Abstract: The etiology of breast cancer (BC) among young women is not well understood. Recent studies have suggested that tobacco exposure is associated with an increased risk of BC but few studies have evaluated risk among women under age 50 or racial and socioeconomic disparities in risk. We hypothesized that racial and socioeconomic differences in age at smoking initiation and lifetime cigarette smoking contribute to disparities in BC risk among young women. Data were examined from a population-based case-control study in women under 50 years of age, the Young Women’s Health History Study. In total, 1,812 women with invasive BC (1,130 Non-Hispanic (NH) White, 682 NH Black) and an area-based sample of 1,381 control women (716 NH White, 665 NH Black), frequency matched to cases by five-year age group, study site and race were identified and interviewed from the Los Angeles County and Metropolitan Detroit SEER registry areas. Lifetime smoking history (including age at initiation, duration, and frequency) were collected from structured in-person interviews. Survey-weighted multivariable logistic regression was used to evaluate the association between lifetime cigarette smoking and BC risk adjusted for matching and known BC risk factors. Additionally, cross-product interaction terms of smoking exposure by race and by socioeconomic position (SEP; based on household percent poverty) were evaluated by Wald’s test. Among controls, 36.5% reported ever smoking at least 1 cigarette a day for at least 6 months in their lifetime with White women compared to Black women (38.3% vs. 32.3%) and women of lower SEP (<150% of poverty) compared to higher SEP (≥150% of poverty) (50.4% vs. 31.5%) being more likely to have ever smoked. In adjusted models, those who ever vs. never smoked were 1.20 times as likely to develop BC; findings were marginally significant (95% confidence interval (CI): 0.99-1.46, p=0.07). No differences were found by race or SEP, nor was there a consistent association with BC risk for duration of smoking history (in pack-years) or average number of cigarettes smoked per day. Age at smoking initiation (never smoker, initiated at age <25 years, initiated at age ≥25 years) was significantly positively associated with BC risk (p trend=0.02). Smoking initiated at 25 years or older was associated with a 78% increased risk of BC compared to never smokers (95% CI: 1.15-2.77). A positive association between age at initiation and BC risk was observed among White (p trend=0.048), but not Black women. A marginally significant increased risk with age at initiation was observed among women of higher SEP (p trend=0.05) but not among those of lower SEP. We found evidence that smoking is associated with an increased risk of BC in young women, especially among those who started smoking at an older age. Despite efforts to reduce smoking, the prevalence of smoking remains highest among people of low socioeconomic position, as we found. Encouraging women not to initiate smoking is important to reduce BC risk among women under age 50. Citation Format: Ugonna Ihenacho, Ann S Hamilton, Wendy J Mack, Anna H Wu, Jennifer B Unger, Dorothy R Pathak, Richard T Houang, Michael F Press, Kendra L Schwartz, Lydia Marcus, Ellen M Velie. Lifetime cigarette smoking and breast cancer risk in young women: Racial and socioeconomic disparities in risk in the Young Women’s Health History Study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A112.

Abstract: Previous studies have found that tobacco exposure is associated with an increased risk of premenopausal breast cancer (BC) overall and some studies suggest that risk is only increased for Luminal A BC. Few studies have described the association between tobacco exposure and BC risk with characterization of the human epidermal growth factor receptor 2 (HER2) subtype. This analysis explored associations between smoking over the life course and BC risk overall and by BC subtype among a socioeconomically diverse population of young non-Hispanic (NH) Black and White women. Data were examined from a population-based case-control study in women under 50 years of age, the Young Women’s Health History Study. In total, 1,812 women with invasive BC (1,130 NH White, 682 NH Black) and an area-based sample of 1,381 (716 NH White, 665 NH Black) control women, frequency matched to cases by five-year age group, study site and self-reported race were identified from the Los Angeles County and Metropolitan Detroit SEER registry areas. Lifetime smoking histories were collected from in-person interviews. Sample-weighted logistic regression analysis was conducted to estimate the association between lifetime cigarette smoking status (never versus ever smoker) and BC risk adjusted for known BC risk factors and study site. Multinomial logistic regression analysis was conducted for analyses by BC subtype. Heterogeneity in the odds ratio (OR) estimates by BC subtype and cross-product interaction terms of smoking status by race and by household percent poverty (HHP) were evaluated by the Wald test. In adjusted models, BC risk overall was not significantly associated with ever smoking at least 1 cigarette a day for 6 months or more (OR 1.18; 95% confidence interval (CI) 0.97- 1.43). By BC subtype, ever smokers displayed a statistically significant 30% increase in Luminal A BC risk compared to never smokers (OR 1.30; 95% CI 1.03-1.64) and a 90% increased risk of HER2-type BC (OR 1.90; 95% CI 1.17-3.08). Smoking was not associated with risk of Luminal B or Triple Negative BC. Associations between ever smoking and BC risk significantly differed by BC subtype (Pheterogeneity=0.02). Statistical interactions by race or by HHP were not observed. However, we noted that in stratified models the association between smoking and risk for HER2-type BC was higher among NH White compared to NH Black women and among women with HHP ≥150% compared to HHP <150%. For Luminal A BC, the association with smoking did not differ by race and risk was higher among women with HHP <150% compared to HHP ≥150%. Although other studies have identified an association between smoking and Luminal A BC, this may be the first study to identify an association between smoking and hormone receptor negative, HER2-type BC risk. An increased risk for HER2-type BC among NH White women and women with HHP ≥150% was suggested. Research in HER2-type BC is a relatively new and evolving field as HER2 expression was often underreported in the pathology reports of cases diagnosed before 2005. Citation Format: Ugonna N. Ihenacho, Ann S. Hamilton, Wendy J. Mack, Anna H. Wu, Jennifer B. Unger, Dorothy R. Pathak, Richard T. Houang, Michael F. Press, Kendra L. Schwartz, Lydia Marcus, Ellen M. Velie. Increased risk of luminal A and HER2-type breast cancer with lifetime cigarette smoking among non-Hispanic Black and White women in the Young Women’s Health History Study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-200.

Purpose

To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP).

Methods

Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression.

Results

YOBC risk associated with ever versus never smoking differed by subtype (P_{heterogeneity} = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP.

Conclusion

Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.

PURPOSE: The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case-control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results. METHODS: Cases were non-Hispanic Black (NHB) and White (NHW) women age 20-49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010-2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected. RESULTS: Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases. CONCLUSIONS: Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.