Two studies from the UAE and Kuwait looking at the value of Oncotype DX testing in clinical practice and treatment decisions. One study looked particularly at the value of Oncotype DX testing on adjuvant treatment decisions based on a retrospective analysis of data for 50 female node-negative ER+ early BC patients who underwent Oncotype DX between October 2009 and June 2012 in the UAE. The test was successful in 47 patients, and the proportion of patients with low, intermediate, and high recurrence scores was 53.2%, 40.4%, and 6.4%, respectively. The risk assessment based on the St. Gallen criteria and Oncotype DX testing were concordant in approximately half of the patients. Treatment decisions were changed (pre-testing vs. post-testing) in 28% of patients, mostly from chemoendocrine therapy to endocrine therapy alone, with a statistically significant change in the low recurrence group (from 56.0 to 8.0%;
Several studies from the GCC looking at the significance of specific markers in the presentation and prognosis of BC. A study from Oman found a strong association between metastasis and younger age (women ≤ 40 years), lymphovascular invasion, and epithelial–mesenchymal transition (EMT) expression, indicating that EMT could possibly predict a higher metastatic potential in tumors and suggesting EMT expression as a surrogate marker for predicting metastasis [
57]. In addition, EMT was found to be associated with Ki67 PI and basal-like tumors [
57]. Further, the expression of nucleostemin was found to be higher in less differentiated, more advanced stage, larger, and lymph-node-positive tumors, as well as in more aggressive molecular subtypes (HER2+ and TN) when evaluated in 51 patient archival specimens from the UAE, although none of these associations reached statistical significance [
58]. A study from Oman observed a statistically significant relationship between high elastosis and ER positivity (
p = 0.015) and HER2-status (
p = 0.045) in 80 female patients who were not treated with neoadjuvant therapy from 2009 to 2019, suggesting that elastosis may be used as a surrogate marker for ER positivity and HER2 negativity in BC [
59]. A study from the UAE found that A20 expression evaluated through immunohistochemistry (IHC) was associated with early grade 1 BC (
p < 0.001) in all molecular subtypes, suggesting its use as a biomarker for early cancer. A20 overexpression was also associated with a lower OS rate in patients treated with endocrine therapy [
60]. Another study found that insulin-like growth factor 1 receptor (IGF1R) membranous and mixed (membranous and cytoplasmic) expression in BC cells was evident in HR + HER2− cases in contrast with HR−HER2+ cases, which showed cytoplasmic or diminished IGF1R expression, suggesting that luminal subtypes may benefit from targeted IGFR therapy [
61]. Trefoil factor 3 (TFF3) expression was found to be associated with residual breast carcinoma following neoadjuvant chemotherapy in 133 cases from the UAE, suggesting that its expression is associated with increased resistance to chemotherapy. Moreover, there was a significant co-expression of TFF3 with antiapoptotic proteins AKT1 (
p = 0.0365), BCl2 (
p = 0.0152), and NF Kappa-B (
p = 0.0243) in breast carcinoma cases with residual carcinoma following neoadjuvant therapy, which reinforces the role of TFF3 in chemoresistance [
62]. Vitamin D receptor (VDR) was also assessed using IHC in 120 Kuwaiti female BC fixed tissues and was found altered in BC, with its absence being associated with high-grade differentiated tumors (
p = 0.01) and its cytoplasmic expression being associated with lymph-node-positive tumors (
p = 0.03) [
63].
5. Management and Outcomes
5.1. Management Trends
Data on BC management trends in the region were very scarce and far from representative of current practice. In the 2018 QNCR, 319 (89%) of the total cases were reported with treatment information. Among them, the top five treatment modalities were Chemotherapy/Surgery (23.20%); Surgery (19.12%); Chemotherapy/Radiation Therapy/Surgery (15.67%); Chemotherapy/Hormonal Therapy/Radiation Therapy/Surgery (12.23%); and Hormonal Therapy/Radiation Therapy/Surgery (8.78%) [
5], while data from the KCCC reported the treatment type for 359 patients with TNBC between 1999 and 2009 [
40]. Recently, KCCC reported the type of treatment among Kuwaiti and non-Kuwaiti for the year 2017, where 82.3% of Kuwaiti nationals had surgery; 60.8% had chemotherapy; 65.8% had radiotherapy; and 74.0% had hormonal-based treatment. On the other hand, 77.6% of non-Kuwaitis had surgery, 70.5% had chemotherapy; 65.9% had radiotherapy; and 67.5% had hormonal-based treatment [
8].
The TRIPOLI study possibly provides a more valid description of current treatment strategies as it reports on more recent data collected between 2017 and 2019; it describes that out of the 387 TNBC cases from Oman, Kuwait, and Qatar, among other Arab countries, with non-metastatic disease who started treatment during that period, 217 patients (56.1%) had upfront surgery and 170 patients (43.9%) started with neoadjuvant chemotherapy [
37].
5.2. Outcomes
Data on outcomes from the GCC were also scarce. Besides data from the GLOBOCAN database [
3], only the UAE’s and Bahrain’s national registries [
4,
6] reported BC deaths. Looking at original papers published from the five countries between 2011 and 2021, most analyzed datasets were of patients diagnosed before 2000 and up to the year 2012 [
10,
13,
22,
40,
41,
66,
67,
68,
69], and one meta-analysis looking at survival rates in patients with BC from the Eastern Mediterranean region included data within the same timeframe [
70]. Only a couple papers reported outcome data up to year 2015 [
71,
72] with the absence of any outcome data from the region thereafter.