Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer-results from an international, multicenter analysis coordinated by the AGMT Study Group.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.

Two-stage hepatectomy: who will not jump over the second hurdle?

BACKGROUND: Two-stage hepatectomy uses compensatory liver regeneration after a first noncurative hepatectomy to enable a second curative resection in patients with bilobar colorectal liver metastasis (CLM). OBJECTIVE: To determine the predictive factors of failure of two-stage hepatectomy. METHOD: Between 2000 and 2010, 48 patients with irresectable CLM were eligible for two-stage hepatectomy. The planned strategy was a) cleaning of the left hepatic lobe (first hepatectomy), b) right portal vein embolisation and c) right hepatectomy (second hepatectomy). Six patients had occult CLM (n = 5) or extra-hepatic disease (n = 1), which was discovered during the first hepatectomy. Thus, 42 patients completed the first hepatectomy and underwent portal vein embolisation in order to receive the second hepatectomy. Eight patients did not undergo a second hepatectomy due to disease progression. RESULTS: Upon univariate analysis, two factors were identified that precluded patients from having the second hepatectomy: the combined resection of a primary tumour during the first hepatectomy (p = 0.01) and administration of chemotherapy between the two hepatectomies (p = 0.03). An independent association with impairment to perform the two-stage strategy was demonstrated by multivariate analysis for only the combined resection of the primary colorectal cancer during the first hepatectomy (p = 0.04). CONCLUSION: Due to the small number of patients and the absence of equivalent conclusions in other studies, we cannot recommend performance of an isolated colorectal resection prior to chemotherapy. However, resection of an asymptomatic primary tumour before chemotherapy should not be considered as an outdated procedure.

[Predictive factors of tumour response after neoadjuvant chemoradiation for locally advanced rectal cancer and correlation of these factors with survival]. / Facteurs prédictifs de réponse à la radiochimiothérapie néoaduvante dans les cancers rectaux localement évolués et corrélation de ces facteurs avec la survie.

PURPOSE: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumour response to survival and to identify predictive factors for tumour response after chemoradiation. PATIENTS AND METHODS: From 1998 to 2008, 168 patients with histologically-proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluoro-uracil-based chemotherapy. Analysis of tumour response was based on the lowering of T stage between pre-treatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival was correlated with tumour response. Tumour response was analysed with predictive factors. RESULTS: The median follow-up was 34 months. Five-year disease-free survival and overall survival were respectively of 44.4% and 74.5% in the whole population, 83.4% and 83.4% in patients with pathological complete response, 38.6% and 71.9% in patients with tumour downstaging, 29.1% and 58.9% in patients with absence of response. A pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was significantly associated with tumour downstaging and significantly independently associated with pathologic complete tumour response (P = 0.019). CONCLUSION: Downstaging and complete response after chemoradiation improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was associated with complete tumour response, hence with tumour downstaging.

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

BACKGROUND: This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. PATIENTS AND METHODS: From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. RESULTS: After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). CONCLUSION: T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy.

Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: New neoadjuvant regimen was safe and provided an interesting pathologic response.

PURPOSE: To assess the safety and efficacy of a new neoadjuvant chemoradiation (CRT) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body. PATIENTS AND METHODS: 34 patients with histologically-confirmed resectable pancreatic adenocarcinoma were included in this prospective two-center phase II study. Radiotherapy was delivered at the dose of 45 Gy in 25 fractions of 1.8 Gy per fractions, 5 days/week, over 5 weeks. Docetaxel was administered as a 1-h intravenous (IV) infusion repeated every week during 5 weeks. The dose was 30 mg/m(2)/week. All patients were restaged after completion of CRT. RESULTS: Tumor progression was documented in 11 patients (32%), stable disease was documented in 20 patients (59%), and partial remission was documented in 3 patients (9%). 23 patients still with local disease at restaging underwent explorative laparotomy. Of this, 17 patients (50%) had a curative pancreaticoduodenectomy with lymphadenectomy. Morbidity and mortality rates were 29% and 0%, respectively. Three patients (17%) had complete histological responses and 5 patients had minimal residual disease. All resected patients (n = 17) underwent R0 resection. The median and five-year survival times for the resected patients were 32 months and 41%, respectively. Among the resected patients, ten (59%) died as a result of recurrent pancreatic cancer without local tumor bed recurrence. CONCLUSIONS: Neoadjuvant docetaxel-based chemoradiation is well-tolerated. Resected patients had a prolonged survival time. Further studies are needed to confirm our findings and determine the role of such a neoadjuvant approach.

Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma.

