Genetic polymorphism and expression of HSF1 gene is significantly associated with breast cancer in Saudi females.

The transcription factor, heat shock factor 1 (HSF1), influences the expression of heat shock proteins as well as other activities like the induction of tumor suppressor genes, signal transduction pathway, and glucose metabolism. We hypothesized that single nucleotide polymorphisms (SNPs) in HSF1 gene might affect its expression or function which might have an influence on the development of breast cancer. The study group included 242 individuals (146 breast cancer patients and 96 healthy controls). From the cancer patients, genomic DNA was extracted from 96 blood samples and 50 Formalin-Fixed Paraffin Embedded (FFPE) tissues, while from the controls DNA were extracted from blood only. Genotype was carried out for four SNPs in the HSF1 gene (rs78202224, rs35253356, rs4977219 and rs34404564) using Taqman genotyping assay method. The HSF1 expression was investigated using immunohistochemistry on FFPE tissues (cancer tissue and adjacent normal tissue). The SNP rs78202224 (G>T) was significantly associated with increased risk of breast cancer. The combined TT + GT genotype (OR: 6.91; p: 0.035) and the T allele showed high risk (OR: 5.81; p:0.0085) for breast cancer development. The SNP rs34404564 (A>G) had a protective effect against the development of breast cancer. The genotype AG (OR: 0.41; p = 0.0059) and GG+AG (OR: 0.52; p: 0.026) occurred at a significantly lower frequency in the breast cancer patients compared to the frequency in healthy controls. No significant relationship was identified between either rs35253356 (A>G) or rs4977219 (A>C) and breast cancer in Saudi. The HSF1 protein expression was higher in all invasive and in situ breast carcinoma compared to the normal tissue. A stronger positive staining for HSF1 was found in the nucleus compared to the cytoplasm. Our results show that HSF1 gene expression is elevated in breast cancer tissue and two of the studied SNPs correlate significantly with cancer development.

A multicenter prospective phase II trial of neoadjuvant epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin-docetaxel with or without trastuzumab in locally advanced breast cancer.

PURPOSE: To evaluate the efficacy and safety profile of the (FEC100) followed by cisplatin/docetaxel with and without trastuzumab as primary chemotherapy for patients with locally advanced breast cancer (LABC). METHODS: Eighty patients with LABC (T2-T4, N0-N2, M0) were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin and docetaxel, plus trastuzumab if HER2 positive. The primary endpoint was pathologic complete response (pCR) in breast and axilla in separate HER2-negative and HER2-positive cohort. RESULTS: Eighty patients were evaluable for analysis of which 51 were HER2 negative and 29 HER2 positive: median age: 43 years, premenopausal: 82%, median tumor size: 7.0 cm (4-10), stage IIB: 25% and IIIA/IIIB: 75%, both ER/PR positive: 56%, HER2 positive (3+) by IHC staining: 36%. Clinical complete response was seen in 48%, and clinical partial response was seen in 52%. Overall the pathologic complete response (pCR) was 36% in breast, 64 % in axilla, and 32% in both breast and axilla. Analysis of pCR in breast and axilla, as a function of the hormonal receptor (HR) and HER2, was as follows: HR(+)/HER2(-): 11%; HR(+)/HER(+): 56 %; HR(-)/HER2(-): 36%; HR(-)/HER2(+): 62%. CONCLUSION: In this series of locally advanced breast cancer, the combination of (FEC100) followed by cisplatin/docetaxel with and without trastuzumab was very active obtaining an impressive rate of pCR, particularly in HER2-positive and triple negative disease, which merits further investigation.

Elevated preoperative serum cancer antigen 15.3 levels are associated with reduced disease-free survival: a single-institution experience.

