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Background: Panitumumab is an antibody targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Consequently, we evaluated the combination of a standard chemotherapy (FEC 100 followed by T) with panitumumab as neoadjuvant therapy of oprable TNBC. Methods: 60 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC 100 (500/100/500 mg/m2) q.3 weeks followed by 4 cycles of T (100 mg/m2) q.3 weeks, in combination with panitumumab (9 mg/kg) for 8 cycles q.3 weeks. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff/J Am Coll Surg 1995; Chevallier: Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characteristics are as follows: mean age 47 [27-72]; T2: 74%, T3: 26%, (mean tumor size: 40 mm [20-120]); N0: 65%, N1: 28% and N2: 7%; invasive ductal carcinoma: 96%; Scarff-Bloom-Richardson Grade III: 72%, grade II: 28%. The median number of cycles was: FEC 100: 4 [2-4], T: 4 [0-4], Panitumumab: 7 [1-8]. Pathological response showed a pCR according to Sataloff's classification of 57.1% [95% IC: 40.7−73.5] and according to Chevallier's classification of 51.4% [95% IC: 34.8−68.0] with an overall clinical response rate of 60% (29% CR) [95% IC: 43.8−76.2]. Conservative surgery was performed in 79% of cases. Skin toxicity was the main side-effect: Cutaneous toxicity grade IV: 12%, grade III: 26%, grade II: 23%. No ocular complications have been reported. Neutropenia grade IV: 23.7%; febrile neutropenia: 4.2%. Infection: 0%. Hand-foot syndrome grade III: 4%. Ungueal toxicity grade IV: 2.5%, grade II: 25 .5%. Conclusions: These results suggest that Panitumumab in combination with FEC100 followed by T appears efficacious with acceptable toxicity in the neoadjuvant therapy of operable TNBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-01.

La chimiotherapie neoadjuvante du cancer du sein correspond a l’utilisation d’un traitement cytostatique systemique avant le traitement locoregional (chirurgie et/ou radiotherapie). Initiee dans les annees 1970 pour le traitement des formes localement avancees et/ou inflammatoires, la chimiotherapie d’induction s’est etendue au debut des annees 1980 aux cancers dits operables, de taille superieure a 3 cm et/ou de position centrale afin de permettre une chirurgie conservatrice plus frequente. Cet objectif est obtenu dans environ 75 % des cas sans augmentation du risque de rechute locale et sans effet deletere sur la survie globale, malgre le retard du traitement locoregional. La chimiotherapie neo–adjuvante a bien sur evolue au fur et a mesure de l’avenement des drogues majeures du cancer du sein que sont les anthracyclines, la vinorelbine et les taxanes. Mais a ce jour, aucun protocole ne s’est impose comme un standard inconteste. Toutefois, il semble que l’obtention d’une reponse complete clinique soit le meilleur garant pour eviter la rechute. Et cela semble ne pouvoir s’observer qu’apres 6 cycles, voire 8 cycles de chimiotherapie combinant au minimum 2 des 3 drogues majeures du traitement du cancer du sein dont le docetaxel qui parait, aujourd’hui, avoir une place incontournable surtout lorsqu’il est utilise en sequentiel apres un traitement a base d’anthracyclines en dehors de toute contre–indication cardiaque.

In order to evaluate the mobilization of peripheral blood progenitor cells (PBPC) after an effective induction regimen in breast cancer, we performed a study on 15 breast cancer patients. Between January 1995 and June 1996, these patients received TNCF (THP-doxorubicin. vinorelbine, cyclophosphamide, fluorouracil for four days, every 21 days) with G-CSF support (5 microg/kg for 10 days after chemotherapy) to reduce aplasia. This regimen is known to result in a complete pathological response in 30% of patients. Between two cycles of TNCF treatment, hematological recovery was observed. Progenitor cells (CFU-GM and CD34+ cells) and mononuclear cells in DNA synthesis (MCDS) counts were performed daily, between the 12th and 17th post-chemotherapy days (81 samples). The results showed a similarity for hematological recovery and PBPC mobilization kinetics depending on the number of treatment cycles. The three methods used for PBPC evaluation were well correlated (P < 0.01) with an optimal mean PBPC recruitment by the last day of G-CSF administration: respectively, 11 520 (1729-26539) CFU-GM/ml of blood, 249 (14-1160) CD34+ cells/microl of blood and 211 (21-554) MCDS/microl of blood. These results suggested that a daily injection of G-CSF after one or two TNCF cycles will produce an effective PBPC mobilization in comparison with currently used regimens.

