Using statistical methods to calculate hazard ratios (an “HR” compares how often a particular event happens in two groups with different characteristics; an HR greater than one indicates that a specific characteristic is associated with an increased risk of the event), the researchers report that women with “very many” nevi had a significantly higher breast cancer risk (a higher risk that was unlikely to have occurred by chance) than women with no nevi. Specifically, the age-adjusted HR for breast cancer among women with “very many” nevi compared to women with no nevi was 1.17. After adjustment for a personal history of benign (noncancerous) breast disease and a family history of breast cancer (two established risk factors for breast cancer), the association between nevi and breast cancer risk among the whole cohort became nonsignificant. Notably, however, the association among only premenopausal women remained significant after full adjustment (HR = 1.34), which corresponded to an increase in ten-year absolute risk of invasive breast cancer from 2,515 per 100,000 women with no nevi to 3,370 per 100,000 women with “very many” nevi.
What Do These Findings Mean?
These findings suggest that among premenopausal women there is a modest association between nevi number and breast cancer risk. This noncausal relationship may indicate that nevi and breast diseases are affected in similar ways by hormones or share common genetic factors, but the accuracy of these findings may be limited by aspects of the study design. For example, self-report of nevi numbers using a qualitative scale may have introduced some inaccuracies into the estimates of the association between nevi number and breast cancer risk. Most importantly, these findings are insufficient to support the use of nevi counts in breast cancer screening or diagnosis. Rather, together with the findings reported by Zhang et al. in an independent PLOS Medicine Research Article, they suggest that further studies into the biological mechanisms underlying the relationship between nevi and breast cancer and the association itself should be undertaken.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001660.
This study is further discussed in a PLOS Medicine Perspective by Fuhrman and Cardenas
An independent PLOS Medicine Research Article by Zhang et al. also investigates the relationship between nevi number and breast cancer risk
The US National Cancer Institute provides comprehensive information about cancer (in English and Spanish), including detailed information for patients and professionals about breast cancer; it also has a fact sheet on moles
Cancer Research UK, a not-for profit organization, provides information about cancer, including detailed information on breast cancer
The UK National Health Service Choices website has information and personal stories about breast cancer; the not-for profit organization Healthtalkonline also provides personal stories about dealing with breast cancer
More information about the E3N prospective cohort study is available; detailed information is available in French
doi:10.1371/journal.pmed.1001660
PMCID: PMC4051602  PMID: 24915306
11.  Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies 
PLoS Medicine  2013;10(7):e1001492.
Ruth Pfeiffer and colleagues describe models to calculate absolute risks for breast, endometrial, and ovarian cancers for white, non-Hispanic women over 50 years old using easily obtainable risk factors.
Please see later in the article for the Editors' Summary
Background
Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.
Methods and Findings
Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health–AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96–1.04) for breast cancer and 1.08 (95% CI: 0.97–1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11–1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57–0.59), 0.59 (95% CI: 0.56–0.63), and 0.68 (95% CI: 0.66–0.70) for the breast, ovarian, and endometrial models, respectively.
Conclusions
These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may assist in clinical decision-making. Limitations are the modest discriminatory ability of the breast and ovarian models and that these models may not generalize to women of other races.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2008, just three types of cancer accounted for 10% of global cancer-related deaths. That year, about 460,000 women died from breast cancer (the most frequently diagnosed cancer among women and the fifth most common cause of cancer-related death). Another 140,000 women died from ovarian cancer, and 74,000 died from endometrial (womb) cancer (the 14th and 20th most common causes of cancer-related death, respectively). Although these three cancers originate in different tissues, they nevertheless share many risk factors. For example, current age, age at menarche (first period), and parity (the number of children a woman has had) are all strongly associated with breast, ovarian, and endometrial cancer risk. Because these cancers share many hormonal and epidemiological risk factors, a woman with a high breast cancer risk is also likely to have an above-average risk of developing ovarian or endometrial cancer.
Why Was This Study Done?
Several statistical models (for example, the Breast Cancer Risk Assessment Tool) have been developed that estimate a woman's absolute risk (probability) of developing breast cancer over the next few years or over her lifetime. Absolute risk prediction models are useful in the design of cancer prevention trials and can also help women make informed decisions about cancer prevention and treatment options. For example, a woman at high risk of breast cancer might decide to take tamoxifen for breast cancer prevention, but ideally she needs to know her absolute endometrial cancer risk before doing so because tamoxifen increases the risk of this cancer. Similarly, knowledge of her ovarian cancer risk might influence a woman's decision regarding prophylactic removal of her ovaries to reduce her breast cancer risk. There are few absolute risk prediction models for ovarian cancer, and none for endometrial cancer, so here the researchers develop models to predict the risk of these cancers and of breast cancer.
