[Show abstract][Hide abstract] ABSTRACT: We screened the 185delAG and 5382insC (BRCA1) and the 6174delT (BRCA2) mutation in 298 Spanish women with breast cancer. Two women (one with Sephardic ancestors) presented the 185delAG mutation and the same haplotype reported in Ashkenazim with this mutation. This suggests a common origin of the 185delAG in both Sephardic and Ashkenazi populations.
Full-text · Article · Apr 1999 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Germline mutations in the BRCA1 gene have been associated with familial breast/ovarian cancer. Furthermore, women diagnosed of early-onset breast cancer have a higher probability of being carriers of BRCA1 mutations. Our aim was to know prevalence of BRCA1 mutations in women with breast cancer diagnosed before 40 years.
We analyzed genomic DNA samples of 159 women with early-onset breast cancer. Ten fragments of BRCA1 gene covering the 36% of cases with mutations described in the literature were screened. Analysis involved polymerase chain reaction (PCR), single-strand conformation polymorphisms (SSCP) and direct sequencing.
Three germline BRCA1 mutations were identified, one of them not previously described. Two mutations were found in women with familial history of breast cancer. Five additional rare variants and polymorphisms were also detected.
The absence of recurrent mutations or mutations detected in other countries, except for the 185delAG mutation, present in Ashkenazim population, shows the influence of ethnic and geographic origin of population studied, and illustrates the difficulties of establishing DNA-based screening tests for hereditary breast cancer.
No preview · Article · Feb 1999 · Medicina Clínica
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Germline mutations in the BRCA1 gene have been associated with familial breast/ovarian cancer. Furthermore, women diagnosed of early-onset breast cancer have a higher probability of being carriers of BRCA1 mutations. Our aim was to know prevalence of BRCA1 mutations in women with breast cancer diagnosed before 40 years. PATIENTS AND METHODS: We analyzed genomic DNA samples of 159 women with early-onset breast cancer. Ten fragments of BRCA1 gene covering the 36% of cases with mutations described in the literature were screened. Analysis involved polymerase chain reaction (PCR), single-strand conformation polymorphisms (SSCP) and direct sequencing. RESULTS: Three germline BRCA1 mutations were identified, one of them not previously described. Two mutations were found in women with familial hystory of breast cancer. Five additional rare variants and polymorphisms were also detected. CONCLUSIONS: The absence of recurrent mutations or mutations detected in other countries, except for the 185delAG mutation, present in Ashkenazim population, shows the influence of ethnic and geographic origin of population studied, and illustrates the difficulties of stablishing DNA-based screening tests for hereditary breast cancer.
No preview · Article · Jan 1999 · Medicina Clínica
[Show abstract][Hide abstract] ABSTRACT: Cellular DNA content and proliferation rates have been suggested as prognostic factors in breast carcinomas. A series of 271 lymph-node negative breast carcinoma patients without adjuvant therapy was reviewed (mean follow-up, 108 mo). Tumor cells from the same paraffin-embedded block tissue (Hedley's method) were analyzed by image analysis (IA) in Feulgen-stained smears and by flow cytometric analysis (FC). Clinicopathologic features, ploidy, S-phase fraction, and percentage of tumor cells with more than 5n DNA content (in diploid tumors, by IA) were related to outcome. The results of IA and FC were compared in 115 cases. Tumor size, histologic grade, desmoplasia and S-phase fraction were significant predictors of survival in multivariate analysis (Cox proportionate regression) (P < or = 0.03). Ploidy by the two methods showed agreement in 100 carcinomas (87%). Of the 15 discordant cases, FC detected 6 multiploid and 4 aneuploid-peridiploid. In contrast, IA detected more tetraploid carcinomas. Tumor size, histologic grade, desmoplasia, and S-phase fraction were independent predictors of long-term prognosis in our patients. Ploidy and percentage of tumor cells with more than 5n DNA content were not prognostic indicators. FC detected aneuploidy more frequently than did IA.
No preview · Article · Apr 1997 · Modern Pathology
[Show abstract][Hide abstract] ABSTRACT: In the last years high dose chemotherapy (HDC) schedules have been developed with autologous bone marrow transplantation (ABMT) which are very effective in breast cancer. Expectation has been raised concerning the cure of a subgroup of patients with metastatic breast cancer and the improvement of prognosis in high risk stages II and III.