BACKGROUND: The most accepted treatment for locally advanced pancreatic adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated by neoadjuvant CRT. METHODS: From January 1996 to December 2006, 64 patients with LAPA (borderline, n=49; unresectable, n=15) received 5-fluorouracil-cisplatin-based CRT. Of the 64 patients, 47 had progressive disease at restaging. Laparotomy was performed for 17 patients, and PD was performed in 9 patients (resected group). Fifty-five patients had CRT followed by gemcitabine-based chemotherapy (unresected group). RESULTS: The median survival and overall 5 years survival duration of all 64 patients were 14 months and 12%, respectively. The mean delay between diagnosis and surgical resection was 5.5 months. Mortality and morbidity from PD were 0% and 33%, respectively. The median survival of the resected group vs. the unresected group was 24 months vs. 13 months. Three specimens presented a major pathological response at histological examination. No involved margins were found and positive lymph nodes were found in one patient. Resected patients developed distant metastases. CONCLUSIONS: PD after CRT was safe and resected patients had interesting survival rates. However, resected patients developed metastatic disease and new neoadjuvant regimens are needed to improve the survival of these patients.

A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802).

BACKGROUND: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse. PATIENTS AND METHODS: A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS). RESULTS: Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (CI) 53% to 66%] and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% CI 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53% to 67%) in arms A and B, respectively. CONCLUSION: Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.

Phase I trial of oxaliplatin with fluorouracil, folinic acid and concurrent radiotherapy for oesophageal cancer.

This dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended doses (RDs) of 5-fluorouracil (5FU), folinic acid and oxaliplatin (FOLFOX) with concomitant radiotherapy in inoperable/metastatic oesophageal squamous cell carcinoma or adenocarcinoma. Patients received three courses of LV5FU2 regimen (folinic acid 200 mg m(-2), bolus 5FU 300-400 mg/m(2), continuous infusion 5FU 400-600 mg m(-2) on days 1 and 2) and escalating doses of oxaliplatin 50 to 100 mg m(-2) on day 1 (FOLFOX). This regimen was repeated every 2 weeks, concomitant to a 50-gray radiotherapy per 5 weeks. Three more cycles were delivered after completion of radiation therapy. Three to six patients were allocated to each of the five dose levels until MTD was reached. Thirty-three patients were enroled and 21 had metastatic disease. Maximum tolerated dose was oxaliplatin 100 mg m(-2), and continuous infusion 5FU was 600 mg m(-2) day(-) (level 5). The most common toxicities were neutropenia, dysphagia and oesophagitis. The RDs were those of FOLFOX-4 regimen (oxaliplatin 85 mg m(-2) and full doses of LV5FU2). The overall response was 48.5%, including 12% complete response. Response rate on primary tumour was 62.9%. This FOLFOX-4 regimen was reasonably well tolerated and effective in inoperable/metastatic oesophageal carcinoma and warrants additional investigation.

Tritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases.

PURPOSE: To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRINOX. PATIENTS AND METHODS: Patients with histologically proven primary colorectal cancer and bidimensionally measurable liver metastasis, not fully resectable based on technical inability to achieve R(0) resection, but potentially resectable after tumor reduction, were given FOLFIRINOX: oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), bolus fluorouracil 400 mg/m(2) and fluorouracil 46-h continuous IV infusion 2,400 mg/m(2), every 2 weeks for a maximum of 12 cycles. RESULTS: Thirty-four patients were enrolled. Response rate before surgery was 70.6% (95%CI: 52.5-84.9). Twenty-eight patients (82.4%) underwent hepatic resection and nine achieved R(0) resection [26.5% (95% CI: 12.9-44.4%)]. The rate of clinical complete remission after surgery was 79.4%. Two-year overall survival was 83%. The most frequent grade 3 or 4 toxicities were neutropenia (64.8%), diarrhea (29.4%), fatigue (23.5%), abdominal cramps (14.7%), neuropathy and nausea (11.8% each), and AST/ALT elevation (14.7/11.8%). Only one patient experienced febrile neutropenia, four patients withdrew due to toxicity and no toxic death was observed. CONCLUSION: FOLFIRINOX, with an acceptable toxicity profile, shows a high response rate in liver metastases from colorectal cancer. The rate of hepatic resection in patients initially not resectable, is attractive and warrants further assessment of this regimen in randomized studies compared to standard regimens.

Multicystic peritoneal mesothelioma: report of three cases.

Multicystic peritoneal mesothelioma is a rare lesion occurring mainly in women in a reproductive age. Its pathogenesis is unclear. We report three cases of multicystic peritoneal mesothelioma in patients that were 28, 38 and 47 years of age (one male, two females). A history of abdominal surgery was reported in two cases. Explorative laparotomy was presumptive of a pseudomyxoma peritoni in two cases, and hyperthermic intraperitoneal chemotherapy was performed. Histological examination demonstrated multicystic lesions with mesothelial cells lining confirmed by immunohistochemical analysis. Unusual findings such as hyperplasia, hobnail features, cytoplasmic vacuolisation and papillary pattern were occasionally noted. The clinical presentation, pathogenesis and pathologic features including differential diagnosis of multicystic peritoneal mesothelioma are discussed.

