High-risk Breast Carcinoma Research Articles

Germline Mutations in BRCA1 and BRCA2 in Breast Cancer Patients with High Genetic Risk in Turkish Population.

Background The guidelines recommend considering the BRCA1 and BRCA2 germline mutations in female patients with breast carcinomas. In this retrospective study, the BRCA1/2 mutation prevalence in high-risk breast carcinoma patients in a Turkish population was investigated. Materials and Methods In high genetic risk breast carcinoma patients, the BRCA1 and BRCA2 germline mutations were identified by applying next-generation sequencing. Results The results showed BRCA1/2 mutations in 19% of the total patients. In those with first-degree relatives with breast carcinoma histories, the BRCA1/2 mutation prevalence was also 19%. In the patients younger than 40 years old, the BRCA1/2 mutation prevalence was 19.5%. In the triple-negative breast carcinoma patients younger than 60 years old, the BRCA1/2 mutation prevalence was 24.2%. In the patients younger than 40 years old with triple-negative breast carcinomas, BRCA1/2 mutation positivity was found in 37.5% of the patients. Overall, in the Turkish population, the BRCA1/2 mutation prevalence ranges from 19% to 37% in patients with high-risk breast carcinomas. Conclusion It is recommended to check for BRCA1/2 mutations in all high-risk breast carcinoma patients in the Turkish population.

The Role of <sup>18</sup>F-FDG-PET/CT in the Management of Patients with High-Risk Breast Cancer: Case Series and Guideline Comparison

Objectives: In grade III-IV breast cancer, dissemination of disease needs to be assessed. Until now this was done by conventional imaging (liver ultrasonography, chest X-ray and bone scintigraphy), but evidence favoring the use of FDG-PET/CT is accumulating. Methods: Patients with high-risk breast cancer, who had received conventional imaging and FDG-PET/CT, were included. Patients were staged and assigned a treatment after 1) conventional imaging and 2) FDG-PET/CT, both by a multidisciplinary oncology team. Equivocal FDG-PET/CT findings were histologically confirmed. Results: 16 patients were included (mean age 59 years). TNM-stage changed in 5 patients (31%) after FDG-PET/CT. In 3 patients (19%) unknown distant metastases were detected by FDG-PET/CT. An adjustment of treatment took place in 4 patients (25%). Conclusions: Our case series emphasizes the role of FDG-PET/CT in the staging of high-risk breast carcinoma, especially in the assessment of distant metastases. We suggest replacing conventional imaging with FDG-PET/CT.

Lobulitis in nonneoplastic breast tissue from breast cancer patients: association with phenotypes that are common in hereditary breast cancer

Lobular inflammation (lobulitis) has been demonstrated in benign breast tissue adjacent to in situ and invasive breast cancers and, more recently, in nonneoplastic tissue from prophylactic mastectomy specimens for hereditary high-risk breast carcinoma. The aim of this study is to investigate the incidence of lobulitis in benign breast tissue of patients with breast cancer and associated clinicopathologic features. We reviewed nonneoplastic breast tissue sections from 334 patients with invasive breast carcinoma to study lobulitis in normal breast tissue and to correlate its presence with clinicopathologic features of the associated tumor. Clinical information (age, menopausal status, and follow-up), tumor characteristics (type, grade, size, lymph node status, stage, estrogen and progesterone receptor, HER2), and survival were recorded. Characteristics of women with and without lobulitis were cross-classified with categories of clinical, pathologic, and histologic characteristics, and differences in distributions were tested in univariate and multivariate analysis. Lobulitis was found in 26 (8%) of 334 patients. The lymphocytic infiltrate was predominantly T-cell type. In a multivariate model, lobulitis in patients with breast cancer was significantly associated with younger age, triple (estrogen receptor, progesterone receptor, HER2)-negative cancers, and medullary phenotypes. Lobulitis in nonneoplastic breast tissue, away from tumor, is associated with clinicopathologic features more commonly seen in hereditary breast cancer.

