Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines and/or taxanes +/- carboplatin. We explored the clinicopathological characteristics of Lehmann subtypes and their association with the pathologic complete response (pCR) to different treatments. The global pCR rate was 37%, and it was unevenly distributed within Lehmann’s subtypes. Basal-like 1 (BL1) tumors exhibited the highest pCR to carboplatin containing regimens (80% vs 23%, p=0.027) and were the most proliferative (Ki-67>50% of 88.2% vs. 63.7%, p=0.02). Luminal-androgen receptor (LAR) patients achieved the lowest pCR to all treatments (14.3% vs 42.7%, p=0.045 when excluding mesenchymal stem-like (MSL) samples) and were the group with the lowest proliferation (Ki-67≤50% of 71% vs 27%, p=0.002). In our cohort, only tumors with LAR phenotype presented non-basal-like intrinsic subtypes (HER2-enriched and luminal A). TNBC patients present tumors with a high genetic diversity ranging from highly proliferative tumors, likely responsive to platinum-based therapies, to a subset of chemoresistant tumors with low proliferation and luminal characteristics.
Finally, although our study does have certain limitations, we believe that it can provide useful information and encouraging evidence that the routine use of bevacizumab as part of first-line treatment of patients with advanced cervical cancer may be associated with outcomes comparable with those obtained in GOG240 study.
BACKGROUND: Currently available therapeutic armamentarium for locally advanced and/or metastatic breast cancer (LA/MBC) allows an increasing tailored approach for each of the major tumor immunophenotypes. Nevertheless, there is scarce information about how these subgroups fare and how the alternative therapeutic approaches are actually being used during the disease course. CASCADE is an epidemiological, retrospective, and multicenter study aimed to retrieve demographic and clinical information from a representative cohort of LA/MBC patients treated within the Spanish National Healthcare System. MATERIALS AND METHODS: Several strategies were used to identify patients diagnosed with LA/MBC for the first time between 01/2007 and 12/2008 in 13 Spanish public hospitals covering nearly 5'000'000 inhabitants (>10% of the national population) and followed throughout their metastatic lifetime until death, lost to follow-up, or until December 2013. Data collected included demographical and clinical information for each line of treatment. Descriptive statistics were applied to analyze the information. RESULTS: We identified 443 LA/MBC patients. Median age at diagnosis was 59 years (CI95%: 49.5 - 71.6). Significant differences in dropout rates per line of treatment were found according to the tumor intrinsic immunophenotype. Patients reaching a 4th line were: whole study population 38.4%, HER2-/HR+ 42.8%, HER2+/HR- 41.5%, HER2+/HR+ 39.5%, and Triple-negative 31.9%. Median Overall survival (OS) and per line Progression Free Survival (PFS) for each line of treatment by tumor subtype were: Median OS and per line PFS by tumor subtype Subtype (%)OS (months)PFS (months)PFS (months)PFS (months)PFS (months)PFS (months)Treatment line--1L2L3L4L5LWhole PopulationAll33.57.25.94.33.73.0HER2-/HR+43.838.68.85.84.43.33.0HER2+/HR-12.036.37.46.74.34.03.0HER2+/HR+17.234.411.27.94.95.83.5Triple-negative16.319.04.03.52.43.32.9 Percent use of the four major pharmacological families per line of LA/MBC treatment was: Pharmacological families used per line of LA/MBC treatmentTreatment line1L2L3L4L5L6L7LChemotherapy75.463.075.979.487.976.178.6Anti-HER219.721.919.420.618.720.921.4Hormone therapy37.939.225.318.811.217.916.7Other targeted therapy13.09.612.212.47.511.914.3 CONCLUSION: Our study identifies differences in OS and PFS among BC immunophenotypes, with Triple-negatives faring the poorest. Among therapeutic families, chemotherapy clearly prevails along the disease lifetime, with hormone therapy being primarily used during the initial lines of treatment. Citation Format: Zamora P, Servitja S, Santaballa A, García J, de Paz L, Plata Y, Garau I, Florian J, Chacón I, de la Haba J, García P, Artime E, Rodríguez-Villanueva J, Velasco A, Martínez E, Segui MA. CASCADE study: Treatment and clinical outcomes of metastatic breast cancer by tumor immunophenotypes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-39.
