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Cancer Med. 2017 Jun;6(6):1482-1489. doi: 10.1002/cam4.1080. Epub 2017 May 4.

Biomarkers expression in benign breast diseases and risk of subsequent breast cancer: a case-control study.

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Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau (IIB Sant Pau), Barcelona, Spain.
Pathology Department, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Research Network on Health Services in Chronic Diseases (REDISSEC), Barcelona, Spain.
Agency for Health Quality and Assessment of Catalonia (AQuAS), Barcelona, Spain.
CIBER of Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
Obstetrics and Gynecology Department, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Clinical Epidemiology and Cancer Screening, Parc Taulí University Hospital, Barcelona, Spain.
Cancer Prevention and Control Program, Catalan Institute of Oncology, Barcelona, Spain.
Direction General of Public Health, Department of Health, Government of Cantabria, Santander, Spain.
Breast Cancer Screening Program of Tarragona, The Foundation League for the Research and Prevention of Cancer, Tarragona, Spain.
Principality of Asturias Breast Cancer Screening Program, Principality of Asturias, Oviedo, Spain.
Radiology Department, Hospital de Santa Caterina, Girona, Spain.
Oncology Department, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.


Women with benign breast diseases (BBD) have a high risk of breast cancer. However, no biomarkers have been clearly established to predict cancer in these women. Our aim was to explore whether estrogen receptor (ER), progesterone receptor (PR), and Ki67 expression stratify risk of breast cancer in screened women with BBD. We conducted a nested case-control study. Women with breast cancer and prior BBDs (86 cases) were matched to women with prior BBDs who were free from breast cancer (172 controls). The matching factors were age at BBD diagnosis, type of BBD, and follow-up time since BBD diagnosis. ER, PR, and Ki67 expression were obtained from BBDs' specimens. Conditional logistic regression was used to estimate odds ratios (ORs), and 95% confidence intervals (CIs) of breast cancer risk according to ER, PR, and Ki67 expression. Women with >90% of ER expression had a higher risk of breast cancer (OR = 2.63; 95% CI: 1.26-5.51) than women with ≤70% of ER expression. Similarly, women with >80% of PR expression had a higher risk of breast cancer (OR = 2.22; 95% CI: 1.15-4.27) than women with ≤40% of PR expression. Women with proliferative disease and ≥1% of Ki67 expression had a nonsignificantly increased risk of breast cancer (OR = 1.16; 95% CI: 0.46-2.90) than women with <1% of Ki67 expression. A high expression of ER and PR in BBD is associated with an increased risk of subsequent breast cancer. In proliferative disease, high Ki67 expression may also have an increased risk. This information is helpful to better characterize BBD and is one more step toward personalizing the clinical management of these women.


Benign breast disease; biomarkers; breast cancer; early detection; screening

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