Risk factors of breast cancer relapse. A case-control study and results of multivariate analysis in a cohort of 348 patients who underwent curative surgery

Background: Breast cancer (BC) is the first leading cause of cancer-related deaths in women, and a major public health problem, especially in western countries. All patients with BC may potentially develop disease progression and will thus need an effective lifelong follow-up. The aim of this study was to assess the overall weight of the main demographics, pathological and biochemical parameters considered as risk factors (RFs) for cancer relapse, obtained from a population of BC patients followed up for at least 60 months. Patients and Methods: We retrospectively reviewed data regarding a series of 348 consecutive women (median age, 60 years, range 28-85 years) who underwent curative surgery for pT1-2, N0-1 (stage I and IIA) invasive ductal breast carcinoma. During five-year follow-up, 54 (15.5%) patients developed cancer relapse (cases), while 294 (84.5%) were cancer-free (controls). In both groups, the analysis was restricted to women who gave complete information. Final pathology defined the size of the tumor (pT), and axillary lymph node involvement (N+). Baseline carcinoembryogenic antigen (CEA, ng/mL) and cancer antigen 15-3 (CA 15-3, U/mL) serum levels were measured by automated testing using a two-site enzyme-linked immunosorbent assay. Both ER and PR were assayed using a quantitative standard immunoenzymatic method and results were expressed as percentage of positivity in the overall cell population. Immunostaining of the Ki-67 antigen was performed using the monoclonal antibody MIB-1 using a microwave antigen retrieval technique, and the MIB-1 labeling index was expressed as a percentage. For each parameter, the number of cases considered as positive were those above the median value. Odds ratio (OR) estimates and the associated 95% CI were obtained, and the significance level was set at p<0.01. Results: As expected, older (>60 years) age (OR=0.82, 95% CI 0.46-1.47, p=0.51), and high ER (OR=0.29, 95% CI 0.24-0.78, p<0.0001) and PR (OR=0.43, 95% CI 0.24-0.78, p=0.005) rate were protective (OR<1) factors, while only axillary node positivity (OR=8.05, 95% CI 4.29-15.0, p<0.0001) and high MIB-1 rate (OR=2.28, 95% CI 1.27-4.11, p=0.006) represented the two statistically significant RFs for cancer recurrence. Size (OR=1.25, 95% CI 0.70-2.25, p=0.44), and CEA (OR=1.05, 95% CI 0.66-2.07, p=0.62) and CA 15-3 (OR=1.27, 95% CI 0.71-2.27, p=0.42) baseline serum levels were not significantly related to cancer recurrence. Conclusions: In this population, axillary node negativity and ER positivity were the most sensitive RFs for cancer recurrence at long-term follow up, while MIB-1 labeling index and PR rates were weak RFs.