Breast cancer screening: the issues
By Fiona Lannigan
Supervisor: Sarah Vinnicombe
Contents Page
1. Introduction – Epidemiology 3
– Anatomy of the breast 3-4
– What is breast cancer? 4
– Risk factors 5
2. What is breast mammography screening? 5-9
3. Advantages 9-10
4. Disadvantages 10-12
5. Conclusion 12
6. References 13-14
1. Introduction
Epidemiology:
In both developed and developing countries, breast cancer is the most common cancer amongst women, with one in ten of all new cancers diagnosed being found in the female breast. Through the mid-1990s, there was a significant increase in incidence rates across European countries, mainly in women over 50. This may be due to the introduction of organised breast mammographic screening, in 1988. However, in Nordic countries, increased incidence had become apparent in the early 1980s, before breast screening was introduced. The increase may have been caused by an increase in risk factors, for example, exogenous hormonal intake (oral contraceptives), childbearing and breastfeeding rates and other factors including obesity and reduced physical activity. Across Europe, mortality rates have decreased (a 30.5% drop in England and Wales) due to the introduction of the breast screening programme, an improvement in surgical techniques and an increase in the use of chemotherapy as a curative treatment.1
Anatomy of the breast:
The breast consists of fatty and connective tissue which overlies the deep fascia of the pectoralis major muscle with the retro-mammary space separating the deep fascia and breast tissue. Within the breast are lactiferous sinuses connected to lactiferous ducts which produce milk for breastfeeding. These lactiferous ducts arise from modified sweat glands known as mammary glands (located in the superficial fascia) and consist of a series of ducts and lobules which are the most common origins of cancer in the breast. Continuous with the dermis of the skin, ligaments support the breast. When a carcinoma is present, it creates tension on these ligaments forming pitting of the skin.2
The lymphatic system is a natural drainage system made up of lymph glands and vessels which contain lymph fluid to remove foreign bodies from the blood stream thus preventing infection.3 In the breast, lymph fluid mainly drains laterally and superiorly into the axillary nodes (located in the axilla). The remaining fluid drains to parasternal nodes (located on the deep surface of the thoracic wall) before draining into broncho-mediastinal trunks and back into the venous system. The fluid from the axillary nodes drains into subclavian trunks and back into the venous system.2 The lymphatic system is very important in breast cancer as some of the cancerous cells can enter the system allowing the cancer to move to other parts of the body (known as metastases).
(4)
What is breast cancer?
Breast cancer is caused by a mutation in the epithelial cells of the acini, lactiferous ducts or lobules of the breast. A breast cancer is classified as in situ or non-invasive when it has not crossed the basement membrane and invasive cancer when the it extends into the surrounding tissues.5 The most common type of invasive breast cancer is ductal of no special type where the cells have no microscopic features to indicate a special (distinct) type of breast cancer. 90% of invasive breast cancers are of no specific type. Invasive lobular breast cancers are an example of a “special type” and only occur in 10% of invasive cases. They are not easily diagnosed as they are less readily palpable and indistinct on mammography Inflammatory breast cancer causes inflammation of the breast tissue due to blockage of the lymphatic vessels which causes possible symptoms of swollen, red, firm breasts in the patient.3
(3)
Risk factors:
There are many risk factors that can lead to breast cancer, including, age, menopausal status and family history of breast cancer. It has been found that increasing age is the greatest risk factor for female breast cancer. “less than 2% of invasive breast cancers are diagnosed in women aged less than 35 years (Ries et al. 2007a).” Breast cancer survival rates and recurrence-free survival rates are considerably decreased in younger patients compared to older women (chung et al. 1996; Winchester et al. 1996; Maggard et al. 2003). There is evidence that shows that there is a distinct biological difference between the breast tumors found in young women when compared with older women (Walker et al. 1996; Anderson and Matsuno 2006; Benz 2008).6
Those women who are premenopausal are said to have more aggressive cancer than postmenopausal women due to the exposure of cycling ovarian hormones. “Approximately 38-64% of breast cancers diagnosed in women aged <40 years have a high grade, compared to only 17-38% in women aged 60 years (Sidoni et al. 2003; Anderson et al. 2007a)”. Thus, the 5-year relative survival rate for women <40 years old is approximately 78-84% but >90% (Ries et al 2007b)6 in women 60 years old. Breast cancer is hereditary in about 5% of cases, many associated with gene defects in the BRCA1 and BRCA2 genes.7
There is a limited understanding as to how breast cancers arise and the best option to reduce mortality rates is the early diagnosis. This can be done by encouraging women to present to clinics as early as possible when they develop breast symptoms or through an organized breast screening programme.
