Introduction

1. Differences in pathological and clinical features of breast cancerin Arab as compared to Jewish women in Northern IsraelJamal Zidan, MD1,2; Natalya Sikorsky, MD3; Walid Basher, MD1; Adi Sharabi, BS1; Eitan Friedman, MD4; Mariana Steiner, MD3 1. Oncology Institute, Ziv Medical Center. Safed, Israel. 2. Faculty of Medicine, Technion, Israel Institute of Technology. Haifa, Israel. 3. Department of Oncology, Lynn Medical Center. Haifa, Israel. 4. Oncogenetic Unit, Sheba Medical Center. Tel Hashomer, Israel. Email:zidan.j@ziv.health.gov.il Methods Abstract Discussion Fig1: Incidence of breast cancer in Israel due to ethnicity. Objectives: To evaluate the clinical, biological and pathological characteristics of breast cancer in Palestinian Arab compared to Jewish women in Israel. Design: Retrospective analysis, multi centre study. Setting: Two oncology centers: Ziv and Lynn Medical Centers at Northern Israel. Participants: Records of 1140 women treated for breast cancer between 2002 and 2007 were reviewed: 872 Jews and 268 Arabs. Results: Mean age at diagnosis was 49.9 years for Arabs and 59.4 years for Jews (p<0.0001). Mean tumor size was < 2 cm in 25% of Arabs and 53% of Jews (p<0.0001). ER was positive in 69% of Arabs and in 78.5% of Jews (p<0.001). Poorly differentiated tumors were found in 28.8% of Arabs versus 12.8% in Jews (p<0.0001). Overexpression of HER-2 was present in 35.4% of Arab and 22% of Jewish women (p<0.001). Study Population: Data for 1140 women who were treated for breast cancer between 2001 and 2005 at the Ziv and Carmel Medical Centers in Northern Israel was retrospectively summarized. All patients had histopathologically-proven breast cancer (including ductal carcinoma in situ). HER-2 Evaluation: HER-2 was evaluated using immunohistochemistry (IHC), chromogenic in situ hybridization (CISH), or the fluorescent in situ hybridization (FISH) test. HER-2 was considered overexpressed if found to be +3 by IHC using the Daco score system, or if positive amplification was shown in the FISH or CISH test. Tumor stage: Tumors were staged using the AJCC (American Joint Committee) (2006). Patients with ductal carcinoma in situ were considered to be at stage 0. Statistical Analyses: Fisher's exact or chi-square tests were used for statistical analyses. Mean values were compared using the student t-test for independent groups. Although breast cancer is the most common malignancy found in Middle Eastern women, few published studies have reported its clinical and pathological features in this population compared to Western and American women. Breast cancer mortality is higher among Arab women, with survival rates of 63% among Arabs and 71% in Jews in Israel 2 The Arab population constitutes 19% of the general population in Israel. The increasing incidence of breast cancer in Israeli Arab women may be due to major lifestyle changes. Although their society is more conservative and religious than Jewish secular society in Israel, there is evidence that Arabs living in Israel are undergoing major modernization, as reflected by increasing urbanization, greater numbers of employed women, and expanded use of healthcare and other services. Israeli Arab women were diagnosed at a more advanced stage of cancer than Jewish women (p<0.0001). In the present study, a higher percentage of Arab women (28.8%) had grade 3 tumors compared with Jewish women (12.8%) (p<0.0001). Similarly higher rates of grade 3 tumors have been reported in African-American (32%) compared to white American women (10%).4 Very interestingly HER-2 overexpression was significantly higher in Arab women (35.4%) than in Jewish women (22%), such a difference may have been caused by ethnic variability in cancer biology or genetic factors. In the present study, no BRCA1 or BRCA2 carriers were identified among the Arab women tested, compared to 6% of the Jewish women. Table 1. Patient characteristics by ethnicity Introduction The most common malignancy in European and North American women is breast cancer, which does not affect all racial and ethnic groups equally1. The incidence of breast cancer among Israeli Palestinian Arab women increased from 13.6 new cases per 100,000 in 1995 to 58 in 2005, while in Israeli Jewish women, new cases decreased from 91 to 87 over the same period of time (Figure1).2 A difference in the incidence of breast cancer between populations influences the same country but with different lifestyles strongly supports the affect of environment and tradition in the development of breast cancer. Lifestyle and other changes in the Israeli Arab population include a shift toward a more Western diet, increased obesity, lower rates of pregnancy, and reduced physical activity, which may contribute to the increasing incidence of breast cancer. Few published studies have reported the clinical and pathological characteristics and risk factors of breast cancer in Arab and Middle East women. In one study, 78% of Arab women with breast cancer in Saudi Arabia were diagnosed below age 50, and 74% had stage II and III disease.3 The present study attempted to characterize whether breast cancer in Israeli Palestinian Arab women may have different biological features compared to breast cancer in sraeli Jewish women in Northern Israel. Results Patient Population A total of 1140 cases were studied  872 Jewish and 268 Arab women. Patient characteristics are presented in Table1. Mean age at diagnosis was 59.5 significantly lower in Arab women: 49.9 years compared to Jewish women 59.4 (p<0.0001). The mean number of children was 4.2 in Arab women and 2.5 in Jewish women. Ethnicity and Clinical Features Tumor size at diagnosis was 2cm in 25% of Arabs compared to 53.8% of Jews (p<0.0001). Locally extensive tumor (T4) was found in 19% of Arabs and in 5.4% of Jews (p<0.0001). A significantly greater number of Arab women presented with metastases to axillary lymph nodes than Jewish women (p<0.0001), (Table 2). Pathological Characteristics and Ethnicity Tumor histological grade was higher in Arabs than Jews. Well-differentiated cancer was found in 44.9% of Jews compared to only 12% of Arabs (p<0.0001), while poorly-differentiated histology was found in 12.8% of Jews and 28.8% of Arabs (p<0.0001) (Table 2). Estrogen and progesterone receptor status was lower in Arabs than Jews (p<0.01) . HER-2 overexpression was found in 35.4% Arab women compared to 22% in Jewish women (p<0.0001). Table 2. Characteristics of breast cancer by ethnicity Conclusion: Ethnicity is an important predictive factor for breast cancer. Arab women present at a younger age, with more advanced disease that is more aggressive clinically and biologically than in Jewish women. Socioeconomic factors alone are not sufficient to explain these differences. Our findings suggest a different genetic susceptibility in the two populations which needs further research. References: 1. Althuis MD, Dozier JM, Anderson WF, Devesa SS, Brinton LA. Global trends in breast cancer incidence and mortality 1973-1997. Int J Epidemiol. 2005;34:405-412. 2. Ministry of Health in Israel: http://www.health.gov.il 3. Ezzat AA, Ibrahim EM, Raja MA, et al. Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population. Med Oncol. 1999;16:95-103. 4. Miller BA, Hankey BF, Thomas TL. Impact of sociodemografic factors, hormone receptor status, and tumor grade on ethnic differences in tumor stage and size of breast cancer in US women. Am J Epidemiol. 2002;155:534-545.