Implications of the 21-gene recurrence score assay (Oncotype DX) on adjuvant treatment decisions in ER-positive early-stage breast cancer patients: experience of Kuwait Cancer Control Center.

BACKGROUND: The Oncotype DX is a quantitative assay of the expression of 16 tumor-related genes and 5 reference genes that predicts the potential of adjuvant chemotherapy benefit in estrogen receptor (ER)-positive early breast cancer patients. The study aims to evaluate the impact of Oncotype DX as a tool for adjuvant treatment decision of ER-positive, HER2-negative, N0/N1 early-stage breast cancer patients and to determine which clinicopathological criteria derived the greatest advantage. RESULTS: A hundred patients at a median age of 50 years were included. TNM stage distribution was 34, 63, and 3 patients for stages I, II, and IIIA respectively. Fifty-four patients had luminal A and 46 had luminal B tumors. The recurrence score (RS) results were low, intermediate, and high risk in 54, 34, and 12 patients respectively. Before the test results, adjuvant chemoendocrine therapy (CET) was recommended for 46 patients while 54 were advised for endocrine therapy (ET). After getting the test results, 25 patients received CET (1, 12, and12 patients in the low-, intermediate-, and high-risk groups respectively) and 75 received ET. Treatment change was documented in 37 patients (8 patients from ET to CET and 29 from CET to ET; p = 0.001, McNemar test). Treatment change was significant among patients ≤ 50 years, luminal B tumors, stage II and IIIA disease, and node-positive disease. CONCLUSION: Oncotype DX testing resulted in significant changes in the adjuvant treatment decisions in ER-positive, HER2-negative early breast cancer particularly in the case of young, luminal B, N1, and stage II-IIIA disease.

Triple Negative Breast Cancer: 10-Year Survival Update of The Applied Treatment Strategy in Kuwait.

BACKGROUND: Triple negative breast cancer (TNBC) is recognized as a distinct clinical and biological entity of poor outcome for almost two decades, yet its treatment strategy still needs to be better specified. The study aim is to update the 10-year survival data of our TNBC patients and to find its association with different treatment modalities. PATIENTS AND METHODS: We updated the 10-year survival data of 359 women diagnosed with TNBC between 1999 and 2009 in the Kuwait Cancer Control Center (KCCC). The overall survival (OS), disease free survival (DFS), distant metastasis free survival (DMFS) and loco-regional recurrence free survival (LRFS) were estimated using Kaplan Meier method. Survival was correlated with different prognostic factors and treatment modalities. Statistical significance was calculated using the log-rank test and defined as p < 0.05. Cox regression is used for Multivariate analysis. RESULTS: TNBC represented 12% of breast cancer in Kuwait with a median age of 48 years. The stage distribution was as follow: stage I, II, III, IV in 15%, 43%, 35% and 7% of patients respectively. Regarding surgery, 33% had Conservative surgery; 67% had mastectomy; 82% had axillary clearance. Chemotherapy was neoadjuvant in 25%, adjuvant in 56% and palliative in 5% of patients. Two-thirds of patients (67%) received adjuvant radiotherapy. After a median follow-up of 108 months, the 10-year OS, DFS, DMFS and LRFS were 66%, 59%, 72% and 77% respectively. The 10-year OS was 92%, 80%, 49% and 0% for Stage I, II, III and IV respectively (p =< 0.0001). OS was significantly worse with the presence of lymphovascular invasion (LVI) with p = 0.003. OS was not significantly affected by age, grade or treatment modality. In multivariate analysis, the clinical stage and LVI were still significant (P<0.0001 and 0.04 respectively). CONCLUSION: In the absence of biological biomarkers, clinical stage and LVI seem to be the only significant prognostic factors for survival of TNBC patients in our study population. Timing of chemotherapy as well as the extent of surgery do not seem to affect the TNBC patients' outcome.

Colon Cancer in Patients below Age of 50 Years: Kuwait Cancer Control Center Experience.

