Abstract
Tumor-induced angiogenesis supplies the tumor with nutrients and oxygen necessary to grow and provides tumor cells with a possibility to intravasate into blood vessels as first step of metastatic spread. In the last two decades, evidence has been accumulating that controlling tumor-associated angiogenesis might be a promising strategy against cancer growth. In breast cancer, a number of angiogenesis inhibitors have been investigated in clinical trials. The antibody against vascular endothelial growth factor (VEGF) bevacizumab has been approved for treatment of metastatic breast cancer in Europe. Although the mechanism of action is still under study, bevacizumab was also tested in other clinical settings of breast cancer treatment such as neoadjuvant and adjuvant therapy, as maintenance therapy, and in combination with both chemotherapy and other targeted agents. Other anti-angiogenic agents, such as oral tyrosine kinase inhibitors sorafenib, sunitinib, and pazopanib, were tested and have not yielded as promising results. In this chapter, we will review the current evidence and clinical relevance of anti-angiogenic treatment in early and metastatic breast cancer.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ashworth TR (1869) A case of cancer in which cells similar to those in tumors were seen in the blood after death. Aus Med J 14:146–149
Azad NS, Posadas EM, Kwitkowski VE, Steinberg SM, Jain L, Annunziata CM, Minasian L, Sarosy G, Kotz HL, Premkumar A, Cao L, McNally D, Chow C, Chen HX, Wright JJ, Figg WD, Kohn EC (2008) Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol 26(22):3709–3714. https://doi.org/10.1200/JCO.2007.10.8332
Bachelot T, Garcia-Saenz JA, Verma S, Gutierrez M, Pivot X, Kozloff MF, Prady C, Huang X, Khosravan R, Wang Z, Cesari R, Tassell V, Kern KA, Blay JY, Lluch A (2014) Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study. BMC Cancer 14:166. https://doi.org/10.1186/1471-2407-14-166
Banys-Paluchowski M, Schutz F, Ruckhaberle E, Krawczyk N, Fehm T (2016) Metronomic chemotherapy for metastatic breast cancer – a systematic review of the literature. Geburtshilfe Frauenheilkd 76(5):525–534. https://doi.org/10.1055/s-0042-105871
Barrios CH, Liu MC, Lee SC, Vanlemmens L, Ferrero JM, Tabei T, Pivot X, Iwata H, Aogi K, Lugo-Quintana R, Harbeck N, Brickman MJ, Zhang K, Kern KA, Martin M (2010) Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. Breast Cancer Res Treat 121(1):121–131. https://doi.org/10.1007/s10549-010-0788-0
Baselga J, Costa F, Gomez H, Hudis CA, Rapoport B, Roche H, Schwartzberg LS, Petrenciuc O, Shan M, Gradishar WJ (2013) A phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc HER2-negative breast CancEr (the RESILIENCE study): study protocol for a randomized controlled trial. Trials 14:228. https://doi.org/10.1186/1745-6215-14-228
Baselga J, Segalla JG, Roche H, Del Giglio A, Pinczowski H, Ciruelos EM, Filho SC, Gomez P, Van Eyll B, Bermejo B, Llombart A, Garicochea B, Duran MA, Hoff PM, Espie M, de Moraes AA, Ribeiro RA, Mathias C, Gil Gil M, Ojeda B, Morales J, Kwon Ro S, Li S, Costa F (2012) Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer. J Clin Oncol 30(13):1484–1491. https://doi.org/10.1200/JCO.2011.36.7771
Baselga J, Zamagni C, Gomez P, Bermejo B, Nagai S, Melichar B, Chan A, Mangel L, Bergh J, Costa FP, Gomez HL, Gradishar W, Hudis C, Rapoport B, Roche H, Maeda P, Huang L, Zhang J, Schwartzberg LS (2014) A phase III randomized, double-blind, trial comparing sorafenib plus capecitabine versus placebo plus capecitabine in the treatment of locally advanced breast cancer (ESMO 2014). Ann Oncol 25(5):1–41
Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N (2015) Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol 16(9):1037–1048. https://doi.org/10.1016/S1470-2045(15)00041-8
Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C (2012) First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol 30(9):921–929. https://doi.org/10.1200/JCO.2011.35.7376
