Breast Cancer Screening (PDQ®)–Health Professional Version - National Cancer Institute

Breast Cancer Screening (PDQ®)–Health Professional Version - National Cancer Institute

Breast Cancer Screening (PDQ®)–Health Professional Version

Description of the Evidence

In This Section

• Breast Cancer Incidence and Mortality
• Evaluation of Breast Symptoms
• Pathologic Evaluation of Breast Tissue
  • Invasive breast cancer
  • Ductal carcinoma in situ (DCIS)
  • Atypia
  • Variability of pathologists’ diagnoses on the interpretation of breast biopsy specimens
• Special Populations
  • Women at increased risk who may receive more benefit from screening
  • Individuals who receive little benefit from screening

Breast Cancer Incidence and Mortality

Breast cancer is the most common noncutaneous cancer in U.S. women, with an estimated 268,600 cases of invasive disease, 62,930 cases of in situ disease, and 41,760 deaths expected in 2019.[1] Women with inherited risk, including BRCA1 and BRCA2 gene carriers, comprise approximately 5% to 10% of breast cancer cases.[2] Males account for 1% of breast cancer cases and breast cancer deaths.[1]

The biggest risk factor for breast cancer is being female followed by advancing age. Other risk factors include hormonal aspects (such as early menarche, late menopause, nulliparity, late first pregnancy, and postmenopausal hormone therapy), alcohol consumption, and exposure to ionizing radiation.

Breast cancer incidence in white women is higher than in black women, who also have a lower survival rate for every stage when diagnosed. This may reflect differences in screening behavior and access to healthcare. Hispanic and Asian-Pacific islanders have lower incidence and mortality than whites or blacks.[3]

Breast cancer incidence depends on reproductive issues (such as early vs. late pregnancy, multiparity, and breastfeeding), participation in screening, and postmenopausal hormone usage. The incidence of breast cancer (especially ductal carcinoma in situ [DCIS]) increased dramatically after mammography was widely adopted in the United States and the United Kingdom.[4] Widespread use of postmenopausal hormone therapy was associated with a dramatic increase in breast cancer incidence, a trend that reversed when its use decreased.[5]

In any population, the adoption of screening is not followed by a decline in the incidence of advanced-stage cancer.

Evaluation of Breast Symptoms

Women with breast symptoms undergo diagnostic mammography as opposed to screening mammography, which is done in asymptomatic women. In a 10-year study of breast symptoms prompting medical attention, a breast mass led to a cancer diagnosis in 10.7% of cases, whereas pain was associated with cancer in only 1.8% of cases.[6]

Pathologic Evaluation of Breast Tissue

Invasive breast cancer

Breast cancer can be diagnosed when breast tissue cells removed during a biopsy are studied microscopically. The breast tissue to be sampled can be identified by an abnormality on an imaging study or because it is palpable. Breast biopsies can be performed with a thin needle attached to a syringe (fine-needle aspirate), a larger needle (core biopsy), or by excision (excisional biopsy). Image guidance can improve accuracy. Needle biopsies sample an abnormal area large enough to make a diagnosis. Excisional biopsies aim to remove the entire region of abnormality.

Ductal carcinoma in situ (DCIS)

DCIS is a noninvasive condition that can be associated with, or evolve into, invasive cancer, with variable frequency and time course.[7] Some authors include DCIS with invasive breast cancer statistics, but others argue that it would be better if the term were replaced with ductal intraepithelial neoplasia, similar to the terminology used for cervical and prostate precursor lesions, and that excluding DCIS from breast cancer statistics should be considered.

DCIS is most often diagnosed by mammography. In the United States, only 4,900 women were diagnosed with DCIS in 1983 before the adoption of mammography screening, compared with approximately 62,930 women who are expected to be diagnosed in 2019.[1,7,8] The Canadian National Breast Screening Study-2, which evaluated women aged 50 to 59 years, found a fourfold increase in DCIS cases in women screened by clinical breast examination (CBE) plus mammography compared with those screened by CBE alone, with no difference in breast cancer mortality.[9] (Refer to the PDQ summary on Breast Cancer Treatment (Adult) for more information.)