Strategies for the treatment of synchronous liver metastasis.

AIM: Observe the outcomes after complete simultaneous or delayed resection of synchronous liver metastasis (SLM) from colorectal cancer (CRC). METHODS: From 1994 to 2005, 119 patients were diagnosed with CRC and SLM; 57 patients had simultaneous resection (group I) and 62 patients had staged resection (group II). Perioperative chemotherapy was considered completed if all expected cycle were administrated. RESULTS: Overall survival rates of group I-group II at 1, 3 and 5 years were respectively 91%-93% (p=0,3), 59%-57% (p=0,09) and 32%-25% (p=0,06). The median survival time of group I-group II were respectively 46 months-40 months (p=0,07). There was no statistical difference on survival regarding location of metastasis (p=0,09) or primary tumor location (p=0,2). Patients with simultaneous or staged resection receiving optimal treatment (R0 liver surgery and complete chemotherapy) were respectively 89% and 67% (p=0,04). Twenty three patients developed isolated liver recurrence with higher frequency in staged patients (26% vs 9% p=0,03) without impairment of survival. CONCLUSIONS: Because of postoperative morbidity and prolonged tiring treatment, many patients having staged resection were under treated. However we did not observe statistical difference on survival but we supported that simultaneous resection has to be prefer to achieve an optimal treatment. Lung and bone metastasis are the new challenge for oncologists.

Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol.

Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTD<12 mg/m2). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m2/day x 5 days. Limiting toxicities were defined as toxic death, grade IV non-haematopoietic or haematopoietic toxicity >6 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m2/day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m2/day. Pharmacokinetic data were linear within the dose range of 4-9.0 mg/m2/day. The MTD was reached at 9 mg/m2/day x 5 days.

Long term morbidity of neoadjuvant chemoradiation for pancreatic head adenocarcinoma.

PURPOSE: To report the long term risks of neoadjuvant chemoradiation (NCRT) after duodenopancreatectomy (DP) for adenocarcinoma of the head of pancreas. METHODS: Between January 1996 and December 2002, 26 patients with biopsy-proven adenocarcinoma of the head of pancreas were treated by this combination of therapies. RESULTS: Two patients had delayed NCRT-related small bowel infarction: one died from superior mesenteric artery stenosis 36 months after DP without recurrence at laparotomy; there was one limited infarction 16 months after DP. CONCLUSIONS: Long term vascular morbidity after NCRT is significant.

[Major hepatectomy for metastasis of colorectal cancer improves survival in the elderly]. / Hépatectomie majeure pour métastases de cancers colorectaux chez le sujet âgé.

OBJECTIVE: Assessing impact of major liver resection (LR) for hepatic metastasis of colorectal cancer (HMCC) on post operative courses and long term survival in the elderly. PATIENTS AND METHOD: Thirty-three consecutive patients aged over 70 years-old were treated in our institution for up to 3 resectable metachronous HMCC. Fifteen patients had major LR (9 right hepatectomy, 3 extended right hepatectomy, 3 left hepatectomy) without pre or postoperative chemotherapy (group 1) and 18 patients were exclusively treated by chemotherapy (group 2) because of high ASA score (ASA 3) or patients refusal. RESULTS: No patients died of another cause that colorectal cancer disease during observation time. All patients of group 2 died during observation time. Post operative mortality and morbidity of group 1 were respectively 0% and 33%. Survival at 1 and 2 years of group 1-2 were respectively 73-50% (P=0,04) and 47-15% (P=0,05). Median survival of group 1 and 2 were respectively 22 and 12 months (P=0,03). CONCLUSIONS: Major LR for HMCC could be proposed regardless the age. High ASA score, multiple (more than 4) metastasis location, evolutive disease could justify an exclusive medical approach.

High-dose alkylating agents with autologous hematopoietic stem cell support and trastuzumab in ERBB2 overexpressing metastatic breast cancer: a feasibility study.