Simultaneous radiotherapy and superficial hyperthermia for high-risk breast carcinoma: A randomised comparison of treatment sequelae in heated versus non-heated sectors of the chest wall hyperthermia

Purpose: In vitro data demonstrate that heat-induced radiosensitisation is maximised if hyperthermia and radiotherapy are given simultaneously, with the radiation fraction delivered midway through a hyperthermia session, rather than sequentially. The long-term normal tissue toxicity of full-dose simultaneous thermoradiotherapy is unknown.Materials and methods: Patients with locally advanced breast cancer (T3, T4 or more than three involved nodes or local recurrence), no prior radiotherapy, received between four and eight sessions of simultaneous thermoradiotherapy. Hyperthermia always included the primary tumour site. In addition an electively heated sector (EHS) was included. The EHS was randomised to either medial or lateral to the tumour site, with the other side an irradiated but unheated control. As per our usual practice, patients received surgery and/or chemotherapy prior to radiotherapy. Radiation doses were 46–50 Gy followed by a boost of ≤16 Gy at 1.8–2 Gy per fraction. EHS and control sectors received the same dose.Results: A total of 57 evaluable cases with average follow-up of 79 months experienced two local and two nodal recurrences. There was no significant difference in ≥grade 2 toxicity for heated versus control sectors (LR χ2 = 0.78, p = 0.38) with no relationship between number of hyperthermia sessions and toxicity (LR χ2 = 2.90, p = 0.09).Conclusions: Simultaneous full-dose thermoradiotherapy for breast cancer is feasible and well tolerated, with no significant difference in late toxicity between electively heated and unheated control sectors. All patients had hyperthermia to the primary tumour site with excellent local control.

The biological, clinical and prognostic implications of p53 transcriptional pathways in breast cancers

We hypothesized that the functional status of p53 transcriptional pathways, rather than p53 protein expression alone, could accurately discriminate between low- and high-risk breast carcinoma (BC) and inform about individuals' tumour biological behaviour. To test this, we studied a well-characterized series of 990 BCs with long-term follow-up, immunohistochemically profiled for p53, its main regulators and downstream genes. Results were validated in an independent series of patients (n = 245) uniformly treated with adjuvant anthracycline-based chemotherapy. Eleven p53 transcriptional phenotypes were identified with just two main clinical outcomes. (a) Low risk/good prognosis group (active/partially inactive p53 pathways), defined as p53(+/-)/MDM4(+)/MDM2(+/-)/Bcl2(+/-)/p21(+/-), p53(-)/MDM4(-)/MDM2(+)/Bcl2(+)/p21(+/-) and p53(+/-)/MDM4(-)/MMD2(-)/Bcl2(+)/p21(+/-). These tumours had favourable clinicopathological characteristics, including ER(+) and long survival after systemic adjuvant-therapy (AT). (b) High risk/poor prognosis group (completely inactive p53 pathways), defined as p53(+/-)/MDM4(-) MDM2(-)/Bcl2(-)/p21(-), p53(-)/MDM4(-) MDM2(+)/Bcl2(-)/p21(-) and p53(+/-)/MDM4(-)/MDM2(-)/Bcl2(-)/p21(+). These tumours were characterized by aggressive clinicopathological characteristics and showed shortened survival when treated with AT. Completely inactive p53 pathways but intact p21 axis p53(+/-)/MDM4(-)/MDM2(-)/Bcl2(-)/p21(+) had the worst prognosis, particularly patients who received AT. Multivariate Cox regression models, including validated prognostic factors for both test and validation series, revealed that the functional status of p53 transcriptional pathways was an independent prognosticator for BC-specific survival (HR 2.64 and 4.5, p < 0.001, respectively) and disease-free survival (HR 1.93 and 2.5, p < 0.001, respectively). In conclusion, p53 functional status determined by assessment of p53 regulatory and downstream targets provides independent prognostic value and may help determine more adequate therapeutic regimens for specific subgroups of breast cancer patients.