This study focused on the correlation between tumor response and patient outcome in 329 breast cancers treated with primary chemotherapy. There were 141 stage IIIB tumors, including 109 inflammatory carcinomas. Other malignancies (34 IIIA, 99 IIB, 55 IIA) were operable but considered to be too large (> 3 cm) for conservative surgery and received primary chemotherapy to avoid mastectomy. All received the AVCF regimen, comprising 4-week cycles of doxorubicin (30 mg/m 2 ) day 1, vincristine (1 mg/m 2 ) day 1, 5-fluorouracil (5-FU; 400 mg/m 2 ) days 2 through 5, cyclophosphamide (300 mg/m 2 ) days 2 through 5. In 189 cases, methotrexate (15 mg/m 2 ) was added at day 2 and day 3. Patients received 6 cycles, then underwent locoregional treatment (surgery, radiotherapy, or both) according to tumor regression. The response rate was assessed by clinical, mammographic, and echographic examinations: a 50% rate of objective responses were noted, of which 15% were complete responses (tumor shrinkage allowed breast conservation in 68% of patients who had stages II or IIIA). For the whole population studied, median follow-up was 111 months (range, 60-196). One hundred fifty-seven patients had disease relapse (48 local, 14 contralateral, 95 distant). Kaplan-Meier estimates showed an increased 10-year overall survival for patients in complete response, as compared with noncomplete response: 70% versus 50% (p < 0.03). Complete response to neoadjuvant chemotherapy seems a good prognostic factor.

Between 1975 and 1986, 326 patients with stage II breast cancer were treated with an adjuvant combination of doxorubicin, vincristine, cyclophosphamide, and 5-fluorouracil (AVCF) following regional therapy (232 modified radical mastectomy, 94 lumpectomies, 304 irradiations). The AVCF regimen consisted of 4-week cycles of doxorubicin (30 mg/m2 day 1, modified radical mastectomy), vincristine (1 mg/m2 day 2), 5-fluorouracil 400 (mg/m2), and cyclophosphamide (300 mg/m2) days 3-6. Two hundred twenty-four patients (pts) had six cycles and 102 pts 12 cycles; 90 pts also received 30 mg daily tamoxifen for 1 year after chemotherapy. As of March 1994, the median follow-up was 130 months (range 86-221). One hundred eighteen pts developed recurrences (7 local, 19 controlateral, 92 metastatic) and 104 died. Estimated disease-free survival (DFS) was 5 years, 76 +/- 5%; 10 years, 64 +/- 5%; 15 years, 54 +/- 9%. Overall survival (OS) was 5 years, 85 +/- 4%; 10 years, 70 +/- 5%; 15 years, 58 +/- 10%. Survival was affected by the number of involved lymph nodes (258 pts were N+), menopausal status (OS at 15 years: 53% for MP+ and 65% for MP-) and Scarff-Bloom-Richardson grading, but not by hormonal receptors, number of courses, or associated hormonotherapy. Minimal cardiac toxicity was induced by doxorubicin either during or subsequent to treatment completion.