What Did the Researchers Do and Find?
Absolute risk prediction models are constructed by combining estimates for risk factors from cohorts with population-based incidence rates from cancer registries. Models are validated in an independent cohort by testing their ability to identify people with the disease in an independent cohort and their ability to predict the observed numbers of incident cases. The researchers used data on white, non-Hispanic women aged 50 years or older that were collected during two large prospective US cohort studies of cancer screening and of diet and health, and US cancer incidence and mortality rates provided by the Surveillance, Epidemiology, and End Results Program to build their models. The models all included parity as a risk factor, as well as other factors. The model for endometrial cancer, for example, also included menopausal status, age at menopause, body mass index (an indicator of the amount of body fat), oral contraceptive use, menopausal hormone therapy use, and an interaction term between menopausal hormone therapy use and body mass index. Individual women's risk for endometrial cancer calculated using this model ranged from 1.22% to 17.8% over the next 20 years depending on their exposure to various risk factors. Validation of the models using data from the US Nurses' Health Study indicated that the endometrial cancer model overestimated the risk of endometrial cancer but that the breast and ovarian cancer models were well calibrated—the predicted and observed risks for these cancers in the validation cohort agreed closely. Finally, the discriminatory power of the models (a measure of how well a model separates people who have a disease from people who do not have the disease) was modest for the breast and ovarian cancer models but somewhat better for the endometrial cancer model.
What Do These Findings Mean?
These findings show that breast, ovarian, and endometrial cancer can all be predicted using information on known risk factors for these cancers that is easily obtainable. Because these models were constructed and validated using data from white, non-Hispanic women aged 50 years or older, they may not accurately predict absolute risk for these cancers for women of other races or ethnicities. Moreover, the modest discriminatory power of the breast and ovarian cancer models means they cannot be used to decide which women should be routinely screened for these cancers. Importantly, however, these well-calibrated models should provide realistic information about an individual's risk of developing breast, ovarian, or endometrial cancer that can be used in clinical decision-making and that may assist in the identification of potential participants for research studies.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001492.
This study is further discussed in a PLOS Medicine Perspective by Lars Holmberg and Andrew Vickers
The US National Cancer Institute provides comprehensive information about cancer (in English and Spanish), including detailed information about breast cancer, ovarian cancer, and endometrial cancer;
Information on the Breast Cancer Risk Assessment Tool, the Surveillance, Epidemiology, and End Results Program, and on the prospective cohort study of screening and the diet and health study that provided the data used to build the models is also available on the NCI site
Cancer Research UK, a not-for-profit organization, provides information about cancer, including detailed information on breast cancer, ovarian cancer, and endometrial cancer
The UK National Health Service Choices website has information and personal stories about breast cancer, ovarian cancer, and endometrial cancer; the not-for-profit organization Healthtalkonline also provides personal stories about dealing with breast cancer and ovarian cancer
doi:10.1371/journal.pmed.1001492
PMCID: PMC3728034  PMID: 23935463
12.  A case–control study of the impact of the East Anglian breast screening programme on breast cancer mortality 
British Journal of Cancer  2007;98(1):206-209.
Although breast cancer screening has been shown to work in randomised trials, there is a need to evaluate service screening programmes to ensure that they are delivering the benefit indicated by the trials. We carried out a case–control study to investigate the effect of mammography service screening, in the NHS breast screening programme, on breast cancer mortality in the East Anglian region of the UK. Cases were deaths from breast cancer in women diagnosed between the ages of 50 and 70 years, following the instigation of the East Anglia Breast Screening Programme in 1989. The controls were women (two per case) who had not died of breast cancer, from the same area, matched by date of birth to the cases. Each control was known to be alive at the time of death of her matched case. All women were known to the breast screening programme and were invited, at least once, to be screened. There were 284 cases and 568 controls. The odds ratio (OR) for risk of death from breast cancer in women who attended at least one routine screen compared to those who did not attend was 0.35 (CI: 0.24, 0.50). Adjusting for self-selection bias gave an estimate of the breast cancer mortality reduction associated with invitation to screening of 35% (OR=0.65, 95% CI: 0.48, 0.88). The effect of actually being screened was a 48% breast cancer mortality reduction (OR=0.52, 95% CI: 0.32, 0.84). The results suggest that the National Breast Screening Programme in East Anglia is achieving a reduction in breast cancer deaths, which is at least consistent with the results from the randomised controlled trials of mammographic screening.
doi:10.1038/sj.bjc.6604123
PMCID: PMC2359716  PMID: 18059396
breast cancer mortality; screening; case–control
13.  Number needed to screen: development of a statistic for disease screening 
BMJ : British Medical Journal  1998;317(7154):307-312.