BACKGROUND: ERBB2 overexpression predicts a worse outcome for patients receiving high-dose chemotherapy (HDC). Trastuzumab improves response rate and survival in ERBB2 overexpressing metastatic breast cancer patients (MBC). We investigated the feasibility of combining high-dose alkylating agents with autologous hematopoietic stem cell (AHSC) support and trastuzumab in ERBB2 overexpressing MBC. PATIENTS AND METHODS: Eleven consecutive patients with pre-treated ERBB2 overexpressing MBC were enrolled. HDC regimen consisted of a single course of cyclophosphamide 120 mg/kg + melphalan 140 mg/m2 (CyMEL, n =8), a single course of Thiotepa 600 mg/m2 (TTP, n = 1) or a sequential combination of Thiotepa 600 mg/m2 followed on day 21 by BCNU 600 mg/m2 (TTP-BCNU, n =2). Trastuzumab (4mg/kg) was started 24 h after AHSC infusion and then administered weekly (2 mg/kg). RESULTS: Median time to neutrophil and platelet recovery was 10 and 14.5 days, respectively. Three patients experienced febrile neutropenia and in 2 Herpes virus infections were documented. Five grade III/IV mucositis/oesophagitis were recorded. One patient experienced a reversible atrial arrhythmia on day 2 of trastuzumab, and another patients had a nonsymptomatic decrease in LVEF >10% on week 12 of trastuzumab. No toxic death was recorded. Median time to progression was 5 months (1 to 38 +). CONCLUSION: Combining alkylating agent-based HDC and trastuzumab appears to be feasible in ERBB2 overexpressing MBC and warrants further investigation in a larger cohort.

A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience.

Resection of localized pancreatic head ductal adenocarcinoma (LPHDA) has a limited impact on survival. Mechanisms of improvement provided by preoperative chemoradiation therapy (CRT) remain under debate. This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT. Among 87 patients with LPHDA, 17 had a pancreaticoduodenectomy alone (group I). Thirty-nine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy (group II). Thirty-one with initially unresectable cancers were similarly treated by CRT (group III). Patients in groups II and III were restaged after completion of CRT. In patients with resectable disease, resection was planned. Patients in groups I and II were statistically comparable in terms of age, sex, and pretherapeutic stage. Median survival and 2-year overall survival in group I were 13.7 months and 31%, respectively. In group II, 23 patients (59%) had a pancreaticoduodenectomy (group IIa) and 16 patients (41%) did not have resection (group IIb). Median survival and 2-year overall survival were as follows: group IIa, 26.6 months and 51%; and group IIb, 6.1 months and 0%, respectively. In group IIa, pathologic examination revealed eight major responses (35%) including two sterilized specimens, and none of the patients had locoregional recurrence. In group III, none of the patients had resection, and median survival was 8 months with one 2-year survivor. Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy. However, a high histologic response rate and excellent local control can also be achieved.

Multivariate analysis of survival in inflammatory breast cancer: impact of intensity of chemotherapy in multimodality treatment.

The prognosis of inflammatory breast cancer (IBC) is poor. We evaluated clinical and biopathological characteristics that could affect survival in 74 women with nonmetastatic IBC consecutively treated in our institution between 1976 and 2000. Patients received primary anthracycline-based chemotherapy at conventional doses (n=20) or high-dose chemotherapy (HDC) with haematopoietic stem cell support (HSCS) (n=54). After chemotherapy, 84% of patients underwent mastectomy, 95% were given radiotherapy and 55% tamoxifen. Immunohistochemistry data (ER, PR, ERBB2, P53) on pre-chemotherapy specimens suggested strong differences between IBC and non-IBC. The rate of pathological complete response to chemotherapy was 26% (27% with HDC and 17% with conventional doses, not significant). No single factor was found predictive of response. With a median follow-up of 48 months after diagnosis, the 5-year projected disease-free survival (DFS) was 24% and overall survival (OS) 41%. In multivariate analysis, the strongest independent prognostic factor was the delivery of HDC. The 5-year DFS and OS of patients were respectively 28 and 50% with HDC and 15 and 18% with conventional chemotherapy. These results and comparisons with other series of patients suggest a role for HDC with HSCS as part of the therapeutic approach in IBC. Further prospective studies are required to confirm it.

Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy.

The purpose of this study was to evaluate the presence of micrometastatic cells in the apheresis products from patients with breast cancer, and also to determine if repeated infusion of contaminated products had any clinical impact. A total of 94 patients with high-risk breast cancer were enrolled in a prospective single center study to evaluate the use of dose-intensified chemotherapy (doxorubicine 75 mg/m(2) and cyclophosphamide 3000 or 6000 mg/m(2) for four cycles) with repeated (x 2) stem cell reinfusion. All women were monitored for the presence of metastatic cells in aphereses, collected after first course of intensive chemotherapy, and following additional mobilization with rhG-CSF. Epithelial cells were screened with monoclonal antibodies directed to cytokeratin. Eight of the 94 patients had detectable tumor cells in one or several aphereses collected after intensive chemotherapy; this was unrelated to other tumor characteristics, including size, histology, Scarff Bloom and Richardson (SBR) grading (presence or absence of hormone receptors). Hemato-poietic reconstitution was similar in the cells from these eight patients, and in the total patient population. Three of these eight patients relapsed. This study has confirmed that contamination of apheresis products remains a rare event, which does not seem to affect clinical evolution, even when reinfused into the patient.