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Screening mammography starting at age 40: Still relevant

Screening mammography is not a perfect test, but it still plays an important role for women even in their 40s, when the incidence of breast cancer is low but the risk of a tumor being aggressive is especially high.

See related counterpoint

SCREENING DETECTS CANCER EARLY

The goal of screening mammography is to reduce breast cancer deaths by detecting cancers early, when treatment is more effective and less harmful.

Mammography detects tumors when they are smaller: the median size of breast cancers found with high-quality, two-view screening mammography is 1.0 to 1.5 cm, whereas cancers found by palpation are 2.0 to 2.5 cm.1 In general, tumors found when they are smaller require less treatment, and patients are more likely to survive.

Moreover, about 10% of invasive cancers smaller than 1 cm have spread to lymph nodes at the time of detection, compared with 35% of those 2 cm in size and 60% of those 4 cm or larger. Women who have a positive lymph node at the time of diagnosis usually undergo more intensive treatment with chemotherapy and more radical surgery than those who do not. The 5-year disease-free survival rate is more than 98% for breast cancer with a tumor smaller than 2 cm that has not spread to lymph nodes (stage I), compared with 86% for stage II disease (tumors 2.1–5 cm or one to three positive axillary lymph nodes).2

The median size of breast cancers found by mammography is 1.0–1.5 cm; by palpation, 2.0–2.5 cm

Treating breast cancer early is also less expensive. In a study of women enrolled in a health maintenance organization in Pennsylvania, 14% of those not screened presented with advanced breast cancer (stage III or IV) compared with 2% who had been screened. The cumulative cost of treating advanced breast cancer was two to three times that of treating early breast cancer (stage 0 or I), not accounting for time lost away from work and family, in addition to pain and suffering.3

SCREENING SAVES LIVES

Multiple prospective, randomized controlled trials have been conducted to assess whether inviting women between ages 40 and 74 to undergo screening mammography reduces the rate of death from breast cancer.4,5 Such trials tend to underestimate the effect of screening because not all women invited to be screened actually are screened, and some in the control group may undergo screening on their own.6

The Canadian National Breast Screening Study (NBSS) had additional problems that underestimated the benefits of screening. The quality of mammography came under question, and an issue with randomization became evident after the first round of screening, as  the group invited to be screened had an excess of women presenting with palpable lumps and advanced breast cancer.6–8 Despite these issues, a meta-analysis of randomized controlled trials of screening mammography, including the NBSS data, found a 15% reduction in deaths.9 When the NBSS data were excluded, the reduction was 24%.10

In 2009, the United States Preventive Services Task Force (USPSTF)11 recommended against mammographic screening for women ages 40 to 49. Using results from trials including the NBSS, they estimated that the number of women needed to be invited to screening to prevent one breast cancer death was:

  • 1,904 for ages 39 to 49
  • 1,339 for ages 50 to 59
  • 377 for ages 60 to 69.

But if the NBSS study were excluded, these results would be 950, 670, and 377, respectively.6

In a review on screening mammography, Feig12 points out that the USPSTF selected the number of women invited to be screened rather than the number that were actually screened to measure the absolute benefit of screening.

Hendrick and Helvie13 reported that the number of women who needed to be screened to prevent one cancer death was:

  • 746 for ages 40 to 49
  • 351 for ages 50 to 59
  • 253 for ages 60 to 69.

The benefit of screening, if analyzed by number of life years gained rather than number of deaths prevented, is even more favorable to younger women with longer life expectancy. The number needed to be screened per life year gained is:

  • 28 at ages 40 to 49
  • 17 at ages 50 to 59
  • 16 at ages 60 to 69.12

These data provide additional support for screening women starting at age 40.

Observational studies, which provide a better measure of effectiveness because only women who actually undergo routine mammography are compared with those who do not, also support this conclusion. An observational study in Sweden with 20 years of follow-up found that women of all ages who participated in screening had a 44% lower risk of death from breast cancer than with those who were not screened; for women in their 40s, the risk reduction was 48%.14 Similarly, an observational study conducted in British Columbia15 found a 40% decrease in deaths in women screened annually between ages 40 and 79, and a 39% decrease in deaths in women first screened between ages 40 and 49.

LOW RATE OF FALSE-POSITIVE RESULTS

Like many screening programs, screening mammography does not benefit all women equally.

Only about 1% of the women screened underwent an unnecessary biopsy

False-positive results occur, for which women need additional imaging or a biopsy for findings that turn out not to be cancer. But the false-positive rate is not high: for every 1,000 women screened in the United States, 80 to 100 (10% or less) are recalled for additional evaluation, 15 (1.5%) undergo biopsy, and 2 to 5 have a cancer, so only about 1% of the women screened underwent an unnecessary biopsy.16

False-positive test results can provoke unnecessary anxiety, but evidence indicates that this tends to be a temporary effect, and even women who had a false-positive result tend to support mammography. In a report by Lerman et al,17 when mood was assessed 3 months after mammography, worry was reported by 26% of women who had had a false-positive report, compared with 9% of women who had had a normal mammogram. Another report addressing the consequences of false-positive mammograms found that although short-term anxiety increased, long-term anxiety did not.18­ In a random telephone survey, 98% of adults who reported having had a false-positive cancer screening result stated that they were nevertheless glad that they had undergone screening.19

 

 

OVERDIAGNOSIS OCCURS BUT IS LIKELY UNCOMMON

Overdiagnosis of breast cancer is a possible drawback of screening mammography. Cancers may be detected that would not have become clinically apparent in a person’s lifetime20 or have affected ultimate prognosis,18 and so would not have needed to be treated.