BACKGROUND: Appraisal of the impact that current therapeutic strategies of advanced breast cancer (ABC) have on the survival expectancy, is vital to understand the prognosis of this disease. This entails assessing simultaneously the tumour phenotype and the therapeutic approach used per line of treatment. CASCADE is an epidemiological, retrospective, multicenter study aimed to retrieve demographic and clinical information from a representative cohort of ABC patients treated within the Spanish National Healthcare System. MATERIAL AND METHODS: 13 Spanish public hospitals serving nearly 5M inhabitants (~10% of the national population) identified 422 ABC patients between 01/2007 and 12/2008 who received active treatment for their disease and were followed until death, lost to follow-up, or until December 2013. Overall Survival (OS) was analysed per tumour immunotype and treatment line from the diagnosis until a minimum of 10 patients were still evaluable. OS resulting from the different therapeutic approaches per line was also revised. Data collected included demographical, pathological, diagnostic, and therapeutic information for the entire follow-up. Descriptive statistics were applied (Methods previously described in SABCS 2015 Poster P3-07-39). RESULTS: Remarkably, by the 2nd line of treatment, on average, one third of the OS is already gone. Tumour type imposes clear differences in this decline rate. As expected, triple-negative patients have the shortest survival expectancy at diagnosis, but their OS attrition rate is the slowest compared to the other subgroups (Table 1). Table 1. OS per tumour type and line of treatment in ABC.PopulationOS from ABC Diagnosis (months)OS from 1L (months)OS from 2L (months)OS from 3L (months)OS from 4L (months)OS from 5L (months)Whole (N=422)33.532.622.616.613.513.3HER2-/HR+ (N=187)38.637.122.415.612.610.2Triple-negative (N=67)19.016.515.814.110.29.5HER2+/HR+ (N=72)34.433.729.421.620.318.9HER2+/HR- (N=53)36.335.423.113.19.314.1 OS time derived from the five mayor therapeutic approaches used at any given line, could only be registered for chemotherapy, hormone therapy and chemo + anti-HER2 therapy. Regardless of their treatment history, patients treated exclusively with hormone therapy portray a less aggressive behaviour than those treated with chemotherapy only, resembling the natural history of HER2-/HR+ and triple-negative phenotypes (Table 2). Table 2. OS per pharmacological approach and line of treatment in ABC.Pharmacological treatmentOS from 1L (months)OS from 2L (months)OS from 3L (months)OS from 4L (months)OS from 5L (months)OS from 6L (months)OS from 7L (months)Chemotherapy (N=155)25.012.513.310.88.310.87.2Hormone therapy (N=92)44.030.922.311.214.0--Chemo + Anti-HER2 thp. (N=57)36.927.218.814.125.8--Chemo + Other Targeted thp. (N=44)19.721.014.121.1---Chemo + Hormone thp. (N=38)44.325.0-----Other Targeted thp.: anti-angiogenic antibody, mTOR inhibitor, anti-EGFR antibody, etc. CONCLUSION: Chances to benefit from effective treatments may be jeopardized if their start is postponed to late lines. Only the most widely used therapies and, ultimately chemotherapy, hold until very late in the treatment of the advanced disease. Citation Format: García J, De La Haba J, Servitja S, Santaballa A, De Paz L, Plata Y, Garau I, Florián J, Chacón JI, García P, Zamora P, Orcajo L, Rodríguez-Villanueva J, San José B, Martínez E, Seguí MA. CASCADE study: Rapid survival decline per treatment line in metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-33.
BACKGROUND: Current treatment strategies for locally advanced and/or metastatic breast cancer (LA/MBC) are meant to prolong survival while maintaining or improving the quality of life. Nevertheless, there is a lack of recent data regarding the actual clinical management and its impact on the prognosis of these patients. It is unknown whether prior diagnosis and treatment of early breast cancer (EBC) make any difference in the outcome of the advanced disease. CASCADE is an epidemiological, retrospective, and multicenter study aimed at retrieving this information from a representative cohort of LA/MBC patients treated within the Spanish National Healthcare System. MATERIALS AND METHODS: Thirteen Spanish public hospitals covering nearly 5'000'000 inhabitants (>10% of the national population) applied several combined systematic strategies to identify patients firstly diagnosed with LA/MBC between 01/2007 and 12/2008. Once identified, patients were followed throughout their metastatic lifetime until death, lost to follow-up, or until December 2013, whichever occurs first. Data collected included demographical, pathological, diagnostic, and therapeutic information for each line of treatment. Descriptive statistics were applied. RESULTS: We identified 443 LA/MBC patients; median age at diagnosis was 59 years (CI95%: 49.5 - 71.6). Previous history of early BC was reported in 69.3% of them with a median disease-free interval of 38 months. Median Overall Survival (OS) for the whole study population was 33.5 months, while numbers for advanced cases originally diagnosed as EBC or the novo LA/MBC were 31.7 (CI95%: 26.8 - 36.0) and 38.8 months (CI95% 32.8 - 45.3; p = 0.0138) respectively. Main tumor immunohistochemical subtypes for EBC and the novo LA/MBC were: HER2+/HR- 11.3% and 15.3%, HER2+/HR+ 16.2% and 19.1%, HER2-/HR+ 41.2% and 51.1%, and Triple-negative 17.9% and 11.5%, respectively. At the end of the study follow-up (Dec 2013) 78.2% of the patients had died. Breakdown of the decaying percentage and OS for the entire study population, early-, and the novo diagnosed LA/MBC from the beginning of each line of treatment was: OS according to the type of diagnosisTreatment line1L2L3L4L5L6L7LWhole pulation Patients (%)95.370.253.538.424.215.19.5Whole pulation OS (months)32.622.616.613.513.312.48.5Early diag. LA/MBC OS (months))30.921.015.612.912.49.17.5The novo diag. LA/MBC OS (months)37.625.921.618.714.016.913.8 CONCLUSION: Our study's OS data supports the hypothesis that highly effective current neo/adjuvant treatment may cure most treatment-sensitive early tumors, allowing only those more aggressive to develop to LA/MBC, which then will fare worse than those of the novo metastatic diagnosis. Citation Format: Servitja S, Zamora P, Santaballa A, García J, de Paz L, Plata Y, Garau I, Florian J, Chacón I, de la Haba J, García P, San José B, Rodríguez-Villanueva J, Orcajo L, Martínez E, Segui MA. CASCADE study: Longer overall survival in the novo versus recidivant patients with locally advanced/metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-43.
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