Bertucci F, Fekih M, Autret A, Petit T, Dalenc F, Levy C, Romieu G, Bonneterre J, Ferrero JM, Kerbrat P, Soulie P, Mouret-Reynier MA, Bachelot T, Lerebours F, Eymard JC, Deblock M, Lortholary A, Hardy-Bessard AC, Barthelemy P, Bonnefoi H, Charafe-Jauffret E, Bidard FC, Viens P, Lemonnier J, Pierga JY (2016) Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study. Lancet Oncol 17(5):600–611. https://doi.org/10.1016/s1470-2045(16)00011-5
Bianchi G, Loibl S, Zamagni C, Salvagni S, Raab G, Siena S, Laferriere N, Pena C, Lathia C, Bergamini L, Gianni L (2009) Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer. Anti-Cancer Drugs 20(7):616–624
Browder T, Butterfield CE, Kraling BM, Shi B, Marshall B, O’Reilly MS, Folkman J (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60(7):1878–1886
Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O’Neill V, Rugo HS (2011) RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 29(32):4286–4293. https://doi.org/10.1200/jco.2010.34.1255
Calleri A, Bono A, Bagnardi V, Quarna J, Mancuso P, Rabascio C, Dellapasqua S, Campagnoli E, Shaked Y, Goldhirsch A, Colleoni M, Bertolini F (2009) Predictive potential of angiogenic growth factors and circulating endothelial cells in breast cancer patients receiving metronomic chemotherapy plus bevacizumab. Clin Cancer Res 15(24):7652–7657. https://doi.org/10.1158/1078-0432.CCR-09-1493
Cameron D, Brown J, Dent R, Jackisch C, Mackey J, Pivot X, Steger GG, Suter TM, Toi M, Parmar M, Laeufle R, Im YH, Romieu G, Harvey V, Lipatov O, Pienkowski T, Cottu P, Chan A, Im SA, Hall PS, Bubuteishvili-Pacaud L, Henschel V, Deurloo RJ, Pallaud C, Bell R (2013) Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol 14(10):933–942. https://doi.org/10.1016/s1470-2045(13)70335-8
Cao L, Yao GY, Liu MF, Chen LJ, Hu XL, Ye CS (2015) Neoadjuvant bevacizumab plus chemotherapy versus chemotherapy alone to treat non-metastatic breast cancer: a meta-analysis of randomised controlled trials. PLoS One 10(12):e0145442. https://doi.org/10.1371/journal.pone.0145442
Chan A, Vanlemmens L, Conte P, Beith J, Samonigg H, Verma S, Srimuninnimit V, Martoni A, Miles D (2008) Efficacy of bevacizumab (BV) plus docetaxel (D) does not correlate with hypertension (HTN) or G-CSF use in patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC) in the AVADO phase III study. Clin Cancer Res 69 (abstract 1027)
Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A (2003) A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30(5 Suppl 16):117–124
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172. https://doi.org/10.1016/s0140-6736(13)62422-8
Di Desidero T, Xu P, Man S, Bocci G, Kerbel RS (2015) Potent efficacy of metronomic topotecan and pazopanib combination therapy in preclinical models of primary or late stage metastatic triple-negative breast cancer. Oncotarget 6(40):42396–42410. https://doi.org/10.18632/oncotarget.6377
Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA (2016) Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (alliance). J Clin Oncol. https://doi.org/10.1200/jco.2015.66.1595
Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L, Investigators AR (2015) Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol 16(6):656–666. https://doi.org/10.1016/S1470-2045(15)70137-3
Fumoleau P, Greil R, Rayson D, Müller V, Barni S, Aleknavicius E, Tellez E, Wilson C, Miles D (2008) Bevacizumab (BV) maintenance therapy significantly delays disease progression (PD) or death compared with placebo (PL) in the AVADO trial (BV + docetaxel [D] vs D + PL in 1st-line HER2-negative locally recurrent [LR] or metastatic breast cancer [mBC]). Cancer Res 69 (abstract 903)
Gadaleta-Caldarola G, Infusino S, Divella R, Ferraro E, Mazzocca A, De Rose F, Filippelli G, Abbate I, Brandi M (2015) Sorafenib: 10 years after the first pivotal trial. Future Oncol 11(13):1863–1880. https://doi.org/10.2217/fon.15.85
