Dr. Ron’s Research Review – August 22, 2012

This week’s research review focuses on Mamography.

Screening is likely to reduce breast cancer mortality. As the effect was lowest in the adequately randomised trials, a reasonable estimate is a 15% reduction corresponding to an absolute risk reduction of 0.05%. Screening led to 30% overdiagnosis and overtreatment, or an absolute risk increase of 0.5%. This means that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress for many months because of false positive findings. It is thus not clear whether screening does more good than harm. (Gotzsche and Nielsen 2011)

Less than 5% of women with screen-detectable cancers have their lives saved. (Keen and Keen 2009)

Accuracy of screening mammography varies by week of menstrual cycle. Premenopausal women who undergo regular screening may benefit from higher sensitivity of mammography if they schedule screening mammography during the 1st week of their menstrual cycle. (Miglioretti, Walker et al. 2011)

Two-view digital mammography and screen-film mammography involve average mean glandular radiation doses of 3.7 and 4.7 mGy, respectively. According to BEIR VII data, these studies are associated, respectively, with lifetime attributable risks of fatal breast cancer of 1.3 and 1.7 cases per 100,000 women aged 40 years at exposure and less than one case per one million women aged 80 years at exposure. Annual screening digital or screen-film mammography performed in women aged 40-80 years is associated with an lifetime attributable risk of fatal breast cancer of 20-25 cases in 100,000. (Hendrick 2010)

Ultrasound is useful to examine dense breast tissue. Recent studies have shown that the detection of small cancers with high-resolution ultrasound is increased by 3-4 cancers per 1,000 women without clinical or mammographic abnormalities. Therefore, an improved cancer detection and differentiation can be expected with high-resolution ultrasound. (Madjar 2010)

Dr. Ron


Articles

Screening for breast cancer with mammography

            (Gotzsche and Nielsen 2011) Download

BACKGROUND: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. OBJECTIVES: To assess the effect of screening for breast cancer with mammography on mortality and morbidity. SEARCH STRATEGY: We searched PubMed (November 2008). SELECTION CRITERIA: Randomised trials comparing mammographic screening with no mammographic screening. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data. Study authors were contacted for additional information. MAIN RESULTS: Eight eligible trials were identified. We excluded a biased trial and included 600,000 women in the analyses. Three trials with adequate randomisation did not show a significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).Numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42) for the two adequately randomised trials that measured this outcome; the use of radiotherapy was similarly increased. AUTHORS' CONCLUSIONS: Screening is likely to reduce breast cancer mortality. As the effect was lowest in the adequately randomised trials, a reasonable estimate is a 15% reduction corresponding to an absolute risk reduction of 0.05%. Screening led to 30% overdiagnosis and overtreatment, or an absolute risk increase of 0.5%. This means that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress for many months because of false positive findings. It is thus not clear whether screening does more good than harm. To help ensure that the women are fully informed of both benefits and harms before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk.


Radiation doses and cancer risks from breast imaging studies

            (Hendrick 2010) Download

PURPOSE: To compare radiation doses and lifetime attributable risks (LARs) of radiation-induced cancer incidence and mortality from breast imaging studies involving the use of ionizing radiation. MATERIALS AND METHODS: Recent literature on radiation doses from radiologic procedures and organ doses from nuclear medicine procedures, along with Biologic Effects of Ionizing Radiation (BEIR) VII age-dependent risk data, is used to estimate LARs of radiation-induced cancer incidence and mortality from breast imaging studies involving ionizing radiation, including screen-film mammography, digital mammography, digital breast tomosynthesis, dedicated breast computed tomography, breast-specific gamma imaging (BSGI), and positron emission mammography (PEM). RESULTS: Two-view digital mammography and screen-film mammography involve average mean glandular radiation doses of 3.7 and 4.7 mGy, respectively. According to BEIR VII data, these studies are associated, respectively, with LARs of fatal breast cancer of 1.3 and 1.7 cases per 100,000 women aged 40 years at exposure and less than one case per one million women aged 80 years at exposure. Annual screening digital or screen-film mammography performed in women aged 40-80 years is associated with an LAR of fatal breast cancer of 20-25 cases in 100,000. A single BSGI study involving a label-recommended dose of 740-1100 MBq (20-30 mCi) of technetium 99m-sestamibi is estimated to involve an LAR of fatal cancer that is 20-30 times that of digital mammography in women aged 40 years. A single PEM study involving a labeled dose of 370 MBq (10 mCi) of fluorine 18 fluorodeoxyglucose is estimated to involve an LAR of fatal cancer that is 23 times higher than that of digital mammography in women aged 40 years. CONCLUSION: A single BSGI or PEM study is associated with a fatal radiation-induced cancer risk higher than or comparable to that of annual screening mammography in women aged 40-80 years.