Overdiagnosis from screening mammography usually refers to finding ductal carcinoma in situ (DCIS) on breast biopsy. Because no randomized controlled study has been done in which breast cancer was diagnosed and not treated, evidence of the danger from DCIS comes from retrospective reviews of 130 cases in which excised tissue initially interpreted as benign was actually cancerous. Over 10 to 30 years, 11% to 60% of these patients developed invasive breast cancer in the same quadrant from which tissue had been excised.21 This rate of cancer development could lead to underestimation of the invasive potential of DCIS because the patients studied all had low-grade DCIS; further, some of the baseline biopsies involved complete removal of the tumor, thereby preventing the development or progression of cancer.

All DCIS is not the same. An ongoing trial22 found a 5-year recurrence rate of 6.1% after surgery for low-grade or intermediate-grade DCIS, and 15% after surgery for high-grade DCIS. Swedish trials23 have shown that most women who die of “early” breast cancer have high-grade DCIS. These findings suggest that although screening mammography may result in overdiagnosis and overtreatment of low-grade DCIS, high-grade DCIS can be lethal and should be treated. Thus, overdiagnosis likely represents a small fraction of all breast cancers.

Most important, it is not yet possible to accurately predict the biologic behavior of an individual tumor. Current clinical practice is to treat patients with DCIS similar to the way we treat patients with early-stage breast cancer, as we cannot determine which types of DCIS may remain indolent and which ones may become invasive.

HOW FREQUENTLY SHOULD YOUNGER WOMEN BE SCREENED?

The frequency of screening mammography has been another area of controversy, but we believe that annual screening offers the greatest benefit, especially for younger women.

Tumors in younger women tend to grow and spread more quickly

The optimum screening frequency depends on how fast breast cancer grows and spreads. Data suggest that tumors in younger women tend to be biologically aggressive and grow and spread more quickly, making the benefit of yearly mammography more dramatic for younger women. A model­ based on data from Swedish studies24–26 predicted that the mortality reduction from breast cancer in women ages 40 to 49 would be 36% with annual screening, 18% with screening every 2 years, and 4% with screening every 3 years. For women in their 50s, the model estimated a reduction of 46% for yearly mammography, and 39% and 34% for screening every 2 or 3 years, respectively.6

In a prospective cohort study of the Breast Cancer Surveillance Consortium,27 in women ages 40 to 49 with extremely dense breasts, screening every 2 years was associated with a higher risk of advanced-stage disease (IIb or higher) and large tumors (> 2 cm) than with annual screening. For women ages 50 to 74, screening every 2 years vs every year did not increase the odds of advanced-stage or larger tumors.

AN INFORMED DECISION

In agreement with the current recommendations from the American Cancer Society, the American College of Radiology, and the American Congress of Obstetricians and Gynecologists, we support starting breast cancer screening with mammography at age 40.

Not all cancers are visible on mammography (false negatives), as they may be masked by mammographically dense breast tissue. Women should be informed of the importance of seeking medical attention for breast symptoms, even if mammography is normal. We need to inform women of the benefits and risks of screening mammography, including the risk of false-positive results that could lead to additional imaging and anxiety, and the uncertainties related to the potential for overdiagnosis and overtreatment. This information, offered in an easily understandable format, can help the patient make an informed decision regarding screening mammography, based on her values and preferences.

