A prospective study of endometriosis and risk of benign breast disease.
OBJECTIVE
Given the altered hormonal and inflammatory environment of women with endometriosis, several studies have suggested a positive association between endometriosis and breast cancer, although findings have been mixed. This study investigates the relationship between endometriosis and benign breast disease (BBD), benign lesions that are associated with an increased risk of breast cancer.


METHODS
Among women in the Nurses' Health Study II followed from 1991-2003 (n = 76,393), we investigated the association between laparoscopically confirmed endometriosis and biopsy-confirmed BBD. Cox proportional hazard models, adjusted for a priori potential confounding factors, were used to calculate hazard ratios (HR) and 95 % confidence intervals (CI). Across follow-up, 2011 BBD biopsies were collected and centrally reviewed by study pathologists (nonproliferative = 675, proliferative = 1336). Effect modification by infertility history and use of screening mammography was investigated.


RESULTS
Endometriosis was associated with a modest increased risk of biopsy-confirmed BBD in crude and multivariable adjusted models (HR 1.20, 95 % CI 1.00-1.43). When evaluating subtypes of BBD, we did not see different associations for nonproliferative or proliferative BBD lesions, as endometriosis was associated with a modest increased risk for both (HR nonproliferative 1.15, 95 % CI 0.84-1.57; HR proliferative 1.22, 95 % CI 0.98-1.52). The association between endometriosis and proliferative BBD appeared strongest among women who had ever experienced infertility (HR 1.50, 95 % CI 1.12-2.03; P value, test for heterogeneity = 0.05). Sensitivity analyses investigating screening behaviors between those with and without endometriosis did not significantly alter results.


CONCLUSIONS
Endometriosis was associated with a modest increased risk of both proliferative and nonproliferative BBD, although future work should replicate this novel finding.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. lfarland@mail.harvard.edu.|Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA. lfarland@mail.harvard.edu.
Leslie V
http://orcid.org/0000-0001-7455-8531
LV
Farland
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.
Rulla M
RM
Tamimi
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.
A Heather
AH
Eliassen
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
Donna
D
Spiegelman
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
Laura C
LC
Collins
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
Stuart J
SJ
Schnitt
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.|Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.
Stacey A
SA
Missmer
D000328:Adult; D001706:Biopsy; D001941:Breast Diseases / Q000175:diagnosis* / Q000453:epidemiology*; D004715:Endometriosis / Q000175:diagnosis* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D010535:Laparoscopy; D009726:Nurses; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires
Benign breast disease; Breast cancer; Endometriosis; Epidemiology