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Systemic therapy for lung cancer has a narrow therapeutic index such that small changes in plasma concentrations or exposure in smokers may result in suboptimal therapy and poor outcomes. Smoking cessation must be emphasized at each clinical visit. However, prospective trials should take into consideration the effects of smoking history on drug pharmacokinetics and efficacy. The metabolizing enzyme phenotype in smokers may require individualized dose algorithms for specific agents.

Background: Chemotherapy-associated neutropenia has been reported to be a pharmacodynamic marker of response in some advanced solid tumors. Factors that accelerate drug clearance lead to lower plasma concentrations and toxicity, including neutropenia. Smoking accelerates the metabolism of several drugs, including chemotherapy. We sought to study the effects of smoking on gemcitabine-induced neutropenia in this retrospective study. Methods: Smoking status and neutropenia along with other clinical parameters were recorded in 151 patients receiving first-line gemcitabine-based chemotherapy for advanced solid tumors. Results: Tumor types included breast (9.3%), lung (4.6%), pancreatobiliary (70.9%), or other/unknown primary cancer (15.2%). Logistic regression showed that never smokers had increased neutropenia versus current smokers (odds ratio: 3.5; 95% confidence interval, CI: 1.1-11.4). A 5-unit increase in pack-years reduced the odds of having higher neutropenia toxicity by 6.3% (95% CI 12 to 1%; p = 0.036). Conclusion: Smokers had less neutropenia than nonsmokers, a finding that was more pronounced with increasing pack-years. This pharmacodynamic marker of gemcitabine-induced neutropenia may result in less efficacy of gemcitabine. Future prospective trials should correlate smoking, metabolizing phenotype, neutropenia, and response to gemcitabine therapy.

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15 Background: Nodal evaluation of the elderly breast cancer patient remains controversial, and some have suggested that selected older women with breast cancer may not require sentinel lymph node biopsy (SLNB). Methods: An IRB-approved database was queried for patients undergoing SLNB for invasive breast cancer from 2000-2006. We compared 8 cohorts: age <40 years, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, and >70 years. Logistic regression and chi-square test were used. Results: Procedure success rate was above 95% for all groups in a total sample size of 1268 patients. Patients >70 years had lower grade tumors than patients <40 years (Grade 1: 25% vs. 7%; Grade 2: 53% vs. 47%; Grade 3: 17% vs. 40%, p<0.0001) and higher ER expression (ER+: 83% vs. 59%, p<0.0005). Patients <40 years also had a higher proportion of multifocal disease (21% vs. 9%, p<0.002), lymphovascular invasion (20% vs. 10%, p<0.007), and number of positive sentinel lymph nodes (PSLN) removed (mean: 3.7 vs. 2.7, p<0.028). Upon multivariate analysis, the odds of a PSLN decrease 9% for every 5-year increase in age (OR 0.91, p<0.003), but increase significantly with certain tumor characteristics (ER+ vs. ER-: OR 1.7, p=0.002), larger size (0.5 cm increase: OR 1.26, p<0.0001), and higher grade (Grades 2-3: OR 1.99, p<0.0007). The predicted probability of a PSLN for patients age 35, 55, and 70 years is 27%, 22%, and 16%, assuming each had a ER+, low grade, 2 cm tumor. Conclusions: Older breast cancer patients have more favorable pathology, and the chance of a PSLN decreases as age increases. However, the odds of a PSLN are significantly higher in patients with certain tumor characteristics, which are known prior to definitive surgery. Given recent reports that older patients are less likely to receive standard treatment for breast cancer and prognosis may worsen as a result, tumor size and characteristics rather than age should dictate the decision to perform SLNB, and we should continue appropriate, aggressive staging of the older breast cancer patient.