Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer.

Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m(2), then 250 mg/m(2)) combined with six cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3-40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD8+ and FOXP3+ tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer.

Approximately 2-5 % of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). 103 consecutive patients with BC were diagnosed with LM and initially treated with intra-CSF liposomal cytarabine from 2007 to 2011 at a single institution. Correlations were determined with respect to patient characteristics and BC subtype with regard to overall survival (OS). At LM diagnosis, 61 % of patients had a 0-2 performance status (PS), the remaining 39 % were severely neurologically impaired. Regardless of PS, all patients received intra-cerebrospinal fluid (CSF) liposomal cytarabine as first-line treatment. Systemic treatment and radiotherapy were also given in 58 and 17 % of patients respectively as clinically appropriate. Second- (intra-CSF thiotepa) and third-line (intra-CSF methotrexate) treatment was administered in 24 and 6 patients respectively. Median OS was 3.8 months (range 1 day-2.8 years). In multivariate analysis, an initial combined treatment, a second-line treatment with intra-CSF thiotepa, an initial clinical response, and a non-'ER/PR/HER2 negative' BC were significantly associated with a better OS. Median OS in this heterogeneous retrospective case series was similar to that of previously observed BC patients treated with intra-CSF methotrexate suggesting intra-CSF liposomal cytarabine is a reasonable first choice therapy of BC-related LM.

Results and special considerations when treating elderly patients with CyberKnife®: a review of 345 cases.

The relatively recent introduction of CyberKnife® in the field of radiotherapy has prompted the question of accessibility and usefulness of this technique for seniors. From June 2007 to June 2009, we treated 345 patients of all ages with CyberKnife as part of a single-center study. Median age was 61 years (range, 8-86 years). Ninety-eight patients were over 70 and 17 were older than 80. The treatment could not be completed with 2% (2/98) patients over 70 vs. 3.6% (9/247) among the younger (ns). Physiologic or psychologic problems in maintaining position for a long time were not more frequent among those over 70. The same was true with those over 80. Patients over 70 years old are able to tolerate CyberKnife treatment as efficiently as their younger counterparts. Elderly patients should not be restricted from access to CyberKnife radiosurgery with curative intent.

Nasal septum perforation: a side effect of bevacizumab chemotherapy in breast cancer patients.

BACKGROUND: Bevacizumab is an anti-vascular endothelial growth factor approved in association with paclitaxel or docetaxel as first line in patients (pts) with metastatic breast cancer. Rare cases of nasal septum perforations have been reported. We report our experience of nasal perforation in breast cancer pts receiving bevacizumab and chemotherapy either in the adjuvant or in the metastatic settings. METHODS: Between 1 January and 31 December 2009, 70 pts received bevacizumab together with chemotherapy. All the pts who had received bevacizumab were referred to the ENT specialist. Symptoms potentially related were looked for. Side effects were graded according to CTCAE. RESULTS: Five nasal septum perforations were diagnosed (5 out of 70; 7.14%). Bevacizumab dose was 15 mg kg(-1) 3 weekly. Three pts were metastatic. Bevacizumab was associated with docetaxel (100 mg m(-2) every 3 weeks) in two pts and with weekly paclitaxel in one. The last two pts received bevacizumab in combination with anthracyclin and then taxanes in the adjuvant setting. In these two cases, nasal septum perforation occurred at the time of docetaxel treatment. CONCLUSION: A high incidence of nasal septum perforation has been shown in pts with breast cancer receiving bevacizumab together with chemotherapy. Several mechanisms could be involved (mucositis, delayed tissue repair, antiangiogenic action of taxanes).

Impact of an all-oral capecitabine and vinorelbine combination regimen on functional status of elderly patients with advanced solid tumours: A multicentre pilot study of the French geriatric oncology group (GERICO).