Neoadjuvant chemotherapy is used to improve patients' survival in locally-advanced and inflammatory breast cancer and to increase conservative surgical procedures in bulky tumours. Pathological complete responses are unusual. The aim of this pilot study was to assess the clinical and pathological response rates and to evaluate toxicity with a new protocol of primary chemotherapy in 50 high-risk breast cancer patients. All tumours were > 3 cm and had at least one other adverse prognostic factor: lymph node involvement (32 N1, 6 N2), SBR grade III (20), aneuploidy (29), negative hormonal receptors (19). Patients were treated by 3-week cycles of THP-doxorubicin 20 mg/m2 D1 to 3, vinorelbine 25 mg/m2 D1 and 4, cyclophosphamide 300 mg/m2 and 5-fluorouracil 400 mg/m2 D1 to 4 (TNCF). 38 patients received G-CSF or GM-CSF support. After 4-6 cycles, all underwent surgery (39 conservative, 11 modified radical). Tumour response was assessed clinically, by mammography and echography and on pathological specimens. An objective clinical response was observed for 43 patients: 26 complete (51%) and 18 partial (37%). After pathological review, 11 patients (22%) were devoid of any tumour cells, 4 others (8%) had only in situ carcinoma. From 253 evaluated cycles, grade III-IV toxicity occurred, 81% with neutropenia, 25% with anaemia, and 20% with thrombocytopenia. All patients recovered. This regimen induced a severe but not life-threatening haematological toxicity and resulted in a high pathological response rate (30%).

Only a few papers have been published concerning the incidence and outcome of patients with a pathological complete response after cytotoxic treatment in breast cancer. The purpose of this retrospective study was to assess the outcome of patients found to have a pathological complete response in both the breast and axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer. Our goal was also to determine whether the residual pathological size of the tumour in breast could be correlated with pathological node status. Between 1982 and 2000, 451 consecutive patients were registered into five prospective phase II trials. After six cycles, 396 patients underwent surgery with axillary dissection for 277 patients (69.9%). Pathological response was evaluated according to the Chevallier's classification. At a median follow-up of 8 years, survival was analysed as a function of pathological response. A pathological complete response rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast tumour persistence was significantly related to positive axillary nodes (P=5.10−6). At 15 years, overall survival and disease-free survival rates were significantly higher in the group who had a pathological complete response than in the group who had less than a pathological complete response (P=0.047 and P=0.024, respectively). In the absence of pathological complete response and furthermore when there is a notable remaining pathological disease, axillary dissection is still important to determine a major prognostic factor and subsequently, a second non cross resistant adjuvant regimen or high dose chemotherapy could lead to a survival benefit. British Journal of Cancer (2002) 86, 1041–1046. DOI: 10.1038/sj/bjc/6600210 www.bjcancer.com © 2002 Cancer Research UK

e11574 Background: Panitumumab is an antiboby targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Consequently, we evaluated the combination of a standard chemotherapy (FEC100 followed by T) with panitumumab as neoadjuvant therapy of operable TNBC. Methods: 58 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC100 (500/100/500 mg/m2) q.3 weeks followed by 4 cycles of T (100 mg/m2) q.3 weeks, in combination with panitumumab (9mg/kg) for 8 cycles q.3 weeks. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff : J Am Coll Surg 1995 ; Chevallier : Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characterisctics are as follows : mean age 50 [38-64] ; T2 : 81%, T3 : 19% (mean tumor size : 42 mm [25-80]) ; N0 : 73% and N1 : 27%; invasive ductal...

Inflammatory breast carcinoma (IBC) has long been accepted as a distinct subgroup of mammary cancer. Case reports appeared in the literature as early as 1814 [2] and the entity was formally described in 1924 [20]. It has been traditionally considered as an uncommon form that carries a particularly gloomy prognosis. There has, however, been considerable controversy with regard to the criteria that should be used for the diagnosis of this disease. In particular, conflicting information is to be found in the literature as to whether IBC is a clinical or pathologic diagnosis [11, 21]. In addition, recent reports have often included patients with IBC within a larger group of patients with locally advanced breast cancer. Despite these shortcomings, the treatment of IBC has evolved favorably over the last 15 years. The introduction of combination chemotherapy in the treatment strategy of IBC before local therapy has resulted in a substantial improvement in the outlook of this patient group.

In inflammatory breast carcinoma (IBC), the pathologic criteria are useful to confirm the clinical diagnosis since this form of mammary cancer needs a rapid and distinct therapeutic strategy [1, 2]. On deep cutaneous biopsies, so-called neoplastic lymphangitis is considered as a characteristic feature of IBC [3, 4].