Objectives: To develop the number needed to screen, a new statistic to overcome inappropriate national strategies for disease screening. Number needed to screen is defined as the number of people that need to be screened for a given duration to prevent one death or adverse event.
Design: Number needed to screen was calculated from clinical trials that directly measured the effect of a screening strategy. From clinical trials that measured treatment benefit, the number needed to screen was estimated as the number needed to treat from the trial divided by the prevalence of heretofore unrecognised or untreated disease. Directly calculated values were then compared with estimate number needed to screen values.
Subjects: Standard literature review.
Results: For prevention of total mortality the most effective screening test was a lipid profile. The estimated number needed to screen for dyslipidaemia (low density lipoprotein cholesterol concentration >4.14 mmol/1) was 418 if detection was followed by pravastatin treatment for 5 years. This indicates that one death in 5 years could be prevented by screening 418 people. The estimated number needed to screen for hypertension was between 274 and 1307 for 5 years (for 10 mm Hg and 6 mm Hg diastolic blood pressure reduction respectively) if detection was followed by treatment based on a diuretic. Screening with haemoccult testing and mammography significantly decreased cancer specific, but not total, mortality. The number needed to screen for haemoccult screening to prevent a death from colon cancer was 1374 for 5 years, and the number needed to screen for mammography to prevent a death from breast cancer was 2451 for 5 years for women aged 50-59.
Conclusion: These data allow the clinician to prioritise screening strategies. Of the screening strategies evaluated, screening for, and treatment of, dyslipidaemia and hypertension seem to produce the largest clinical benefit.
Key messages Number needed to screen is a new statistic defined as the number of people that need to be screened for a given duration to prevent one death or one adverse event. It can be directly calculated from clinical trials of disease screening, and can also be estimated from clinical trials of treatment and the prevalence of so far unrecognised or untreated disease For prevention of all cause death, 418 people need to be screened with a lipid profile if detection of dyslipidaemia was followed by pravastatin treatment for 5 years The estimated number needed to screen for hypertension to prevent all cause death was 274 to 1307 for 5 years if detection was followed by treatment with thiazide diuretic Screening with haemoccult testing or mammography did not significantly prevent all cause death. Haemoccult screening significantly decreased deaths from colon cancer with a number needed to screen of 1274 for 5 years. Mammography significantly reduced deaths from breast cancer with a number needed to screen of 2451 for 5 years of women aged 50-59
PMCID: PMC28622  PMID: 9685274
14.  What is the point: will screening mammography save my life? 
Background
We analyzed the claim "mammography saves lives" by calculating the life-saving absolute benefit of screening mammography in reducing breast cancer mortality in women ages 40 to 65.
Methods
To calculate the absolute benefit, we first estimated the screen-free absolute death risk from breast cancer by adjusting the Surveillance, Epidemiology and End Results Program 15-year cumulative breast cancer mortality to account for the separate effects of screening mammography and improved therapy. We calculated the absolute risk reduction (reduction in absolute death risk), the number needed to screen assuming repeated screening, and the survival percentages without and with screening. We varied the relative risk reduction from 10%–30% based on the randomized trials of screening mammography. We developed additional variations of the absolute risk reduction for a screening intervention, including the average benefit of a single screen, as well as the life-saving proportion among patients with earlier cancer detection.
Results
Because the screen-free absolute death risk is approximately 1% overall but rises with age, the relative risk reduction from repeated screening mammography is about 100 times the absolute risk reduction between the starting ages of 50 and 60. Assuming a base case 20% relative risk reduction, repeated screening starting at age 50 saves about 1.8 (overall range, 0.9–2.7) lives over 15 years for every 1000 women screened. The number needed to screen repeatedly is 1000/1.8, or 570. The survival percentage is 99.12% without and 99.29% with screening. The average benefit of a single screening mammogram is 0.034%, or 2970 women must be screened once to save one life. Mammography saves 4.3% of screen-detectable cancer patients' lives starting at age 50. This means 23 cancers must be found starting at age 50, or 27 cancers at age 40 and 21 cancers at age 65, to save one life.