Simultaneous Radiation Therapy and Hyperthermia in the Elective Treatment of Subclinical Disease in High Risk Breast Carcinoma: A Phase III Comparison of Post Treatment Normal Tissue Effects in Heated and Unheated Portions of the Chest Wall

Simultaneous Radiation Therapy and Hyperthermia in the Elective Treatment of Subclinical Disease in High Risk Breast Carcinoma: A Phase III Comparison of Post Treatment Normal Tissue Effects in Heated and Unheated Portions of the Chest Wall

Randomized trial of high‐dose chemotherapy and autologous hematopoietic stem cell support for high‐risk primary breast carcinoma

The authors previously reported results from a randomized trial of standard-dose chemotherapy with combined 5-fluorouracil (1000 mg/m2 per cycle), doxorubicin (50 mg/m2 per cycle), and cyclophosphamide (500 mg/m2 per cycle) (FAC) versus FAC followed by high-dose chemotherapy (HDCT) and autologous stem cell support (ASCS) for patients with high-risk primary breast carcinoma. After a median follow-up of 6.5 years, no significant differences were observed in recurrence-free survival (RFS) or overall survival (OS) between the 2 arms. This report updates the survival analyses. Patients with >or=10 positive axillary lymph nodes after primary surgery or >or=4 positive lymph nodes at surgery after neoadjuvant chemotherapy were eligible. All patients were to receive 8 cycles of FAC. Patients were assigned randomly to receive either no further chemotherapy or 2 cycles of combined high-dose cyclophosphamide (5250 mg/m2 per cycle), etoposide (1200 mg/m2 per cycle), and cisplatin (165 mg/m2 per cycle) with ASCS. Primary endpoints were RFS and OS. RFS and OS were calculated by using the Kaplan-Meier method. The log-rank statistic was used to compare treatment arms. Between 1990 and 1997, 78 patients were registered, and 39 patients were assigned randomly to each arm. The median follow-up for all patients who were alive at last follow-up was 142.5 months (range, 45-169 months). An intention-to-treat analysis showed no significant difference between the 2 arms in terms of RFS (at 10 years: 40% with FAC vs. 26% with FAC plus HDCT; P=.11) or OS (at 10 years: 47% with FAC vs. 42% with FAC plus HDCT; P=.13). With a median follow-up of nearly 12 years for patients who remained alive, this trial continued to demonstrate no RFS or OS advantage for patients with high-risk primary breast carcinoma treated with HDCT after standard-dose FAC chemotherapy.

Studienteilnahme verbessert Therapiestrategien und individuelle Patientenversorgung in teilnehmenden Zentren

Die ADEBAR-Studie ist eine prospektive multizentrische Phase III Studie, die überprüft, ob Hochrisiko-Mammakarzinompatientinnen (>4 befallene axilläre Lymphknoten) von einem sequenziellen Anthrazyklin-Docetaxel Regime (E90C-D: 4 Zyklen Epirubicin [E] 90mg/m2 KOF plus Cyclophosphamid [C] 600mg/m2 KOF q21d, gefolgt von 4 Zyklen Docetaxel [D] 100mg/m2 KOF q21d) gegenüber der Standard-Chemotherapie mit Anthrazyklinen (FE120C: 6 Zyklen E60mg/m2 KOF d 1+8, 5-Fluorouracil 500mg/m2 KOF d 1+8 und C 75mg/m2 KOF d 1–14, q28d) profitieren. Mit insgesamt 198 aktiv rekrutierenden Zentren und einem medianen Patientinneneinschluss von 33,0 Patientinnen/Monat war die ADEBAR Studie die bis zum Studienende am besten rekrutierende Studie Deutschlands in ihrem Indikationsbereich.