The natural history of DCIS is poorly understood because nearly all DCIS cases are detected by screening and nearly all are treated. Development of breast cancer after treatment of DCIS depends on the pathologic characteristics of the lesion and on the treatment. In a randomized trial, 13.4% of women whose DCIS was excised by lumpectomy developed ipsilateral invasive breast cancer within 90 months, compared with 3.9% of those treated by both lumpectomy and radiation.[10] Among women diagnosed and treated for DCIS, the percentage of women who died of breast cancer is lower than that for the age-matched population at large.[11,12] This favorable outcome may reflect the benign nature of the condition, the benefits of treatment, or the volunteer effect (i.e., women who undergo breast cancer screening are generally healthier than those who do not do so).

Atypia

Atypia, which is a risk factor for breast cancer, is found in 4% to 10% of breast biopsies.[13,14] Atypia is a diagnostic classification with considerable variation among practicing pathologists.[15]

Variability of pathologists’ diagnoses on the interpretation of breast biopsy specimens

The range of pathologists' diagnoses of breast tissue includes benign without atypia, atypia, DCIS, and invasive breast cancer. The incidence of atypia and DCIS breast lesions has increased over the past three decades as a result of widespread mammography screening, although atypia is generally mammographically occult.[16,17] Misclassification of breast lesions may contribute to either overtreatment or undertreatment of lesions—with variability especially in the diagnoses of atypia and DCIS.[15,18-22]

The largest study on this topic, the B-Path study, involved 115 practicing U.S. pathologists who interpreted a single-breast biopsy slide per case, and it compared their interpretations with an expert consensus-derived reference diagnosis.[15] While the overall agreement between the individual pathologists’ interpretations and the expert reference diagnoses was highest for invasive carcinoma, there were markedly lower levels of agreement for DCIS and atypia.[15] As the B-Path study included higher proportions of cases of atypia and DCIS than typically seen in clinical practice, the authors expanded their work by applying Bayes’ theorem to estimate how diagnostic variability affects accuracy from the perspective of a U.S. woman aged 50 to 59 years having a breast biopsy.[18] At the U.S. population level, it is estimated that 92.3% (confidence interval [CI], 91.4%–93.1%) of breast biopsy diagnoses would be verified by an expert reference consensus diagnosis, with 4.6% (CI, 3.9%–5.3%) of initial breast biopsies estimated to be overinterpreted and 3.2% (CI, 2.7%–3.6%) under interpreted. Figure 1 shows the predicted outcomes per 100 breast biopsies, overall and by diagnostic category.

ENLARGE

Figure 1. Predicted outcomes per 100 breast biopsies, overall and by diagnostic category. From Annals of Internal Medicine, Elmore JG, Nelson HD, Pepe MS, Longton GM, Tosteson AN, Geller B, Onega T, Carney PA, Jackson SL, Allison KH, Weaver DL, Variability in Pathologists' Interpretations of Individual Breast Biopsy Slides: A Population Perspective, Volume 164, Issue 10, Pages 649–55, Copyright © 2016 American College of Physicians. All Rights Reserved. Reprinted with the permission of American College of Physicians, Inc.

To address the high rates of discordance in breast tissue diagnosis, laboratory policies that require second opinions are becoming more common. A national survey of 252 breast pathologists participating in the B-Path study found that 65% of respondents reported having a laboratory policy that requires second opinions for all cases initially diagnosed as invasive disease. Additionally, 56% of respondents reported policies that require second opinions for initial diagnoses of DCIS, while 36% of respondents reported mandatory second opinion policies for cases initially diagnosed as atypical ductal hyperplasia.[23] In this same survey, pathologists overwhelmingly agreed that second opinions improved diagnostic accuracy (96%).

