Active smoking and risk of Luminal and Basal-like breast cancer subtypes in the Carolina Breast Cancer Study

Abstract

Purpose Growing evidence suggests an association between active cigarette smoking and increased breast cancer risk. However, the weak magnitude of association and conflicting results have yielded uncertainty and it is unknown whether associations differ by breast cancer subtype. Methods Using population-based case–control data from phases I and II of the Carolina Breast Cancer Study, we examined associations between self-reported measures of smoking and risk of Luminal and Basal-like breast cancers. We used logistic regression models to estimate case–control odds ratios (OR) and 95 % confidence intervals (CI). Results Ever smoking (current and former) was associated with a weakly increased risk of Luminal breast cancer (OR 1.12, 95 % CI 0.92–1.36) and was not associated with risk of Basal-like breast cancer (OR 0.96, 95 % CI 0.69–1.32). Similarly, smoking duration of more than 20 years was associated with increased risk of Luminal (OR 1.51, 95 % CI 1.19–1.93), but not Basal-like breast cancer (OR 0.90, 95 % CI 0.57–1.43). When stratified by race, elevated odds ratios between smoking and Luminal breast cancer risk were found among black women across multiple exposure measures (ever smoking, duration, and dose); conversely, among white women odds ratios were attenuated or null. Conclusions Results from our study demonstrate a positive association between smoking and Luminal breast cancer risk, particularly among black women and women with long smoking histories. Addressing breast cancer heterogeneity in studies of smoking and breast cancer risk may elucidate associations masked in prior studies.

Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study

“…Interestingly, gene ontology analysis revealed different enrichment terms associated with smoking in HR− and HR+ tumors, with smoking-related terms in HR− tumors related to response to organic chemicals and stress, while those in HR+ tumors were associated with transcriptional regulation, suggesting that these tumor subsets may both be associated with smoking but via different pathways. Smoking-related epigenetic differences also varied somewhat by race in that the hypermethylation in HR+ breast tumors was more pronounced in black smokers, which may be consistent with epidemiologic findings from CBCS indicating that smoking was associated with the development of luminal breast cancer mainly among black women [16]. …”

“…Studies in the Carolina Breast Cancer Study (CBCS) have reported the associations of smoking and breast cancer mainly among long-term smokers and recent quitters, and observed stronger associations for luminal breast cancer, particularly among African Americans [9, 16]. Additionally, we observed worse disease-specific survival among breast cancer cases who smoked (unpublished observations).…”

“…Recent studies in the CBCS indicated that smoking was more strongly associated with the development of luminal (HR+) breast cancers among blacks [16], but worse long-term survival among black smokers and smokers with ER− breast tumors (unpublished observations).…”

“…On average, interviews were conducted 6 months following case ascertainment. Since a breast cancer diagnosis may influence decisions concerning smoking cessation, current smokers were defined as women who self-reported active smoking at the time of interview and women who reported smoking cessation at the same age (within a year) of case selection [16]. Former smokers quit at any age prior to the age at case selection.…”

“…The epidemiologic data on active smoking in breast cancer has been mixed [4, 5], but more recent studies support a modest role for smoking in breast cancer development [6–8], most often among women who smoked for a long time [6, 9–12], recently quit [12, 13], or began smoking at an early age or prior to first birth [6, 7, 10, 11, 14]. Several reports have also described stronger associations of smoking with either ER+ [7, 8, 15, 16] or ER− breast cancer [17–20]. In addition to putative etiologic effects, tobacco smoking at the time of breast cancer diagnosis is associated with worse disease-specific and overall survival [21, 22]; however, the biological mechanisms through which smoking might influence the risk of developing or dying from breast cancer are not fully understood.…”