Conclusion
The life-saving absolute benefit of screening mammography increases with age as the absolute death risk increases. The number of events needed to save one life varies depending on the prospective screening subset or reference class. Less than 5% of women with screen-detectable cancers have their lives saved.
doi:10.1186/1472-6947-9-18
PMCID: PMC2670293  PMID: 19341448
15.  Personalizing Mammography by Breast Density and Other Risk Factors for Breast Cancer: Analysis of Health Benefits and Cost-Effectiveness 
Annals of internal medicine  2011;155(1):10-20.
Background
Current guidelines recommend mammography every 1 or 2 years starting at age 40 or 50 years, regardless of individual risk for breast cancer.
Objective
To estimate the cost-effectiveness of mammography by age, breast density, history of breast biopsy, family history of breast cancer, and screening interval.
Design
Markov microsimulation model.
Data Sources
Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and the medical literature.
Target Population
U.S. women aged 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years with initial mammography at age 40 years and breast density of Breast Imaging Reporting and Data System (BI-RADS) categories 1 to 4.
Time Horizon
Lifetime.
Perspective
National health payer.
Intervention
Mammography annually, biennially, or every 3 to 4 years or no mammography.
Outcome Measures
Costs per quality-adjusted life-year (QALY) gained and number of women screened over 10 years to prevent 1 death from breast cancer.
Results of Base-Case Analysis
Biennial mammography cost less than $100 000 per QALY gained for women aged 40 to 79 years with BI-RADS category 3 or 4 breast density or aged 50 to 69 years with category 2 density; women aged 60 to 79 years with category 1 density and either a family history of breast cancer or a previous breast biopsy; and all women aged 40 to 79 years with both a family history of breast cancer and a previous breast biopsy, regardless of breast density. Biennial mammography cost less than $50 000 per QALY gained for women aged 40 to 49 years with category 3 or 4 breast density and either a previous breast biopsy or a family history of breast cancer. Annual mammography was not cost-effective for any group, regardless of age or breast density.
Results of Sensitivity Analysis
Mammography is expensive if the disutility of false-positive mammography results and the costs of detecting nonprogressive and nonlethal invasive cancer are considered.
Limitation
Results are not applicable to carriers of BRCA1 or BRCA2 mutations.
Conclusion
Mammography screening should be personalized on the basis of a woman’s age, breast density, history of breast biopsy, family history of breast cancer, and beliefs about the potential benefit and harms of screening.
Primary Funding Source
Eli Lilly, Da Costa Family Foundation for Research in Breast Cancer Prevention of the California Pacific Medical Center, and Breast Cancer Surveillance Consortium.
doi:10.7326/0003-4819-155-1-201107050-00003
PMCID: PMC3759993  PMID: 21727289
16.  Breast cancer mortality in organised mammography screening in Denmark: comparative study 
Objective To determine whether the previously observed 25% reduction in breast cancer mortality in Copenhagen following the introduction of mammography screening was indeed due to screening, by using an additional screening region and five years additional follow-up.
Design We used Poisson regression analyses adjusted for changes in age distribution to compare the annual percentage change in breast cancer mortality in areas where screening was used with the change in areas where it was not used during 10 years before screening was introduced and for 10 years after screening was in practice (starting five years after introduction of screening).
Setting Copenhagen, where mammography screening started in 1991, and Funen county, where screening was introduced in 1993. The rest of Denmark (about 80% of the population) served as an unscreened control group.
Participants All Danish women recorded in the Cause of Death Register and Statistics Denmark for 1971-2006.
Main outcome measure Annual percentage change in breast cancer mortality in regions offering mammography screening and those not offering screening.
Results In women who could benefit from screening (ages 55-74 years), we found a mortality decline of 1% per year in the screening areas (relative risk (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.01) during the 10 year period when screening could have had an effect (1997-2006). In women of the same age in the non-screening areas, there was a decline of 2% in mortality per year (RR 0.98, 95% CI 0.97 to 0.99) in the same 10 year period. In women who were too young to benefit from screening (ages 35-55 years), breast cancer mortality during 1997-2006 declined 5% per year (RR 0.95, CI 0.92 to 0.98) in the screened areas and 6% per year (RR 0.94, CI 0.92 to 0.95) in the non-screened areas. For the older age groups (75-84 years), there was little change in breast cancer mortality over time in both screened and non-screened areas. Trends were less clear during the 10 year period before screening was introduced, with a possible increase in mortality in women aged less than 75 years in the non-screened regions.
