The survival rate of Iranian breast cancer patients with focus on prognostic factors

Introduction: Breast cancer is the most prevalent cancer in women. Several studies showed that TNM stage, grade cancer, lymph node involvement, and the status of hormone receptors are the most important factor of breast cancer prognosis. Objectives: To evaluate the clinical characteristics, prognostic factors, and survival rate in patients with breast cancer who underwent surgery in Ahvaz, Southwest of Iran. Patients and Methods: This historical cohort study was conducted on 561 patients who underwent surgery for breast cancer between May 1997 and June 2016. Clinical characteristics, pathological profile, stage, and treatments of the patients were recorded. The prognostic factor, two and five-year overall survival (OS) rates, disease-free survival (DFS) were evaluated by the Cox proportional hazards model and the Kaplan-Meier test, respectively. Results: The two and five-year OS rates were 92.1% and 81.7%, respectively. The most important prognostic factors in breast cancer survival were age, the size of the tumor, regional lymph node involvement, metastasis, stage, relapse, estrogen receptor (ER), progesterone receptor (PR), and hormone therapy. There was no significant relationship between tumor type, tumor site, metastasis, surgery kind, chemotherapy, radiation therapy, and the status of human epidermal growth factor receptor 2 (HER2) and the five-year survival rate. Conclusion: This study showed that the most important factors affecting the high survival rate of patients with breast cancer are hormonal receptors, non-involvement of the lymph nodes, early-stage cancer, no recurrence, and no metastasis.


Introduction
Breast cancer is the leading cause of death due to cancer in women and also the most common cancer identified in women. It is also ranked as the fifth most important cause of mortality (1). The age-standardized incidence rate ( ASR) of breast cancer in Iran was 23.1 per 100 000 populations (2). Fiveyear survival is one of the most important indicators to evaluate the quality of care and treatment in breast cancer. The overall survival (OS) refers to the time between the diagnosis of the disease and the death of the patient or last visit. The survival depends on factors, such as race, socioeconomic status, age, genetic background, and quality of care (3)(4)(5)(6). In a study on 441 breast cancer patients in Iran from 1994 to 2007, the 5and 10-year survival rates were 81% and 77%, respectively (7). In recent years, deaths from this cancer have declined, especially in developed countries (8). However, the survival rate of women with breast cancer in Iran stands between western and eastern European countries (9). Breast cancer is classified according to different histological and clinical criteria for different purposes. The main divisions are based on histological features, tumor grade, tumor staging, receptor status, and gene expression (10). Several studies showed that high cancer grade and its stage, more lymph node involvement, hormone receptor-negative, metastasis, poor socioeconomic status, premenopausal status, different fertility status and high body mass index are factors associated with breast cancer with a poor prognosis (11). It has also shown that breast cancer patients with positive human epidermal growth factor

Key point
In a historical cohort study on 561 patients who underwent surgery for breast cancer between May 1997 and June 2016, we found most important factors affecting the high survival rate of patients with breast cancer are hormonal receptors, noninvolvement of the lymph nodes, early-stage cancer, no recurrence and no metastasis.

Objectives
The aim of our study was to determine the survival rate and its related prognostic factors in patients with breast cancer in Ahvaz, Southwest of Iran.

Study design
This investigation was a historical cohort study conducted on 561 patients who underwent surgery for breast cancer in Ahvaz city between May 1997 and June 2016. Ahvaz city is the province center, the largest city of the Khuzestan province in the southwest of Iran, and also the proper diagnostic and therapeutic facilities are available in the city. Therefore, the patients in this study were those referring to the Khuzestan province and neighboring provinces. The inclusion criteria were all patients with a definitive diagnosis of breast cancer who underwent surgery for breast cancer. The exclusion criteria were patients with incomplete records, lack of follow-up, no access to patients, and lack of consent to participate in the study. The patients' demographic data, including age, gender, and family history and prognostic factors such as tumor characteristics, the status of hormone receptor (ER and PR), HER2 expression, regional lymph node involvement, metastasis, stage, and therapeutic interventions were recorded. Additionally, two and five-year OS and diseasefree survival (DFS), metastasis, and recurrence, were collected based on the patients' medical records and last follow-up using a telephone interview by trained staff and supervised by an expert surgical oncologist.