2. What is breast cancer mammography screening?
Breast screening detected cancer (circled in black pen)
*both images obtained from a consultant breast surgeon at Wishaw General Hospital, North Lanarkshire NHS
The resected cancer found in the mammogram above
Mammography is a type of X-ray imaging that can be used to detect cancers in the breast tissue. It uses ionizing radiation to obtain the image so it should only be used in times of clinical benefit. This type of imaging is less effective in denser breasts as it obscures the early signs of cancer. Many young women have denser breasts due to the increased amount of glandular tissue compared to fatty tissue in the premenopausal stage (glandular tissue is needed to allow production of milk for breastfeeding). Sensitivity of mammography in women >60 years is approximately 95% compared to <50% of cancers detected in women <40 years.7 Digital mammography instead of X-ray films are more beneficial as the whole density range of the breast can be visualized easily on a single image. The overall imaging is also clearer.7 Some evidence suggests breast density is increased by taking hormone replacement therapy (HRT), causing difficulties in reading the screening mammograms.8 However, more recent evidence has arisen that has concluded that HRT has no effect on breast density or increase in incidence of malignancy.9
The goal of breast cancer screening across the UK is to decrease the mortality rates of breast cancer. To allow that to happen, breast cancer must be identified in the pre-clinical phase when the patient is asymptomatic as treatment is more effective during this time – around 90% of women with small breast tumours (<10mm) survive. It must have a high sensitivity and be applied to a large amount of the target population.10
In 1986, a committee chaired by Sir Patrick Forrest published a report that concluded that the introduction of a mass screening mammography programme would lead to a reduction in breast cancer deaths. Thus, in 1988 a universally available programme was introduced to provide breast cancer screening across the UK. The evidence to support this shows that of women in the 50-74 age category, screening reduces death rates by 26%, regardless of the duration of follow up, number of mammographic views per screen or the screening interval. Today, mobile “Forrest” units are used to screen a population of 41,000 women (aged between 50-70) and are staffed by trained, female healthcare professionals. These mobile units along with GP practices are given a screening quota that states that for the targeted screening to be successful, over 70% of women must accept their invitation.11
In early screening guidelines, women at their first screening would have a two-view mammography then screenings in the single oblique view were then repeated every three years (till the age of 64). The women were asked to fill out a questionnaire detailing any symptoms/ lack of symptoms for the benefit of the radiology team. The films were collected from the mobile unit and read by a radiologist specializing in breast screening.11 In recent screening guidelines, two-view screens are now repeated every three years instead of the single oblique view and continue till the age of 70. In England, the age range has been extended to 47-73 years.12 Women can request a mammogram three yearly when they stop being eligible for an invitation.
However, from 2009-2014, breast screening uptake has begun to decline. Only 69.4% of women attended their breast screening appointment (from the previous 3 years), this is below the target of 70% uptake. The graph shows the counties that have fallen below the uptake guidelines in 2014.13
As shown, Greater Glasgow and Clyde have the lowest uptake statistics in Scotland with Orkney and Shetland having the highest uptake percentage with >80% of women attending their appointment.