Twelve-year follow-up of a randomized trial of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell support (ASCS) for high-risk primary breast carcinoma

663 Background: We previously reported on the results of a randomized trial of standard-dose chemotherapy with 5-fluorouracil, Adriamycin and cyclophosphamide (FAC) versus FAC followed by HDC and ASCS for high-risk primary breast cancer (J Natl Cancer Inst. 2000;92[3]:225–33). At a median follow-up of 6.5 years, no relapse-free (RFS) or overall survival (OS) advantage was seen between the two arms. Morbidity was increased with HDC. This report updates the survival analysis. Methods: Patients with ≥ 10 positive axillary nodes after primary surgery or ≥ 4 positive nodes at surgery following primary chemotherapy were eligible. All patients were to receive 8 cycles of FAC. Patients were stratified by stage, and randomly assigned to receive no further chemotherapy or 2 cycles of high-dose cyclophosphamide, etoposide, and cisplatin with ASCS. Primary endpoints were RFS and OS. Survival was calculated by the Kaplan-Meier method. The log-rank statistic was used to compare survival between treatment arms. Results: From 1990 to 1997, 78 patients were registered: 48 after primary surgery and 30 after primary chemotherapy. 39 patients were randomly assigned to FAC alone, and 39 to FAC followed by HDC. The median follow-up of live patients is 143 months (range 45 to 169 months). Detailed outcomes are shown in the table below. In intention-to-treat analysis, there was no significant difference in RFS (p = 0.114) or OS (p = 0.136) between the two groups by log-rank test. There have been no late toxicities since the last report. Conclusions: With 12 years of follow-up, this study continues to show no RFS or OS advantage associated with the use of HDC for high-risk primary breast carcinoma. No significant financial relationships to disclose.

Skin‐sparing mastectomy and immediate reconstruction is an acceptable treatment option for patients with high‐risk breast carcinoma

Skin-sparing mastectomy (SSM) followed by immediate reconstruction is an effective treatment option for patients with early-stage breast carcinoma, but its use in patients with more advanced disease is controversial. A retrospective review was performed that included 38 consecutive patients with high-risk breast carcinoma who underwent SSM and immediate reconstruction (between July 1996 and January 2002). Tumor characteristics, type of reconstruction, margin status, timing of adjuvant therapy, postoperative complications, and incidence of recurrence were evaluated. High-risk patients (Stage IIA [n=4 patients] Stage IIB [n=23 patients] Stage IIIA [n=8 patients] and Stage IIIB [n=3 patients]) underwent immediate reconstruction after SSM with the use of a transverse rectus abdominis myocutaneous flap (n=31 patients), a latissimus dorsi myocutaneous flap plus an implant (n=3 patients), or tissue expanders with subsequent implant placement (n=4 patients). The median follow-up was 52.9 months (range, 27.5-92.0 months), and the median time to recurrence has not yet been reached at the time of last follow-up. The median interval from surgery to the initiation of postoperative adjuvant therapy was 38 days (range, 25-238 days). Local recurrence was seen in 1 patient (2.6%), systemic recurrence in was seen in 10 patients (26.3%), and both local and distant metastases in were seen in 2 other patients (5.3%). SSM with immediate reconstruction appeared to be an oncologically safe treatment option for high-risk patients with advanced stages of breast carcinoma. In addition to the aesthetic and psychological benefits of performing SSM with immediate reconstruction, local recurrence rates and disease-free survival were favorable when combined with the use of radiation therapy and adjuvant chemotherapy, as indicated.

Prognostic significance of the immunocytochemical detection of contaminating tumor cells (CTC) in apheresis products of patients with high-risk breast cancer treated with high-dose chemotherapy and stem cell transplantation.