Garcia-Saenz JA, Martin M, Calles A, Bueno C, Rodriguez L, Bobokova J, Custodio A, Casado A, Diaz-Rubio E (2008) Bevacizumab in combination with metronomic chemotherapy in patients with anthracycline- and taxane-refractory breast cancer. J Chemother 20(5):632–639. https://doi.org/10.1179/joc.2008.20.5.632
Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G (2014) Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol 15(12):1351–1360. https://doi.org/10.1016/S1470-2045(14)70444-9
Gradishar WJ, Kaklamani V, Sahoo TP, Lokanatha D, Raina V, Bondarde S, Jain M, Ro SK, Lokker NA, Schwartzberg L (2013) A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer. Eur J Cancer 49(2):312–322. https://doi.org/10.1016/j.ejca.2012.08.005
Gray R, Bhattacharya S, Bowden C, Miller K, Comis RL (2009) Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 27(30):4966–4972
Hein A, Lambrechts D, von Minckwitz G, Haberle L, Eidtmann H, Tesch H, Untch M, Hilfrich J, Schem C, Rezai M, Gerber B, Dan Costa S, Blohmer JU, Schwedler K, Kittel K, Fehm T, Kunz G, Beckmann MW, Ekici AB, Hanusch C, Huober J, Liedtke C, Mau C, Moisse M, Muller V, Nekljudova V, Peuteman G, Rack B, Rubner M, Van Brussel T, Wang L, Weinshilboum RM, Loibl S, Fasching PA (2015) Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: results from the randomized phase 3 GeparQuinto study. Int J Cancer. https://doi.org/10.1002/ijc.29656
Hyams DM, Chan A, de Oliveira C, Snyder R, Vinholes J, Audeh MW, Alencar VM, Lombard J, Mookerjee B, Xu J, Brown K, Klein P (2013) Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized phase II study. Investig New Drugs 31(5):1345–1354. https://doi.org/10.1007/s10637-013-9991-2
Johnston SR, Gomez H, Stemmer SM, Richie M, Durante M, Pandite L, Goodman V, Slamon D (2013) A randomized and open-label trial evaluating the addition of pazopanib to lapatinib as first-line therapy in patients with HER2-positive advanced breast cancer. Breast Cancer Res Treat 137(3):755–766. https://doi.org/10.1007/s10549-012-2399-4
Konecny GE, Meng YG, Untch M, Wang HJ, Bauerfeind I, Epstein M, Stieber P, Vernes JM, Gutierrez J, Hong K, Beryt M, Hepp H, Slamon DJ, Pegram MD (2004) Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 10(5):1706–1716
Lam SW, Nota NM, Jager A, Bos MM, van den Bosch J, van der Velden AM, Portielje JE, Honkoop AH, van Tinteren H, Boven E (2016) Angiogenesis- and hypoxia-associated proteins as early indicators of the outcome in patients with metastatic breast cancer given first-line bevacizumab-based therapy. Clin Cancer Res 22(7):1611–1620. https://doi.org/10.1158/1078-0432.ccr-15-1005
Ledermann JA, Embleton AC, Raja F, Perren TJ, Jayson GC, Rustin GJ, Kaye SB, Hirte H, Eisenhauer E, Vaughan M, Friedlander M, Gonzalez-Martin A, Stark D, Clark E, Farrelly L, Swart AM, Cook A, Kaplan RS, Parmar MK, collaborators I (2016) Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 387 (10023):1066–1074. https://doi.org/10.1016/S0140-6736(15)01167-8
Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA (2014) Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol 15(11):1207–1214. https://doi.org/10.1016/S1470-2045(14)70391-2
Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, Lee H, Whalen C, Tyburski K, Winer E, Ivy P, Matulonis UA (2013) A phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer 49(14):2972–2978. https://doi.org/10.1016/j.ejca.2013.05.020
Lustberg MB, Pant S, Ruppert AS, Shen T, Wei Y, Chen L, Brenner L, Shiels D, Jensen RR, Berger M, Mrozek E, Ramaswamy B, Grever M, Au JL, Wientjes MG, Shapiro CL (2012) Phase I/II trial of non-cytotoxic suramin in combination with weekly paclitaxel in metastatic breast cancer treated with prior taxanes. Cancer Chemother Pharmacol 70(1):49–56. https://doi.org/10.1007/s00280-012-1887-x
Mackey JR, Ramos-Vazquez M, Lipatov O, McCarthy N, Krasnozhon D, Semiglazov V, Manikhas A, Gelmon KA, Konecny GE, Webster M, Hegg R, Verma S, Gorbunova V, Abi Gerges D, Thireau F, Fung H, Simms L, Buyse M, Ibrahim A, Martin M (2015) Primary results of ROSE/TRIO-12, a randomized placebo-controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. J Clin Oncol 33(2):141–148. https://doi.org/10.1200/JCO.2014.57.1513
Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G (2010) Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28(20):3239–3247. https://doi.org/10.1200/jco.2008.21.6457
Miles DW, Dieras V, Cortes J, Duenne AA, Yi J, O’Shaughnessy J (2013) First-line bevacizumab in combination with chemotherapy for HER2-negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients. Ann Oncol 24(11):2773–2780. https://doi.org/10.1093/annonc/mdt276
Miller K, O’Neill AM, Dang CT, Northfelt DW, Gradishar WJ, Goldstein LJ, Mayer IA, Brufsky A, Bloom SH, Sparano JA, Tevaarwerk A, Fox KR, Hendricks CB, Balcueva EP, Sledge GW (2014) Bevacizumab (Bv) in the adjuvant treatment of HER2-negative breast cancer: final results from Eastern Cooperative Oncology Group E5103. J Clin Oncol 32(5s) (suppl abstract 500)
Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676
Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23(4):792–799. https://doi.org/10.1200/JCO.2005.05.098
Mina LA, Yu M, Johnson C, Burkhardt C, Miller KD, Zon R (2013) A phase II study of combined VEGF inhibitor (bevacizumab+sorafenib) in patients with metastatic breast cancer: Hoosier Oncology Group study BRE06-109. Investig New Drugs 31(5):1307–1310. https://doi.org/10.1007/s10637-013-9976-1
Moreno-Aspitia A, Morton RF, Hillman DW, Lingle WL, Rowland KM Jr, Wiesenfeld M, Flynn PJ, Fitch TR, Perez EA (2009) Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracyclines or taxanes: north central cancer treatment Group and Mayo Clinic trial N0336. J Clin Oncol 27(1):11–15. https://doi.org/10.1200/JCO.2007.15.5242
Paget S (1889) Distribution of secondary growths in cancer of the breast. Lancet 1:571
Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nat Rev Cancer 4(6):448–456. https://doi.org/10.1038/nrc1370
Papetti M, Herman IM (2002) Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 282(5):C947–C970. https://doi.org/10.1152/ajpcell.00389.2001
Pierga JY, Petit T, Delozier T, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roche H, Bachelot T, Charafe-Jauffret E, Pavlyuk M, Kraemer S, Bidard FC, Viens P (2012) Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol 13(4):375–384. https://doi.org/10.1016/S1470-2045(12)70049-9
Pivot X, Schneeweiss A, Verma S, Thomssen C, Passos-Coelho JL, Benedetti G, Ciruelos E, von Moos R, Chang HT, Duenne AA, Miles DW (2011) Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: results from AVADO. Eur J Cancer 47(16):2387–2395. https://doi.org/10.1016/j.ejca.2011.06.018
Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O’Shaughnessy J (2011a) RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 29(10):1252–1260. https://doi.org/10.1200/jco.2010.28.0982
Robert NJ, Saleh MN, Paul D, Generali D, Gressot L, Copur MS, Brufsky AM, Minton SE, Giguere JK, Smith JW 2nd, Richards PD, Gernhardt D, Huang X, Liau KF, Kern KA, Davis J (2011b) Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial. Clin Breast Cancer 11(2):82–92. https://doi.org/10.1016/j.clbc.2011.03.005
Santos LV, Cruz MR, Lopes Gde L, Lima JP (2015) VEGF-A levels in bevacizumab-treated breast cancer patients: a systematic review and meta-analysis. Breast Cancer Res Treat 151(3):481–489. https://doi.org/10.1007/s10549-015-3410-7
Schneider BP, Radovich M, Sledge GW, Robarge JD, Li L, Storniolo AM, Lemler S, Nguyen AT, Hancock BA, Stout M, Skaar T, Flockhart DA (2008a) Association of polymorphisms of angiogenesis genes with breast cancer. Breast Cancer Res Treat 111(1):157–163
Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, Flockhart DA, Hancock B, Davidson N, Gralow J, Dickler M, Perez EA, Cobleigh M, Shenkier T, Edgerton S, Miller KD, ECOG (2008b) Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 26(28):4672–4678. https://doi.org/10.1200/JCO.2008.16.1612
