Breast cancer is defined as an uncontrollable growth of breast cells that result in malignant tumors(12). Tumors are cells that rapidly grow into clusters of cells. Theses clusters are then classified as malignant or benign. A malignant tumor is a cancerous tumor that can spread not only locally, place of origin, but also invasively, to other organs. Benign tumors are not of much importance in most circumstances as long as there is not pain associated with the tumor. These tumors are a result of overgrowth in the cells and do not appear to cause cancer in most cases. Malignant tumors are the tumors associated with cancers of all types and are named based on the location of the tumor, i.e. breast cancer. In order to answer the controversial question of whether or not mammography provides a net benefit to society, one must fully understand breast cancer, objective of a screening test, and how mammography screening correlates with this public health issue. This paper will provide assess three breast cancer studies to determine if early detection using mammography reduces mortality and morbidity and thus provides a net benefit to society.
Breast cancer is a tremendous public health problem due to the alarming rate of incidence and mortality among women developing this disease.Women are more likely to develop breast cancer than man, however, it is expected to be an increase of cases in males (11) . 1 in 8 women will be diagnosed with breast cancer within their lifetime (11). Currently, breast cancer is expected to affect approximately 266,120 women in the U.S. in this year alone (4). This alarming incidence rate attributes to the importance of breast cancer as a public health challenge. Incidence of breast cancer is more common in non-hispanic white women over 45 years of age, however, African-American women younger than 45 have a higher mortality rate(11). Since the year 2000, breast cancer rates have been declining compared to the past two decades but it still remains a problem. Researchers believe this decline is due to the reduction of menopausal hormone therapy which has been shown to increase risk of breast cancer (4).
The current tool for primary prevention and early detection of breast cancer to reduce mortality and morbidity among all women is mammography screening. The Centers for Disease Controls (CDC) defines mammography as an X-ray screening tool that assist physicians in diagnosing breast cancer tumors (2). The process includes an X-ray machine examining the breast for tumors that are possibly cancerous. This tool detects suspicious lumps or tumors during the X-ray. Physicians then determine and diagnosis the patient with a stage of cancer or a benign tumors. If cancerous, the physician will state to the patient treatment options that are best for their tumor stage. The screening itself is quite uncomfortable to women, but physicians have state that the pain will subside shortly after the screening test is complete. Mammography screening is deemed the optimum way of early detection and prevention of breast cancer mortality in some studies(6).
The United States Preventative Service Task Force (USPSTF) recommends women ages 50 to 74 to biennially undergo mammography with a grade of “B”. A recommendation grade of “B” by the USPSTF infers that the service in question has a high certainty that the net benefit is moderate or the net benefit is moderate to substantial and should be provided to everyone(5). Moderate grading is a recommendation grade given to the general public based off of the available data that has to be proven sufficient in the prevention of the health outcome(5). Although the task
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force might recognize this screening tool as an adequate detection test for that disease, the data or evidence provided does not meet the standard in essence of generalizability to primary care practice, number, size or quality of individual studies, inconsistency of findings, and lack of coherence in the chain of evidence (5).
The purpose of a screening test according to the National Institute of Health (NIH) is to access the likelihood of a particular disease in subjects that are asymptomatic. A screening test is designed to reduce morbidity or mortality in the screen population with an available treatment(9). This test or procedure should correctly detect the disease of interest to prove validity and be able to work outside of controlled conditions to prove reliable. A screening test should also have high sensitivity, the ability to of the test to correctly designate a positive subject diseased, and specificity, the ability of the test to correctly designate a negative subject non-diseased(9). According to the World Health Organization, the ten principles of a screening test to be effective are as follows:
1. The condition sought should be a public health problem.
2. There should be an accepted treatment for patients with recognized
disease.
3. Facilities for treatment and diagnosis should be available.
4. There should be a recognizable latent or early symptomatic stage.
5. There should be a suitable test or examination.
6. The test should be acceptable to the population.
7. The natural history of the condition, including development from latent to
declared disease, should be adequately understood.
8. There should be an agreed policy on whom to treat as patients.
9. The cost of case findings (including diagnosis and treatment of patients
diagnosed) should be economically balanced in relation to possible
expenditure on medical care as a whole.
10. Case findings should be a continuous process and not a ‘one for all’
project (8).
There are a variety of principles, guidelines, and recommendations for screening
test and public health issues such as breast cancer. The only way to test the effectiveness of these screening test and it’s true effect on the disease in question is to conduct a well defined study or clinical trial.