The aim of this study was to determine whether the detection of CTC in the apheresis product contribute significantly to treatment failure of patients with high-risk breast carcinoma treated with high-dose chemotherapy (HDC) and stem cell transplantation (SCT). Patients were with stage II and III adenocarcinoma of the breast with > or = 10 axillary lymph nodes affected after primary surgery (> or = 10 N+) who had received HDC with SCT. We analyzed retrospectively the presence of CTC as assessed by immunocytochemistry (ICC) in the apheresis products obtained after standard adjuvant chemotherapy. We compared the clinical outcome of patients who received HDC and SCT with or without CTC-positive apheresis. One hundred and twenty-seven apheresis products samples were obtained from 51 patients. Fourteen (27.4%) of these samples were CTC positive. After a median follow-up of 4.6 years, 20 patients have relapsed, 14 died from progression of their disease and 30 patients remain alive and free of progression. For the whole group of patients the 5 year probabilities of DFS and OS were 60% (IC 95%, 47-75%) and 71% (IC 95%, 55-83%), respectively. However, the 5 year probabilities of DFS were 23% (IC 95%, 0-46) and 75% (IC 95%, 60-89) for patients with CTC positive and negative, respectively. The 5 year probabilities of OS were 42% (IC 95%, 15-68) and 83% (IC 95%, 70-95) for patients with CTC positive and negative, respectively. Both univariate and multivariate analysis showed that the presence of CTC in the apheresis product was the only prognostic factor associated with a higher incidence of clinically overt disease relapse (P = 0.002) and shorter survival (P = 0.003). The presence of cytokeratin-positive metastatic cells in the apheresis product increases the risk of relapse after HDC and SCT in patients with stage II and III adenocarcinoma of the breast with > or = 10 N+.

High-dose mitoxantrone and cyclophosphamide without stem cell support in patients with high-risk and advanced breast carcinoma

Currently employed high-dose regimens for patients with breast carcinoma consist mainly of single-cycle combinations of alkylating agents. In a previous Phase I trial, the authors developed a tandem high-dose combination of two cycles of mitoxantrone and cyclophosphamide for the treatment of patients with metastatic breast carcinoma (MBC) and high-risk breast carcinoma (HRBC). Treatment was delivered with granulocyte-colony stimulating factor (G-CSF) but without stem cell support to avoid potential tumor cell reinfusion. The objective was to validate the safety and obtain preliminary efficacy assessment of this combination in a Phase II trial.Fifty-three patients were included: 27 patients with MBC and 26 patients with HRBC. After standard induction treatment, patients received two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 separated by a 4-week interval. Patients received G-CSF and ciprofloxacin until hematologic recovery. Follow-up was performed in an outpatient setting.One hundred one of 106 projected cycles (95%) were delivered. The mean dose intensities achieved were mitoxantrone 5.8 mg/m2 per week and cyclophosphamide 933 mg/m2 per week. Infection developed in 46% of the cycles, and platelet transfusions were required in 42%. Nonhematologic toxicity was mainly Grade 3 emesis. There were no toxic deaths. In 17 evaluable patients with MBC, 13 patients (77%) had response improvements, including 7 complete responses (41%).Treatment with two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 with G-CSF but without stem cell support was well tolerated. The dose intensities achieved approach those obtained with conventional high-dose therapy. This combination warrants further investigation as an alternative to conventional high-dose regimens.

EDITOR'S NOTE: re: randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma

EDITOR'S NOTE: re: randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma

RESPONSE: re: randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma

RESPONSE: re: randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma

Long term follow‐up of women treated with 16‐week, dose‐intensive adjuvant chemotherapy for high risk breast carcinoma

Long term follow‐up of women treated with 16‐week, dose‐intensive adjuvant chemotherapy for high risk breast carcinoma

Long term follow-up of women treated with 16-week, dose-intensive adjuvant chemotherapy for high risk breast carcinoma