Conclusions We were unable to find an effect of the Danish screening programme on breast cancer mortality. The reductions in breast cancer mortality we observed in screening regions were similar or less than those in non-screened areas and in age groups too young to benefit from screening, and are more likely explained by changes in risk factors and improved treatment than by screening mammography.
doi:10.1136/bmj.c1241
PMCID: PMC2844939  PMID: 20332505
17.  Effectiveness of the public health policy for breast cancer screening in Finland: population based cohort study. 
BMJ : British Medical Journal  1997;314(7084):864-867.
OBJECTIVE: To evaluate the effectiveness of screening for breast cancer as a public health policy. DESIGN: Follow up in 1987-92 of Finnish women invited to join the screening programme in 1987-9 and of the control women (balanced by age and matched by municipality of residence), who were not invited to the service screening. SETTING: Finland. SUBJECTS: Of the Finnish women born in 1927-39, 89893 women invited for screening and 68862 controls were followed; 1584 breast cancers were diagnosed. MAIN OUTCOME MEASURES: Rate ratio of deaths from breast cancer among the women invited for screening to deaths among those not invited. RESULTS: There were 385 deaths from breast cancer, of which 127 were among the 1584 incident cases in 1987-92. The rate ratio of death was 0.76 (95% confidence interval 0.53 to 1.09). The effect was larger and significant (0.56; 0.33 to 0.95) among women aged under 56 years at entry. 20 cancers were prevented (one death prevented per 10000 screens). CONCLUSIONS: A breast screening programme can achieve a similar effect on mortality as achieved by the trials for breast cancer screening. However, it may be difficult to justify a screening programme as a public health policy on the basis of the mortality reduction only. Whether to run a screening programme as a public health policy also depends on its effects on the quality of life of the target population and what the resources would be used for if screening was not done. Given all the different dimensions in the effect, mammography based breast screening is probably justifiable as a public health policy.
PMCID: PMC2126259  PMID: 9093096
18.  Breast cancer mortality with varying invitational policies in organised mammography 
British Journal of Cancer  2008;98(3):641-645.
We examined the effect of different invitational policies on the reduction of breast cancer mortality at 60–79 years of age within the Finnish mammography programme in 1992–2003, which varied in its coverage at 60–69 years of age. The data from 260 municipalities were grouped into three categories: regular invitations at 50–59 years of age only, regular invitations at 50–69 years of age, and regular invitations at 50–59 years of age with irregular invitations at 60–69 years of age. Observed deaths from breast cancer were compared to those expected without screening among all women and among the screened and non-screened women. Observed deaths were obtained from population data and from a cohort follow-up in 1992–2003. Expected deaths were derived by modelling breast cancer mortality at population level in 1974–1985 and 1992–2003. The reduction in breast cancer mortality was strongest, 28% (0.72, 0.51–0.97), in municipalities with regular invitations at 50–69 years of age. No overall effect at 60–79 years of age was observed with regular invitations at 50–59 years of age. The study confirms a reduction by screening of breast cancer mortality in Finland. Uniform extension of invitations to 60–69 years of age would increase the number of prevented breast cancer deaths among the elderly.
doi:10.1038/sj.bjc.6604203
PMCID: PMC2243161  PMID: 18231108
effectiveness; mammography; breast cancer; screening; policy; epidemiology
19.  Mortality results from the Göteborg Randomised Prostate Cancer Screening Trial 
The lancet oncology  2010;11(8):725-732.
Summary
Background
Prostate cancer is one of the leading causes of death from malignant disease among men in the Western world. One strategy to decrease the risk of dying from this disease is screening with Prostate-Specific Antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate.
Methods
In December 1994, 20 000 men born 1930 to 1944, randomly sampled from the Population Register, were computer randomised in a 1:1 ratio to a screening group invited for biennial PSA testing or to a control group not invited. In each arm, 48 men were excluded from analysis due to either death or emigration before randomization date or prevalent prostate cancer. The primary endpoint was prostate cancer specific mortality analyzed according to the intention-to-screen principle. Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with elevated PSA were offered additional tests such as digital rectal examination and prostate biopsies. The study is still ongoing inviting men who have not yet reached the upper age limit. This is the first planned report on cumulative prostate cancer incidence and mortality calculated up to Dec 31 2008. This study is registered [as an International Standard Randomised Controlled Trial], number [ISRCTN49127736].