CTCb (cyclophosphamide 6 g/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2) was administered with autologous peripheral hematopoietic progenitor cells transplantation (TACPHP) and granulocytic colony stimulating factor (G-CSF) 5 micrograms/kg/day to 27 patients with breast cancer: 9 in stage IV in complete remission, 12 in stage II with > or = 10 affected lymph nodes and 6 in stage III.
No toxic deaths were reported. The median time to achieve > or = 0.5 x 10(9) neutrophils/l was 8 days, to > or = 20 x 10(9) platelets/l 9 days and to > or = 50 x 10(9) platelets/l 12 days. Fever was observed in 85% of the patients although its median duration was of only one day. Extrahematologic toxicity was moderate with grade III nausea/vomiting in 48% of patients, grade III mucositis in 22%, grade III hepatitis in 19%, and grade III diarrhea in 4%. No grade IV toxicity was observed. The median follow-up is still short (10 months, range: 2-25). All the patients maintain normal hematologic peripheral blood counts and only 4 (in stage IV) have relapsed.
The slight extrahematologic toxicity observed in the high dose chemotherapy with cyclophosphamide, thiotepa and carboplatin, and the rapid hematologic recovery provided by the TACPHP and G-CSF allow the above schedule to be administered with moderate toxicity and no mortality. This low toxic profile leads to the possibility of future trials with this chemotherapy schedule in other subgroups of patients with breast cancer.
No preview · Article · Oct 1995 · Medicina Clínica
[Show abstract][Hide abstract] ABSTRACT: One hundred patients with metastatic breast cancer were randomly selected to receive combined chemotherapy treatment with adriamycin (50 mg/m2) or mitoxantrone (12 mg/m2) associated with 5-fluorouracil (600 mg/m2) and cyclophosphamide (600 mg/m2) administered intravenously every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherapy for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statistically significant differences in pretreatment characteristics or metastatic disease location between the two groups. Ninety-four patients were assessable for response. No differences were observed in response rate or in survival between the groups. The response rate (complete response (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients were assessable for toxicity. There were no differences in gastrointestinal and cardiac toxicity. More grade I-II hematologic toxicity episodes (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were observed with the CNF group, and more grade III alopecia (p < 0.001) was observed with the CAF group. Patients received further therapeutic manoeuvres after finishing the study with a sequential treatment consisting of hormonal therapy and chemotherapy with mitomycin (M) -vinblastine (Vbl) (M 10 mg/m2 day 1, Vbl 5 mg/m2 days 1, 15 and 29; maximum 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34% and grade III-IV hematologic toxicity of 37%. Treatment with CNF can be considered a good alternative to CAF for first-line treatment of metastatic breast cancer. M-Vbl treatment is useful as second-line treatment in patients with prior adriamycin exposure.
No preview · Article · Apr 1995 · Breast Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic progenitor cells mobilized to peripheral blood by a chemotherapy combined or not with hematopoietic growth factors and harvested with cyto-apheresis (CTA) provide a rapid hematological recovery when infused as a support step after intensive chemotherapy (IC).
Cyclophosphamide (CI) 4 g/m2 and G-CSF 5 mcg/kg/d were administered to 19 patients with a solid tumor or lymphoma. Daily CTA were performed during hematological recovery to harvest > 2.5 x 10(6) cells CD34+/kg. Seventeen patients received IC with infusion of peripheral hematopoietic progenitor cells (PHPC) and G-CSF.
A total of 52 CTA were performed, with a median (M) of 2 per patient. A M of 4.4 x 10(8) mononucleated cells/kg and 9.8 x 10(6) CD34+/kg were harvested per patient. Hematological recovery after IC with support of PHPC and G-CSF was rapid in all cases, but the aplastic period was shorter in the ten patients who received > 5 x 10(6) CD34+/kg cells than in the seven patients with < 5 x 10(6) kg: The median of recovery to neutrophils > 0.5 x 10(9)/l was 8 days compared with 9 days (p = 0.0005), to platelets > 20 x 10(9)/l of 8 days compared with 12 days (p = 0.001), and to platelets > 50 x 10(9)/l of 11 days compared with 14 days (p = 0.001).
Toxicity of IC (4 g/m2) with G-CSF is moderate and allows the harvesting of an adequate number of PHPC. Its infusion after IC provides a rapid hematological recovery, which was more marked in patients receiving 5 x 10(6) CD34+/kg cells, than with the same IC schedules of IC with autologous bone marrow transplantation.
