Circulating tumor cell count and thrombosis in metastatic breast cancer.

Essentials Tumor cells circulating in blood (CTC) may favor thrombotic events in cancer patients. We assessed the impact of CTC on the risk of thrombosis in metastatic breast cancer. Baseline CTC detection was the only independent factor associated with the risk of thrombosis. CTC detection under therapy may be the hidden link between tumor progression & thrombosis. SUMMARY: Background Circulating tumor cell (CTC) count is a major prognostic factor in metastatic breast cancer (MBC) and has been reported to be associated with thrombosis in short-term studies on MBC patients. Objective To assess whether CTC detection (CellSearch® ) before first-line chemotherapy impacts the risk of thrombosis throughout the course of MBC. Patients/Methods Among patients included before first-line chemotherapy for MBC in the prospective IC2006-04 CTC detection study (NCT00898014), the electronic medical files of those patients treated at Institut Curie (Paris, France) were searched in silico and manually checked for incident venous or arterial thrombotic events (TE) in the course of MBC. Univariate and multivariate analyses were performed using Cox and Fine-Gray models, adjusted for age and Khorana score. Results/Conclusions With a median follow-up of 64 months (25-81 months), among the 142 patients included, 34 (24%) experienced a TE (incidence rate, 8 TE/100 patient-years). The TE incidence rate was 13 TE/100 patient-years for the 80 patients with ≥ 1 CTC/7.5 mL of blood before initiating first-line chemotherapy, vs. only 4 TE/100 patient-years for the 62 CTC-negative patients. Fine-Gray multivariate analysis (with death as competing event) included age, Khorana score and baseline lactate dehydrogenase and CTC levels: detectable CTC was the only factor significantly associated with an increased risk of TE (sub-distribution hazard ratio [SHR] for patients with [1-4] CTC = 3.1, 95% CI [1.1; 8.6], SHR for patients with ≥ 5 CTC = 1.4, 95% CI [0.5; 4.6]). This study shows that CTC detection before starting first-line chemotherapy is an independent risk factor for TE in MBC patients.

Survival of breast cancer patients with meningeal carcinomatosis treated by intrathecal thiotepa.

Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1-50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6-7.2) and history of more than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50-5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line.

Platinum-based chemotherapy in metastatic triple-negative breast cancer: the Institut Curie experience.

BACKGROUND: Although recent experimental data strongly suggest that platinum-based chemotherapy (PBCT) could improve the outcome of triple-negative breast cancer (TNBC), clinical data are lacking. Here, the authors reviewed clinical outcome in patients with metastatic TNBC treated with PBCT. PATIENTS AND METHODS: We conducted a retrospective analysis of all patients (N=143) treated for metastatic breast cancer with PBCT between 2000 and 2008, at Institut Curie, Paris, France. Ninety-three of them (63.7%) had TNBC. One-hundred twenty patients received cisplatin (CDDP). The main combination used was CDDP-ifosfamide, in 101 patients (70.2%). RESULTS: Median follow-up was 44 months. For the overall population (N=143), median overall survival (OS) and median progression-free survival (PFS) were 11 and 5 months, respectively. Objective response rate was 33.3% in the TNBC group versus 22% in non-TNBC, P=0.1. We observed no difference of OS, PFS and response duration. Other prognostic factors for poor OS were visceral metastasis sites (P<0.001). One patient died from sepsis during aplasia, 15 had to switch from CDDP to carboplatin because of CDDP-related toxicity. CONCLUSIONS: Metastatic TNBC patients treated with PBCT tended to have a higher response rate, without a significant improvement of PFS or OS, compared with other subtypes. Toxicity was acceptable. Longer observation and further analysis are warranted.

Survival of breast cancer patients with meningeal carcinomatosis.

BACKGROUND: Breast cancer is the leading nonhematologic cause of meningeal carcinomatosis (MC). The aim of this study was to report the outcome of patients diagnosed with breast cancer MC and treated in single institution by a high-dose intrathecal methotrexate (MTX) regimen. METHODS: Ninety-one patients were diagnosed with breast cancer MC from 2000 to 2007. Intrathecal treatment was MTX 15 mg/day (days 1-5), hydrocortisone acetate (day 1) and oral folinic acid (days 1-5), repeated every 2 weeks. Patients and tumor characteristics were associated with the early clinical and biological outcome and with the overall survival (OS). RESULTS: The median survival was 4.5 months (range 0-53). In multivariate analysis, adverse prognostic factors at diagnosis were performance status >2 [P = 0.006, response rate (RR) = 0.33 (0.15-0.71)], more than three chemotherapy regimens before MC diagnosis [P = 0.03, RR = 0.40 (0.19-0.93)], negative hormone receptor status [P = 0.02, RR = 0.4 (0.19-0.90)] and high Cyfra 21-1 level [P = 0.048, RR = (0.09-0.99)]. Clinical progression after one cycle and biological response after two cycles were independently associated with OS [P < 0.001, RR = 0.09 (0.02-0.37) and P = 0.003, RR = 3.6 (1.5-8.5), respectively]. We propose a prognostic score in order to define three distinct groups of prognosis. CONCLUSIONS: MC presents a poor prognosis, but 1-year survival rate was 25%. This score may become a useful tool for treatment decision and clinical trials.