BACKGROUND: This study was undertaken to analyze and evaluate the clinico-pathological profile and the outcome of young patients diagnosed with colon cancer. PATIENTS AND METHODS: Patients diagnosed with adenocarcinoma of the colon at or below the age of 50 years from January 2000 to December 2007 in Kuwait were analyzed. This study retrieved 130 patients diagnosed = 50 years, representing 22% of colon cancer patients in this period, 67 females and 63 males. Patients = 40 years were 48 while those 41-50 years were 82. Median follow-up was 61 months. RESULTS: According to the TNM system, 82% patients had T3 and T4 disease, 55% had node negative disease and 15% had distant metastasis at presentation. All patients except three underwent surgery. Chemotherapy was given in 82% of patients either for adjuvant or palliative intent. The 5-year overall survival (OS) and progression free survival (PFS) were 78% and 75% respectively. Survival was significantly affected by the disease stage and grade. The OS was 96%, 83%, 6% for stage I and II, III and IV respectively (p<0.001). OS was 91% for grade 1 and 2 tumors vs. 60% for grade 3 tumors (p=0.007). Patients who presented = 40 years had relatively more grade 3 (19% vs. 7%) compared to 41-50-years age group. CONCLUSIONS: Colonic adenocarcinoma is frequently diagnosed below the age of 50 in our population. Younger age (=40 years) seems to present more with high grade tumors. Clinicians should consider full colonoscopic evaluation while investigating symptomatic young patients.

Second Primary Tumors associated with Breast Cancer: Kuwait Cancer Control Center Experience.

OBJECTIVES: To review the clinico-epidemiologic characteristics of patients who presented with two or more primary cancers, one of which was breast cancer (BC) and to develop a follow-up program for the high risk patients. PATIENTS AND METHODS: Patients who were diagnosed with BC and one or more non breast cancer (NBC) were retrospectively reviewed. Medical files were retrieved and epidemiological as well as clinical data were analyzed. RESULTS: Sixty-two patients were retrieved. BC was the first primary in 26 patients while it was the second in 36 patients. Two were males and 60 were females. The median age was 48 years and the median follow-up was 11.5 years. The median interval between the 1st and 2nd primary was 6 years. The most commonly associated NBCs were colon and thyroid cancers, each accounts for 24% of cases followed by endometrial cancer, 18%; Hodgkin's disease, 6.5%; renal and ovarian neoplasm and NHL, 5% each. Others included prostate, lung, cervical and gastric cancers, soft tissue sarcoma and osteosarcoma. Thyroid cancer was more common as first cancer while endometrial cancer was more as second cancer. All patients who developed BC following Hodgkin's disease had received chest irradiation. Seven patients developed 3rd primary (4 lung cancers, 2 NHL, and 1 AML). CONCLUSION: Patients who were diagnosed with BC should be screened for colon and endometrial cancer. Similarly, patients received chest irradiation at young age, and those diagnosed with thyroid or colon cancer should be screened for BC. Protocol of surveillance needs to be defined. Genetic counseling should be offered to individuals who have experienced multiple primary cancers particularly those with family history and young age of onset.

Metaplastic breast carcinoma: Analysis of 31 cases from a single institute.

PURPOSE: Metaplastic carcinoma of the breast (MBC) accounts for less than 1% of all mammary tumors. This study aimed at revision of the clinico-pathological features, treatment strategy and outcome for MBC patients presented to the Kuwait Cancer Control Center to define the clinical behavior and prognostic factors of these neoplasms in our population. PATIENT AND METHODS: Thirty-one patients were retrieved from our surgical pathology registry between January 2005 and December 2014. Medical records were revised regarding the clinico-pathological features and treatment outcome. RESULTS: MBC represented 1% of our breast cancer patients. The median age was 50years (32-70years). Two patients presented with metastatic disease. Mastectomy was done for 24 patients and 7 had conservative surgery. The median tumor size at the time of surgery was 5.5cm (1.5-12cm). Axillary nodes were negative in 21 patients (N0), 5 patients were N1, 4 patients were N2 and one Nx. Three histological subtypes were presented: carcinosarcoma (7 cases), squamous cell carcinoma/IDC with squamous differentiation (15 cases), high grade IDC with metaplastic differentiation (9 cases). Immunohistochemically, 26 were negative hormone receptors and all were negative for Her2/neu overexpression. Chemotherapy was used in 28 patients, and adjuvant radiotherapy in 24 patients. The median follow-up was 47months (7-126months), six patients lost follow-up. The 5-year OS was 69% and 5-year PFS was 50%. CONCLUSION: MBC is a rare entity among breast carcinoma in Kuwait. Most of the cases present with poor prognostic indicators and often show lack of expression of ER, PR and Her2/neu.

Phyllodes tumors of the breast: Analysis of 35 cases from a single institution.