A Phase II study was performed evaluating the disease free and overall survival rates associated with a dose-intensive, 16-week, doxorubicin-based adjuvant chemotherapy regimen in women with breast carcinoma and > or = 10 involved axillary lymph nodes. Eligible patients underwent staging with computed tomography and bone scanning and were treated with a 16-week, dose-intensive chemotherapy regimen, comprised of 8 2-week courses of cyclophosphamide, 100 mg/m2 orally, on Days 1-7; doxorubicin, 40 mg/m2 intravenously (i.v.), on Day 1; methotrexate, 100 mg/m2 i.v., on Day 1 with leucovorin rescue, 10 mg/m2, every 6 hours for 6 doses orally on Day 2; vincristine, 1 mg i.v. on Day 1; 5-fluorouracil (5-FU), 600 mg/m2 i.v., on Day 2 over 2 hours; and 5-FU, 300 mg/m2/day continuous i.v. on Days 8 and 9. Tamoxifen, 20 mg daily, was administered to patients with estrogen receptor positive tumors treated after October 1988. All patients were offered locoregional radiation therapy. Sixty-four women were treated on protocol. The median follow-up of 27 surviving patients was > 8 years at last follow-up. Three patients were lost to follow-up. The median time to progression was 54 months, the Kaplan-Meier estimate of event free survival at 5 years was 44% (95% confidence interval [CI], 31-56%), and the Kaplan-Meier estimate of overall survival at 5 years was 57% (95% CI, 44-69%). At 98 months the Kaplan-Meier estimate of freedom from recurrence was 31% (95% CI, 19-43%) and the Kaplan-Meier estimate of survival at 111 months was 36% (95% CI, 23-49%). Despite the use of dose-intensive, doxorubicin-based, adjuvant chemotherapy, and intensive staging prior to study entry, the results of the current study are similar to those of previous reports for standard dose chemotherapy and appear inferior to those reported for high dose therapy.

Establishment of Histological Criteria for High-risk Node-negative Breast Carcinoma for a Multi-institutional Randomized Clinical Trial of Adjuvant Therapy

A multi-institutional randomized clinical trial of adjuvant therapy for patients with high-risk node-negative (n0) breast cancer has been undertaken in Japan. The pathology panel was organized in order to establish histological criteria to identify patient groups with higher rates of recurrence. Initially, three pathologists independently judged the nuclear grade, composed of nuclear atypia and mitotic counts, of 100 n0 invasive ductal carcinomas, focusing on interobserver variation of the nuclear grade and its correlation with patient prognosis. These pathologists then gave consensus histological types and nuclear grades for 130 other n0 breast carcinomas and examined the prognostic significance of the grade. In the first study, nuclear grade 2-3 significantly identified a patient group with a rate of recurrence of 17-20% by any pathologists and the degree of agreement for the grade was fair. In the second study, the consensus type and nuclear grade identified a group (n = 66) with a 22% recurrence rate and another group (n = 64) with a 3.6% recurrence rate at 10 years. In 12 tumors, the resection-fixation interval of the tumor did not generate any significant difference in mitotic counts. The histological type and the nuclear grade clearly identified a higher-risk patient group with n0 breast carcinoma, and may be applied to the multi-institutional protocol study when the criteria have been well standardized by the pathologists.

Breast conservation without axillary dissection: the role of axillary radiotherapy

Breast cancer is a heterogeneous disease. Many women who are given adjuvant cytotoxic chemotherapy for breast cancer receive no benefit from this treatment because established micrometastases are resistant to the chemotherapy. Integrated analysis of genetic alterations that i) disregulate the cell division process, resulting in faster cell proliferation, ii) affect physiologically cell death mechanisms that cause slower rates of cell loss and iii) enhance drug resistance, may be useful for defining the biology of response of breast carcinoma to adjuvant treatment. Immunohistochemistry with antibodies recognizing ER, PgR, Ki-67, HER-2/neu, ~53, bcl-2, encoded products was performed on 156 primary high risk breast carcinoma (Premenopausal patients: T> 1 cm, G2-3, NO1, any ER/PgR status; Postmenopausal: T> 1 cm, G2-3, NO-l, ER-/PgR-) who received four cycles of adjuvant HD EC (Epirubicin 120 mg/m’ iv. on day 1, Cyclophosphamide 600 mg/m2 i.v. on day 1) with or without Lonidamine between March 1991 and December 1993. Graphical correspondence analysis of multivariate relationship showed that a p53-, bcl-2+, HER-Uneu-phenotype with nuclear grade 2 and low Ki-67 score characterizes most lobular carcinomas (ILC) while ductal carcinomas (IDC) were frequently identified by a bc12-, p53+, HER-2/ neu-phenotype with nuclear grade 3 and high Ki-67 score. Separate multivatiate analysis (Cox model) demonstrated an independent prognostic role of ~53, nodal status and Ki-67 score in predicting short-term (36 months) disease-free-survival in the IDC group whereas only bcl-2 emerged as significant predictive parameter in the ILC group. Multiparametric analysis conducted on several biopathological parameters might be useful for distinguishing different biological behaviours of breast carcinoma in the adjuvant setting. Our findings suggest that bcl-2 and ~53 may play an important role in ILC and IDC respectively.

