Prospective phase II study of neoadjuvant doxorubicin followed by cisplatin/docetaxel in locally advanced breast cancer.

The objective of this study is to evaluate the efficacy and safety profile of the doxorubicin followed by cisplatin/docetaxel as primary chemotherapy for patients with locally advanced breast cancer (LABC). For this evaluation, 59 patients with LABC (T2-T4, N0-N2, M0) received three cycles of doxorubicin, followed by three cycles of cisplatin/docetaxel and followed by definitive surgery and locoregional radiotherapy with or without tamoxifen. The primary end point was pathologic complete response (pCR) in breast and axilla. Fifty-nine patients were evaluable for analysis: median age: 41 years, premenopausal: 68%, median tumor size: 6.0 cm (4-10), Stage IIB: 32% and IIIA/IIIB: 68%, both ER/PR positive: 53%, Her2/neu (3+) by IHC staining: 29%. Clinical complete response was seen in 44%, and clinical partial response was seen in 56%. Breast conserving surgery was performed in 44%, and MRM in 56%. pCR in the breast was 30.5%, in axilla was 37%, and pCR in both breast and axilla was 24%. Overall at follow-up of 60 months, the disease-free (DFS) and overall survival (OS) were 70 and 82%, respectively. The DFS and OS of patients who achieved complete pathologic response in breast and axilla were 78 and 100%, respectively, while 14 patients relapsed of which 46% were Her2 positive. Sequential combination of doxorubicin followed by docetaxel/cisplatin is a safe, feasible, and active combination, which offers the possibility of conservative surgery and is associated with high clinical and pathologic response rates, with promising and encouraging survival outcomes.

The present and the future of breast cancer burden in the Kingdom of Saudi Arabia.

BACKGROUND: Despite the low cancer incidence in the Kingdom of Saudi Arabia (KSA), the country must be ready to face the challenge of foreseeable increase in cancer burden attributed to growth and aging of population. This work was designed to study female breast cancer as a model to assess future cancer burden and the impact on healthcare resources. METHODS: Cancer statistics for the KSA were compared with that for the USA. The Joinpoint regression program was used to identify changes in secular trends, while the GLOBOCAN 2002 software projected future incidence and mortality. RESULTS: In the KSA, the age-standardized cancer rate (ASR) is 61 per 100,000 population, while the median age at diagnosis is 54 and 49 years for men and women, respectively. Fitting the ASR for breast cancer did not show any significant trend over a 10-year calendar period (16.2-18.2 per 100,000), a pattern that was similar to that for the USA in the prescreening mammography era. Considering the growth and aging of population and using conservative estimates for the annual percent change in incidence (increase) and mortality (decrease) by 2025, incidence and mortality cases are expected to increase by about 350% and 160%, respectively. CONCLUSION: In developing countries, future cancer rates could demonstrate a considerable increase and enormous demands on healthcare resources. The present work may provide an impetus to study other prevalent cancer types particularly in developing countries.

Metaplastic carcinoma of the breast clinical presentation, treatment results and prognostic factors.

Metaplastic carcinoma of the breast (MCB) is a rare form of cancer containing mixture of epithelial and mesenchymal elements in variable combinations. Few and conflicting clinical data are available in the literature addressing optimal treatment modalities, prognosis and outcome. A retrospective study was conducted to review all patients with MCB diagnosed and treated at King Faisal Specialist Hospital and Research Center between 1994-2004. The aim is to describe patient's clinicopathologic features and to analyze treatment results. Nineteen female patients were studied. The median age was 48 years (range, 14-58). The median tumor size was 9 cm (range, 3-18). Stage distribution was II in 8 patients, III in 9 and IV in 2. Nine cases were identified as purely epithelial and 10 (53%) as mixed epithelial and mesenchymal metaplasia. Hormone receptors were positive in only 2 patients. Modified radical mastectomy performed in 11 patients and 15 underwent axillary node dissection. Adjuvant chemotherapy was given to 9 patients and postoperative radiotherapy to 8. Twelve patients relapsed with median time of relapse of 12 months (range, 2-28). At a median follow-up of 21 months (range, 7-83), the 3-year event free survival (EFS) and overall survival for the patients diagnosed with loco-regional disease were 15% and 48% respectively. Tumor size correlated significantly with EFS. MCB is an aggressive form of breast cancer associated with poor outcome, high incidence of local recurrence and pulmonary metastases. The disease tends to be estrogen/progesterone receptor negative. Tumor size has an important impact on outcome. The best treatment approach is yet to be defined.

