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.

P53 gene polymorphisms and breast cancer risk in Arab women.

The association between polymorphisms in the p53 tumor suppressor gene and breast cancer risk has been studied in many human populations with conflicting conclusions. However, similar studies in Arab women are not available, and the status of these polymorphisms in this ethnic population is not known. We investigated the status of four known p53 gene polymorphisms and their possible role in breast cancer risk in Arab women. Genotyping was performed for 288 breast cancer women and 188 controls to determine Pro47Ser, Arg72Pro, Intron 3 Ins16 bp and intron 6 (G > C) polymorphisms. The p53 variant Pro47Ser was detected only in one Kuwaiti breast cancer patient and was not detected in any of the control subjects. Frequency of Arg/Arg at codon 72 was 26.6% in controls and 28.1% in patients, Arg/Pro frequency was 59.6% in controls and 69.4% in patients, the Pro/Pro genotype was 13.8% in controls and 2.4% in patients. We observed that women with Pro/Pro genotype have decreased risk for developing breast cancer (OR=0.166, 95% CI=0.067-0.411, p<0.001). The intron 3 genotypes were A1/A1 (48.9%), A1/A2 (40.6%) and A2/A2 (10.5%) in controls and A1/A1(42.4%), A1/A2 (52.8%) and A2/A2 (4.8%) in cases. The intron 6 genotypes were 92.4% (GG), 7.6% (GC) and 0% (CC) in controls and 96.5% (GG), 3.5% (GC) and 0% (CC) in cases. No statistically significant differences between patients and controls were observed for intron 3 and intron 6 polymorphisms. Our data show that proline homozygosity at p53 codon 72 is associated with decreased breast cancer risk in Arab women.

Health - related quality of life of Kuwaiti women with breast cancer: a comparative study using the EORTC Quality of Life Questionnaire.

BACKGROUND: The Kuwaiti perspective on quality of life (QOL) in breast cancer is important because it adds the contribution from a country where the disease affects women at a relatively younger age and seems to be more aggressive. We used the EORTC QLQ - C30 and its breast-specific module (BR-23) to highlight the health-related QOL of Kuwaiti women with breast cancer, in comparison with the international data, and assessed the socio-demographic and clinical variables that predict the five functional scales and global QOL (GQOL) scale of the QLQ - C30. METHODS: Participants were consecutive clinic attendees for chemotherapy, in stable condition, at the Kuwait Cancer Control Center. RESULTS: The 348 participants were aged 20-81 years (mean 48.3, SD 10.3); 58.7% had stages III and IV disease. Although the mean scores for QLQ - C30 (GQOL, 45.3; and five functional scales, 52.6%-61.2%) indicated that the patients had poor to average functioning, only 5.8% to 11.2% had scores that met the < or = 33% criterion for problematic functioning, while 12.0% to 40.0% met the >66% criterion for more severe symptoms. Most (47.8%-70.1%) met the >66% criterion for "good functioning" on the BR-23 functional scales. The mean scores of the QLQ - C30 indicated that, despite institutional supports, Kuwaiti women had clinically significantly poorer global QOL and functional scale scores, and more intense symptom experience, in comparison with the international data (i.e., < or = 10% difference between groups). For the BR-23, Kuwaiti women seemed to have clinically significantly better functional scale scores, but more severe symptoms, especially systemic side effects and breast symptoms. Younger women had poorer HRQOL scores. In regression analysis, social functioning accounted for the highest proportion of variance for GQOL. CONCLUSION: The relatively high number that met the criterion for good functioning on the functional scales is an evidence base to boost national health education about psychosocial prognosis in cancer. In view of the poor performance on the symptom scales, clinicians treating Kuwaiti women with breast cancer should prepare them for the acute toxicities of treatment and address fatigue. The findings call for the institution of a psycho-oncology service to address psycho-social issues.

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.