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

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.

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

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 1971-2006, 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% <20mm) and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred risk for ER-positive (OR=5.48, 95%CI=2.14-14.01) with only one ER-negative case); p-heterogeneity=0.45. Presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in 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.

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

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 1971-2006, 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% <20mm) and stage I/II (91%). Having had an age at first birth <30 years was associated with reduced risk of ER-positive breast cancer (OR=0.69, 95%CI=0.49-0.98), but not of ER-negative disease (OR=1.08, 95%CI=0.51-2.30) p-heterogeneity=0.24. Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred higher risk for ER-positive (OR=5.48, 95%CI=2.14-14.01) than ER-negative disease (OR=1.52, 95%CI=0.18-13.05, with only one ER-negative case); p-heterogeneity=0.45. Presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with 1.5-fold risk for both ER-positive and ER-negative tumors, with a 2-fold risk (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 moderate increased risk, independent of BBD histology, and irrespective of ER status.

Adolescent intakes of alcohol and folate and risk of proliferative benign breast disease.

169 Background: Given the importance of exposure between menarche and first childbirth in breast cancer risk, adolescent alcohol consumption may influence the risk of proliferative benign breast disease (BBD). Folate may modify the adverse effect of alcohol on breast cancer. Methods: We used data from 29,329 women in the Nurses’ Health Study II who completed both adolescent alcohol consumption questions in 1989 and an adolescent diet questionnaire in 1998. A total of 666 women with proliferative BBD between 1991 and 2001 were confirmed by centralized pathology review. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for established risk factors of breast cancer. Results: Adolescent alcohol consumption was dose-dependently associated with an increased risk of proliferative BBD (HR = 1.12 per 10g/day consumption; 95% CI, 1.03-1.22). There was no significant association with adolescent folate intake. While the interaction between adolescent alcohol and folate intake was not statistically significant, among women with low folate intake (<279 mg/day) the BBD risk was significantly increased with moderate alcohol intake (HR = 1.62; 95% CI, 1.14-2.28) and with high alcohol intake (HR = 1.90; 95% CI, 0.98-3.70; Ptrend <0.01). Adolescent alcohol consumption was not associated with increased risk among women with higher adolescent folate intake. Conclusions: Adolescent alcohol consumption is associated with higher risk of proliferative BBD, especially in women with low adolescent folate intake.