Receptor Negative Early Breast Cancer Research Articles

Serum metabolomic profiles evaluated after surgery may identify patients with oestrogen receptor negative early breast cancer at increased risk of disease recurrence. Results from a retrospective study

Purpose: Metabolomics is a global study of metabolites in biological samples. In this study we explored whether serum metabolomic spectra could distinguish between early and metastatic breast cancer patients and predict disease relapse.Methods: Serum samples were analysed from women with metastatic (n = 95) and predominantly oestrogen receptor (ER) negative early stage (n = 80) breast cancer using high resolution nuclear magnetic resonance spectroscopy. Multivariate statistics and a Random Forest classifier were used to create a prognostic model for disease relapse in early patients.Results: In the early breast cancer training set (n = 40), metabolomics correctly distinguished between early and metastatic disease in 83.7% of cases. A prognostic risk model predicted relapse with 90% sensitivity (95% CI 74.9–94.8%), 67% specificity (95% CI 63.0–73.4%) and 73% predictive accuracy (95% CI 70.6–74.8%). These results were reproduced in an independent early breast cancer set (n = 40), with 82% sensitivity, 72% specificity and 75% predictive accuracy. Disease relapse was associated with significantly lower levels of histidine (p = 0.0003) and higher levels of glucose (p = 0.01), and lipids (p = 0.0003), compared with patients with no relapse.Conclusions: The performance of a serum metabolomic prognostic model for disease relapse in individuals with ER-negative early stage breast cancer is promising. A confirmation study is ongoing to better define the potential of metabolomics as a host and tumour-derived prognostic tool.

Abstract P3-14-18: Dose-dense neoadjuvant chemotherapy in locally advanced breast cancer. Long term results of a cooperative retrospective study

Abstract BACKGROUND: Dose-dense chemotherapy results in better overall (OS) and disease free survival (DFS) in women with hormone receptor-negative early breast cancer as shown with a systematic review and meta-analysis by Bonilla et al (JNCI 2010). Aim of our study was to compare neoadjuvant dose-dense chemotherapy with standard dose schedule in T4 patients in terms of DFS and OS, according to hormone-receptor status. PATIENTS AND METHODS: we analysed, retrospectively, 160 consecutive T4 patients, of median age 52 ys (range 29-73) who received neoadjuvant anthra-based chemotherapy with and without taxanes, observed from 1989 to 2009; 74 patients (46%) received dose-dense schedule (q14) and 86 (54%) conventional dose (q21); 68 (42%) patients were ER-negative (32 q14; 36 q21) and 92 (58%) patients were ER-positive (42 q14; 50 q21). No Trastuzumab was allowed during neoadjuvant treatment. RESULTS: at a median follow-up of 130 months (range 8-241 months), overall, 10 y DFS was 41.9% and 30.2% on q14 and q21 schedules, respectively (p = 0.085); 10 y OS was 48.6% on q14 and 44.2% on q21 schedule, (p = 0.343). ER-negative patients who received q14 schedule had better DFS (46.9%) than those on q21 schedule (16.7%), (p = 0.007) [Relative Risk 0,63 and Odds Ratio 0,22] and better OS (50%) than those on q21 schedule (30.6%) (p = 0.083) [Relative Risk 0,61 and Odds Ratio 0,44]. DFS and OS did not differ on q14 and q21 schedules in ER- positive patients. CONCLUSIONS: Our findings are consistent with published data and suggest that there is no appreciable survival benefit from increasing dose density among T4 ER-positive patients. Dose-dense neoadjuvant chemotherapy may be justified in LABC patients with T4 ER-negative tumors. DFS OS q 14q 21pq 14q 21pER-46,9%16,7%0.00750%30,6%0.083ER+38,1%40,0%0.51247,6%54,0%0.344 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-18.

Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.