References
  1. Güth U, Huang DJ, Huber M, et al. Tumor size and detection in breast cancer: self-examination and clinical breast examination are at their limit. Cancer Detect Prev 2008; 32:224–228.
  2. Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J, editors. SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988–2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD; 2007:101–110. http://seer.cancer.gov/archive/publications/survival/seer_survival_mono_lowres.pdf. Accessed April 9, 2015.
  3. Legorreta AP, Brooks RJ, Leibowitz AN, Solin LJ. Cost of breast cancer treatment. A 4-year longitudinal study. Arch Intern Med 1996; 156:2197–2201.
  4. Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up: a randomised controlled trial. Lancet 2006; 368:2053–2060.
  5. Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347–360.
  6. Feig SA. Screening mammography benefit controversies: sorting the evidence. Radiol Clin North Am 2014; 52:455–480.
  7. Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ 1992; 147:1477–1488.
  8. Miller AB, To T, Baines CJ, Wall C. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50–59 years. J Natl Cancer Inst 2000; 92:1490–1499.
  9. Smart CR, Hendrick RE, Rutledge JH 3rd, Smith RA. Benefit of mammography screening in women ages 40 to 49 years. Current evidence from randomized controlled trials. Cancer 1995; 75:1619–1626.
  10. Breast-cancer screening with mammography in women aged 40-49 years. Swedish Cancer Society and the Swedish National Board of Health and Welfare. Int J Cancer 1996; 68:693–699.
  11. US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 151:716–726.
  12. Feig SA. Number needed to screen. Appropriate use of this new basis for screening mammography guidelines. AJR Am J Roentgenol 2012; 198:1214–1217.
  13. Hendrick RE, Helvie MA. Mammography screening: a new estimate of number needed to screen to prevent one breast cancer death. AJR Am J Roentgenol 2012; 198:723–728.
  14. Tabar L, Yen MF, Vitak B, Chen HH, Smith RA, Duffy SW. Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet 2003; 361:1405–1410.
  15. Coldman A, Phillips N, Warren L, Kan L. Breast cancer mortality after screening mammography in British Columbia women. Int J Cancer 2007; 120:1076–1080.
  16. Rosenberg RD, Yankaskas BC, Abraham LA, et al. Performance benchmarks for screening mammography. Radiology 2006; 241:55–66.
  17. Lerman C, Trock B, Rimer BK, Boyce A, Jepson C, Engstrom PF. Psychological and behavioral implications of abnormal mammograms. Ann Intern Med 1991; 114:657–661.
  18. Tosteson AN, Fryback DG, Hammond CS, et al. Consequences of false-positive screening mammograms. JAMA Intern Med 2014; 174:954–961.
  19. Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG. Enthusiasm for cancer screening in the United States. JAMA 2004; 291:71–78.
  20. Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer 2013; 108:2205–2240.
  21. Feig SA. Ductal carcinoma in situ. Implications for screening mammography. Radiol Clin North Am 2000; 38:653–668,
  22. Hughes LL, Wang M, Page DL, et al. Local excision alone without irradiation for ductal carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009; 27:5319–5324.
  23. Tabár L, Vitak B, Chen HH, et al. The Swedish two-county trial twenty years later. Updated mortality results and new insights from long-term follow-up. Radiol Clin North Am 2000; 38:625–651.
  24. Duffy SW, Chen HH, Tabar L, et al. Estimation of mean sojourn time in breast cancer screening using a Markov chair model of entry to and exit from the preclinical detectable phase. Stat Med 1995; 14:1521-1534.
  25. Chen HH, Duffy SW, Tabar L, et al. Markov chain models for progression of breast cancer. Part I: tumor attributes and the preclinical screening detectable phase. J Epidemiol Biostat 1997; 2:9–25.
  26. Chen HH, Duffy SW, Tabar L, et al. Markov chain models for progression of breast cancer. Part II: prediction of outcomes for different screening regimes. J Epidemiol Biostat 1997; 2:25–35.
  27. Kerlikowske K, Zhu W, Hubbard RA, et al; Breast Cancer Surveillance Consortium. Outcomes of screening mammography by frequency, breast density, and postmenopausal hormone therapy. JAMA Intern Med 2013; 173:807–816.
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Karthik Ghosh, MD
Breast Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN

Dietlind Wahner-Roedler, MD
Breast Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN

Kathleen Brandt, MD
Breast Imaging, Department of Radiology, Mayo Clinic, Rochester, MN

Address: Karthik Ghosh, MD, Breast Clinic, Division of General Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail: ghosh.karthik@mayo.edu

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Breast Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN

Dietlind Wahner-Roedler, MD
Breast Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN

Kathleen Brandt, MD
Breast Imaging, Department of Radiology, Mayo Clinic, Rochester, MN

Address: Karthik Ghosh, MD, Breast Clinic, Division of General Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail: ghosh.karthik@mayo.edu

Author and Disclosure Information

Karthik Ghosh, MD
Breast Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN

Dietlind Wahner-Roedler, MD
Breast Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN

Kathleen Brandt, MD
Breast Imaging, Department of Radiology, Mayo Clinic, Rochester, MN

Address: Karthik Ghosh, MD, Breast Clinic, Division of General Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail: ghosh.karthik@mayo.edu

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Related Articles

Screening mammography is not a perfect test, but it still plays an important role for women even in their 40s, when the incidence of breast cancer is low but the risk of a tumor being aggressive is especially high.

See related counterpoint

SCREENING DETECTS CANCER EARLY

The goal of screening mammography is to reduce breast cancer deaths by detecting cancers early, when treatment is more effective and less harmful.

Mammography detects tumors when they are smaller: the median size of breast cancers found with high-quality, two-view screening mammography is 1.0 to 1.5 cm, whereas cancers found by palpation are 2.0 to 2.5 cm.1 In general, tumors found when they are smaller require less treatment, and patients are more likely to survive.