One screening trial that tested the effectiveness of mammography screening is the “Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial.” This Canadian randomized screening trial consisted of 15 screening centers in six Canadian provinces (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia) (10). The objective of this study was to compared the incidence and mortality rates of breast cancer in women ages 40 to 59 with a follow-up of 25 years. The study researchers collected their data by study coordinators, study centers, and linkage to cancer registries and vital statistics databases to ensure these women were diagnosed and died due to breast cancer thus ensuring internal validity of their study (10). There were approximately 90,000 women included in this study that were randomized to mammography (five annual mammography screening) or control (no mammography).
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The research team recruited these participants by reviewing a population list, sending out letters through personal invitations, group mailing, and family doctors. The eligibility criteria for this study was women ages 40 to 59 who had not had a mammography within the past 12 months, no history of breast cancer, and not pregnant. The group of women ages 40 to 49 who were randomized to mammography were given an annual physical breast examination. Women in the control arm ages 40 to 49 were given a single examination followed by usual care in the community. All women 50-59 in both arms of the study received annual physical breast examinations. The main outcome of this randomized screening trial was death of breast cancer (10). Figure 1 depicts the framework of this study.
Figure 1: Process of randomisation and initial screening (screen 1). Breast examination was carried out by nurses unless stated otherwise (+ve indicates abnormality found by examiner, -ve no abnormality found). MA=mammography (+ve indicates abnormality found by radiologist, -ve no abnormality found). Study surgeon could order diagnostic mammography or consult with the study radiologist if necessary before sending recommendations to family doctors. Bracketed interventions indicate protocol at subsequent screens (10).
As a result, approximately 1200 women were diagnosed with breast cancer during the screening period with 666 from the mammography arm and 524 in the control arm (10). Of the 666 women diagnosed with breast cancer, 484 were screen detected cancers and 176 were internal cancers. Both arms of the study found large percentages of node positive and palpable tumors. All in all, 1005 women died of breast cancer during the duration of this 25 year follow-up period which included 351 cases that were diagnosed within the study. An important finding was in the mortality rate comparisons of the mammography and control arm of the study. This study found that all cause mortality was only 10.6% in the follow up years. The 25 year follow-up was the same for
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all cause mortality rate of the mammography screened group and control group. The 25 year cumulative follow-up for breast cancer mortality was also similar in both the mammography arm and the control arm (10).
Figure 2: Breast cancer specific mortality from cancers diagnosed in screening period, by assignment to mammography or control arms(10).
Additionally, an excess of 22% (142) of the breast cancer cases occurred in the mammography arm compared to the control arm. This approximates one over-diagnosed case per 424 women who received mammography screening in this trial (10). Figure 2 depicts the study association findings of the rate of mortality found in this randomized screening trial. The screening trial concluded that based off of the data they collected for 25 years of follow-up, mammography screening does not reduce breast cancer specific mortality in women ages 40 to 59 beyond that of physical examination or usual community care. The authors believe the value of mammography screening should be revisited and reassessed in order to be effective (10).
In addition to interpreting the results of this trial, it is of relevance to point out the limitations of this study. When comparing the recommendations and results to the U.S. population, the age range for the randomized screening trial was 40 to 59. Current recommendations in the U.S. is for women 50 to 74. This study included only about a 2 and 6 tenths of the U.S. target population of women for breast cancer screening. Although, the results do not directly applies to the United States women population, it is of great use to analyze and take into account these findings when inquiring if mammography provides a net benefit to society.
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Another trial conducted in the United States that tests the validity of mammography as a screening test for breast cancer is the “Effect of Three Decades of Screening Mammography on Breast Cancer Incidence” c ohort study . T his study examines the effects of mammography screening and the three decades of clinician knowledge and use of this screening test. One of study’s objectives were to examine the temporal effects of mammography in women 40 years of age and/or older on stage-specific incidence of breast cancer (3). The notable objective of this study was to quantify the expected increase in incidence of early stage cancer and determine to what extent this has on the decrease of incidence in the late stage of cancer. The researchers of this study defined the purpose of a screening test as 1) advances the time of diagnosis of cancers that is known to cause death 2) early treatment of these cancers must confer some advantage over treatment at the clinical level (3).
The study consisted of collecting Surveillance, Epidemiology, and End Results breast cancer data to analyze trends from 1976 until 2008 in the incidence of early and late stage breast cancer (3). Early stage breast cancer was defined as ductal carcinoma in situ (DCIS) and localized disease. Late stage breast cancer was defined as regional and distant (3). A baseline of breast cancer incidence was collected at the beginning of each year of the study and used to assess the excess incidence within that specific year. A direct method was applied to adjust for the age distribution of the United States. To analyze the study objectives, data from the National Health Interview Survey to collect data on women 40 years and/or older that underwent screening mammography within the study’s time period. The study also utilized the U.S. census data to account for the annual estimates of women 40 years or older in the population.