No preview · Article · Mar 1995 · Revista Clínica Española
[Show abstract][Hide abstract] ABSTRACT: Advanced ovarian neoplasm has bad prognosis. There is little knowledge as to the effect of surgical and chemotherapy treatments on long-term survival.
Seventy-two patients with advanced epithelial ovary carcinoma (53 stage III and 19 stage IV) were treated according to a treatment regimen with reduction surgery, five cycles of chemotherapy with cyclophosphamide, adriamycin and cisplatin (CAP) followed by second revision laparotomy.
The rate of response for the CAP schedule was 80%, of which 16 patients (23%) showed complete response (CR), 7 (10%) partial microscopic response (PMiR) and 33 (47%) partial macroscopic response (PMR). Complete resection of residual masses was performed on the second laparotomy in 14 of the 33 patients with parital response. The median survival for all the group was 36 months with overall actuarial survival of 27% at 10 years. The survival of the group of patients with CR was significantly longer than that of PMiR and other groups. Significant differences favorable for the group of partial response with second attempt radical surgery were found versus the group in which te second surgical resection was not radical. FIGO III stage and prechemotherapy tumor size less than 5 cm were found to have favorable effect in the rate of response and survival.
The use of CAP chemotherapy achieved complete response in 23% of the patients studied. This group of patients showed to have a greater probability of longer survival. Second attempt surgery on the second laparotomy offers therapeutic benefits when radical.
No preview · Article · Mar 1995 · Medicina Clínica
[Show abstract][Hide abstract] ABSTRACT: Endometrial cancer is the most frequent gynaecologic neoplasia in women. Stages I and II account for 75% of endometrial cancers.
Diagnostic features, treatment and outcome based on therapy with surgery and/or irradiation of 185 endometrial cancer patients in Stage I and II were analysed retrospectively.
There were 148 patients (80%) in Stage I and 37 (20%) in Stage II. Twenty-nine patients (16%) relapsed and 18 have died of cancer. The 5 and 10 year specific actuarial survival was 89% and 81% respectively. The 5 and 10 years disease free survival was 82% and 78% respectively. In our analysis of prognostic factors we observed a significantly worse survival for postmenopausal and Stage II patients, high grade tumors (grade III) and greater myometrial penetration (outer 2/3).
Endometrial cancer has a relatively good prognosis partly because of its early diagnosis. There is general consensus that surgery is the optimal treatment in Stages I and II. While it is well documented that complementary irradiation improves survival in Stage II, there is no general agreement regarding the value of complementary irradiation in Stage I. Further studies are needed to delimit Stage I patients who would benefit from complementary irradiation.
No preview · Article · Feb 1995 · European journal of gynaecological oncology
[Show abstract][Hide abstract] ABSTRACT: A patient with an asymptomatic primary ovarian carcinoma preceded several months before by a solitary intracranial metastasis is reported. The rarity of this phenomenon, the therapeutic experience in this patient, and the possible mechanism of spread are discussed. Also, a review of the literature is made.
No preview · Article · Jun 1992 · Gynecologic Oncology
[Show abstract][Hide abstract] ABSTRACT: The effects of tamoxifen (TAM) versus the alternating sequential combination of TAM plus medroxy-progesterone acetate (MPA) has been evaluated in 20 postmenopausal patients with advanced breast cancer in a randomized controlled trial. In the TAM arm, patients received 20 mg b.i.d. of TAM. In the TAM-MPA arm, patients received only 20 mg b.i.d. of TAM for 7 days and, on the following 7 days. TAM plus an oral daily dose of 500 mg of MPA, in alternating sequence. Objective tumor reduction was achieved in 22 (41%) of the 54 patients in the TAM arm and in 25 (43%) of the 58 patients in the TAM-MPA arm. With regard to the stabilization of disease, a significant difference was observed between patients treated with the TAM-MPA combination and those treated with TAM alone (47% vs 22%). The percentage of nonresponders was also significantly higher in the TAM group (37%) than in the TAM-MPA group (10%). The time to progression was significantly shorter for the TAM arm than for the TAM-MPA arm (median, 7 vs 15 months), but the duration of remission was not significantly different for either treatment.
No preview · Article · Aug 1991 · Annals of Oncology