Prolonged nausea and vomiting after high dose chemotherapy and autologous peripheral stem cell transplantation in the treatment of high risk breast carcinoma.

Nausea and vomiting immediately after chemotherapy is a well recognized complication of cancer drug treatment; it is usually short-lived and controllable by modem antiemetics. The authors report a high incidence of prolonged nausea and vomiting after high dose chemotherapy with autologous peripheral stem cell transplantation (PSCT) in the treatment of high risk breast carcinoma patients. Patients with high risk breast carcinoma were conditioned with high dose carmustine, cisplatin, and cyclophosphamide followed by autologous PSCT. In Part I of the study, patients who received PSCT at UCLA Medical Center were identified if they were either readmitted with dehydration secondary to nausea and vomiting or referred to a gastroenterology specialist for the treatment of intractable nausea and vomiting. In Part II of the study, the authors examined a series of 38 women treated at UCLA Medical Center in 1993 for high risk breast carcinoma to determine the incidence of prolonged postchemotherapy nausea and vomiting (PPNV) after PSCT. These women were followed at 2-week intervals with a quality of life evaluation that included questions about nausea and vomiting. In Part I of the study, the authors identified 9 women with more than 1 month of significant nausea and vomiting after PSCT without evidence of obstruction or mucositis. Hospitalization was frequently required for hydration. Gastroparesis was found in all four patients who underwent gastric emptying studies. The nausea and vomiting responded to the promotility drug cisapride and high dose corticosteroids. In Part II of the study, the authors found that PPNV was frequent; 24% of patients had significant nausea and 18% had significant vomiting 6 weeks after PSCT, despite treatment with standard antiemetics. PPNV is a frequent complication of high dose chemotherapy with the aforementioned regimen. It may be due to gastroparesis and represents a form of gastrointestinal toxicity to chemotherapy not previously reported.

971 Preliminary results of a randomized study of 1 VS 2 910 MG/M/SQM doses of amifostine in high-RDI cyclophosphamide (CPM)-epirubicin (EDOX) in patients with high risk breast carcinoma

In an effort to reduce hematological toxicity of a dose-intensive regimen (CPM 1200 mg/m2 & EDOX 75 mg/m2 every 14 days) given for 6 courses in patients with metastatic, inflammatory or N + > 5, patients received in a randomized parallel design 1 dose (arm A) (910 mg/m2) or 2 doses (arm B) 4 hours apart. This design aimed at giving the 2nd dose at the expected Cmax of phosphoramide mustard. This exploratory analysis concerns 6 pts and 30 cycles in each arm. No growth factor was allowed. Efficacy was estimated through blood-cell counts (G/1) at d14 (mean), as no recovery period was considered. WBC PLT C1 C2 C3 C4 C5 C6 C1 C2 C3 C4 C5 C6 A 1.2 2.1 1.5 2.4 .9 NA 293 262 384 155 154 NA B 1.6 1.2 1.9 .8 .9 NA 327 238 222 76 300 NA While incidence of emesis was similar, hypotension was observed in 15/30 cycles in arm B as compared to 0/30 in arm A. This preliminary analysis does not suggest increased efficacy of 2 doses of amifostine compared to 1 in patients receiving dose intensive CPM-EDOX while amifostine induced hypotension was observed more often in patients scheduled to receive 2 protective doses.