In addition to population screening, women who have a family history of breast cancer undergo risk assessment and enter a programme of screening for women at increased risk of breast cancer. For those women at moderate or high risk of breast cancer (>17% lifetime risk of breast cancer or >3% 10-year risk between the ages 40-50) but that also have a 30% or lower probability of being a BRCA or TP53 carrier, are invited to get screened annually, starting from 5 years before the age at which the youngest relative became affected (but no younger than 35 years). Annual mammographic screening is also offered to women (aged 30-39) who have a >30% probability of being a BRCA carrier but have not been tested or those who have a known BRCA1/BRCA2 mutation. The NICE guidelines are shown below:14
1.6.3 Offer annual mammographic surveillance to women:
• aged 40–49 years at moderate risk of breast cancer
• aged 40–59 years at high risk of breast cancer but with a 30% or lower probability of being a BRCA or TP53 carrier
• aged 40–59 years who have not had genetic testing but have a greater than 30% probability of being a BRCA carrier
• aged 40–69 years with a known BRCA1 or BRCA2 mutation.
1.6.4 Offer mammographic surveillance as part of the population screening programme to women:
• aged 50 years and over who have not had genetic testing but have a greater than 30% probability of being a TP53 carrier
• aged 60 years and over at high risk of breast cancer but with a 30% or lower probability of being a BRCA or TP53 carrier
• aged 50 years and over at moderate risk of breast cancer
• aged 60 years and over who have not had genetic testing but have a greater than 30% probability of being a BRCA carrier
• aged 70 years and over with a known BRCA1 or BRCA2 mutation.
1.6.6 Do not offer mammographic surveillance to women:
• aged 29 years and under
• aged 30–49 years who have not had genetic testing but have a greater than 30% probability of being a TP53 carrier
• of any age with a known TP53 mutation.
Magnetic resonance imaging is also offered to those with familial history of breast cancer with the following guidelines:
1.6.7 Offer annual MRI surveillance to women:
• aged 30–49 years who have not had genetic testing but have a greater than 30% probability of being a BRCA carrier
• aged 30–49 years with a known BRCA1 or BRCA2 mutation
• aged 20–49 years who have not had genetic testing but have a greater than
30% probability of being a TP53 carrier
• aged 20–49 years with a known TP53 mutation
• aged 50–69 years who have not had genetic testing but have a greater than 30% probability of being a BRCA or a TP53 carrier, and where mammography has shown a dense breast pattern
• aged 50–69 years with a known BRCA1 or BRCA2 mutation, and where mammography has shown a dense breast pattern
• under 30 years, only in rare very high risk situations, for example TP53 gene carrier.
1.6.8 Consider annual MRI surveillance for women aged 50–69 years with a known TP53 mutation.
3. Advantages
The main advantage of breast screening is that it has been proven to reduce mortality rates in women. A range of 11 randomised controlled trials were carried out (around 20-30 years ago). Meta-analysis of these trials with a 13-year follow-up reported a 20% decrease in mortality rates of women invited for breast screening. The panel found that the absolute mortality benefit was closer to 20% at the age range of 55-79 for women in the UK, when it was assumed women aged 50 would gain no benefit in the first 5 years. Therefore, for approximately every 235 women invited to be screened, one breast cancer death would be prevented, thus at least 180 women needed to attend their breast screening appointment to prevent one breast cancer death.15 Overall, between the 1st April 2015 to the 31st March 2016, across Scotland (excluding Dundee, due to their new use of SBSS), 159,724 women were screened for breast cancer. Of these women, 1,437 cancers were detected. Of these 1,147 were invasive, 241 were non-invasive or micro-invasive. Of the invasive cancers, 639 were <15mm, allowing 582 (91.1%) of these women to have conservation surgery instead of a mastectomy (only 8.9% of women with invasive cancers had a mastectomy in 2015/16).16
Unknown (49)
Non-invasive (239)