Moreover, about 10% of invasive cancers smaller than 1 cm have spread to lymph nodes at the time of detection, compared with 35% of those 2 cm in size and 60% of those 4 cm or larger. Women who have a positive lymph node at the time of diagnosis usually undergo more intensive treatment with chemotherapy and more radical surgery than those who do not. The 5-year disease-free survival rate is more than 98% for breast cancer with a tumor smaller than 2 cm that has not spread to lymph nodes (stage I), compared with 86% for stage II disease (tumors 2.1–5 cm or one to three positive axillary lymph nodes).2

The median size of breast cancers found by mammography is 1.0–1.5 cm; by palpation, 2.0–2.5 cm

Treating breast cancer early is also less expensive. In a study of women enrolled in a health maintenance organization in Pennsylvania, 14% of those not screened presented with advanced breast cancer (stage III or IV) compared with 2% who had been screened. The cumulative cost of treating advanced breast cancer was two to three times that of treating early breast cancer (stage 0 or I), not accounting for time lost away from work and family, in addition to pain and suffering.3

SCREENING SAVES LIVES

Multiple prospective, randomized controlled trials have been conducted to assess whether inviting women between ages 40 and 74 to undergo screening mammography reduces the rate of death from breast cancer.4,5 Such trials tend to underestimate the effect of screening because not all women invited to be screened actually are screened, and some in the control group may undergo screening on their own.6

The Canadian National Breast Screening Study (NBSS) had additional problems that underestimated the benefits of screening. The quality of mammography came under question, and an issue with randomization became evident after the first round of screening, as  the group invited to be screened had an excess of women presenting with palpable lumps and advanced breast cancer.6–8 Despite these issues, a meta-analysis of randomized controlled trials of screening mammography, including the NBSS data, found a 15% reduction in deaths.9 When the NBSS data were excluded, the reduction was 24%.10

In 2009, the United States Preventive Services Task Force (USPSTF)11 recommended against mammographic screening for women ages 40 to 49. Using results from trials including the NBSS, they estimated that the number of women needed to be invited to screening to prevent one breast cancer death was:

  • 1,904 for ages 39 to 49
  • 1,339 for ages 50 to 59
  • 377 for ages 60 to 69.

But if the NBSS study were excluded, these results would be 950, 670, and 377, respectively.6

In a review on screening mammography, Feig12 points out that the USPSTF selected the number of women invited to be screened rather than the number that were actually screened to measure the absolute benefit of screening.

Hendrick and Helvie13 reported that the number of women who needed to be screened to prevent one cancer death was:

  • 746 for ages 40 to 49
  • 351 for ages 50 to 59
  • 253 for ages 60 to 69.

The benefit of screening, if analyzed by number of life years gained rather than number of deaths prevented, is even more favorable to younger women with longer life expectancy. The number needed to be screened per life year gained is:

  • 28 at ages 40 to 49
  • 17 at ages 50 to 59
  • 16 at ages 60 to 69.12

These data provide additional support for screening women starting at age 40.

Observational studies, which provide a better measure of effectiveness because only women who actually undergo routine mammography are compared with those who do not, also support this conclusion. An observational study in Sweden with 20 years of follow-up found that women of all ages who participated in screening had a 44% lower risk of death from breast cancer than with those who were not screened; for women in their 40s, the risk reduction was 48%.14 Similarly, an observational study conducted in British Columbia15 found a 40% decrease in deaths in women screened annually between ages 40 and 79, and a 39% decrease in deaths in women first screened between ages 40 and 49.

LOW RATE OF FALSE-POSITIVE RESULTS

Like many screening programs, screening mammography does not benefit all women equally.

Only about 1% of the women screened underwent an unnecessary biopsy

False-positive results occur, for which women need additional imaging or a biopsy for findings that turn out not to be cancer. But the false-positive rate is not high: for every 1,000 women screened in the United States, 80 to 100 (10% or less) are recalled for additional evaluation, 15 (1.5%) undergo biopsy, and 2 to 5 have a cancer, so only about 1% of the women screened underwent an unnecessary biopsy.16

False-positive test results can provoke unnecessary anxiety, but evidence indicates that this tends to be a temporary effect, and even women who had a false-positive result tend to support mammography. In a report by Lerman et al,17 when mood was assessed 3 months after mammography, worry was reported by 26% of women who had had a false-positive report, compared with 9% of women who had had a normal mammogram. Another report addressing the consequences of false-positive mammograms found that although short-term anxiety increased, long-term anxiety did not.18­ In a random telephone survey, 98% of adults who reported having had a false-positive cancer screening result stated that they were nevertheless glad that they had undergone screening.19

 

 

OVERDIAGNOSIS OCCURS BUT IS LIKELY UNCOMMON

Overdiagnosis of breast cancer is a possible drawback of screening mammography. Cancers may be detected that would not have become clinically apparent in a person’s lifetime20 or have affected ultimate prognosis,18 and so would not have needed to be treated.

Overdiagnosis from screening mammography usually refers to finding ductal carcinoma in situ (DCIS) on breast biopsy. Because no randomized controlled study has been done in which breast cancer was diagnosed and not treated, evidence of the danger from DCIS comes from retrospective reviews of 130 cases in which excised tissue initially interpreted as benign was actually cancerous. Over 10 to 30 years, 11% to 60% of these patients developed invasive breast cancer in the same quadrant from which tissue had been excised.21 This rate of cancer development could lead to underestimation of the invasive potential of DCIS because the patients studied all had low-grade DCIS; further, some of the baseline biopsies involved complete removal of the tumor, thereby preventing the development or progression of cancer.

