The risk of second primary lung carcinoma in breast cancer patients

Abstract: The overall aim of this thesis was to investigate the risk of second primary malignancies - with a special focus on lung cancer - in a cohort of approximately 152,000 Swedish women diagnosed with breast cancer between 1958 and 2000. With recent advances in early diagnosis and treatment, breast cancer is becoming an increasingly survivable disease. Women with breast cancer normally receive post surgical adjuvant therapy, either as radio-, chemo-, or hormonal therapy, or as a combination of any of those modalities. Adjuvant radiotherapy reduces the risk of local recurrence, and its use is increasing as more women today choose partial mastectomies as their surgical choice. However one of the growing concerns is the chronic or late-occurring complications to the normal tissue from treatment of primary malignancies, among them therapy-related second primary cancer. We found a statistically significant increased risk of second primary lung cancers more than 5 years after breast cancer diagnosis. The highest risk of a second primary lung cancer was observed among women <50 years of age at the time of breast cancer diagnosis. The risk of lung cancer increased with time between breast cancer diagnosis and the diagnosis of second primary lung cancer, independently of the age at breast cancer diagnosis. In addition, the risk of lung cancer increased with birth year cohort, which mirrors the increasing smoking prevalence seen among women in Sweden. The completeness and quality of the information on tobacco use is most important when studying the risk of lung cancer. We contacted next-of-kin and living patients by mailed questionnaire to validate the quality of smoking information of the studied patients given in patient records. The total response rates were 89% and 93% for next-of-kin and living patients respectively. When information about overall smoking history from patient records and next-ofkin was compared, an almost perfect agreement was found (kappa=0.83), and similar result was found for living patients (kappa=0.86). Our results demonstrated that next-of-kin data are reliable and that the time between patient death and contact with next-of-kin did riot affect the response rate nor the agreement. Patient records and radiotherapy charts were abstracted for detailed information about treatment for 182 cases. Information about smoking history was identified in patient records or retrieved from nextof-kin. Our results demonstrated that in women treated with radiotherapy the risk of lung cancer increased after a follow-up time of more (ban 15 years. This risk was mostly confined to squamous cell carcinomas. In addition, the increased risk was restricted to women who smoked at the time of radiotherapy. Notably, non smoking women who received radiotherapy were not found to have an increased risk of lung cancer. The estimated excess relative risk for women with follow-up time >10 years after radiotherapy for breast cancer was 0.11 per gray. Women previously diagnosed with breast cancer have a 20% increased risk of a second primary malignancy except breast cancer. The overall risk for second primary malignancy did not vary by follow-up period, but large differences were noted between individual cancer sites, probably reflecting different etiologies. Women with a breast cancer diagnosis before the age of 50 years and women with a family history of breast cancer had elevated risks of developing a number of second primary cancers indicating a genetic predisposition to develop multiple tumours and/or susceptibility to the carcinogenic effect of breast cancer therapy. In conclusion, we have been able to establish an association between radiotherapy, smoking and risk of second primary lung cancer. We have shown that next-of-kin can provide reliable information on lifetime smoking status and should be considered as a valuable resource in studies where information on tobacco use is missing. We confirmed that women diagnosed with breast cancer have increased risks of most second primary malignancies. Finally, we showed that family history of breast cancer as well as young age at the time of breast cancer diagnosis increases these risks.