What is the point: will screening mammography save my life?

            (Keen and Keen 2009) Download

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.

Role of Breast Ultrasound for the Detection and Differentiation of Breast Lesions

            (Madjar 2010) Download

Diagnosis of breast cancer has been widely improved since the development of high-resolution ultrasound equipment. In the past, ultrasound was only considered useful for the diagnosis of cysts. Meanwhile, it improves the differential diagnosis of benign and malignant lesions, local preoperative staging and guided interventional diagnosis. In dense breasts, mammography has limited sensitivity. Furthermore, women with dense parenchyma have a highly increased risk of breast cancer development. Ultrasound is useful to examine dense breast tissue. Recent studies have shown that the detection of small cancers with high-resolution ultrasound is increased by 3-4 cancers per 1,000 women without clinical or mammographic abnormalities. Furthermore, stage distribution is similar between mammographically and sonographically detected carcinomas. Ultrasound is routinely used for curative diagnosis, to overcome the limitations of mammography. However, within the mammographic screening in Germany, breast density is not considered as important. Ultrasound is only used if a suspicious lesion is detected by mammography. Interestingly, 2 years ago, a screening project started in Austria in which ultrasound is always added in cases of dense breasts. Preliminary data show that the detection of additional carcinomas is increased in the same order as shown in previous studies. Therefore, an improved cancer detection and differentiation can be expected with high-resolution ultrasound.

Accuracy of screening mammography varies by week of menstrual cycle

            (Miglioretti, Walker et al. 2011) Download

PURPOSE: To investigate sensitivity, specificity, and cancer detection rate of screening mammography according to week of menstrual cycle among premenopausal women. MATERIALS AND METHODS: In this institutional review board-approved HIPAA-compliant study, sensitivity, specificity, and cancer detection rate of 387,218 screening mammograms linked to 1283 breast cancers in premenopausal women according to week of menstrual cycle were studied by using prospectively collected information from the Breast Cancer Surveillance Consortium. Logistic regression analysis was used to test for differences in mammography performance according to week of menstrual cycle, adjusting for age and registry. RESULTS: Overall, screening mammography performance did not differ according to week of menstrual cycle. However, when analyses were subdivided according to prior mammography, different patterns emerged. For the 66.6% of women who had undergone regular screening (mammography had been performed within the past 2 years), sensitivity was higher in week 1 (79.5%) than in subsequent weeks (week 2, 70.3%; week 3, 67.4%; week 4, 73.0%; P = .041). In the 17.8% of women who underwent mammography for the first time in this study, sensitivity tended to be lower during the follicular phase (week 1, 72.1%; week 2, 80.4%; week 3, 84.6%; week 4, 93.8%; P = .051). Sensitivity did not vary significantly by week in menstrual cycle in women who had undergone mammography more than 3 years earlier. There were no clinically meaningful differences in specificity or cancer detection rate. Conclusion: Premenopausal women who undergo regular screening may benefit from higher sensitivity of mammography if they schedule screening mammography during the 1st week of their menstrual cycle. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100974/-/DC1.


References

Gotzsche, P. C. and M. Nielsen (2011). "Screening for breast cancer with mammography." Cochrane Database Syst Rev(1): CD001877.

Hendrick, R. E. (2010). "Radiation doses and cancer risks from breast imaging studies." Radiology 257(1): 246-53.

Keen, J. D. and J. E. Keen (2009). "What is the point: will screening mammography save my life?" BMC Med Inform Decis Mak 9: 18.

Madjar, H. (2010). "Role of Breast Ultrasound for the Detection and Differentiation of Breast Lesions." Breast Care (Basel) 5(2): 109-114.

Miglioretti, D. L., R. Walker, et al. (2011). "Accuracy of screening mammography varies by week of menstrual cycle." Radiology 258(2): 372-9.