Concordance in Hormone Receptor Status between First and Second Breast Cancers.
Authors: Huo D. , Melkonian S. , Rathouz P. , Khramtsov A. , Olopade O. 
Published: December 2010

Abstract
Background: Women with breast cancer are more likely to have second breast cancer. It is uncertain on the biologic relationship between the two tumor lesions. Whether the second cancer represents an independent second primary versus recurrent or metastatic disease has implications in both cancer treatment and understanding of carcinogenesis. This study was conducted to evaluate the concordance of estrogen receptor (ER) and progesterone receptor (PR) status, and examine factors that influence the concordance. This study also examined whether there is a difference in the proportion of hormone receptor positivity between two breast cancers.Methods: 37,362 patients with diagnoses of two breast cancers between 1990 and 2006 were identified through 17 cancer registries of the Surveillance, Epidemiology, and End Results program. Logistic regressions were used to assess the association in hormone receptor status between two cancers. Odds ratios (OR) and 95% confidence interval (CI) were used to indicate the strength of association. Conditional logistic regressions were used to examine the change in proportion of hormone receptor positivity.Results: The two breast cancers were contralateral in 79% of patients and ipsilateral in 21% of patients. There was a strong association in ER status between two tumors, with OR of 17.8 (CI: 14.2-22.3) for ipsilateral pairs and 8.85 (CI: 8.08-9.69) for bilateral pairs. The strength of association in ER status depended on lag interval between first and second tumor. In patients with ipsilateral cancers, the OR was 170 for synchronous tumors (&lt;1 month) and 6.6 for metachronous cases separated by 5 years or longer. In patients with contralateral cancers, the corresponding OR was 31.5 and 4.12. The strength of association also depended on age at diagnosis. In patients with contralateral cancers, the OR was 11.7 and 7.03 for patients with first breast cancer diagnosed before and after 50 years old, respectively. There was also a strong association in PR status between two tumors, with OR of 8.39 (CI: 6.95-10.1) for ipsilateral pairs and 4.84 (CI: 4.48-5.24) for bilateral pairs. The ER positive proportion in second tumors occurred within 1 year was similar to that of first tumors. However, compared with the first tumors, the odds of ER positivity was decreased by 47% and 21%, respectively, in second ipsilateral and contralateral breast cancers occurred 1-5 years after first tumors.Conclusions: Hormone receptor status of the primary breast cancer is strongly predictive of that of the second breast cancer, occurred either in the same or in contralateral breast, and the predictive value was very good even after 5 years. These findings suggest that two breast cancers of the same patient arise in a common predisposing milieu, which is probably predetermined by genetic makeup and/or environmental exposures in early life. The second cancer occurred after 1-5 years was more likely to be hormone receptor negative compared with the first cancer, suggesting that treatment for the first cancer, possibly tamoxifen, can modify the expression of subsequent breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4144.