1. Reduced Lung Cancer Mortality Risk Among Breast Cancer Patients Treated With Anti- Estrogens Rapiti E et al. SABCS 2009;Abstract 35.

2. Introduction Women in the post-intervention period of the Women’s Health Initiative (WHI) trial who were assigned to combined hormone replacement therapy had a higher risk of cancer compared to those on placebo (JAMA 2008;299:1036). Post-hoc analysis of the WHI trial demonstrated increased lung cancer mortality in women administered postmeno- pausal hormone replacement therapy of estrogen with progesterone versus placebo (Lancet 2009;374:1243). –73 (0.11%) versus 40 (0.06%) deaths (hazard ratio=1.71, p=0.01) Current study objective: –Assess if anti-estrogen therapy in patients with breast cancer is associated with a decreased lung cancer mortality risk. Rapiti E et al. SABCS 2009;Abstract 35.

3. Methods Study group of 6,655 patients diagnosed with breast cancer between 1980 to 2003 were identified from the Geneva Cancer Registry. –Patients having received anti-estrogens: 3,066 (46%) Lung cancer incidence and mortality were followed until December 31, 2007, and were compared to age-, sex- and period-adjusted population rates using: –Standardized incidence ratios (SIRs) –Standardized mortality ratios (SMRs) Subgroup analyses performed by period and smoking history. –Prior to 1990, women were less likely to have been administered anti-estrogen therapy, and related data on smoking history were limited. Rapiti E et al. SABCS 2009;Abstract 35.

4. Smoking History of Study Population Versus General Female Population Smoking History Anti-Estrogen Use General Female Population* Yes (n=2,105) No (n=1,217) Smoker30%29% Ex-smoker14%13%16% Non-smoker57%58%55% *Enquête sur la Consommation de Tabac en Suisse. Rapport 2001/2002. Zurich University 2003. Rapiti E et al. SABCS 2009;Abstract 35.

5. Risk of Developing Lung Cancer After Breast Cancer All Patients Anti-estrogen therapy Incidence rates* Observed cases Expected cases SIRp-value Yes55.41219.10.630.058 No78.82825.01.120.294 Patients Diagnosed from 1990 Anti-estrogen therapy Incidence rates* Observed cases Expected cases SIRp-value Yes56.71117.20.640.123 No79.8119.91.110.491 Rapiti E et al. SABCS 2009;Abstract 35. *Age-standardized (Geneva population distribution) incidence rates per 100,000 person-years.

6. Risk of Death From Lung Cancer After Breast Cancer All Patients Anti-estrogen therapy Mortality rates* Observed cases Expected cases SMRp-value Yes9.2215.30.13<0.0001 No45.01621.10.760.158 Patients Diagnosed from 1990 Anti-estrogen therapy Mortality rates* Observed cases Expected cases SMRp-value Yes10.3213.30.15<0.001 No36.257.70.650.340 Rapiti E et al. SABCS 2009;Abstract 35. *Age-standardized (Geneva population distribution) mortality rates per 100,000 person-years.

7. Conclusions Patients treated with anti-estrogens for breast cancer have a significantly reduced risk of death from lung cancer compared to the general population. Residual confounding cannot be excluded due to the observational nature of the study. This study further supports the hypothesis that estrogen plays a role in lung cancer prognosis. Rapiti E et al. SABCS 2009;Abstract 35.