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Influence of Smoking History on Breast Cancer Prognosis: Retrospective Study of 240 Operable Breast Cancer Patients Who Received Adjuvant Cyclophosphamide, Doxorubicin, and 5‐Fluorouracil Chemotherapy Regimen

While tobacco use clearly increases the breast cancer risk, little is known about its effect on survival in breast cancer patients (1). There is a complex relationship between smoking and breast cancer. Smoking has an anti-estrogenic effect, reducing premenopausal urinary estrogens (2), elevating postmenopausal androgens (3), inducing an earlier menopause (4). Therefore, theoretically, this addiction could have some favorable effect on breast cancer survival (5). Conversely, smoking is associated with an increased occurrence of hormone receptor negative tumors (6). This could be interpreted as negative effect of smoking on the development of endocrine-responsive tumors. All these information suggest that smoking may induce more aggressive cancer types with a poor prognosis. We retrospectively studied the effect of smoking on the survival in 240 consecutive female patients diagnosed with stage I–III breast cancer and treated with adjuvant cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) ± radiotherapy between January 1990 and December 2000 at Hacettepe University Institute of Oncology. Positive smoking history was defined as smoking more than 1 pack year. Sixty-six (27.5%) patients were either current or former smokers and 174 (72.5%) patients were never-smoker. The mean age of smokers and nonsmokers were 45.1 ± 9.1 and 44.5 ± 9.4, respectively (p = 0.69). The mean cigarette consumption of smokers was 13.5 ± 11.9 (1–50) pack-years. All patients and treatment characteristics including menopausal status, tumor size, lymph nodes, vascular invasion, stage, estrogen and progesterone receptor status, histological grade, stage, radiotherapy treatment, and medical comorbidities were similar in both groups (p > 0.05). All patients received standard 6 cycles of CAF. The median follow-up time was 27.6 months (range: 6–156) for all patients. Of 240 patients treated, 52 (21.6%) patients relapsed. A total of 32 (13.3%) patients died from metastatic breast cancer during follow-up time. The mean DFS was 41.8 ± 4.4 months (95% CI: 33.2–50.4) in smoking group and 92.4 ± 10.7 months in nonsmoking group (p = 0.21). The mean OS was 42.5 ± 4.2 months (95% CI: 34.2–50.9) in smoking group and 110.3 ± 11.7 months (95% CI: 87.2–133.4) in nonsmoking group (p = 0.0069) (Fig. 1). Smokers had a significantly increased risk of death compared with nonsmokers in multivariate Cox regression analysis (hazard ratio 4.0, 95% CI: 1.7–9.3) (p = 0.001). Death risk in patients with ‡4 lymph nodes was 5.5 times more than in patients with <4 nodes in multivariate Cox regression analysis (hazard ratio 5.5, 95% CI: 1.7–17.1) (p = 0.03).