Contralateral breast cancer : risk and prognosis

The objective of this thesis was to investigate different aspects of contralateral breast cancer. This disease is of increasing importance as the mortality of breast cancer is decreasing while the incidence remains very high, consequently the population at risk for non-simultaneous (metachronous) contralateral breast cancer is increasing. Further, both simultaneously occurring (synchronous) contralateral breast cancer and non-simultaneous (metachronous) contralateral breast cancer have a worse prognosis than breast cancer in general. The population-based cohort used in all four studies includes all patients diagnosed with contralateral breast cancer in the Stockholm region during 1976-2005 (N=1422).

In the first paper, which investigates the timing of diagnosis of contralateral breast cancer, we conclude that the diagnostic work-up has not improved over the last 25 years; the second cancers are neither found earlier, nor at smaller tumor size. In our second study we investigate the effect of adjuvant radiotherapy for the first breast cancer and conclude that radiotherapy seems to worsen tumor characteristics (TNM-stage and differentiation grade) and prognosis after contralateral breast cancer. In analyzing estrogen receptors of the two breast tumors we, in our third study, show how estrogen receptors of both tumors taken together have an important prognostic value. We also find several indications of endocrine therapy resistance in patients with two metachronous estrogen receptor positive tumors. The fourth and final study investigates mammographic density as a risk factor for contralateral breast cancer, studying both mammographic density at diagnosis of the first cancer and changes in density following the first cancer. We find no effect on the risk of contralateral breast cancer by mammographic density at the time of diagnosis of the first cancer; however, there is a significant risk decrease for patients who experience a decrease in breast density during follow-up after the first cancer.

List of scientific papers

I. Diagnostic work-up of contralateral breast cancers has not improved over calendar period. Maria EC. Sandberg, Mikael Hartman, Gustaf Edgren, Sandra Eloranta, Alexander Ploner, Per Hall, Kamila Czene. Breast Cancer Res Treat. 2010 Aug; 122(3):889-95.
https://doi.org/10.1007/s10549-010-0748-8

II. Aggressiveness of contralateral breast cancer is influenced by radiotherapy for the first tumor. Maria EC. Sandberg, Sara Alkner, Mikael Hartman, Sandra Eloranta, Lisa Rydén, Alexander Ploner, Hans-Olov Adami, Per Hall, Kamila Czene. [Submitted]
https://doi.org/10.1002/ijc.27890

III. Prognostic implications of estrogen receptor pattern of both tumors in contralateral breast cancer. Maria EC. Sandberg, Mikael Hartman, Daniel Klevebring, Sandra Eloranta, Alexander Ploner, Per Hall, Kamila Czene. Breast Cancer Res Treat. 2012 Jul; 134(2):793-800.
https://doi.org/10.1007/s10549-012-2096-3

IV. Change of mammographic density predicts the risk of contralateral breast cancer. Maria EC. Sandberg, Jingmei Li, Per Hall, Mikael Hartman, Isabel dos-Santos-Silva, Keith Humphreys, Kamila Czene. [Submitted]
https://doi.org/10.1186/bcr3451