Statistical analysis
The qualitative variables were expressed as frequency and percentage, whereas quantitative variables were reported as mean ± SD and range. The mean and median of two and five-year OS and DFS in each group of variables were also reported using the Kaplan-Meier method. Then, Cox regression was used to investigate the factors affecting the survival of patients, which examined the significance of variables on survival rate. The P value <0.05 was considered significant. Data were analyzed using SPSS 16 software.

Results
A total of 561 patients were studied, out of the 557 patients (99.3%) were female and others were male with the mean age of 53.27 ± 12.29 years (age range, 27-90 years) with most cases (58.2%) being 40-60 years. The most common breast complaints were breast mass (87.0%) followed by pain, nipple discharge, ulcer, edema, dimpling, and thickening of the skin, respectively. In addition, 46.4% of the patients had right breast cancer, 51.8% left breast cancer, and others  (Figures 1 and 2; Table 3). It seems that recurrence and cancer staging is the most important prognostic factors in survival rate. Other results of our investigation indicated that the regional lymph node involvement (HR = 4.86, 95% CI: 1.84-12.88, P = 0.001), larger tumor size (P < 0.001), negative ER (P = 0.03), negative PR (P = 0.008) play a key role in the prediction of poor survival rate in breast cancer patients (Table 3) (Table 3).

Discussion
Disease survival is an important indicator that helps physicians and policymakers identify appropriate prognosis rates, and employ appropriate methods to prevent and treat the disease.  (19). These rates are somewhat less than the survival of our patients, which may be due to the different settings of studies,   especially different stages of breast cancer patients at the time of diagnosis. Therefore, in our study, the five-year survival rate from stage I to IV cancer was 92.0%, 90%, 73.0%, and 52.0%, respectively, with the lowest survival rate in cases with stage IV cancer (HR = 14.58%). In this study, lymph node involvement, negative hormone receptor, metastasis, T3 and T4 tumors, and recurrence of the disease were important factors that significantly reduced survival in patients, which has been confirmed in other studies (11). Lymph node involvement increased the risk of death by 4.86 times which is confirmed in other studies (20). Likewise, patients with hormone receptorpositive tumors (ER+ and PR+) had a significantly higher five-year survival compared with those with hormone receptor-negative tumors. In general, the status of hormone receptors is one of the most important prognostic and preventive factors of cancer, which has been confirmed in other studies (11,(21)(22)(23)(24)(25).
Considering the factors affecting the survival of patients, the five-year survival rate in cases with and without chemotherapy was 86% and 82%, and 84% and 82% in cases with and without radiotherapy, respectively. No significant relationship was found between these values. Also, in other studies, the positive effect of radiotherapy and chemotherapy on survival has sometimes been rejected (17,23) or confirmed (11,24). This inconsistency in different studies could be due to different treatment options by physicians for adjuvant treatment, patients' personal opinions, or differences in health care facilities (18). Regarding tumor type, the five-year survival in invasive ductal carcinoma, invasive lobular carcinoma, and other types was 80%, 78%, and 89%, respectively. Accordingly, no significant relationship was found between tumor type and survival (20). Besides, no significant relationship was found between surgical methods and survival (26). Although in our study there was no association between tumor site and survival, in a study among Egyptian patients despite right-sided tumors seemed more aggressive, Leftsided ones tend to confer worse survival than right-sided tumors (27). Regarding age at diagnosis, there was no significant difference in survival (20) although there is a controversy pointed out in the literature regarding its effect on the prognosis of the disease (28,29).
It is worth saying the impact of some prognostic factors on breast cancer survival has been shown to vary with time since diagnosis (30).

Conclusion
The results of this study showed that the most important factors affecting the high survival rate of patients with breast cancer include the existence of hormonal receptors (ER+, PR+), no involvement of lymph nodes, early-stage disease, and no recurrence. In our country, due to the correct and timely diagnostic process and timely surgical treatment, and optimal use of adjuvant treatments, patients are in a better condition and have a longer life expectancy compared to other developing countries. The lifespan of our patients is similar to western countries and in some cases, it is even better than theirs. Although, the need for further use of appropriate methods for the prevention and early treatment of breast cancer and the subsequent follow-up is mandatory.

Study limitations
The lack of access to all patients' records, not answering the phone to complete the data by patients, the relatively small sample size, missing some patients in the follow-up, and unawareness of some patients about the treatment process were the limitations of this study.