Micro-invasive (2) Invasive (1147)
Number of cancers detected 2015/16
NHSBSP audit of screen detected breast cancers 2015/1116
In 2008/09, over 2 million women were screened for breast cancer, with 16,535 cancers diagnosed (>10,000 of these were <15mm invasive cancers or ductal carcinoma in situ). The Swedish Two County Trial has also been published recently showing data from a long-term 30-year follow up. It shows that there has been a “significant reduction in breast cancer mortality in females invited for screening”17 In the UK, 1,5 and 10-year survival rates have increased over the past three decades and an overall decrease in deaths even though there has been an increase in incidence – 78% of women in England and Wales survived breast cancer for 10+ years in 2010-11.18 In Scotland over the past 10 years to 2014, there has been a 20% decrease in mortality rates.19 In the period 2007-2011, 82.8% of female breast cancers had a 5-year age-standardised survival rate.20
4. Disadvantages
Although, it has been stated that breast screening can cause a 20% reduction in mortality rates, it can be argued that these results are not reliable. A panel chaired by Michael Marmot published a review in 2012 concluding that these uncertainties include, since “the 95% confidence interval (CI) around the relative risk reduction of 20% was 11-27%” and there were uncertainties as to what was the cause of death in certain women.15 It can also be shown that although breast screening does reduce mortality rates, the advances in cancer treatments has a much larger influence.15
One of the main disadvantages of the breast cancer screening programme doesn’t come from the screening itself but from anxiety associated with recall for further assessment. This could have been avoided in benign or in false-positive results (both of which are more likely in younger women).9 During screening, most women (up to 91%) report some form of pain, with some women (<15%) reporting intense pain (Kornguth et al. 1996).10
Another adverse effect is that it can be argued there is now an over-diagnosis of breast cancer. This refers to women that may have never needed treatment as their breast cancer was not life threatening, causing them extra, unwanted anxiety over (some may argue) unnecessary treatment. “The conclusion of the Advisory Committee Report of 2006 was that such cases that might not have progressed to symptomatic disease amount to one-eighth of all invasive cancers detected.”17 However, it is difficult to predict as a small cluster of micro calcification can be caused by a low grade ductal carcinoma in situ (DCIS) or may be a sign of a grade invasive cancer.18 Currently, there is no way to know if the screen detected cancer is “over-diagnosed” or not, especially in DCIS. It was found that after wide local excision only, 10% of these women still developed invasive breast cancer within 10 years.15 Although it is difficult to quantify the statistics of over-diagnosis, a study in 2013 showed that in the UK the proportion of over-diagnosed female breast cancers (invasive and non-invasive) was likely to be around 19% to 35%.21 When shorter duration trials were carried out, it was suggested about 11% of breast cancers were over-diagnosed during the screening period and the remainder of the women’s lifetime, or 19% of cancers diagnosed during the screening period only.15
False-positive results decrease with age, for example, a 40-year-old has a 28% chance of obtaining a false-positive if she is screened annually for 10 years, whereas a 70-year-old woman has a 22% chance under the same conditions.10 However, this is still a relatively high proportion, greater than the risk of getting breast cancer itself (irrespective of age – shown in the table below).10 In 2008/09, of all females screened in the UK, 4.4% were recalled and 0.8% were diagnosed with cancer.
Age (Years)
Risk
40
50
60
>70
Abnormal Exam
30%
26%
23%
26%
False-positive Exam
28%
23%
20%
22%
Biopsy
7.5%
10.4%
10.4%
10%
Invasive Breast Cancer
1.5%
2.4%
3.4%
3.5%
DCIS
0.5%
1.0%
1.2%
1.1%
Risk of obtaining one of the following if screened annually for 10 yearsa
aAdapted from references (Kerlikowske and Barclay 1997) and (Ries et al. 2007) Copyright © 1997, Oxford University Press. All Rights reserved.