Findings
Among men randomised to screening 7578/9952 (76%) attended at least once (attendees). During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer resulting in a cumulative incidence of prostate cancer of 12.7% in the screening arm and 8.2% in the control arm (hazard ratio 1.64; 95% confidence interval [CI] 1.50–1.80; p<0.0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40% (95% CI 0.17–0.64%), from 0.90% in the control group to 0.50% in the screening group. The incidence rate ratio for death from prostate cancer was 0.56 (95% CI 0.39–0.82; p=0.002) in the screening compared to the control group. The incidence rate ratio of attendees compared to the control group was 0.44 (95% CI 0.28–0.68; p=0.0002). Overall, 293 men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death.
Interpretation
The benefit of prostate cancer screening compares favourably to other cancer screening programs and in this study prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over diagnosis is substantial and the number needed to treat is at least as high as in breast cancer screening.
Funding
The Swedish Cancer Society, the Swedish Research Council and the National Cancer Institute.
doi:10.1016/S1470-2045(10)70146-7
PMCID: PMC4089887  PMID: 20598634
20.  Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc): a multicentre randomized controlled trial 
BMC Cancer  2012;12:440.
Background
To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test.
The aim of the Familial MRI Screening Study (FaMRIsc) is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density.
Methods/Design
This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1) has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30–55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000), and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000).
Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor.
Discussion
Personalized breast cancer screening might optimize mortality reduction with less over diagnosis. Breast density may be a key discriminator for selecting the optimal screening strategy for women < 55 years with familial breast cancer risk; mammography or MRI. These issues are addressed in the FaMRIsc study including high risk women due to a familial predisposition.
Trial registration
Netherland Trial Register NTR2789
doi:10.1186/1471-2407-12-440
PMCID: PMC3488502  PMID: 23031619
Breast cancer; Familial risk; Screening; MRI; Breast density; Cost-effectiveness
21.  Misconceptions about efficacy of mammography screening: a public health dilemma 
OBJECTIVE—This study assessed accuracy of women's opinions about reduction in mortality from breast cancer attributable to mammography screening.
DESIGN—Cross sectional survey.
SETTING—General population of Geneva, Switzerland.
PARTICIPANTS—895 randomly selected women aged 40 to 80 years, free of breast cancer.
RESULTS—Women estimated the proportion of deaths from breast cancer that regular mammography screening prevents in women over age 50. Only 19.3% of the respondents assessed screening efficacy realistically (that is, reduction by about one fourth); 52.0% overestimated efficacy; 26.0% "didn't know", and 2.6% stated that screening prevents no death. Women who believed mammography screening to be effective had more positive attitudes toward screening (higher scores of pros and lower scores of cons) and were more likely to plan to have a mammogram (both p<0.001). Lack of opinion about the benefit of mammography screening was more common among women who had not consulted a gynaecologist recently (p=0.02) nor had had a mammogram during the past two years (p=0.009), who had no opinion about their risk of breast cancer (p<0.001), and who were 70 to 80 years old (p=0.04). Compared with women who provided realistic estimates of screening efficacy, those who overestimated efficacy believed to be at higher risk of breast cancer than other women (p=0.04) and were more likely to be Swiss nationals (p=0.001).
CONCLUSIONS—Most women overestimated and many were uninformed about the efficacy of mammography screening. Therefore, few women were able to take truly informed decisions about screening mammography.


Keywords: mammography screening; patient information; decision making
doi:10.1136/jech.55.11.799
PMCID: PMC1763315  PMID: 11604435
22.  Update in Women’s Health 
ABSTRACT
INTRODUCTION
The aim of this clinical update is to summarize articles and guidelines published in the last year with the potential to change current clinical practice as it relates to women’s health.
METHODS
We used two independent search strategies to identify articles relevant to women’s health published between March 1, 2007 and February 29, 2008. First, we reviewed the Cochrane Database of Systematic Reviews and journal indices from the ACP Journal Club, Annals of Internal Medicine, Archives of Internal Medicine, British Medical Journal, Circulation, Diabetes, JAMA, JGIM, Journal of Women’s Health, Lancet, NEJM, Obstetrics and Gynecology, and Women’s Health Journal Watch. Second, we performed a MEDLINE search using the medical subject heading term “sex factors.” The authors, who all have clinical and/or research experience in the area of women’s health, reviewed all article titles, abstracts, and, when indicated, full publications. We excluded articles related to obstetrical aspects of women’s health focusing on those relevant to general internists. We had two acceptance criteria, scientific rigor and potential to impact women’s health. We also identified new and/or updated women’s health guidelines released during the same time period.