BACKGROUND: Phyllodes tumors are rare fibroepithelial breast tumors with diverse biological behavior. Our study aim is to review the clinico-pathological features, prognostic factors and treatment outcome for patients presenting with phyllodes tumors of the breast to the Kuwait Cancer Control Center (KCCC). PATIENTS AND METHODS: We retrospectively reviewed the clinical and pathological data of 35 women of histologically proved phyllodes tumors of the breast retrieved between January 1994 and December 2012. RESULTS: The median age was 40years (21-63years). The median pathological tumor size was 6.8cm (3-25cm). Histologically, one patient (3%) presented with benign, 13 (37%) with borderline and 21 (60%) with malignant phyllodes. Twenty-eight patients (80%) were premenopausal. Twenty (57%) were ultimately treated with mastectomy (3 borderline, and 17 malignant) and 15 (43%) with conservative surgery (1 benign, 10 borderline and 4 malignant). Axillary staging was carried out in 9 patients (1 borderline and 8 malignant), none of them had nodal metastasis. Four patients with malignant phyllodes received postoperative radiotherapy. After a median follow-up period of 52months (range 5-211months), 5 developed local recurrence (1 benign, 2 borderline and 2 malignant). One patient with malignant phyllodes developed distant lung metastasis. The overall 5-year relapse free survival (RFS) was 74% (68% for borderline and 84% for malignant phyllodes). According to the treatment modality, the 5-year RFS was 69% for conservative surgery compared to 87% for mastectomy. It was 100% for irradiated patients versus 71% for non irradiated patients. CONCLUSION: Phyllodes tumors are rare tumors that occur in relatively young women, when compared with the classical adenocarcinoma of the breast. They have a tendency to reach large sizes with absence of nodal metastasis. Although surgery is the mainstay of management, postoperative radiotherapy also appears to decrease the local recurrence rates in certain presentations.

Significance of Magnetic Resonance Imaging-Assessed Tumor Response for Locally Advanced Rectal Cancer Treated With Preoperative Long-Course Chemoradiation.

PURPOSE: To study the predictive and prognostic value of magnetic resonance imaging (MRI)-assessed tumor response after long-course neoadjuvant therapy for locally advanced rectal cancer. METHODS: This study included 79 patients who had T3 or T4 and/or N+ rectal cancer treated with long-course neoadjuvant chemoradiation. MRI-assessed tumor regression grade (mrTRG) was assessed in 64 patients. MRIs were reviewed by the study radiologist. Surgical and pathologic reports for those who underwent surgery were reviewed. Disease-free survival (DFS) was estimated. Progression during therapy, local relapse, metastasis, and death resulting from the tumor were classified as events. Statistical significance was calculated. RESULTS: In 11 patients, the tumor completely disappeared on MRI; that is, it had an mrTRG of 1. All but one patient, who chose deferred surgery, had a complete pathologic response (pCR), with a positive predictive value of nearly 100%. Of the 20 patients who had an mrTRG of 2 on MRI, six had a pCR. mrTRG 3, mrTRG 4, and mrTRG 5 were detected in 24, six, and three patients, respectively, of whom only one patient had a pCR. The 2-year DFS was 77%. The mrTRG was significant for DFS. The 2-year DFS was 88% for patients with a good response versus 66% for those with a poor response (P = .046). CONCLUSION: MRI-assessed complete tumor response was strongly correlated with pCR and, therefore, can be used as a surrogate marker to predict absence of viable tumor cells. Our results can be used to implement use of mrTRGs in larger prospective correlative studies as a tool to select patients for whom deferred surgery may be appropriate. Also, those with a poor response may be offered further treatment options before definitive surgery.

Clinicopathological features and prognosis of triple negative breast cancer in Kuwait: A comparative/perspective analysis.

AIM: The aim of this study was to determine the incidence of TNBC in Kuwait, to analyze the clinicopathologic features and prognosis of this type of breast cancer, and compare it with reports from other regions of the world. BACKGROUND: Triple negative breast cancer (TNBC) is defined as a subtype that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). There is a growing evidence of the heterogeneity of such entity on the molecular level that may cause discrete outcomes. METHODS: We analyzed the clinicopathologic features of 363 TNBC cases which were diagnosed in Kuwait from July 1999 to June 2009. The disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Comparison was done with reports from USA, Europe, Middle and Far East. RESULTS: Among 2986 patients diagnosed with breast cancer in Kuwait, 363 patients (12.2%) were TNBC. The median age was 48 years, 57.2% had lymph nodes (LN) metastasis, 56.9% were of grade III tumor and 41.9% had stage II disease. 81% developed recurrences and 75% of deaths occurred by 2.5 years after treatment. There is marked variation of clinicopathologic features according to country of patients' cohort. CONCLUSION: The incidence of TNBC in our study is similar to other studies. TNBC patients showed an early major recurrence surge peaking at approximately year 2.5. Regional variation of clinicopathologic features indicates a need for molecular studies to define underlying molecular features and its impact on survival.