A simulation study that used B-Path study data evaluated 12 strategies for obtaining second opinions to improve interpretation of breast histopathology.[24] Accuracy improved significantly with all second-opinion strategies, except for the strategy limiting second opinions only to cases of invasive cancer. Accuracy improved regardless of the pathologists’ confidence in their diagnosis or their level of experience. While the second opinions improved accuracy, they did not completely eliminate diagnostic variability, especially in the challenging case of breast atypia.

Special Populations

Women at increased risk who may receive more benefit from screening

Women with BRCA1 and BRCA2 genetic mutations

Women with an increased risk of breast cancer caused by a BRCA1 or BRCA2 genetic mutation might benefit from increased screening. (Refer to the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information.)

Recipients of thoracic radiation

Women with Hodgkin and non-Hodgkin lymphoma who were treated with mantle irradiation have an increased risk of breast cancer, starting 10 years after completing therapy and continuing life-long. Therefore, screening mammography has been advocated, even though it may begin at a relatively young age.[25,26]

Individuals who receive little benefit from screening

Women with limited life expectancy

The potential benefits of screening mammography occur well after the examination, often many years later, whereas the harms occur immediately. Therefore, women with limited life expectancy and comorbidities who suffer harms may do so without benefit. Nonetheless, many of these women undergo screening mammography.[27] In one study, approximately 9% of women with advanced cancer underwent cancer screening tests.[28]

Elderly women

Screening mammography may yield cancer diagnoses in approximately 1% of women aged 66 to 79 years, but most of these cancers are low risk.[29] The question remains whether the diagnosis and treatment of localized breast cancer in elderly women is beneficial.

Young women

There is no evidence of benefit in performing screening mammography in average-risk women younger than 40 years.

Men

Approximately 1% of all breast cancers occur in men.[30] Most cases are diagnosed during the evaluation of palpable lesions, which are generally easy to detect. Treatment consists of surgery, radiation, and systemic adjuvant hormone therapy or chemotherapy. (Refer to the PDQ summary on Male Breast Cancer Treatment for more information.) Screening is unlikely to be beneficial.

