The widespread use of mammography, a form of breast imaging using low-dose x-rays, for early detection of breast cancer, has contributed to the increase in newly diagnosed women with in situ breast cancer. Women with in situ breast cancer have localized, non-invasive cancer that is only found in the breast; more than 63,000 patients are diagnosed with this cancer every year in the United States. Despite having early stage breast cancer and effective treatment options, these women are at a significantly higher risk of developing a second primary breast cancer, a new cancer that is different from the first in situ cancer, though current epidemiological evidence is limited in its ability to draw firm conclusions. Family history of breast cancer has been reported to be associated with risk of in situ and invasive breast cancer. However, little is known about the relationship between family history of breast cancer and risk of second primary breast cancer among in situ breast cancer survivors. As the numbers of newly diagnosed in situ breast cancer patients continue to increase, there is a pressing need to identify factors associated with second breast cancer events so that risk prediction and prevention strategies can be developed. Furthermore, very little is known about why some women with in situ breast cancer develop second primary breast cancers later on.
To address these crucial issues, Drs. Michelle Baglia and Christopher Li (Public Health Sciences) and Dr. Peggy Porter (Human Biology), and their colleagues evaluated the association between first degree family history of breast cancer and the risk of developing a second in situ or invasive breast cancer using a nested case-control study of women previously diagnosed with in situ breast cancer. Included in the study were 539 cases with a second primary breast cancer and 994 matched controls. The results of this study were published in the journal Cancer Epidemiology, Biomarkers and Prevention, and definitively showed that first degree family history of breast cancer may be an important risk factor. Additionally, in situ breast cancer patients had an even greater risk of developing a second primary breast cancer if they had two or more affected first-degree family members, or whose affected relative was less than 50 years old.
Figure provided by Yiting Lim
When patients were stratified according to menopausal status, there was no difference in risks associated with number or age of affected relatives. When stratified for presence or absence of the estrogen receptor, associations between first degree family history of breast cancer and risk of developing a second primary breast cancer were only observed among women positive for the estrogen receptor. The authors did not observe any differences in risk when patients were stratified by treatment for in situ breast cancer, laterality of the second breast cancer, or the carcinoma histology of in situ cancer.
This study represents the most comprehensive, population-based study of in situ breast cancer survivors for examining risk factors for developing second breast cancers, and identified first degree family history of breast cancer to be an important risk factor. Given that survival rates for in situ breast cancer patients are very high, some patients who may not develop second breast cancers may be over-treated by current clinical care standards. On the other hand, as there is currently no way to determine which patients will have future breast cancer diagnoses and may benefit from early treatment, identifying risk factors for second breast cancers among in situ breast cancer patients will have the potential to significantly improve clinical decision making and surveillance.
Image provided by Dr. Peggy Porter
Dr. Peggy Porter further explained: “Although the result is not surprising given that a few smaller studies have indicated a similar association between family history and second cancers, this study has the advantage of including large numbers of primary and second cancers. This allowed us to assess the relationship of many risk factors and the development of a second cancer after a diagnosis of in situ breast cancer. The emergence of family history as a contributing factor to second cancers strengthens our understanding of this association and has potential to affect patient counseling about their risk of future disease.” When asked about next steps, Dr. Porter revealed: “Data from this large study continue to be collected and analyzed. My lab is performing gene expression studies to identify molecular features of ductal carcinoma in situ that are associated with second cancers.”
Baglia ML, Tang MC, Malone KE, Porter P, Li CI. 2018. Family history and risk of second primary breast cancer after in situ breast carcinoma. Cancer Epidemiol Biomarkers Prev. 27(3); 315-20 doi:10.1158/1055-9965.EPI-17-0837
Funding was provided by the National Cancer Institute.
This study was a Cancer Consortium collaboration between the Fred Hutchinson Cancer Research Center and the University of Washington, led by Kathleen Malone, Peggy Porter and Christopher Li.