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.

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.

Modification and implementation of NCCN guidelines on breast cancer in the Middle East and North Africa region.

Published data from the Middle East and North Africa (MENA) region indicate suboptimal quality of cancer care, while the World Health Organization predicts an increase in cancer cases in developing countries. Major advances in breast cancer management mandate the development of guidelines to improve the quality and efficacy of oncology practice in the MENA region. A Breast Cancer Regional Guidelines Committee was organized and activated, comprising experts from various regional cancer institutions. The multidisciplinary team included 12 medical oncologists, 3 radiation oncologists, 2 radiologists, 2 surgeons, and 1 pathologist. The committee members agreed on adapting the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Breast Cancer for use in the MENA region to achieve common practice standards for treating patients. The members suggested several modifications to the guidelines, especially those related to risk factor profiles. United States-based NCCN experts reviewed these recommendations before final approval. The MENA-NCCN Breast Cancer Guidelines modification process was the first initiative in the development of common practice guidelines in the region. This project may serve as a foundation for the development of evidence-based practice standards, and improve collaborative projects and initiatives.

Neoadjuvant docetaxel and epirubicin in large and locally advanced breast cancer: kuwait cancer control centre experience.

PURPOSE: To evaluate the efficacy of neoadjuvant (NA) docetaxel (DOC) and Epirubicin (EPI) as a part of multimodality treatment of large and locally advanced breast cancer. PATIENTS AND METHODS: Patients with large or locally advanced breast cancer received four cycles of DOC 75mg/m2 and Epirubicine (EPI) 90mg/m2 (DE). Clinical tumor response was assessed. Patients with operable disease were subjected to modified radical mastectomy (MRM) or breast conserving surgery (BCT) and axillary lymph node dissection (ALND). All patients received four cycles of DOC 100mg/m2 as post operative chemotherapy and local radiotherapy. Tamoxifen was given to patients with hormone receptor positive tumors. RESULTS: A total of 80 patients were enrolled; 75 patients completed at least 3 cycles of NA CT and were evaluable. Out of these 75 patients, 67 (89.3 %) patients completed all 4 cycles of DE, while 8 (10.7 %) patients received 3 cycles of DE. Out of all 75 patients; 25 patients (33.3 %) achieved clinical complete response (cCR), while 41 patients (54.7 %) achieved clinical partial response (cPR), making a total of 66 patients (88.0 %) who achieved a clinical response (cPR or cCR). Five patients (6.7 %) had stable disease (cSD), while two patients (2.7 %) had progression of disease (cPD). A total of 69 patients underwent surgery, out of those, 65 patients (94.2 %) underwent MRM and 4 patients (5.8 %) had BCT and ALND. Out of 69 patients evaluated for pathological response, 7 patients (10.1 %) had pathologic CR (pCR) and 62 (89.9 %) patients had pathological PR (pPR). Axillary lymph node examination revealed no residual tumor in 23 (33.3 %) patients. Grade IV neutropenia occurred in 92 (30.9 %) cycles while febrile neutropenia occurred in 17 (5.7 %) cycles. CONCLUSION: NA DE is an effective regimen with an acceptable toxicity profile. KEY WORDS: Advanced cancer breast - Neoadjuvant chemotherapy.

Multidisciplinary approach to breast cancer management in Kuwait, 1993-1998.

BACKGROUND AND OBJECTIVES: In Kuwait, breast cancer is the most common form of cancer among women. The present study reviews the clinical features, treatment methods and treatment results of breast cancer patients registered in the Kuwait Cancer Control Center (KCCC) and compares these features with those reported in other Arab countries, Europe and North America. MATERIAL AND METHODS: The present study examines 823 patients with breast cancer who were registered in the KCCC from 1993 to 1998. Patients were identified through the Kuwait Cancer Registry and their cases were followed for at least five years. RESULTS: Eleven males accounted for 1.3% of all patients. The average age was one decade younger than that reported in western countries but similar to reports from Egypt and GCC countries. Surgery was applied in 90.4% of patients. Breast conservation (lumpectomy and axillary clearance) was performed in 19.6% of patients, while mastectomy and axillary clearance was adopted in 60.8%. Radiotherapy was applied in 67.7% of patients and chemotherapy in 60.8%. The long-term overall survival and disease-free survival amounted to 76+/-6.4% and 54+/-4.6% respectively. Prognostic factors were analyzed using univariate and multivariate analysis. According to multivariate analysis the nodal status, the number of involved nodes and histopathology were independent prognostic factors. Comparable results were achieved after both breast conservation and mastectomy. CONCLUSIONS: Since breast conservation protocols yield results similar to mastectomy, its use should be extended. Search for biological prognostic indicators should continue for their potential use as guides for treatment decisions.