The results of this observational cohort study is quite similar to the previous study mentioned in this paper. Due to the increase of breast cancer screening in 1980, the incidence rate of early stage detection rose substantially as depicted in Figure 3A . However, in Figure 3B , no difference in incidence were seen between women who did not undergo mammography and younger than 40 years of age(3). The increase of breast cancer incidence resulted from the screening test detecting localized tumors but also DCIS. DCIS are tumors that are not localized and if not screened would have possibly never caused harm to the individual or become cancerous. Table 1 shows a subtle decrease in latent stage cancer which correspond to the hypothesis that the screening test is catching less cases in the regional areas. This table also shows an estimate of a decrease incidence of latent stage cancer and an increase of early stage cancer both localized and DCIS.
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Figure 3A and 3B : Mammography use and incidence of stage specific breast cancer rates. Incidence rates of early stage disease increases while late stage decreases(3).
Table 1 : Displays the change in incidence of stage specific breast cancer among women 40 years of age or older after the introduction of mammography as a screening tool for breast cancer. This table shows the estimated number of women affected by overdiagnosis and the incident rates of early and late stage breast cancer.
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Likewise, the review estimated that the overdiagnosis rate attributed to mammography screening exceed 1 million women over three decades (3). With such an alarming rate of overdiagnosis, it is surprising that more research has not been conducted on the validity of mammography and breast cancer mortality rates. This study concluded that mammography screening does provide a benefit to society in the reduction of mortality, however, it possess a harm to by additional detection of early detected cancers. A reduction in mortality was observed over the course of the study period in women 40 years of age or older. When assessing if the reduction in mortality was attributable to mammography or better treatment options, only 28% of the reduction in mortality was attributed by mammography (3). Referring back to the study’s purpose of a screening test, mammography does not fit this criteria. Furthermore, women with distant disease only have 25% survival rate after 5 years compared to latent stage disease which has an available treatment and survival rate of 85% (3).
The final study review of this paper is the “Mortality reductions due to mammography screening: Contemporary population-based data”, 2000-2013. This population-based cohort was conducted in two regions of the Republic of Ireland. The two regions implemented a screening program, Breast Check, which was administered eight years apart. This procedure was conducted to estimate the steady-state mortality rate the screening program might introduce (6). Subject were ‘invited’ to participate in the study if they were a women age 50 to 64 years only within those two specific regions. There was a 68-70% response rate of the target population for this study. The regions were chosen due to similar population size with Region 1 being the East and North half of the country and Region 2 being the West and South of the country (6).The one objective of the study was to compare the contemporary breast cancer mortality rates in the two regions using data from the Irish National Cancer Registry on the diagnosis of all breast cancer from the first initiation of the screening program to eight years afterwards (6). Another objective of this study was to use the incidence of stages 2 and 4 as markers for mortality reductions. The final objective of this population-based study is to methodically depict the association between mortality and the amount breast cancer screenings.
The data was collected via the Irish National Cancer Registry to assure incident cases and cause of mortality. There was 99% completeness rate of the cases of diagnosed breast cancer starting at the implementation of Breast Check in 2000 (6). Diagnosis were linked to death certificates with a follow up until 2013. An alerting result of 94% of breast cancer mortality being attributable to breast cancer diagnosis appears to prove mammography very effective (6). Figure 4 depicts the results of this study in one specific cohort. Approximately 9,000 women age 54 were in Region 2 in the year 2000 when the study began. Due to the design of the study, these women did not receive breast cancer screening until 2007. Sixty-six women died of breast cancer due to a late diagnosis. The study implies that the premature mortality could have been avoided if the cancer was detected at an earlier age, 50, instead of eight years later.
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Figure 4: The Lexis diagram shows 9,208 women, the age of diagnosis of breast cancer and age of the 66 that died of cancer in the cohort of Region 2. The light gray shows the maximum amount screening could have detected the tumor and saved their lives (6).
The study concluded that the underlying solution to reduction in breast cancer mortality is to understand the amount of future deaths that will need to be averted by public health officials (6). The authors encourage mammography funders to conduct more contemporary population-based studies to examine the rate of mortality at two year intervals. This study focused more on time difference of mammography and its association to reduction of mortality of breast cancer. There was not a significant reduction in incidence of stage 2 to 4 tumors. However, there was a 20% deceit of incidence of these tumors in Region 1 before Region 2 started Breast Check. Essentially, this study is more towards mammography providing a benefit to society if given within the right time frame to prevent and treat the disease.
