Prognosefaktoren bei operablem Brustkrebs unter neoadjuvanter Chemotherapie: Auf dem Weg zu einer Quantifizierung der Residualerkrankung

2015 ◽  
Vol 2 (2) ◽  
pp. 86-87
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Adjuvante Therapie ◽  
Residual Disease ◽  
Prognostische Faktoren ◽  
Operable Breast Cancer ◽  
Neoadjuvante Chemotherapie ◽  
Multivariate Analysen

Ziel: Die neoadjuvante Chemotherapie (NACT) ermöglicht es, häufiger brusterhaltend zu operieren; außerdem stellt sie ein In-vivo-Modell für die individuelle Tumorsensitivität dar und erlaubt so die Erkennung neuer prognostischer Faktoren für die Personalisierung der Therapie. Methoden: Zwischen 2000 und 2012 wurden 318 Patientinnen mit primärem invasivem Mammakarzinom mit im Median 6 Zyklen NACT behandelt; sie erhielten entweder ein anthracyklinhaltiges FEC-100-Protokoll (31,1%) oder Anthracykline + Taxane (53,5%), bei entsprechender Indikation zusätzlich auch Trastuzumab (15,4%). Ergebnisse: Nach einer medianen Nachbeobachtungszeit von 44,2 Monaten betrug die Rate pathologisch gesicherter Vollremissionen gemäß der Klassifikation von Chevallier et al. (Am J Clin Oncol 1993;16:223-228) 19,3%, und die 10-Jahres-Raten des Gesamtüberlebens (OS) und des krankheitsfreien Überlebens (DFS) betrugen 60,2 bzw. 69,6%. Univariate Analysen belegten, dass der RDBN-Index (RDBN = Residual Disease in Breast and Nodes) der signifikanteste Prognosefaktor für das OS (p = 0,0082) und DFS war (p = 0,0022), während multivariate Analysen vor allem ergaben, dass das Volumen des Residualtumors, die Anzahl residualer befallener Lymphknoten sowie der Scarff-Bloom-Richardson(SBR)-Grad nach Chemotherapie die signifikantesten prognostischen Faktoren waren. Schlussfolgerungen: In einer Kohorte von Patientinnen, die allesamt mit einigen der gängigsten medikamentösen Brustkrebs-Therapien behandelt wurden, wiesen wir nach, dass eine NACT zusätzliche prognostische Faktoren liefern und den RDBN-Index bestätigen kann. Da dieser Index wiederum Vorhersagen in Bezug auf das Überleben bei verschiedenen Brustkrebs-Subtypen erlaubt, schlagen wir vor, ihn standardmäßig zu berechnen, um Kliniker bei der Auswahl von Kandidatinnen für eine adjuvante Therapie zu unterstützen. Übersetzung aus Mombelli S, et al: Prognostic factors in operable breast cancer treated with neoadjuvant chemotherapy: towards a quantification of residual disease. Oncology 2015;88:261-272 (DOI: 10.1159/000368557)

Prognostic Factors in Operable Breast Cancer Treated with Neoadjuvant Chemotherapy: Towards a Quantification of Residual Disease

Oncology ◽  
2015 ◽  
Vol 88 (5) ◽  
pp. 261-272 ◽  
Author(s):  
Sarah Mombelli ◽  
Fabrice Kwiatkowski ◽  
Catherine Abrial ◽  
Qian Wang-Lopez ◽  
Paul de Boissieu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Operable Breast Cancer

scholarly journals High Prognostic Significance of Residual Disease After Neoadjuvant Chemotherapy: a Retrospective Study in 710 Patients with Operable Breast Cancer

2006 ◽  
Vol 98 (3) ◽  
pp. 365-365
Author(s):  
Sophie Catherine Abrial ◽  
Frédérique Penault-Llorca ◽  
Rémi Delva ◽  
Philippe Bougnoux ◽  
Bernard Leduc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Study ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Operable Breast Cancer

High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer

2005 ◽  
Vol 94 (3) ◽  
pp. 255-263 ◽  
Author(s):  
Sophie Catherine Abrial ◽  
Frédérique Penault-Llorca ◽  
Rémi Delva ◽  
Philippe Bougnoux ◽  
Bernard Leduc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Study ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Operable Breast Cancer

Prognostic factors for survival after neoadjuvant chemotherapy in operable breast cancer

2003 ◽  
Vol 39 (8) ◽  
pp. 1089-1096 ◽  
Author(s):  
J.-Y Pierga ◽  
E Mouret ◽  
V Laurence ◽  
V Diéras ◽  
A Savigioni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Operable Breast Cancer

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer

2008 ◽  
Vol 26 (25) ◽  
pp. 4072-4077 ◽  
Author(s):  
Jennifer K. Litton ◽  
Ana M. Gonzalez-Angulo ◽  
Carla L. Warneke ◽  
Aman U. Buzdar ◽  
Shu-Wan Kau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Pathologic Complete Response ◽  
Operable Breast Cancer ◽  
Obese Patients ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Response To Neoadjuvant Chemotherapy

Purpose To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. Patients and Methods From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI of 25 to < 30 kg/m2), or normal/underweight (BMI < 25 kg/m2). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer–specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided. Results Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years. Conclusion Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.

scholarly journals Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

2017 ◽  
Vol 63 (3) ◽  
pp. 691-699 ◽  
Author(s):  
Francesca Riva ◽  
Francois-Clement Bidard ◽  
Alexandre Houy ◽  
Adrien Saliou ◽  
Jordan Madic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Minimal Residual Disease ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Tp53 Mutations ◽  
Tumor Dna ◽  
Minimal Residual

Abstract BACKGROUND In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. METHODS Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 (TP53) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). RESULTS Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS (r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index (P = 0.003), tumor grade (P = 0.003), and stage (P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free (P &lt; 0.001) and overall (P = 0.006) survival. CONCLUSIONS Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival.

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