All DCIS is not the same. An ongoing trial22 found a 5-year recurrence rate of 6.1% after surgery for low-grade or intermediate-grade DCIS, and 15% after surgery for high-grade DCIS. Swedish trials23 have shown that most women who die of “early” breast cancer have high-grade DCIS. These findings suggest that although screening mammography may result in overdiagnosis and overtreatment of low-grade DCIS, high-grade DCIS can be lethal and should be treated. Thus, overdiagnosis likely represents a small fraction of all breast cancers.

Most important, it is not yet possible to accurately predict the biologic behavior of an individual tumor. Current clinical practice is to treat patients with DCIS similar to the way we treat patients with early-stage breast cancer, as we cannot determine which types of DCIS may remain indolent and which ones may become invasive.

HOW FREQUENTLY SHOULD YOUNGER WOMEN BE SCREENED?

The frequency of screening mammography has been another area of controversy, but we believe that annual screening offers the greatest benefit, especially for younger women.

Tumors in younger women tend to grow and spread more quickly

The optimum screening frequency depends on how fast breast cancer grows and spreads. Data suggest that tumors in younger women tend to be biologically aggressive and grow and spread more quickly, making the benefit of yearly mammography more dramatic for younger women. A model­ based on data from Swedish studies24–26 predicted that the mortality reduction from breast cancer in women ages 40 to 49 would be 36% with annual screening, 18% with screening every 2 years, and 4% with screening every 3 years. For women in their 50s, the model estimated a reduction of 46% for yearly mammography, and 39% and 34% for screening every 2 or 3 years, respectively.6

In a prospective cohort study of the Breast Cancer Surveillance Consortium,27 in women ages 40 to 49 with extremely dense breasts, screening every 2 years was associated with a higher risk of advanced-stage disease (IIb or higher) and large tumors (> 2 cm) than with annual screening. For women ages 50 to 74, screening every 2 years vs every year did not increase the odds of advanced-stage or larger tumors.

AN INFORMED DECISION

In agreement with the current recommendations from the American Cancer Society, the American College of Radiology, and the American Congress of Obstetricians and Gynecologists, we support starting breast cancer screening with mammography at age 40.

Not all cancers are visible on mammography (false negatives), as they may be masked by mammographically dense breast tissue. Women should be informed of the importance of seeking medical attention for breast symptoms, even if mammography is normal. We need to inform women of the benefits and risks of screening mammography, including the risk of false-positive results that could lead to additional imaging and anxiety, and the uncertainties related to the potential for overdiagnosis and overtreatment. This information, offered in an easily understandable format, can help the patient make an informed decision regarding screening mammography, based on her values and preferences.

Screening mammography is not a perfect test, but it still plays an important role for women even in their 40s, when the incidence of breast cancer is low but the risk of a tumor being aggressive is especially high.

See related counterpoint

SCREENING DETECTS CANCER EARLY

The goal of screening mammography is to reduce breast cancer deaths by detecting cancers early, when treatment is more effective and less harmful.

Mammography detects tumors when they are smaller: the median size of breast cancers found with high-quality, two-view screening mammography is 1.0 to 1.5 cm, whereas cancers found by palpation are 2.0 to 2.5 cm.1 In general, tumors found when they are smaller require less treatment, and patients are more likely to survive.

Moreover, about 10% of invasive cancers smaller than 1 cm have spread to lymph nodes at the time of detection, compared with 35% of those 2 cm in size and 60% of those 4 cm or larger. Women who have a positive lymph node at the time of diagnosis usually undergo more intensive treatment with chemotherapy and more radical surgery than those who do not. The 5-year disease-free survival rate is more than 98% for breast cancer with a tumor smaller than 2 cm that has not spread to lymph nodes (stage I), compared with 86% for stage II disease (tumors 2.1–5 cm or one to three positive axillary lymph nodes).2

The median size of breast cancers found by mammography is 1.0–1.5 cm; by palpation, 2.0–2.5 cm

Treating breast cancer early is also less expensive. In a study of women enrolled in a health maintenance organization in Pennsylvania, 14% of those not screened presented with advanced breast cancer (stage III or IV) compared with 2% who had been screened. The cumulative cost of treating advanced breast cancer was two to three times that of treating early breast cancer (stage 0 or I), not accounting for time lost away from work and family, in addition to pain and suffering.3

SCREENING SAVES LIVES

Multiple prospective, randomized controlled trials have been conducted to assess whether inviting women between ages 40 and 74 to undergo screening mammography reduces the rate of death from breast cancer.4,5 Such trials tend to underestimate the effect of screening because not all women invited to be screened actually are screened, and some in the control group may undergo screening on their own.6

The Canadian National Breast Screening Study (NBSS) had additional problems that underestimated the benefits of screening. The quality of mammography came under question, and an issue with randomization became evident after the first round of screening, as  the group invited to be screened had an excess of women presenting with palpable lumps and advanced breast cancer.6–8 Despite these issues, a meta-analysis of randomized controlled trials of screening mammography, including the NBSS data, found a 15% reduction in deaths.9 When the NBSS data were excluded, the reduction was 24%.10

In 2009, the United States Preventive Services Task Force (USPSTF)11 recommended against mammographic screening for women ages 40 to 49. Using results from trials including the NBSS, they estimated that the number of women needed to be invited to screening to prevent one breast cancer death was:

  • 1,904 for ages 39 to 49
  • 1,339 for ages 50 to 59
  • 377 for ages 60 to 69.