RESULTS
We identified over 250 publications with potential relevance to women’s health. Forty-six articles were selected for presentation as part of the Clinical Update, and nine were selected for a more detailed discussion in this paper. Evidence-based women’s health guidelines are listed in Table 1. Table 1Important Women’s Health Guidelines in 2007–2008: New or UpdatedTopicIssuing organizationUpdated recommendations and commentsMammography screening in women 40–4917ACPIndividualized risk assessment and informed decision making should be used to guide decisions about mammography screening in this age group.To aid in the risk assessment, a discussion of the risk factors, which if present in a woman in her 40s increases her risk to above that of an average 50-year-old woman, is provided in the guidelines. In addition, available risk prediction models, such as the NIH Web site calculator (http://www.cancer.gov/bcrisktool/) can also be used to estimate quantitative breast cancer risk. This model was updated in 2008 with race-specific data for calculating risk in African-American women.18The harms and benefits of mammography should be discussed and incorporated along with a woman’s preferences and breast cancer risk profile into the decision on when to begin screening. If a woman decides to forgo mammography, the decision should be readdressed every 1 to 2 years.STD screening guidelines19USPSTF and CDCRoutine screening for this infection is now recommended for ALL sexually active women age 24 and under, based on the recent high prevalence estimates for chlamydiaIt is not recommended for women (pregnant or nonpregnant) age 25 and older, unless they are at increased risk for infection.STD treatment guidelines20CDCFlouroquinolones are NO longer recommended for treatment of N. gonorrhea, due to increasing resistance (as high as 15% of isolates in 2006).For uncomplicated infections, treatment of gonorrhea should be initiated with ceftriaxone 125 mg IM or cefixime 400 mg PO and co-treatment for chlamydia infection (unless ruled out with testing). Recent estimates demonstrate that almost 50% of persons with gonorrhea have concomitant chlamydia infection21.STD = sexually transmitted disease, NIH = National Institutes of Health, ACP = American College of Physicians, USPSTF = United States Prevention Services Task Force, CDC = Centers for Disease Control
doi:10.1007/s11606-009-0917-9
PMCID: PMC2686759  PMID: 19259751
women’s health; osteoporosis; preconception counseling; HPV vaccine; obesity; cardiovascular disease
23.  Long term breast cancer screening in Nijmegen, The Netherlands: the nine rounds from 1975-92. 
STUDY OBJECTIVE: To assess the performance of breast cancer screening in different age categories over two decades. DESIGN: Important determinants of reduced breast cancer mortality such as attendance, mammography performance, cancer detection, and disease stage were recorded. SETTING: Nijmegen, The Netherlands, 1975-92. SUBJECTS: Since 1975 more than 40,000 women aged 35 years and older have been invited biennially for breast screening in a population based project in Nijmegen. MAIN RESULTS: Rates of attendance, referral, detection, and disease stage were calculated, as well as the specificity of screening mammography and the predictive value of referral and biopsy. From round 3 onwards, the attendance rate of women younger than 50 years stabilised at 70%, in women of 50-69 years it was 62%, and in women aged 70 and over it was 22%. In these three age categories, the referral rates of a positive screening mammography per 1000 screened women were 4.9, 6.2, and 11.8, respectively. Specificity rates were between 99% and 100%. Current predictive values of referral were high: in the specific age categories 39%, 59%, and 68% of the referred women had cancer. Detection rates remained fairly stable over the rounds 4-9, at 1.9, 3.6, and 8.0 cancers per 1000 screened women. In the two year period between screening the numbers of interval cancers per 1000 screened women were 2.2, 2.2, and 2.9, for the three age categories respectively. With regard to invasive cancers detected during screening, the percentage of small tumours (< or = 20 mm on the mammogram) was 84% in each age category. For women younger than 50 years, the proportion of intraductal carcinoma in all the cancers detected at screening was 40%, while it was 15% in the other age categories. CONCLUSION: Throughout the nine rounds, the screening outcomes were found to be adequate, particularly considering the high specificity rate and the predictive value of referral without the interference of a low detection rate. Although the occurrence of interval cancers seemed high, it was similar to other screening programmes. Despite a relatively low referral rate, the ratios of screen detected versus interval cancer cases were favourable. Well organised screening programmes can achieve good mammography results without too many false positives. It is important that women continue to participate in a screening programme because cancer can still be detected even after several successive negative screening examinations.
