Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)

Fulvio Ricceri, Francesca Fasanelli, Maria Teresa Giraudo, Sabina Sieri, Rosario Tumino, Amalia Mattiello, Liliana Vagliano, Giovanna Masala, J. Ramõn Quirõs, Noemie Travier, María José Sánchez, Nerea Larranaga, María Dolores Chirlaque, Eva Ardanaz, Anne Tjonneland, Anja Olsen, Kim Overvad, Jenny Chang-Claude, Rudolf Kaaks, Heiner BoeingFrançoise Clavel-Chapelon, Marina Kvaskoff, Laure Dossus, Antonia Trichopoulou, Vassiliki Benetou, George Adarakis, H. Bas Bueno-De-Mesquita, Petra H. Peeters, Malin Sund, Anne Andersson, Signe Borgquist, Salma Butt, Elisabete Weiderpass, Guri Skeie, Kay Tee Khaw, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Marc Gunter, Mai Kadi, Elio Riboli, Paolo Vineis, Carlotta Sacerdote

Research output: Contribution to journalArticlepeer-review


Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval - CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. What's new? For the first time, researchers have used cohort data to show that people who survive breast cancer have a higher risk of developing another cancer later. By collecting data on 10,000 breast cancer patients over 11 years, these authors calculated a 30% boost in the patients' risk of developing a second primary malignancy, particularly colorectal cancer, lymphoma, melanoma, endometrial cancer, and kidney cancer. These findings, plus the data they collected on risk factors such as age, smoking, body mass index, and others, will help guide clinicians in screening procedures and follow up care for breast cancer patients.

Original languageEnglish
Pages (from-to)940-948
Number of pages9
JournalInternational Journal of Cancer
Issue number4
Publication statusPublished - Aug 15 2015


  • Aalen-Johansen estimator
  • breast cancer
  • second primary tumours
  • tumour size

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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