To demonstrate the cost effectiveness of the breast screening programme, a life table model was created based on the findings of the UK Panel on Breast Cancer Screening. The participants were 364,500, 50-year-old women from England and Wales (who were followed-up for 35 years) but not screened, compared to a similar cohort who had regular mammographic screening between the ages 50-70 (followed-up for 15 years). The table found that screening was associated with 2040 additional quality adjusted life years (QALYs) which would cost the NHS £42.5m in total. In other words, £20,800 per QALY gained. The screening was found to be cost effective in 45% of scenarios where the cost was £20,000 per QALY gained compared to the 12% of scenarios where screening was associated with a reduction in QALYs. Its conclusion was that the breast screening programme is only moderately effective at a standard threshold, however, the study is not definitive and further studies are needed.22
Breast cancer screening has a minimum target of 70% attendance at breast screening for it to be effective. Some areas in the country fail to reach this target. These areas are usually socially deprivated with less knowledge of breast cancer and the importance of screening. Other barriers include the inability to take time off work, to get transport to the GP practice or mobile unit, embarrassment, language barriers or the worry that the screening may be painful. For example, a UK survey reported that 45% of black ethnic women have never attended a breast screening, despite being of age. 76% of these women said it was because they had never had an invitation (Breast Cancer Care, 2005). Women of a higher socioeconomic status were also twice as likely to attend their breast screening than those in lower income households.23
Those with physical disabilities also face barriers as many of the mobile screening centers have equipment unsuitable for someone with disabilities. “34% of women with disabilities that were interviewed reported difficulty in positioning as the reason for not getting a mammogram.” (Nosek et al.,1997)24 It is also estimated that women with disabilities are more likely to be depressed (28% more likely than women with no disabilities) thus are less likely to obtain their annual breast screening.24
5. Conclusion
In conclusion, breast cancer is the most common cancer amongst women. Despite an increased incidence, there has been an estimated reduction of 20% in mortality rates across the UK, since 1988, when the breast cancer screening programme was introduced.
However, there are limitations. Over-diagnosis of cancer in breast screening is challenging, where cancers are being detected that may have never become life-threatening. It is thought that between 19-35% of cancers are over-diagnosed but it is not yet possible to tell which cancers may become invasive. False-positive results can cause great anxiety to a person and may prevent them from returning for further screening. The cost of the screening programme for breast cancer has been shown to be £20,800 per quality adjusted life years (QALYs) gained. However, it is thought to only be effective when the cost is in the threshold of £20,000 per QALY and so only moderately effective in cost terms. There are also barriers that may prevent people from being able to attend/want to attend their breast screening appointment. This can cause a reduction in the uptake causing the programme to become less effective, unable to reach its target uptake of 70%.
At present the advantages and disadvantages of breast screening are discussed in panels across the world and a definitive answer as to whether the screening programme is worthwhile has yet to be found. Through my research, I have found that although there are disadvantages, the positive effects of screening out-way the negatives. Improved uptake of screening will increase the efficiency of the programme and thus improve the cost effectiveness. Targeting minority groups where uptake is low using increased advertising schemes and GP specific programmes may achieve this.
Finally, a risk adapted screening programme should be promoted across the UK to detect familial breast cancer. This would allow a personalised plan of early detection for each woman depending on her age and relative risk of getting breast cancer.
6. References
1. Ferlay, J., Héry, C., Autier, P., & Sankaranarayanan, R. (2010). Global Burden of Breast Cancer. In Breast Cancer Epidemiology (pp. 1–19). New York, NY: Springer New York. https://doi.org/10.1007/978-1-4419-0685-4_1
2. Drake, R. L. (Richard L., Vogl, W., Mitchell, A. W. M., & Gray, H. (2015). Gray’s anatomy for students (Third Edition) (pp. 139-141, 749).