Schwartzberg LS, Tauer KW, Hermann RC, Makari-Judson G, Isaacs C, Beck JT, Kaklamani V, Stepanski EJ, Rugo HS, Wang W, Bell-McGuinn K, Kirshner JJ, Eisenberg P, Emanuelson R, Keaton M, Levine E, Medgyesy DC, Qamar R, Starr A, Ro SK, Lokker NA, Hudis CA (2013) Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res 19(10):2745–2754. https://doi.org/10.1158/1078-0432.CCR-12-3177
Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP (2015) Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (alliance). J Clin Oncol 33(1):13–21. https://doi.org/10.1200/JCO.2014.57.0572
Slamon D, Swain S, Buyse M, Martin M, Geyer C, Im Y-H, Pienkowski T, Kim B, Robert N, Steger G, Crown J, Verma S, Eiermann W, Ostantino J, Im S, Mamounas E, Schwartzberg L, Paterson A, Mackey J, Provencher L, Press M, Thirlwell M, Bee-Munteanu V, Henschel V, Crepelle-Flechais A, Wolmark N (2013) BETH: a randomized phase III study evaluating adjuvant Bevacizumab added to Trastuzumab/chemotherapy for treatment of HER2+ early breast cancer San Antonio Breast Cancer Symposium. Abstract S01–03
Spigel DR, Hainsworth JD, Burris HA 3rd, Molthrop DC, Peacock N, Kommor M, Vazquez ER, Greco FA, Yardley DA (2011) A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel and sorafenib in women with node-positive or high-risk early-stage breast cancer. Clin Adv Hematol Oncol 9(4):280–286
Tabouret E, Bertucci F, Pierga JY, Petit T, Levy C, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roche H, Bachelot T, van Laere S, Ueno NT, Toiron Y, Finetti P, Birnbaum D, Borg JP, Viens P, Chinot O, Goncalves A (2016) MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study. Oncotarget. https://doi.org/10.18632/oncotarget.7612
Tan AR, Johannes H, Rastogi P, Jacobs SA, Robidoux A, Flynn PJ, Thirlwell MP, Fehrenbacher L, Stella PJ, Goel R, Julian TB, Provencher L, Bury MJ, Bhatt K, Geyer CE Jr, Swain SM, Mamounas EP, Wolmark N (2015) Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP foundation FB-6, a phase II study. Breast Cancer Res Treat 149(1):163–169. https://doi.org/10.1007/s10549-014-3221-2
von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Muller BM, Denkert C, Loibl S, Nekljudova V, Untch M (2012) Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 366(4):299–309. https://doi.org/10.1056/NEJMoa1111065
von Minckwitz G, Loibl S, Untch M, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Gerber B, groups GA-Bs (2014a) Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto). Ann Oncol 25 (12):2363–2372. https://doi.org/10.1093/annonc/mdu455
von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J (2014b) Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol 15(11):1269–1278. https://doi.org/10.1016/S1470-2045(14)70439-5
Welt A, Marschner N, Lerchenmueller C, Decker T, Steffens CC, Koehler A, Depenbusch R, Busies S, Hegewisch-Becker S (2016) Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial. Breast Cancer Res Treat 156(1):97–107. https://doi.org/10.1007/s10549-016-3727-x
Yardley DA, Dickson N, Drosick D, Earwood C, Inhorn R, Murphy P, Hainsworth JD (2016) Sorafenib plus Ixabepilone as first-line treatment of metastatic HER2-negative breast cancer: a Sarah Cannon research institute phase I/II trial. Clin Breast Cancer 16(3):180–187. https://doi.org/10.1016/j.clbc.2016.02.003
Ziyad S, Iruela-Arispe ML (2011) Molecular mechanisms of tumor angiogenesis. Genes Cancer 2(12):1085–1096. https://doi.org/10.1177/1947601911432334
Acknowledgments
We thank Dr. Anna-Sophia McKenney (Memorial Sloan Kettering Cancer Center, New York, NY) for critically revising the manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Banys-Paluchowski, M., Fehm, T., Müller, V. (2019). The Value of Anti-angiogenics in Breast Cancer Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_24
Download citation
DOI: https://doi.org/10.1007/978-3-319-33673-2_24
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-33671-8
Online ISBN: 978-3-319-33673-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences