br The Mean CRP levels for patients and controls were

The Mean CRP levels for patients and controls were 1.50 ± 1.37 and 0.58 ± 0.55, respectively. Range of CRP was 0.2-6.5 mg/dl and 0-2.6 mg/dl in patients and controls respectively. The levels of CRP were significantly elevated in breast cancer patients in comparison with controls (Table 2) and showed a significant association with the disease (P < 0.0001). The distribution of patients possessing high, moderate, and normal levels has been given in Table 3. There was a signifi-cant difference in these levels between the patients and controls (Table 3). There was significant association of high CRP levels with progesterone (P < 0.02) but CRP levels did not show any significant association with ER and HER2 receptor subtypes (P > 0.05). A significant association of infiltrating ductal carcinoma and triple negative breast cancer with moderate and high lev-els of CRP was also observed (P < 0.05 in each case). CRP levels associated significantly with body mass index (obese vs underweight: P < 0.05) among breast cancer patients. However, no significant association was observed in obese vs normal and normal vs underwight (P > 0.05). Patients were divided into 3 groups based on their age that is 20-40, 40-60, and 60-80 years. High and moderate levels of CRP associated significantly with the age groups 40-60 and 60-80. However, we could not apply Mann-Whitney test on the patients belonging to the age group 20-40 as number of patients was less (only 5) in this group. There was no significant difference in the CRP levels between the pre and postmenopausal breast cancer patients. The breast cancer cases had Grade 2 (69%) or Grade 3 (27%). However, none of the patients were found to be in Grade 1. r> As per follow-up interviews metastasis and recurrence was observed in 28% of patients fol-lowed by death in 26% of cases. Disease free survival was observed in 76% of patients after 1 year of follow-up. However, this was observed to be 72% at the last follow-up. As far as overall survival is concerned 87% of patients were alive for 1 year after disease detection but this num-ber dropped to 74% an account of death, recurrence, and metastasis at the end of 27 months follow-up. Death rate associated significantly with high levels of CRP [P = 0.02; 95% CI; odds ratio: 2.75 (0.9868-7.664)]. Poor outcome that is metastasis and recurrence was found to be associated significantly with high levels of CRP [P = 0.03; 95% of CI; odds ratio: 2.954 (0.9125-9.561)].
Discussion
Several studies in different populations have demonstrated that CRP levels may be associ-ated with poor prognosis of different types of solid cancers like colorectal, cervical, pancre-atic, prostate, ovarian, and Trichostatin A cancer.14–17 Emerging evidence suggests that inflam-mation pathway plays a major role in the breast cancer progression in spite of the fact that breast cancers are rarely characterized by significant histologic inflammation. A recent study published by Wang et al, has demonstrated the role of established prognostic markers including carcinoembryonic antigen, cancer antigen-15.3, cyclopentyladenosine, Tissue polypeptide specific antigen (TPS), and interleukin-6 in breast cancer. This study reported decreased sensitivity and specificity of each marker and advised that combination of 2 makers can be used to assess the poor outcome among patients.18 However, in comparison to these markers CRP assessment is a simple and inexpensive prognostic marker in breast cancer.19 Several epidemiological studies have also demonstrated the association between CRP and breast cancer risk.3,8 However, there have been discrepancies in results of different studies evaluating the association of CRP with breast cancer in various ethnic groups.8,9 Some studies have shown an association of elevated CRP and poor prognosis whereas others did not find an association.2,20,21 The largest study was carried out by Guo et al, involving a total of 5286 breast cancer patients. This meta-analysis indicated that increased CRP levels are associated with increased risk of breast cancer.2
Pierce et al, carried out a meta-analysis including 700 women who were treated successfully for early stage breast cancer and reported that elevated CRP levels, measured after 2 years and 6 months of diagnosis of the disease, were associated with reduced overall survival and disease-free.22 Another study has reported elevated CRP levels at the time of diagnosis of breast cancer to be associated with reduced overall and disease fee survival and with increased death from breast cancer.8 In the present study we found that the levels of CRP were significantly elevated in breast cancer patients at the time of diagnosis (P < 0.0001) in comparison with healthy con-trols. There was a significant difference in CRP levels between patients belonging to different age groups. The variation in CRP levels among breast cancer patients belonging to different age groups has not been evaluated previously. However, a study involving gastric cancer patients re-ported an elevated level of CRP in patients belonging to older age group.23 Evaluating the associ-ation of elevated CRP with various histologic subtypes that is infiltrating lobular and infiltrating ductal, we found that elevated CRP levels associated significantly with infiltrating ductal carci-noma as well as progesterone receptor but no significant association of elevated CRP levels with other receptor subtypes (ER/HER2) was observed. This is in contradiction with the recent study that reported a significant association of ER receptor status with elevated CRP levels.24 However, this study was carried out involving only 60 breast cancer patients and therefore, needs to be confirmed involving a larger cohort of patients.