The Risk of Breast Cancer and the Role of Chemoprevention in Women With Atypical Ductal or Lobular Hyperplasia

Main Article Content

Mahtab Vasigh
Ahmad Kaviani
Abdolali Assarian
Faina Nakhlis


Chemoprevention, Breast cancer, Atypical breast lesion


Background: Women with atypical hyperplasia are about 4 times more likely to develop breast cancer compared with the general population. Atypical hyperplasia has been recommended to be used as a criterion for the inclusion of women in chemoprevention programs. Chemoprevention offers promise as a strategy for reducing the incidence of breast cancer in high-risk population.

Methods: A literature search was conducted in PubMed and Scopus databases using the search terms “breast atypia,” “chemoprevention,” and “risk-reducing therapy” for papers published from 1966 to Aug 2017. The search was limited to English-language papers and human studies. It yielded 114 search items. Article selection for possible inclusion was performed using the title and abstract. Finally, 12 studies were identified as eligible for inclusion in the review.

Results: The rates of atypical ductal hyperplasia (ADH) ranged from a low of 2 per 10000 mammograms in 1995 to a high of 6 per 10000 mammograms in 2011. Lobular neoplasia was an incidental finding in 0.5%–3.5% of core biopsies. True incidence of lobular neoplasia is unknown. Women with atypical breast lesions have a 5%–11% risk of developing breast cancer within 5 years and a 17%–26% risk of developing breast cancer within 10 years. The reported risk of breast cancer with atypical hyperplasia (ADH and ALH are often grouped together) is approximately 19% within 15 years. It is believed that the initiation of chemoprevention would be appropriate if the 10-year breast cancer risk is 4% to 8%. Breast cancer risk reduction by chemoprevention is reported to be 32% to 55% in breast atypia.

Conclusion: According to our findings, patients with a diagnosis of ADH, ALH, or severe ADH should be considered for chemoprevention if they are at least 35 years of age and have no contraindications to treatment. Only 4%–20% of high-risk women decide to take chemoprevention, on average.


1. Sismondi P, D’Alonzo M, Pecchio S, Bounous VE, Robba E, Biglia N. Chemoprevention or mastectomy for women at high risk of developing breast cancer. Maturitas. 2015;82(3):271-3.
2. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. 1985;312(3):146-51.
3. Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, et al. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005;353(3):229-37.
4. Degnim AC, Visscher DW, Berman HK, Frost MH, Sellers TA, Vierkant RA, et al. Stratification of breast cancer risk in women with atypia: a Mayo cohort study. J Clin Oncol. 2007;25(19):2671-7.
5. Coopey SB, Mazzola E, Buckley JM, Sharko J, Belli AK, Kim EM, et al. The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions. Breast Cancer Res Treat. 2012;136(3):627-33.
6. Wheeler JE, Enterline H, Roseman JM, Tomasulo JP, McIlvaine CH, Fitts WT, et al. Lobular carcinoma in situ of the breast (Long‐term followup. Cancer. 1974;34(3):554-63.
7. Rosen PP, Kosloff C, Lieberman PH, Adair F, Braun DW, Jr. Lobular carcinoma in situ of the breast. Detailed analysis of 99 patients with average follow-up of 24 years. Am J Surg Pathol. 1978;2(3):225-51.
8. Schnitt SJ, Morrow M, editors. Lobular carcinoma in situ: current concepts and controversies. Seminars in diagnostic pathology. 1999; 16 (3): 209-223.
9. Anderson BO, Calhoun KE, Rosen EL. Evolving concepts in the management of lobular neoplasia. J Natl Compr Canc Netw. 2006;4(5):511-22.
10. Bevers TB, Ward JH, Arun BK, Colditz GA, Cowan KH, Daly MB, et al. Breast Cancer Risk Reduction, Version 2.2015. J Natl Compr Canc Netw. 2015;13(7):880-915.
11. Lee S, Mohsin SK, Mao S, Hilsenbeck SG, Medina D, Allred DC. Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer. Breast Cancer Res. 2006;8(1):R6.
12. Hartmann LC, Radisky DC, Frost MH, Santen RJ, Vierkant RA, Benetti LL, et al. Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prevention Research. 2014;7(2):211-7.
13. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. JNCI: Journal of the National Cancer Institute. 1989;81(24):1879-86.
14. Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med. 2004;23(7):1111-30.
15. Boughey JC, Hartmann LC, Anderson SS, Degnim AC, Vierkant RA, Reynolds CA, et al. Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) model for breast cancer risk prediction in women with atypical hyperplasia. J Clin Oncol. 2010;28(22):3591-6.
16. Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer. 1994;73(3):643-51.
17. Tice JA, Cummings SR, Smith-Bindman R, Ichikawa L, Barlow WE, Kerlikowske K. Using clinical factors and mammographic breast density to estimate breast cancer risk: development and validation of a new predictive model. Annals of internal medicine. 2008;148(5):337-47.
18. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371-88.
19. Euhus D, Bu D, Xie XJ, Sarode V, Ashfaq R, Hunt K, et al. Tamoxifen downregulates ets oncogene family members ETV4 and ETV5 in benign breast tissue: implications for durable risk reduction. Cancer Prev Res (Phila). 2011;4(11):1852-62.
20. Jordan VC. The 4Ps of breast cancer chemoprevention: putting proven principles into practice. AACR; 2017.
21. Hartmann LC, Degnim AC, Santen RJ, Dupont WD, Ghosh K. Atypical hyperplasia of the breast--risk assessment and management options. N Engl J Med. 2015;372(1):78-89.
22. Menes TS, Kerlikowske K, Lange J, Jaffer S, Rosenberg R, Miglioretti DL. Subsequent Breast Cancer Risk Following Diagnosis of Atypical Ductal Hyperplasia on Needle Biopsy. JAMA Oncol. 2017;3(1):36-41.
23. McEvoy MP, Coopey SB, Mazzola E, Buckley J, Belli A, Polubriaginof F, et al. Breast cancer risk and follow-up recommendations for young women diagnosed with atypical hyperplasia and lobular carcinoma in situ (LCIS). Annals of surgical oncology. 2015;22(10):3346-9.
24. Dyrstad SW, Yan Y, Fowler AM, Colditz GA. Breast cancer risk associated with benign breast disease: systematic review and meta-analysis. Breast Cancer Res Treat. 2015;149(3):569-75.
25. Khan SA, Rogers MA, Khurana KK, Meguid MM, Numann PJ. Estrogen receptor expression in benign breast epithelium and breast cancer risk. J Natl Cancer Inst. 1998;90(1):37-42.
26. Tan-Chiu E, Wang J, Costantino JP, Paik S, Butch C, Wickerham DL, et al. Effects of tamoxifen on benign breast disease in women at high risk for breast cancer. Journal of the National Cancer Institute. 2003;95(4):302-7.
27. Zhou WB, Xue DQ, Liu XA, Ding Q, Wang S. The influence of family history and histological stratification on breast cancer risk in women with benign breast disease: a meta-analysis. J Cancer Res Clin Oncol. 2011;137(7):1053-60.
28. Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis. Journal of Clinical Oncology. 2010;28(18):3090.
29. Cuzick J, DeCensi A, Arun B, Brown PH, Castiglione M, Dunn B, et al. Preventive therapy for breast cancer: a consensus statement. Lancet Oncol. 2011;12(5):496-503.
30. Visvanathan K, Hurley P, Bantug E, Brown P, Col NF, Cuzick J, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. Journal of Clinical Oncology. 2013;31(23):2942-62.

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