Colorectal carcinoma from Saudi Arabia. Analysis of MLH-1, MSH-2 and p53 genes by immunohistochemistry and tissue microarray analysis.

OBJECTIVE: To document the incidence and role of p53 and DNA mismatch repair proteins in colorectal carcinomas, and to evaluate the relative frequency of major molecular pathways in colorectal cancers from Saudi Arabia. METHODS: We collected the formalin fixed, paraffin embedded tissues from 154 colorectal tumors (83 patients from King Faisal Specialist Hospital and Research Centre and 71 from Saudi Aramco Dhahran Health Centre) between January 1989 and December 2003. We analyzed the p53 and mismatch repair gene expression (hMSH-2, hMLH-1) by immunohistochemistry in tissue microarray format. RESULTS: Expression loss of at least one mismatch repair gene was found in 33.8% of cases and significantly associated with the right-sided tumor location (p=0.0047). The p53 positivity was observed in 57.5% of tumors, and was inversely linked to expression loss of mismatch repair genes (p=0.0102). CONCLUSION: The strong confirmation of the previously established associations between tumor phenotype, and mismatch repair gene alteration provided strong evidence for the validity of our experimental approach. Together with the higher incidence of right sided location in Saudi (46.6%) than in Western colon cancers (34.9%), the observed high prevalence of mismatch gene expression loss in Saudi tumors argues for a higher importance of microsatellite instability in this population. If confirmed, it will be interesting to see whether an increased level of familial or sporadic microsatellite instability cases is causing this variation.

Adjuvant chemotherapy in 780 patients with early breast cancer: 10-year data from Saudi Arabia.

BACKGROUND: By and large, data about adjuvant chemotherapy for breast cancer in the Middle East are lacking. Retrospective analysis of prospectively captured data from a main referral center in the Kingdom of Saudi Arabia (KSA) may shed some light on the clinicopathological features and survival of patients offered adjuvant chemotherapy in a similar population in that part of the world. PATIENTS AND METHODS: Data on patients with invasive breast cancer (Stages I to IIIA) seen between 1992 and the end of 2001 and who received adjuvant chemotherapy were analyzed. A total of 780 patients were considered eligible and constitute the basis of this report. RESULTS: The median age +/- SD of the 780 patients was 42 +/- 9.6 yr. The majority of patients were younger than 50 yr (78%) and premenopausal (83%). Ten percent, 69%, and 21% of patients had Stage I, II, and IIIA, respectively. Patients expressed relatively high prevalence of adverse clinicopathological characteristics. Most patients (523 patients, 67%) received anthracyclines-containing adjuvant chemotherapy, 610 patients (78%) received adjuvant radiotherapy, and 296 (38%) received adjuvant tamoxifen. At a median follow-up of 42 mo (95% CI, 38.1-62.8 mo), the median overall (OS) and disease-free survival (DFS) were not reached; however, the 5-yr actuarial survival was estimated as 74% and 59%, respectively. Cox proportional regression hazard model identified positive axillary nodal status, and positive vascular invasion are the only variables that influenced OS adversely. The model also distinguished the same variables plus negative estrogen receptor status as covariates with negative effect on DFS. CONCLUSION: In conclusion, this series of 780 predominantly young patients with breast cancer receiving adjuvant chemotherapy highlighted the disease patterns and survival outcome in the KSA. The current series is significant being one of the few reports about adjuvant chemotherapy experience in a developing country and certainly the first from that part of the world.

Epigenetic changes and their clinical relevance in Saudi diffuse large B-cell lymphoma. A molecular and tissue microarray analysis of 100 cases.