BACKGROUND: We aimed to evaluate the prognostic significance of the preoperative tumor-marker cancer antigen (CA) 15.3 in Saudi patients with breast cancer and to find out whether any correlation exists between preoperative CA 15.3 and tumor size and nodal status. MATERIALS AND METHODS: Preoperative blood samples for serum CA 15.3 levels were taken in 112 breast cancer patients who underwent breast-conserving surgery or modified radical mastectomy between February 1988 and August 2008. Serum levels of CA 15.3 below 35 U/mL were considered normal. The correlation between pre- and postoperative CA 15.3 levels with tumor size and nodal status was calculated using Pearson correlative coefficients. Kaplan-Meier curves were used to determine disease-free survival (DFS) according to CA 15.3 groups (<35, 36-100 and above >100 U/mL). RESULTS: The mean age of the cohort was 47.0 years (range 23-76, standard deviation 10.3). According to menopausal status, 93 patients (83.0%) were premenopausal, and 19 patients (17.0%) were postmenopausal. Mean preoperative CA 15.3 levels were 43.69 U/mL (1.0-209.87). Ten-year DFS rates were 100%, 84%, and 57.7% for CA 15.3 <35 U/mL, 36-100 U/mL, and >100 U/mL, respectively (P = 0.003). Preoperative CA 15.3 levels showed positive correlation with primary tumor size (R = 0.43, R (2) = 0.83, P = 0.03) and nodal status (R = 0.59, R (2) = 0.28, P < 0.0001), respectively. CONCLUSION: Elevated preoperative CA 15.3 above 35 U/mL in Saudi women breast cancer patients showed correlation with primary tumor size and nodal status, and preoperative CA 15.3 level is an independent prognostic factor for DFS. Preoperative serum CA 15.3 levels may be helpful for risk stratification along with other factors.

Breast carcinoma during pregnancy.

The medical records of patients with pregnancy associated breast carcinoma were critically reviewed to identify the tumor characteristics, maternal details, type of treatment delivered, and disease outcome. Over the last 5 years, there were 5 patients out of 220 giving a percentage prevalence of 2.27%. The median age at presentation was 33 years. Three patients were diagnosed by the sixth week of gestational age. Three out of 5 presented with stage IIIA. Four patients has > or = 6 positive axillary lymph nodes and grade III disease. So in spite of the discovery of the tumor in the early weeks of pregnancy, our patients presented with advanced disease, which is consistent with the presentation of breast carcinoma in non-pregnant women in this part of the world. So it could be an ignored disease, which became evident with the pregnancy. We highly encourage the obstetricians to perform thorough breast examination during the prenatal period with prompt referral of any suspicious cases.

Echocardiographic abnormalities in adolescent and adult Saudi patients with sickle cell disease.

OBJECTIVE: Cardiovascular complications in sickle cell disease (SCD) have been well documented but cardiac involvement in Saudi patients with SCD is not known. We sought to identify cardiac abnormalities by echocardiography in adolescent and adult Saudi patients with stable SCD. METHODS: Sixty-five consecutive patients with SCD followed at King Khalid University Hospital, Riyadh, were prospectively studied from January 2005 to December 2005. All patients underwent echocardiographic examination to determine chamber dimensions, left ventricular function, valvular anomalies and pulmonary artery pressure. Data were compared to normal age and gender-matched controls. Hematological data were also collected from the patients and correlated with the echocardiographic results. RESULTS: Twenty-eight males and 37 females were evaluated. The mean age of the group was 24.5+/-9.2 (range 14-44) years. The most common abnormality found was pulmonary hypertension (PH) present in 25 (38%) patients. The majority of these patients had mild PH and only 6 (9%) patients had pulmonary artery systolic pressure (PASP) more than 40 mm Hg. Older age, lower level of fetal hemoglobin and high serum ferritin were associated with increased PASP. Other abnormalities present included dilated left atrium in 17 (26%) patients, dilated right atrium 13 (20%), dilated left ventricle 10 (15%), valvular anomalies 21 (32%) and reduced ejection fraction in 4 (6%) patients. CONCLUSION: Cardiac abnormalities are found in a significant proportion of Saudi patients with SCD. Pulmonary hypertension is the most common finding while other abnormalities are less frequent.

Brain metastasis as an initial manifestation of a gallbladder carcinoma.

Though autopsy studies demonstrated 5% metastasis to the brain, clinical presentation of a central nervous system metastasis from gallbladder cancer is rare. We report a case of a 72-year-old woman who initially presented with a solitary brain metastasis from an adenocarcinoma of the gallbladder, which was diagnosed pre-operatively as glioblastoma multiforme. This is the second of such a case in the English literature. We emphasize the importance of including metastasis in the differential diagnosis of single intracranial tumor for proper planning of patient management.