But if the NBSS study were excluded, these results would be 950, 670, and 377, respectively.6

In a review on screening mammography, Feig12 points out that the USPSTF selected the number of women invited to be screened rather than the number that were actually screened to measure the absolute benefit of screening.

Hendrick and Helvie13 reported that the number of women who needed to be screened to prevent one cancer death was:

  • 746 for ages 40 to 49
  • 351 for ages 50 to 59
  • 253 for ages 60 to 69.

The benefit of screening, if analyzed by number of life years gained rather than number of deaths prevented, is even more favorable to younger women with longer life expectancy. The number needed to be screened per life year gained is:

  • 28 at ages 40 to 49
  • 17 at ages 50 to 59
  • 16 at ages 60 to 69.12

These data provide additional support for screening women starting at age 40.

Observational studies, which provide a better measure of effectiveness because only women who actually undergo routine mammography are compared with those who do not, also support this conclusion. An observational study in Sweden with 20 years of follow-up found that women of all ages who participated in screening had a 44% lower risk of death from breast cancer than with those who were not screened; for women in their 40s, the risk reduction was 48%.14 Similarly, an observational study conducted in British Columbia15 found a 40% decrease in deaths in women screened annually between ages 40 and 79, and a 39% decrease in deaths in women first screened between ages 40 and 49.

LOW RATE OF FALSE-POSITIVE RESULTS

Like many screening programs, screening mammography does not benefit all women equally.

Only about 1% of the women screened underwent an unnecessary biopsy

False-positive results occur, for which women need additional imaging or a biopsy for findings that turn out not to be cancer. But the false-positive rate is not high: for every 1,000 women screened in the United States, 80 to 100 (10% or less) are recalled for additional evaluation, 15 (1.5%) undergo biopsy, and 2 to 5 have a cancer, so only about 1% of the women screened underwent an unnecessary biopsy.16

False-positive test results can provoke unnecessary anxiety, but evidence indicates that this tends to be a temporary effect, and even women who had a false-positive result tend to support mammography. In a report by Lerman et al,17 when mood was assessed 3 months after mammography, worry was reported by 26% of women who had had a false-positive report, compared with 9% of women who had had a normal mammogram. Another report addressing the consequences of false-positive mammograms found that although short-term anxiety increased, long-term anxiety did not.18­ In a random telephone survey, 98% of adults who reported having had a false-positive cancer screening result stated that they were nevertheless glad that they had undergone screening.19

 

 

OVERDIAGNOSIS OCCURS BUT IS LIKELY UNCOMMON

Overdiagnosis of breast cancer is a possible drawback of screening mammography. Cancers may be detected that would not have become clinically apparent in a person’s lifetime20 or have affected ultimate prognosis,18 and so would not have needed to be treated.

Overdiagnosis from screening mammography usually refers to finding ductal carcinoma in situ (DCIS) on breast biopsy. Because no randomized controlled study has been done in which breast cancer was diagnosed and not treated, evidence of the danger from DCIS comes from retrospective reviews of 130 cases in which excised tissue initially interpreted as benign was actually cancerous. Over 10 to 30 years, 11% to 60% of these patients developed invasive breast cancer in the same quadrant from which tissue had been excised.21 This rate of cancer development could lead to underestimation of the invasive potential of DCIS because the patients studied all had low-grade DCIS; further, some of the baseline biopsies involved complete removal of the tumor, thereby preventing the development or progression of cancer.

All DCIS is not the same. An ongoing trial22 found a 5-year recurrence rate of 6.1% after surgery for low-grade or intermediate-grade DCIS, and 15% after surgery for high-grade DCIS. Swedish trials23 have shown that most women who die of “early” breast cancer have high-grade DCIS. These findings suggest that although screening mammography may result in overdiagnosis and overtreatment of low-grade DCIS, high-grade DCIS can be lethal and should be treated. Thus, overdiagnosis likely represents a small fraction of all breast cancers.

Most important, it is not yet possible to accurately predict the biologic behavior of an individual tumor. Current clinical practice is to treat patients with DCIS similar to the way we treat patients with early-stage breast cancer, as we cannot determine which types of DCIS may remain indolent and which ones may become invasive.

HOW FREQUENTLY SHOULD YOUNGER WOMEN BE SCREENED?

The frequency of screening mammography has been another area of controversy, but we believe that annual screening offers the greatest benefit, especially for younger women.