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7. Dixon J. Breast surgery. 3rd ed. Edinburgh: Saunders/Elsevier; 2006. (pp. 1-10)
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9. Nevler, A., Shabtai, E. L., Gutman, M., & Shabtai, M. (2014). The effects of hormonal replacement therapy (HRT) on mammographic breast density and abnormal mammograms prompting further investigation. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 32(26_suppl), 8. https://doi.org/10.1200/jco.2014.32.26_suppl.8
10. Kerlikowske, K. (2010). Breast Cancer Screening. In Breast Cancer Epidemiology (pp. 343–369). New York, NY: Springer New York. https://doi.org/10.1007/978-1-4419-0685-4_16
11. Farndon J. Breast and Endocrine Surgery (companion to specialist surgical practice). 5th ed. London: W.B. Saunders Company Ltd; 1997. (pp. 215-221)
12. UK, C. R. (2016). Breast cancer screening in the UK. Retrieved from http://www.cancerresearchuk.org/about-cancer/type/breast-cancer/about/screening/who-is-screened-for-breast-cancer
13. NHSL, Cancer Research UK. Breast screening GP Practice Handbook
14. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer | 1-Recommendations | Guidance and guidelines | NICE. (n.d.). Retrieved from https://www.nice.org.uk/guidance/cg164/chapter/1-Recommendations#surveillance-and-strategies-for-early-detection-of-breast-cancer
15. Marmot, M. G., Altman, D. G., Cameron, D. A., Dewar, J. A., Thompson, S. G., Wilcox, M., & Screening, T. I. U. P. on B. C. (2013). The benefits and harms of breast cancer screening: an independent review. British Journal of Cancer, 108(11), 2205–40. https://doi.org/10.1038/bjc.2013.177
16. Breast, S., & Programme, S. (2016). SCOTTISH BREAST SCREENING PROGRAMME AN AUDIT OF SCREEN DETECTED BREAST CANCERS FOR THE YEAR OF SCREENING MAIN SURGICAL AUDIT REPORT, (March), 1–45. Retrieved from BASO Main Report 1516.pdf
17. Michell, M. J. (2012). Breast screening review–a radiologist’s perspective. The British Journal of Radiology, 85(1015), 845–7. https://doi.org/10.1259/bjr/21332901
18. Breast cancer survival statistics | Cancer Research UK. (n.d.). Retrieved January 2, 2017, from http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/survival
19. A National Statistics Publication for Scotland. (2015). Retrieved from http://www.isdscotland.org/Health-Topics/Cancer/Publications/2015-11-17/2015-11-17-CancerMortality-Report.pdf
20. A National Statistics Publication for Scotland. (n.d.). Retrieved from https://www.isdscotland.org/Health-Topics/Cancer/Publications/2015-03-03/2015-03-03-CancerSurvival-Report.pdf?40525454283
21. Hersch, J., Jansen, J., Barratt, A., Irwig, L., Houssami, N., Howard, K., … McCaffery, K. (2013). Women’s views on overdiagnosis in breast cancer screening: a qualitative study. BMJ, 346. Retrieved from http://www.bmj.com/content/346/bmj.f158
22. Pharoah, P. D. P., Sewell, B., Fitzsimmons, D., Bennett, H. S., & Pashayan, N. (2013). Cost effectiveness of the NHS breast screening programme: life table model. BMJ (Clinical Research Ed.), 346, f2618. https://doi.org/10.1136/bmj.f2618
23. Edgar, L., Glackin, M., Hughes, C., & Ann Rogers, K. M. (2013). Factors influencing participation in breast cancer screening. British Journal of Nursing, 22(17), 1021–1026. https://doi.org/10.12968/bjon.2013.22.17.1021
24. Todd, A., & Stuifbergen, A. (2012). Breast cancer screening barriers and disability. Rehabilitation Nursing : The Official Journal of the Association of Rehabilitation Nurses, 37(2), 74–9. https://doi.org/10.1002/RNJ.00013
Student declaration
I, Fiona Lannigan, declare that the above SSC, titled “Breast cancer screening: the issues” is all my own work with the aid of the resources referenced above.