OBJECTIVE: The gene encoding the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in several human cancers including diffuse large B-cell lymphoma (DLBCL). We explored the aberrant promoter methylation of MGMT in Saudi diffuse large B-cell lymphoma and to investigate MGMT hypermethylation has an effect on patient's overall survival. METHODS: In a retrospective cohort study, 100 cases of DLBCL were collected from the Department of Pathology at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. We used methylation specific polymerase chain reaction to analyze the MGMT promoter methylation status in 100 tumor DNA of Saudi DLBCL patients receiving multi drug regimens. Tissue microarray (TMA) of these cases was also constructed. The MGMT protein expression was analyzed immunohistochemically. Molecular data were correlated with clinical outcome. RESULTS: Seventy one percent (71%) of 100 DLBCL patients showed MGMT promoter hypermethylation in their lymphoma. The presence of MGMT methylation was associated with statistically significant increase in the overall survival (p=0.02). The MGMT promoter hypermethylation was independent and a strong prognostic factor. CONCLUSION: The MGMT promoter hypermethylation appears to be useful marker for predicting survival in patient with DLBCL treated with multi drug regimens including cyclophosphamide, at the same time the study shows that TMA technology is useful for immunohistochemical analysis of large lymphoma populations.

HER-2/Neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer.

Data about the prognostic and predictive value of HER-2/neu overexpression in patients with locally advanced breast cancer (LABC) treated with primary chemotherapy is limited. Therefore, this retrospective study was performed to examine this issue. Fifty-four consecutive patients with LABC were prospectively managed using a uniform multimodality approach. Response to neoadjuvant chemotherapy and survival were examined against HER-2/neu overexpression as determined by an immunohistochemistry method on formalin-fixed, paraffin-embedded samples of breast cancer using the commercially available, United States Food and Drug Administration-approved kit HercepTest (Dako Corp, Carpinteria, CA). The number of patients in each HercepTest immunostaining group were as follows; 0 in 12 patients (22%), 1+ in 8 (15%), 2+ in 12 (22%), and 3+ in 22 (41%). None of the clinical variables was significantly associated with HER-2/neu expression. After primary therapy, 22% of patients attained clinical complete response and an additional 70% achieved clinical partial response with an overall response rate of 92% (95% confidence interval: 100% to 79%). There was no significant correlation between clinical response and HercepTest positivity (p = 0.85). Of 52 patients with complete pathological data, there was no significant difference in HercepTest status between those who attained complete pathological response (46%) and those who did not (38%) (p = 0.74). Moreover, there was no significant difference in disease-free survival (75% vs 84%, [p = 0.26]) or overall survival (81% vs 84% [p = 0.31]) between those who overexpressed HER-2/neu and those with negative HercepTest, respectively. In patients with LABC, HER-2/neu overexpression determined using HercepTest assay and according to the manufacturer's approved guidelines failed to demonstrate a predictive or a prognostic role.

Appraisal of communication skills and patients' satisfaction in cross-language encounters in oncology practice.

OBJECTIVE: Communication skills are the most important determinant of patients' satisfaction with care. Data about the adverse effects of cross-language encounters are scarce. This prospective study was designed to examine the association between the communication language and patients' satisfaction in oncology practice. PATIENTS AND METHODS: The Art of Medicine questionnaire was used to assess patients' perceptions of clinicians' communication behaviors and patients' global satisfaction. Mean scores of patients cared for by Arabic-speaking oncologists were compared with those of patients who had communications translated from English by interpreters. RESULTS: 255 patients were eligible. Patients' median age was 44 years (95% CI, 42.8-46.2). Communication was in Arabic and interpreted English for 136 (53%) and 119 (47%) patients, respectively. The two groups were comparable for various demographic and clinical variables. On a nine-point scale, mean scores for the eight questionnaire items ranged from 6.24 (95% CI, 5.91-6.56) to 8.24 (95% CI, 8.03-8.45). There was no significant difference in communication skills between Arabic- and English-speaking clinicians for any questionnaire item. Moreover, a multiple regression analysis failed to identify any variable that independently influenced overall patients' satisfaction with the delivered care. CONCLUSIONS: The findings do not support a disadvantageous effect on interpersonal skills and patients' satisfaction as a result of cross-language communication.