Tumors in younger women tend to grow and spread more quickly

The optimum screening frequency depends on how fast breast cancer grows and spreads. Data suggest that tumors in younger women tend to be biologically aggressive and grow and spread more quickly, making the benefit of yearly mammography more dramatic for younger women. A model­ based on data from Swedish studies24–26 predicted that the mortality reduction from breast cancer in women ages 40 to 49 would be 36% with annual screening, 18% with screening every 2 years, and 4% with screening every 3 years. For women in their 50s, the model estimated a reduction of 46% for yearly mammography, and 39% and 34% for screening every 2 or 3 years, respectively.6

In a prospective cohort study of the Breast Cancer Surveillance Consortium,27 in women ages 40 to 49 with extremely dense breasts, screening every 2 years was associated with a higher risk of advanced-stage disease (IIb or higher) and large tumors (> 2 cm) than with annual screening. For women ages 50 to 74, screening every 2 years vs every year did not increase the odds of advanced-stage or larger tumors.

AN INFORMED DECISION

In agreement with the current recommendations from the American Cancer Society, the American College of Radiology, and the American Congress of Obstetricians and Gynecologists, we support starting breast cancer screening with mammography at age 40.

Not all cancers are visible on mammography (false negatives), as they may be masked by mammographically dense breast tissue. Women should be informed of the importance of seeking medical attention for breast symptoms, even if mammography is normal. We need to inform women of the benefits and risks of screening mammography, including the risk of false-positive results that could lead to additional imaging and anxiety, and the uncertainties related to the potential for overdiagnosis and overtreatment. This information, offered in an easily understandable format, can help the patient make an informed decision regarding screening mammography, based on her values and preferences.