References

1. American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available onlineExit Disclaimer. Last accessed December 12, 2019.
2. Kurian AW, Griffith KA, Hamilton AS, et al.: Genetic Testing and Counseling Among Patients With Newly Diagnosed Breast Cancer . JAMA 317 (5): 531-534, 2017. [PUBMED Abstract]
3. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2011. Bethesda, Md: National Cancer Institute, 2014. Also available online. Last accessed August 2, 2019.
4. Johnson A, Shekhdar J: Breast cancer incidence: what do the figures mean? J Eval Clin Pract 11 (1): 27-31, 2005. [PUBMED Abstract]
5. Haas JS, Kaplan CP, Gerstenberger EP, et al.: Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results. Ann Intern Med 140 (3): 184-8, 2004. [PUBMED Abstract]
6. Barton MB, Elmore JG, Fletcher SW: Breast symptoms among women enrolled in a health maintenance organization: frequency, evaluation, and outcome. Ann Intern Med 130 (8): 651-7, 1999. [PUBMED Abstract]
7. Allegra CJ, Aberle DR, Ganschow P, et al.: National Institutes of Health State-of-the-Science Conference statement: Diagnosis and Management of Ductal Carcinoma In Situ September 22-24, 2009. J Natl Cancer Inst 102 (3): 161-9, 2010. [PUBMED Abstract]
8. Virnig BA, Tuttle TM, Shamliyan T, et al.: Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst 102 (3): 170-8, 2010. [PUBMED Abstract]
9. Miller AB, To T, Baines CJ, et al.: Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years. J Natl Cancer Inst 92 (18): 1490-9, 2000. [PUBMED Abstract]
10. Fisher B, Dignam J, Wolmark N, et al.: Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 16 (2): 441-52, 1998. [PUBMED Abstract]
11. Ernster VL, Barclay J, Kerlikowske K, et al.: Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program. Arch Intern Med 160 (7): 953-8, 2000. [PUBMED Abstract]
12. Welch HG, Prorok PC, O'Malley AJ, et al.: Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness. N Engl J Med 375 (15): 1438-1447, 2016. [PUBMED Abstract]
13. Weaver DL, Rosenberg RD, Barlow WE, et al.: Pathologic findings from the Breast Cancer Surveillance Consortium: population-based outcomes in women undergoing biopsy after screening mammography. Cancer 106 (4): 732-42, 2006. [PUBMED Abstract]
14. Rubin E, Visscher DW, Alexander RW, et al.: Proliferative disease and atypia in biopsies performed for nonpalpable lesions detected mammographically. Cancer 61 (10): 2077-82, 1988. [PUBMED Abstract]
15. Elmore JG, Longton GM, Carney PA, et al.: Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA 313 (11): 1122-32, 2015. [PUBMED Abstract]
16. Bleyer A, Welch HG: Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 367 (21): 1998-2005, 2012. [PUBMED Abstract]
17. Hall FM: Identification, biopsy, and treatment of poorly understood premalignant, in situ, and indolent low-grade cancers: are we becoming victims of our own success? Radiology 254 (3): 655-9, 2010. [PUBMED Abstract]
18. Elmore JG, Nelson HD, Pepe MS, et al.: Variability in Pathologists' Interpretations of Individual Breast Biopsy Slides: A Population Perspective. Ann Intern Med 164 (10): 649-55, 2016. [PUBMED Abstract]
19. Rosai J: Borderline epithelial lesions of the breast. Am J Surg Pathol 15 (3): 209-21, 1991. [PUBMED Abstract]
20. Schnitt SJ, Connolly JL, Tavassoli FA, et al.: Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria. Am J Surg Pathol 16 (12): 1133-43, 1992. [PUBMED Abstract]
21. Wells WA, Carney PA, Eliassen MS, et al.: Statewide study of diagnostic agreement in breast pathology. J Natl Cancer Inst 90 (2): 142-5, 1998. [PUBMED Abstract]
22. Della Mea V, Puglisi F, Bonzanini M, et al.: Fine-needle aspiration cytology of the breast: a preliminary report on telepathology through Internet multimedia electronic mail. Mod Pathol 10 (6): 636-41, 1997. [PUBMED Abstract]
23. Geller BM, Nelson HD, Carney PA, et al.: Second opinion in breast pathology: policy, practice and perception. J Clin Pathol 67 (11): 955-60, 2014. [PUBMED Abstract]
24. Elmore JG, Tosteson AN, Pepe MS, et al.: Evaluation of 12 strategies for obtaining second opinions to improve interpretation of breast histopathology: simulation study. BMJ 353: i3069, 2016. [PUBMED Abstract]
25. Mariscotti G, Belli P, Bernardi D, et al.: Mammography and MRI for screening women who underwent chest radiation therapy (lymphoma survivors): recommendations for surveillance from the Italian College of Breast Radiologists by SIRM. Radiol Med 121 (11): 834-837, 2016. [PUBMED Abstract]
26. Allen SD, Wallis MG, Cooke R, et al.: Radiologic features of breast cancer after mantle radiation therapy for Hodgkin disease: a study of 230 cases. Radiology 272 (1): 73-8, 2014. [PUBMED Abstract]
27. Walter LC, Lindquist K, Covinsky KE: Relationship between health status and use of screening mammography and Papanicolaou smears among women older than 70 years of age. Ann Intern Med 140 (9): 681-8, 2004. [PUBMED Abstract]
28. Sima CS, Panageas KS, Schrag D: Cancer screening among patients with advanced cancer. JAMA 304 (14): 1584-91, 2010. [PUBMED Abstract]
29. Smith-Bindman R, Kerlikowske K, Gebretsadik T, et al.: Is screening mammography effective in elderly women? Am J Med 108 (2): 112-9, 2000. [PUBMED Abstract]
30. Fentiman IS, Fourquet A, Hortobagyi GN: Male breast cancer. Lancet 367 (9510): 595-604, 2006. [PUBMED Abstract]