Epidemiological and pathological characteristics of post-surgical cases of invasive breast cancer among ethnicities of Iran in 2018: A single center cross-sectional study

Mazani, Sistanei, Turk/Azeri, etc.), familial history of breast cancer (in first or second degree relatives), type of cancer (invasive ductal carcinoma or invasive lobular carcinoma), stage of cancer (stages 1-4, based on TNM SUMMARY Background: Present study aimed to investigate immunohistochemical parameters in post-surgical cases of invasive breast cancer. Methods: In this single center cross-sectional study we investigated ethnicity, familial history, type of cancer, stage of cancer, lymph node positivity, bilateral involvement, metastasis and immunohistochemical parameters (estrogen and progesterone receptor, human epidermal growth factor receptor 2, as well as frequency of triple positive and triple negative patients merely based on immunohistochemical parameters). Results: Frequency of positive familial history was 27.42% (16.31-38.52%). Lymph node involvement was detected in 55.93% (43.26-68.60%) of the cases. Frequency of positive HER2 was 38.60% (25.96-51.23%). There were 17.54% (7.67-27.42%) of triple positive and 7.02% (0.39-13.65%) of triple negative cases. The most common stage at the time of diagnosis was stage 3 with 43.33% (30.79-55.87%) frequency. In Lur/Lak population higher frequency of positive HER2 cases was detected whereas in Mazani population frequency of positive HER2 cases was low (p=0.0291). Conclusions: These results could contribute to understanding of breast cancer patterns among different ethnicities. In order to draw clear conclusion future investigations have to be done in several health centers, for longer time periods and with larger number of patients.


Background
Breast cancer is the most common solid malignancy in women in Iran. Reported incidence in 2009 was 24 per 100000 (1). The data obtained from National cancer registry of Iran in 2015 reported incidence of 22.1-23.1 per 100000 for 10-year period. This type of cancer covers 24.6% of all female cancers in Iran. In the national cancer registry report there was no information on staging or immunohistochemical (IHC) results of breast cancer patients (2). One of breast cancer studies in Iran suggested that different provinces have different relative risks and therefore therapy, education and screening should rely on different policies (3). A data mining study performed on 3010 breast cancer patients from 1998 to 2014 indicated that typical Iranian breast cancer patient was a 40-50 year old married women with two children, mostly diagnosed at stage 2 of the disease (4). Akbari et al. investigated 313 Iranian patients with early or late recurrence of breast cancer. This study indicated that the most common site of recurrence was bone (27.4%) followed by local recurrence (21.4%). Increased hazard ratio of recurrence was observed in cases when patients were <40 years old, with stage 3 of the disease, and positive lymphovascular invasion and lymph node involvement. However, human epidermal growth factor receptor 2 (HER2) positivity was not associated with risk of recurrence (5). Breast cancer screening and early detection can reduce mortality and recurrence rate (6). The screening and early detection methods are selfexamination, clinical examination and mammography. Studies showed that early detection methods were not common among Iranian women, and therefore education has been suggested (7,8). One of the most common complications and cause of morbidity in breast cancer patients was lymphedema. Education and training of patients has been suggested to increase quality of life (9, 10).
Pathology wise, most common breast cancers are ductal or lobular carcinomas. Breast sarcoma and lymphoma are rare types of breast malignancies (11). Evaluation of the most common immunohistochemical markers like estrogen receptor (ER), progesterone receptor (PR) and HER2 has opened a door for personalized medicine in breast cancer (12).

Objectives
In the registry-based articles on epidemiology of breast cancer in Iran some clinical and pathological characteristics such as IHC results have not been included. Therefore, the present study aimed to investigate these parameters from post-surgical cases of invasive breast cancers among different ethnicities of Iran during year 2018 using data from referral Firoozgar Clinical Research Development Center (FCRDC). The investigated parameters were ethnicity, familial history of breast cancer, type of cancer, stage of cancer, lymph node positivity, bilateral involvement, metastasis and IHC results, as well as frequency of triple positive and triple negative patients based on IHC.

Study design and samples
The present research is a single center cross-sectional study. The samples were from invasive breast cancer patients who referred to Firoozgar Clinical Research Development Center (FCRDC) for post-surgical follow up during 2018.

Items and definitions
The investigated items were ethnicity (Fars, Arab, Gilak, Lur/Lak, Mazani, Sistanei, Turk/Azeri, etc.), familial history of breast cancer (in first or second degree relatives), type of cancer (invasive ductal carcinoma or invasive lobular carcinoma), stage of cancer (stages 1-4, based on TNM staging), lymph node positivity (involvement of at least one lymph node like sentinel lymph node in permanent slide), bilateral involvement (at the same time or recurrence, and both should be invasive), metastasis (based on bone scan or magnetic resonance imaging, MRI) and IHC positivity (ER and PR with any percentage, HER2 with 1, 2 or 3 plus positivity) as well as frequency of triple positive (ER+, PR+ and HER2+) and triple negative patients (ER-, PR-and HER2-), based on IHC.

RESULTS
In this one year census period, 62 patients were evaluated. Type of cancer in 60 patients was invasive ductal carcinoma (96.77%) and in two patients was invasive lobular carcinoma (3.22%). Growth pattern for each cancer has not been commonly reported; however there was one report for mucinous growth pattern and two reports for medullary growth pattern (one of them belonged to a triple negative patient  (Figure 1). Cluster analysis of ethnicities based on IHC results showed that Fars and Turk/Azeri patients had similar response. Lur/Lak patients had the highest frequency of HER2 positive cases (6 out of 7, with one missing data) whereas Mazani patients had the lowest (1 out of 7) (Figure 2). This difference in the frequency of HER2 positive cases between Lur/Lak and Mazani patients was statistically significant according to Fisher's exact test (p=0.0291).

Summary of evidence
This study was aimed to report clinical and pathological characteristics of Iranian patients with invasive breast cancer. According to the results, the most common type of breast cancer in Iran was invasive ductal carcinoma, but reporting of its growth pattern has not been a common practice.
The most frequently positive IHC marker was ER (it was positive in about 75% of cases). These findings suggest hormone therapy as a default therapy for breast cancer in Iran. Positivity of HER2 was high (at about 38%); however all of these patients were not candidates for trastuzumab (Herceptin®) therapy because some of them were 1+ or 2+ positive with negative result for fluorescence in situ hybridization (FISH) test. The most common stage at the time of diagnosis was stage 3, indicating that majority of patients refer to a physician when they have significant clinical manifestations. Significant number of patients was diagnosed with stage 1 which could indicate positive impact of education on early detection. Frequency of treatment challenging triple negative breast cancer was about 7%. Cluster analysis showed differences in IHC results among different ethnicities (Figure 3). But, presented frequencies for ethnicities were not representative due to referral relationships between Firoozgar Clinical Research Development Center (FCRDC) and some cities in Iran. Harirchi et al. (2000) reported 903 breast cancer cases for 1985 to 1995 period (13). About 71% of patients were stage 3 at the time of diagnosis and lymph node positivity was higher (69%) than in our study (about 55%). In another report for 1996 to 2000 period the most common stage was 2 and about 96% of the patients had stage 2 or 3 (14).

CONCLUSION
These results could contribute to understanding of breast cancer patterns among different ethnicities. In order to draw clear conclusion future investigations have to be done in several health centers, for longer time periods and with larger number of patients.