References
  1. Güth U, Huang DJ, Huber M, et al. Tumor size and detection in breast cancer: self-examination and clinical breast examination are at their limit. Cancer Detect Prev 2008; 32:224–228.
  2. Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J, editors. SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988–2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD; 2007:101–110. http://seer.cancer.gov/archive/publications/survival/seer_survival_mono_lowres.pdf. Accessed April 9, 2015.
  3. Legorreta AP, Brooks RJ, Leibowitz AN, Solin LJ. Cost of breast cancer treatment. A 4-year longitudinal study. Arch Intern Med 1996; 156:2197–2201.
  4. Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up: a randomised controlled trial. Lancet 2006; 368:2053–2060.
  5. Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347–360.
  6. Feig SA. Screening mammography benefit controversies: sorting the evidence. Radiol Clin North Am 2014; 52:455–480.
  7. Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ 1992; 147:1477–1488.
  8. Miller AB, To T, Baines CJ, Wall C. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50–59 years. J Natl Cancer Inst 2000; 92:1490–1499.
  9. Smart CR, Hendrick RE, Rutledge JH 3rd, Smith RA. Benefit of mammography screening in women ages 40 to 49 years. Current evidence from randomized controlled trials. Cancer 1995; 75:1619–1626.
  10. Breast-cancer screening with mammography in women aged 40-49 years. Swedish Cancer Society and the Swedish National Board of Health and Welfare. Int J Cancer 1996; 68:693–699.
  11. US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 151:716–726.
  12. Feig SA. Number needed to screen. Appropriate use of this new basis for screening mammography guidelines. AJR Am J Roentgenol 2012; 198:1214–1217.
  13. Hendrick RE, Helvie MA. Mammography screening: a new estimate of number needed to screen to prevent one breast cancer death. AJR Am J Roentgenol 2012; 198:723–728.
  14. Tabar L, Yen MF, Vitak B, Chen HH, Smith RA, Duffy SW. Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet 2003; 361:1405–1410.
  15. Coldman A, Phillips N, Warren L, Kan L. Breast cancer mortality after screening mammography in British Columbia women. Int J Cancer 2007; 120:1076–1080.
  16. Rosenberg RD, Yankaskas BC, Abraham LA, et al. Performance benchmarks for screening mammography. Radiology 2006; 241:55–66.
  17. Lerman C, Trock B, Rimer BK, Boyce A, Jepson C, Engstrom PF. Psychological and behavioral implications of abnormal mammograms. Ann Intern Med 1991; 114:657–661.
  18. Tosteson AN, Fryback DG, Hammond CS, et al. Consequences of false-positive screening mammograms. JAMA Intern Med 2014; 174:954–961.
  19. Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG. Enthusiasm for cancer screening in the United States. JAMA 2004; 291:71–78.
  20. Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer 2013; 108:2205–2240.
  21. Feig SA. Ductal carcinoma in situ. Implications for screening mammography. Radiol Clin North Am 2000; 38:653–668,
  22. Hughes LL, Wang M, Page DL, et al. Local excision alone without irradiation for ductal carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009; 27:5319–5324.
  23. Tabár L, Vitak B, Chen HH, et al. The Swedish two-county trial twenty years later. Updated mortality results and new insights from long-term follow-up. Radiol Clin North Am 2000; 38:625–651.
  24. Duffy SW, Chen HH, Tabar L, et al. Estimation of mean sojourn time in breast cancer screening using a Markov chair model of entry to and exit from the preclinical detectable phase. Stat Med 1995; 14:1521-1534.
  25. Chen HH, Duffy SW, Tabar L, et al. Markov chain models for progression of breast cancer. Part I: tumor attributes and the preclinical screening detectable phase. J Epidemiol Biostat 1997; 2:9–25.
  26. Chen HH, Duffy SW, Tabar L, et al. Markov chain models for progression of breast cancer. Part II: prediction of outcomes for different screening regimes. J Epidemiol Biostat 1997; 2:25–35.
  27. Kerlikowske K, Zhu W, Hubbard RA, et al; Breast Cancer Surveillance Consortium. Outcomes of screening mammography by frequency, breast density, and postmenopausal hormone therapy. JAMA Intern Med 2013; 173:807–816.
References
  1. Güth U, Huang DJ, Huber M, et al. Tumor size and detection in breast cancer: self-examination and clinical breast examination are at their limit. Cancer Detect Prev 2008; 32:224–228.
  2. Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J, editors. SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988–2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD; 2007:101–110. http://seer.cancer.gov/archive/publications/survival/seer_survival_mono_lowres.pdf. Accessed April 9, 2015.
  3. Legorreta AP, Brooks RJ, Leibowitz AN, Solin LJ. Cost of breast cancer treatment. A 4-year longitudinal study. Arch Intern Med 1996; 156:2197–2201.
  4. Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up: a randomised controlled trial. Lancet 2006; 368:2053–2060.
  5. Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347–360.
  6. Feig SA. Screening mammography benefit controversies: sorting the evidence. Radiol Clin North Am 2014; 52:455–480.
  7. Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ 1992; 147:1477–1488.
  8. Miller AB, To T, Baines CJ, Wall C. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50–59 years. J Natl Cancer Inst 2000; 92:1490–1499.
  9. Smart CR, Hendrick RE, Rutledge JH 3rd, Smith RA. Benefit of mammography screening in women ages 40 to 49 years. Current evidence from randomized controlled trials. Cancer 1995; 75:1619–1626.
  10. Breast-cancer screening with mammography in women aged 40-49 years. Swedish Cancer Society and the Swedish National Board of Health and Welfare. Int J Cancer 1996; 68:693–699.
  11. US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 151:716–726.
  12. Feig SA. Number needed to screen. Appropriate use of this new basis for screening mammography guidelines. AJR Am J Roentgenol 2012; 198:1214–1217.
  13. Hendrick RE, Helvie MA. Mammography screening: a new estimate of number needed to screen to prevent one breast cancer death. AJR Am J Roentgenol 2012; 198:723–728.
  14. Tabar L, Yen MF, Vitak B, Chen HH, Smith RA, Duffy SW. Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet 2003; 361:1405–1410.
  15. Coldman A, Phillips N, Warren L, Kan L. Breast cancer mortality after screening mammography in British Columbia women. Int J Cancer 2007; 120:1076–1080.
  16. Rosenberg RD, Yankaskas BC, Abraham LA, et al. Performance benchmarks for screening mammography. Radiology 2006; 241:55–66.
  17. Lerman C, Trock B, Rimer BK, Boyce A, Jepson C, Engstrom PF. Psychological and behavioral implications of abnormal mammograms. Ann Intern Med 1991; 114:657–661.
  18. Tosteson AN, Fryback DG, Hammond CS, et al. Consequences of false-positive screening mammograms. JAMA Intern Med 2014; 174:954–961.
  19. Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG. Enthusiasm for cancer screening in the United States. JAMA 2004; 291:71–78.
  20. Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer 2013; 108:2205–2240.
  21. Feig SA. Ductal carcinoma in situ. Implications for screening mammography. Radiol Clin North Am 2000; 38:653–668,
  22. Hughes LL, Wang M, Page DL, et al. Local excision alone without irradiation for ductal carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009; 27:5319–5324.
  23. Tabár L, Vitak B, Chen HH, et al. The Swedish two-county trial twenty years later. Updated mortality results and new insights from long-term follow-up. Radiol Clin North Am 2000; 38:625–651.
  24. Duffy SW, Chen HH, Tabar L, et al. Estimation of mean sojourn time in breast cancer screening using a Markov chair model of entry to and exit from the preclinical detectable phase. Stat Med 1995; 14:1521-1534.
  25. Chen HH, Duffy SW, Tabar L, et al. Markov chain models for progression of breast cancer. Part I: tumor attributes and the preclinical screening detectable phase. J Epidemiol Biostat 1997; 2:9–25.
  26. Chen HH, Duffy SW, Tabar L, et al. Markov chain models for progression of breast cancer. Part II: prediction of outcomes for different screening regimes. J Epidemiol Biostat 1997; 2:25–35.
  27. Kerlikowske K, Zhu W, Hubbard RA, et al; Breast Cancer Surveillance Consortium. Outcomes of screening mammography by frequency, breast density, and postmenopausal hormone therapy. JAMA Intern Med 2013; 173:807–816.
Issue
Cleveland Clinic Journal of Medicine - 82(5)
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Cleveland Clinic Journal of Medicine - 82(5)
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276-279
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276-279
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Screening mammography starting at age 40: Still relevant
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Screening mammography starting at age 40: Still relevant
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mammography, breast cancer screening, Karthik Ghosh, Dietlind Wahner-Roedler, Kathleen Brandt
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mammography, breast cancer screening, Karthik Ghosh, Dietlind Wahner-Roedler, Kathleen Brandt
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