1082 Background: This study was performed to evaluate retrospectively the efficacy and tolerance of gemcitabine plus oxaliplatin (GEMOX) as salvage chemotherapy in patients with metastatic breast cancer (MBC) in a mono-institutional series. Methods: From January 2003 to March 2005, 38 MBC patients were treated at disease progression according to three schedules: (a) gemcitabine 1000 mg/m2 on day 1 and 8 and oxaliplatin 100 mg/m2 on day 1 every three weeks (n=30); (b) gemcitabine 1,000 mg/m2 on day 1, followed same day by oxaliplatin 100 mg/m2 every two weeks (n=7); (c) gemcitabine 1250 mg/m2 on days 1 and 8 and oxaliplatin 100 mg/m2 on day 1 every four weeks (n=1). Results: All patients (median age, 58 years) received prior chemotherapy for metastatic disease (median of four lines). Radiological response was assessed in 36 patients: 12 patients (33%) experienced a partial response and 11 patients (31%) had a stable disease. The median times to progression and survival were 4 months (range, 0–21 months) and 10 months (range, 2–24 months), respectively. A total of 233 cycles were administered with a median of 5.5 cycles per patient (range, 1–21 cycles). Grade 3/4 toxicity consisted of myelotoxicity in 26% of patients and neurotoxicity in 8%. Conclusions: This retrospective study suggests that GEMOX is an effective combination with a good tolerance profile in heavily pretreated MBC. Further evaluation of this regimen is warranted in this tumor indication. No significant financial relationships to disclose.

In order to avoid modified radical mastectomy a neoadjuvant approach was adopted in our institute for non-inflammatory tumours. From 01/88 to 12/94,238 patients (pts) received as primary chemotherapy 3 different regimens (all doses mg/m 2 ): (l) AVCF/AVCFM, 126 pts (adriamycin 30, vincristine I dl, cyclophosphamide 300, fluorouracil 400 d2–d5 and methotrexate 20 d2 and 4, every 28 d); (2) NEM, 69 pts (navelbine 25, epirubicin 35, methotrexate 20 dl and d8, every 28 d) and (3) TNCF, 43 pts (THP-adria 20, dl–3, navelbine 25 dl and d4, cyclophoshamide 300, fluorouracile 400 dl–d4, every 21 d). In spite of good results with AVCF, the new combinations with navelbine seemed promising (NEM regimen concerned mainly stage II and TNCF stage III tumours): they were all operated for (2) and (3), partially for (l), and showed a progression in pathological complete response rate (pCR). Evaluation comprised 3 methods: clinical (C), echographic (E), mammographic (M). If breast conservation rate (85/85/77%) was quite similar in the 3 regimens, the overall objective response rate (C: 8573/93; E: 75/66/85; M: 58/59/80%) and more importantly pCR (7/16/26%) increased with regimens 2 and 3, with a rise in toxicity with TNCF ( ASCO 1995, abst. 218). If cases where remains only ″ in situ ″ are added, pCR reached 21% with NEM and 28% with TNCF. These navelbine–anthracyclins associations and dose intensity improved pCR, but the impact on survival has to be confirmed.

A relationship has been sought between the classical marker, active E-rosette and the surface antigens of T-lymphocytes, defined by OKT 4 and 8 monoclonal antigens, in the peripheral blood of normal human people. It was found that no significant correlation existed in the case of OKT 4 antigen; conversely the OKT 8-positive cells were significantly enriched after E-rosette-forming cell isolation (about 2.5 times in comparison with the negatively selected cells). In this latter case, some partial correlation could exist between SRBC-high affinity of T-lymphocytes and the subsets defined by OKT 8 antigen.

beta-Thromboglobulin (beta TG) plasma levels were determined in 52 female breast cancer patients at different stages and in 39 healthy controls (22 women and 17 men) of similar age distribution. Beta TG levels were high (mean +/- SD:61.6 +/- 59.1 ng/ml) in patients before any treatment compared to controls (mean +/- SD:21.2 +/- 7.4 ng/ml) and the difference was statistically significant (p less than 0.001). No correlation with disease stage was observed. No other coagulation parameters were abnormal except fibrinogen, which increased. Fibrinogen degradation products (FDP) also increased but only in metastatic patients. Chemotherapy appeared to induce a considerable decrease in initial values at the end of the first cycle without modifying the platelet count. In addition, an attempt was made to correlate the beta TG plasma level investigated serially for several months with disease evolution.