Estrogen receptor status in relation to risk of contralateral breast cancer-a population-based cohort study

Abstract

Background: It is unclear whether estrogen receptor (ER)-status of first primary breast cancer is associated with risk of metachronous (non-simultaneous) contralateral breast cancer (CBC), and to what extent endocrine therapy affects this association.

Methods: We studied the effect of ER-status of the first cancer on the risk of CBC overall, and for different ER-subtypes of CBC, using a large, population-based cohort. The cohort consisted of all women diagnosed with breast cancer in the Stockholm region 1976-2005; 25715 patients, of whom 940 suffered CBC. The relative risk was analyzed mainly using standardized incidence ratios (SIR).

Results: Women with breast cancer had a doubled risk of CBC compared to the risk of breast cancer in the general female population (SIR: 2.22 [2.08-2.36]), for women with a previous ER-positive cancer: SIR=2.30 (95% CI:2.11-2.50) and for women with a previous ER-negative cancer: SIR=2.17 (95% CI:1.82-2.55). The relative risk of ER-positive and ER-negative CBC was very similar for women with ER-positive first cancer (SIR=2.02 [95%CI: 1.80-2.27] and SIR=1.89 [95%CI: 1.46-2.41] respectively) while for patients with ER-negative first cancer the relative risk was significantly different (SIR=1.27 [95% CI:0.94-1.68] for ER-positive CBC and SIR=4.96 [95%CI:3.67-6.56] for ER-negative CBC). Patients with ER-positive first cancer who received hormone therapy still had a significantly higher risk of CBC than the risk of breast cancer for the general female population (SIR=1.74 [95% CI:1.47-2.03]).

Conclusion: The risk of CBC for a breast cancer patient is increased to about two-fold, compared to the risk of breast cancer in the general female population. This excess risk decreases, but does not disappear, with adjuvant endocrine therapy. Patients with ER-positive first cancers have an increased risk for CBC of both ER subtypes, while patients with ER-negative first cancer have a specifically increased risk of ER-negative CBC.

Figure 1. Nelson –Aalen plots.

Cumulative incidence of CBC for women with ER-negative vs. ER-positive first breast cancer. Panel A shows the cumulative incidence of CBC of any ER-subtype by ER-status of the first cancer. The p-value for the log-rank test of cumulative incidence of CBC overall was 0.338, thus the cumulative incidence of CBC did not differ between patients with ER-positive vs. ER-negative first primary breast cancer. Panel B shows the cumulative incidence of ER-positive and ER-negative CBC by ER-status of the first cancer. (The p-value for the log-rank test of cumulative incidence of ER-positive CBC show significant difference between patients with ER-positive vs. ER-negative first breast cancer (P-value = <0.001) and similarly the p-value for the log-rank test of cumulative incidence of ER-negative CBC also show significant difference between patients with ER-positive vs. ER-negative first breast cancer (P-value = <0.001). See Table 5 for number of women at risk.