BACKGROUND: Elderly metastatic cancer patients typically have short life expectancy and frequently suboptimal treatment. Goals of therapy should include preservation of functional status as well as clinical response. For elderly patients, oral chemotherapy could be a valuable strategy, avoiding the constraints and risks of intravenous drugs. METHODS: This study assessed effect of an all-oral combination of capecitabine and vinorelbine on functional status (measured by basic Activities of Daily Living [ADL]), toxicity, efficacy and compliance in patients ≥70 years with advanced breast, prostate or lung cancer. RESULTS: Eighty patients were enrolled. After three cycles, 81.8% of patients had stabilised or improved ADL, and 8.6% and 42.9% had a response or stabilised disease. Compliance was excellent (68.8%). The most common grade 3-4 toxicities were haematological (17.9%) and gastrointestinal (7.7%). CONCLUSION: In elderly cancer patients, an all-oral combination of capecitabine and vinorelbine maintains functional status, is well tolerated, and provides good disease control.

[Ductal carcinoma in situ of the breast. Analysis of 882 cases]. / Carcinome canalaire in situ du sein. Analyse de 882 cas.

OBJECTIVE: This study assesses the results of "current clinical practice" among 882 women treated in nine French Cancer Centers from 1985 to 1995 for pure ductal carcinoma in situ (DCIS) of the breast. METHOD: Median age was 53 years (range 21-87); 177 (20%) patients underwent mastectomy (M), 190 (22%) conservative surgery alone (CS) and 515 (58%) conservative surgery with radiotherapy (CS + RT). RESULTS: The crude 7-year local relapse (LR) rates were 2%, 31% and 13% among the M, CS and CS+RT subgroups (p<0.0001). All four LR after M were invasive as well as 31 (52%) out of 59 and 40 (61%) out of 66 in the CS and CS+RT groups. Distant metastases occurred in 1%, 3% and 1% of the three treatment groups. No LR factors were found in the M group. Among women treated with CS, the 7-year LR rates were 36%, 31% and 30% among women aged 40 or less, 41 to 60 and 61 or more (NS). For women treated by CS+RT, the LR rates in these age subgroups were 33%, 13% and 8%, respectively (p<0.0001). Patients with negative, positive or uncertain margins had 7-year LR rates of 26%, 56% and 29% respectively if treated with CS (p=0.02) and 11%, 23% and 9% if treated with CS+RT (p=0.0008). RT reduced LR rates by 65% in all histological subgroups, but more particularly in comedocarcinoma and mixed cribriform/papillary subgroups. The 7-year rate of contralateral breast cancer was 7%, identical in all subgroups. CONCLUSION: Mastectomy remains the safest treatment for women with DCIS, with a 98% 7-year control rate. After conservative surgery, RT reduces very significantly LR rates, according to the NSABP B-17 and EORTC 10853 randomized trial results. The RT benefit is present in all clinical/histological subgroups, but its magnitude varies. Young age (<40 years) and incomplete excision are the most important LR risk factors.

Ductal carcinoma in situ of the breast results of conservative and radical treatments in 716 patients.

Until now, less than 5% of the patients with breast ductal carcinoma in situ (DCIS) have been enrolled in clinical trials. Consequently, we have analysed the results of "current practice" among 716 women treated in eight French Cancer Centres from 1985 to 1992: 441 cases (61.6%) corresponded to impalpable lesions, 92 had a clinical size of less than or equal to 2 cm and 70 from 2 to 5 cm; in 113 cases, the size was unspecified. Median age was 53.2 years (range: 21-87 years). 145 patients underwent mastectomy (RS) and 571 conservative surgery (CS) without (136) or with (435) radiotherapy (CS+RT). The mean histological tumour sizes in these three groups were 25.6, 8.2, 14.8 mm, respectively (P<0.0001). After a 91-month median follow-up, local recurrence (LR) rates were 2.1, 30.1 and 13.8% in the RS, CS and CS +RT groups, respectively (P=0.001); LR were invasive in 59 and 60% in the CS and CS+RT groups, respectively. In these groups, the 8-year LR rates were 31.3 and 13.9%, respectively (P=0.0001). Nodal recurrence occurred in 3.7 and 1.8% in the CS and CS+RT groups. Metastases rates were 1.4, 4.4 and 1.4% in the RS, CS and CS+RT groups. Among the 60 cases of invasive LR, in CS and CS+RT groups 19% developed metastases. After multivariate analysis, we did not identify any significant LR risk factor in the CS group, whereas young age (<40 years) and incomplete excision were significant in the CS+RT group (P=0.012 and P=0.02, respectively).