Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec;18(4):378-85.
doi: 10.4048/jbc.2015.18.4.378. Epub 2015 Dec 23.

Risk of Second Primary Malignancy in Breast Cancer Survivors: A Nested Population-Based Case-Control Study

Raffaella Marcheselli  1 , Luigi Marcheselli  1 , Laura Cortesi  1 , Alessia Bari  1 , Claudia Cirilli  2 , Samantha Pozzi  1 , Paola Ferri  1 , Martina Napolitano  1 , Massimo Federico  1 , Stefano Sacchi  1
Affiliations

Risk of Second Primary Malignancy in Breast Cancer Survivors: A Nested Population-Based Case-Control Study

Raffaella Marcheselli et al. J Breast Cancer. 2015 Dec.

Abstract

Purpose: Evolving therapies have improved the prognoses of patients with breast cancer; and currently, the number of long-term survivors is continuously increasing. However, these patients are at increased risk of developing a second cancer. Thus, late side effects are becoming an important issue. In this study, we aimed to investigate whether patient and tumor characteristics, and treatment type correlate with secondary tumor risk.

Methods: This case-control study included 305 patients with a diagnosed second malignancy after almost 6 months after the diagnosis of primary breast cancer and 1,525 controls (ratio 1:5 of cases to controls) from a population-based cohort of 6,325 women. The control patients were randomly selected from the cohort and matched to the cases according to age at diagnosis, calendar period of diagnosis, disease stage, and time of follow-up.

Results: BRCA1 or BRCA2 mutation, human epidermal growth factor receptor 2 (HER2)+ status, chemotherapy, and radiotherapy were related to increased risk of developing a second cancer, whereas hormonotherapy showed a protective effect. Chemotherapy, radiotherapy, and estrogenic receptor level <10% increased the risk of controlateral breast cancer. HER2+ status increased the risk of digestive system and thyroid tumors, while BRCA1 or BRCA2 mutation increased the risk of cancer in the genital system.

Conclusion: Breast cancer survivors are exposed to an excess of risk of developing a second primary cancer. The development of excess of malignancies may be related either to patient and tumor characteristics, such as BRCA1 or BRCA2 mutation and HER2+ status, or to treatments factors.

Keywords: Breast neoplasms; Case-control studies; Human epidermal growth factor receptor 2; Second primary neoplasms.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST: The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Flow-chart of patients included in the analysis, starting from 6,325 women with primary breast cancer recorded by Modena Cancer Registry between 1996 and 2007.
See this image and copyright information in PMC

References

    1. Hortobagyi GN, de la Garza Salazar J, Pritchard K, Amadori D, Haidinger R, Hudis CA, et al. The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer. 2005;6:391–401. - PubMed
    1. De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE: 5-a population-based study. Lancet Oncol. 2014;15:23–34. - PubMed
    1. Cortesi L, De Matteis E, Rashid I, Cirilli C, Proietto M, Rivasi F, et al. Distribution of second primary malignancies suggests a bidirectional effect between breast and endometrial cancer: a population-based study. Int J Gynecol Cancer. 2009;19:1358–1363. - PubMed
    1. Mellemkjaer L, Friis S, Olsen JH, Scélo G, Hemminki K, Tracey E, et al. Risk of second cancer among women with breast cancer. Int J Cancer. 2006;118:2285–2292. - PubMed
    1. Mellemkjær L, Christensen J, Frederiksen K, Pukkala E, Weiderpass E, Bray F, et al. Risk of primary non-breast cancer after female breast cancer by age at diagnosis. Cancer Epidemiol Biomarkers Prev. 2011;20:1784–1792. - PubMed