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Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort - Differential effects by tumour subtype, NAT2 status, BMI and alcohol intake.
Cancer Epidemiol 2014; 38(4):419-26CE

Abstract

BACKGROUND

Inconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking.

METHODS

We used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50-74 and diagnosed with invasive tumours 2001-2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed.

RESULTS

Overall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93-1.64, and HR 1.29, 95% CI 0.95-1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13-2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60-1.98; Pheterogeneity=0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02-3.65, and HR 2.08, 95% CI 1.40-3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22-10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (<25 kg/m(2): HR 2.52, 95% CI 1.52-4.15 vs. ≥25 kg/m(2): HR 0.94, 95% CI 0.38-2.36; Pheterogeneity=0.04).

CONCLUSION

The harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened.

Authors+Show Affiliations

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: p.seibold@dkfz.de.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; Department for Health Evidence, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands. Electronic address: Alina.Vrieling@radboudumc.nl.University Cancer Center Hamburg (UCCH) and University Medical Center Hamburg-Eppendorf, Martinistraβe 52, 20246 Hamburg, Germany. Electronic address: j.heinz@uke.uni-hamburg.de.University Cancer Center Hamburg (UCCH) and University Medical Center Hamburg-Eppendorf, Martinistraβe 52, 20246 Hamburg, Germany. Electronic address: n.obi@uke.de.Institute of Pathology, Heidelberg University, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany. Electronic address: peter.sinn@med.uni-heidelberg.de.University Cancer Center Hamburg (UCCH) and University Medical Center Hamburg-Eppendorf, Martinistraβe 52, 20246 Hamburg, Germany. Electronic address: flesch@uke.uni-hamburg.de.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: j.chang-claude@dkfz.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24950597

Citation

Seibold, Petra, et al. "Pre-diagnostic Smoking Behaviour and Poorer Prognosis in a German Breast Cancer Patient Cohort - Differential Effects By Tumour Subtype, NAT2 Status, BMI and Alcohol Intake." Cancer Epidemiology, vol. 38, no. 4, 2014, pp. 419-26.
Seibold P, Vrieling A, Heinz J, et al. Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort - Differential effects by tumour subtype, NAT2 status, BMI and alcohol intake. Cancer Epidemiol. 2014;38(4):419-26.
Seibold, P., Vrieling, A., Heinz, J., Obi, N., Sinn, H. P., Flesch-Janys, D., & Chang-Claude, J. (2014). Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort - Differential effects by tumour subtype, NAT2 status, BMI and alcohol intake. Cancer Epidemiology, 38(4), pp. 419-26. doi:10.1016/j.canep.2014.05.006.
Seibold P, et al. Pre-diagnostic Smoking Behaviour and Poorer Prognosis in a German Breast Cancer Patient Cohort - Differential Effects By Tumour Subtype, NAT2 Status, BMI and Alcohol Intake. Cancer Epidemiol. 2014;38(4):419-26. PubMed PMID: 24950597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort - Differential effects by tumour subtype, NAT2 status, BMI and alcohol intake. AU - Seibold,Petra, AU - Vrieling,Alina, AU - Heinz,Judith, AU - Obi,Nadia, AU - Sinn,Hans-Peter, AU - Flesch-Janys,Dieter, AU - Chang-Claude,Jenny, Y1 - 2014/06/17/ PY - 2014/02/10/received PY - 2014/05/14/revised PY - 2014/05/18/accepted PY - 2014/6/22/entrez PY - 2014/6/22/pubmed PY - 2015/4/4/medline KW - Acetylation status KW - Breast cancer survival KW - Effect modification KW - NAT2 KW - Smoking KW - Tobacco SP - 419 EP - 26 JF - Cancer epidemiology JO - Cancer Epidemiol VL - 38 IS - 4 N2 - BACKGROUND: Inconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking. METHODS: We used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50-74 and diagnosed with invasive tumours 2001-2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed. RESULTS: Overall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93-1.64, and HR 1.29, 95% CI 0.95-1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13-2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60-1.98; Pheterogeneity=0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02-3.65, and HR 2.08, 95% CI 1.40-3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22-10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (<25 kg/m(2): HR 2.52, 95% CI 1.52-4.15 vs. ≥25 kg/m(2): HR 0.94, 95% CI 0.38-2.36; Pheterogeneity=0.04). CONCLUSION: The harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened. SN - 1877-783X UR - https://www.unboundmedicine.com/medline/citation/24950597/Pre_diagnostic_smoking_behaviour_and_poorer_prognosis_in_a_German_breast_cancer_patient_cohort___Differential_effects_by_tumour_subtype_NAT2_status_BMI_and_alcohol_intake_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1877-7821(14)00098-8 DB - PRIME DP - Unbound Medicine ER -