All and all, the three trials have provided adequate evidence to support their conclusions of whether or not mammography provides a net benefit to society. One can understand the controversy of mammography through this review. Two studies found mammography to be insufficient and in need of reassessment while one study believes mammography attributes more benefit than harm. A common factor within all of these studies are overdiagnosis, overtreatment, and importance of age/time of diagnosis. There should be more mammography specific breast cancer studies to update the current studies we have from the 1900s and early 2000s. Treatment options such as hormone therapy and a variety of other factors such as access to health care are potential effects of the rate of breast cancer incidence. More studies are needed to find concrete information on the attribution of mammography in reduction of incidence for high risk breast cancer stages.
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In my opinion, screening mammography does not provide a net benefit to society. There is a lack of evidence as stated previously in the effectiveness of this screening tool. The USPSTF recommends mammography to society with a grade of “B”. Within the definition of grade “B”, it explicitly states that evidence or data provided does not meet the standard in essence of generalizability to primary care practice, number, size or quality of individual studies, inconsistency of findings, and lack of coherence in the chain of evidence (5). If there is an uncertainty or inconsistency of findings in a manner as important as cancer, it is better to not screen then cause unnecessary harm. The USPSTF also includes women ages 70 to 74 in the recommendation when there is evidence showing that all cause mortality did not differ with screening(1). Mammography does not reduce cancers at high risk which was proven in the “ Effect of Three Decades of Screening Mammography on Breast Cancer Incidence” c ohort study(3).
Additionally, the rate of false positives with mammography is not valid. Nearly 50% of U.S. women that undergo mammography will receive a false positive at some point in their lifetime (7). A false positive result can affect an individual psychologically, physically, and even financially. Treating individuals who if had not been screened would not have developed disease is overdiagnosis. Mammography has a prevalent rate of overdiagnosis that each study in this review has mentioned. 31% of mammography detected breast cancers are attributable to overdiagnosis (1). In essence, nearly half of the detected breast cancers are overdiagnosis which can lead to overtreatment (3). Treatments including but not limited to biopsies, chemotherapy, and radiation therapy which are gateways to other chronic conditions such as heart damage, nerve damage, and loss of memory (7). To endure horrific and unnecessary treatments due to a tumor that if one had not followed the USPSTF recommendations would not have been harmful is unethical. More research should be conducted before mammography is accepted into society. For the reasons stated above, mammography does not have enough evidence to be proven effective to benefit the society.
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References:
1. Autier, P., & Boniol, M. (2018). Mammography screening: A major issue in medicine. 90, 34-62. (overdiagnosis and rate)
2. Breast Cancer. (2018, September 11). Retrieved from https://www.cdc.gov/cancer/breast/basic_info/mammograms.htm (1)
3. Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence | NEJM. (n.d.). Retrieved from https://www.nejm.org/doi/full/10.1056/NEJMoa1206809(9)
4. Find Breast Cancer Statistics at Susan G. Komen. (n.d.). Retrieved from https://ww5.komen.org/BreastCancer/Statistics.html(2)
5. Grade Definitions. (n.d.). Retrieved from https://www.uspreventiveservicestaskforce.org/Page/Name/grade-definitio ns(5)
6. Hanley, J. A., Hannigan, A., & O’Brien, K. M. (2017). Mortality reductions due to mammography screening: Contemporary population-based data. PLOS ONE, 12( 12), e0188947. (10)
7. Løberg, M., Lousdal, M. L., Bretthauer, M., & Kalager, M. (2015). Benefits and harms of mammography screening. Breast cancer research : BCR , 17( 1), 63. doi:10.1186/s13058-015-0525-z (12)
8. Mackay, J. (2012). Breakthrough Breast Cancer & Cancer Research UK Genetic Breast Cancer Trial. Http://isrctn.org/. doi:10.1186/isrctn43372330 (7)
9. Maxim, L. D., Niebo, R., & Utell, M. J. (2014). Screening tests: a review with examples. Inhalation toxicology , 26 (13), 811-28.(6)
10.Miller, A. B., Wall, C., Baines, C. J., Sun, P., To, T., & Narod, S. A. (2014, February 11). Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised
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screening trial. Retrieved from
https://www.bmj.com/content/348/bmj.g366(8)
11.U.S. Breast Cancer Statistics. (n.d.). Retrieved from
https://www.breastcancer.org/symptoms/understand_bc/statistics(3)
12. What Is Breast Cancer? (n.d.). Retrieved from https://www.breastcancer.org/symptoms/understand_bc/what_is_bc(4)