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. 2021 Mar 18;23(1):34.
doi: 10.1186/s13058-021-01410-1.

Risk factors for breast cancer development by tumor characteristics among women with benign breast disease

Jonine D Figueroa #  1   2   3 , Gretchen L Gierach #  4 , Máire A Duggan  5 , Shaoqi Fan  4 , Ruth M Pfeiffer  4 , Yihong Wang  6 , Roni T Falk  4 , Olivier Loudig  7 , Mustapha Abubakar  4 , Mindy Ginsberg  8 , Teresa M Kimes  9 , Kathryn Richert-Boe  9 , Andrew G Glass  9 , Thomas E Rohan  10
Affiliations

Risk factors for breast cancer development by tumor characteristics among women with benign breast disease

Jonine D Figueroa et al. Breast Cancer Res. .

Abstract

Background: Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown.

Methods: Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models.

Results: Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14-14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21-3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size.

Conclusion: Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.

Keywords: Benign breast disease; Breast cancer; Columnar cell lesions; Epidemiology; Estrogen receptor; Tumor characteristics.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A representative hematoxylin and eosin stained breast biopsy × 200 μm image of columnar cell change showing dilated acini lined by a columnar epithelium demonstrating apical cytoplasmic snouts
See this image and copyright information in PMC

References

    1. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. 1985;312(3):146–151. - PubMed
    1. Allison KH, Abraham LA, Weaver DL, Tosteson AN, Nelson HD, Onega T, Geller BM, Kerlikowske K, Carney PA, Ichikawa LE, Buist DS, Elmore JG. Trends in breast biopsy pathology diagnoses among women undergoing mammography in the United States: a report from the Breast Cancer Surveillance Consortium. Cancer. 2015;121(9):1369–78. 10.1002/cncr.29199. - PMC - PubMed
    1. Neal L, Sandhu NP, Hieken TJ, Glazebrook KN, Mac Bride MB, Dilaveri CA, Wahner-Roedler DL, Ghosh K, Visscher DW. Diagnosis and management of benign, atypical, and indeterminate breast lesions detected on core needle biopsy. Mayo Clin Proc. 2014;89(4):536–547. - PubMed
    1. 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. - PMC - PubMed
    1. Cuzick J, Sestak I, Thorat MA. Impact of preventive therapy on the risk of breast cancer among women with benign breast disease. Breast. 2015;24(Suppl 2):S51–S55. - PMC - PubMed

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