PMCID: PMC1060295  PMID: 8935470
24.  Mammography screening: views from women and primary care physicians in Crete 
BMC Women's Health  2008;8:20.
Background
Breast cancer is the most commonly diagnosed cancer among women and a leading cause of death from cancer in women in Europe. Although breast cancer incidence is on the rise worldwide, breast cancer mortality over the past 25 years has been stable or decreasing in some countries and a fall in breast cancer mortality rates in most European countries in the 1990s was reported by several studies, in contrast, in Greece have not reported these favourable trends. In Greece, the age-standardised incidence and mortality rate for breast cancer per 100.000 in 2006 was 81,8 and 21,7 and although it is lower than most other countries in Europe, the fall in breast cancer mortality that observed has not been as great as in other European countries. There is no national strategy for screening in this country. This study reports on the use of mammography among middle-aged women in rural Crete and investigates barriers to mammography screening encountered by women and their primary care physicians.
Methods
Design: Semi-structured individual interviews. Setting and participants: Thirty women between 45–65 years of age, with a mean age of 54,6 years, and standard deviation 6,8 from rural areas of Crete and 28 qualified primary care physicians, with a mean age of 44,7 years and standard deviation 7,0 serving this rural population. Main outcome measure: Qualitative thematic analysis.
Results
Most women identified several reasons for not using mammography. These included poor knowledge of the benefits and indications for mammography screening, fear of pain during the procedure, fear of a serious diagnosis, embarrassment, stress while anticipating the results, cost and lack of physician recommendation. Physicians identified difficulties in scheduling an appointment as one reason women did not use mammography and both women and physicians identified distance from the screening site, transportation problems and the absence of symptoms as reasons for non-use.
Conclusion
Women are inhibited from participating in mammography screening in rural Crete. The provision of more accessible screening services may improve this. However physician recommendation is important in overcoming women's inhibitions. Primary care physicians serving rural areas need to be aware of barriers preventing women from attending mammography screening and provide women with information and advice in a sensitive way so women can make informed decisions regarding breast caner screening.
doi:10.1186/1472-6874-8-20
PMCID: PMC2588567  PMID: 18990253
25.  Outcomes of screening to prevent cancer: analysis of cumulative incidence of cervical abnormality and modelling of cases and deaths prevented 
BMJ : British Medical Journal  2003;326(7395):901.
Objective
To determine the frequency of different outcomes in women participating in cervical screening.
Design
Analysis of screening records from 348 419 women, and modelling of cases of cervical cancer and deaths with and without screening.
Setting
Cervical screening programme in Bristol.
Results
For every 10 000 women screened from 1976 to 1996, 1564 had abnormal cytology, 818 were investigated, and 543 had abnormal histology. One hundred and seventy six had persistent abnormality for two years or more. In the absence of screening 80 women would be expected to develop cancer of the cervix by 2011, of whom 25 would die. With screening 10 of these deaths would be avoided. Comparison of cumulative abnormality rates with numbers expected to develop cancer in the absence of screening suggests that at least 80% of high grade dyskaryosis and of high grade dysplasia would not progress to cancer. The lifetime risk of having abnormal cytology detected could be as high as 40% for women born since 1960.
Conclusions
Screening is labour and resource intensive. It involves treatment for many women not destined to develop invasive cancer. The increased intervention rate for cervical abnormality in England is due to change in practice, not a cohort effect, and is probably the reason for the marked fall in incidence and mortality during the 1990s. For other cancers there is scope for major iatrogenic harm from screening because of invasive tests and treatments.
What is already known on this topicSince the mid-1980s incidence of and mortality from cervical cancer in women born since the 1930s in England and Wales has fallen; screening is the most likely explanationFor each death prevented many women have to be screened and many are treated who would not have developed a problemWhat this study addsIn the NHS cervical screening programme around 1000 women need to be screened for 35 years to prevent one deathOver 80% of women with high grade cervical intraepithelial neoplasia will not develop invasive cancer, but all need to be treatedFor each death prevented, over 150 women have an abnormal result, over 80 are referred for investigation, and over 50 have treatmentBefore the 1988 relaunch of screening with strict quality standards, for each death prevented there were 57 000 tests and 1955 women had abnormal results
PMCID: PMC153831  PMID: 12714468

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