Prognostic and Predictive Factors in Breast Cancer Relapse. Long-term Retrospective Study in a Cohort of Patients with Invasive Ductal Carcinoma

Background: Serum tumor markers (STM) are still widely used in cancer patients, either in monitoring the response to therapy or in predicting recurrence of the disease. However, only in selected cases they are useful for screening purposes, due to their limited sensitivity. In patients with breast cancer (BC) the most common STM used are carcinoembryogenic antigen (CEA) and cancer antigen 15-3 (CA 15-3). Other useful prognostic markers are estrogen (ER) and progesterone (PR) receptors rate, monoclonal antibody MIB-1 against the Ki-67 proliferating antigen, epidermal growth factor receptor 2 (HER2) status and the expression of p53. The aim of this study was to evaluate relationship between the main prognostic markers in BC women with and without cancer relapse. Patients and Methods: Overall, data from 348 medical charts of women with stage I or IIA (pT1-2, pN0, and M0 at the time of surgery) primary BC (invasive ductal carcinoma in all cases) not requiring adjuvant chemotherapy, who had undergone curative surgery, were retrospectively reviewed. Two groups were considered: Group A (cases), 54 (15.5%) patients with cancer relapse, and Group B (controls), 294 (84.5%) cancer-free patients at ≥60-month follow-up. The following parameters were analyzed: age of the patients, size of the tumor (pT), CEA and CA 15-3 baseline serum levels, MIB-1, ER, and PR rate. Student’s t-test, and Spearman’s correlation coefficient (R) calculation were used to test the results. P<0.05 was considered statistically significant. Results: As expected, there was a significant difference between groups (A vs. B) in age (56.9±12.0 vs. 61.2±12.9, p=0.023), size (20.3±7.3 vs. 16.7±10.2, p=0.014), and ER rate (66.0±12.3 vs. 58.8±17.1, p=0.003), while PR (56.6±19.5 vs. 54.4±17.3, p=0.40) and MIB-1 (22.6±10.6 vs. 21.6±13.3, p=0.58) rates, as well as baseline CEA (6.1±5.8 vs. 6.3±5.0, p=0.79) and CA 15-3 (27.7±13.6 vs. 26.1±12.4, p=0.39) serum levels did not differ (p=NS). In both groups (A; B), a significant correlation between CEA and CA 15-3 (R=0.43, p=0.002; R= 0.29, p=0.0008), and between ER and PR (R=0.37, p=0.003; R=0.52, p<0.0001) was observed. There was no correlation between size and CA 15-3 (R=0.18, p=00.19; R=0.10, p=0.07) or CEA (R=-0.11, p=0.33; R=-0.006, p=0.92), while MIB-1 correlated with age (R=0.37, p=0.003), size (R=0.44, p=0.0004) and CEA (R=-0.37, p=0.003) only in patients with cancer recurrence (Group A). No correlation (p=NS) was found between hormone receptors and CEA, CA 15-3, and MIB-1 in both groups. Conclusions: Our results suggests that (1) baseline STM CEA and CA 15-3 are not useful for prognostic purposes, (2) age, size, and ER are week isolated prognostic factors, and (3) the cumulative risk of relapse increases in the presence of multiple factors, such younger age associated with highest levels of STMs and MIB-1, and low ER rate, together.