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. 2021 Oct;81(10):1101-1111.
doi: 10.1055/a-1519-7089. Epub 2021 Oct 6.

AGO Algorithms for the Treatment of Breast Cancer: Update 2021

Andreas Schneeweiss  1 , Peter A Fasching  2 , Tanja Fehm  3 , Bernd Gerber  4 , Christian Jackisch  5 , Sibylle Loibl  6 , Marcus Schmidt  7 , Elmar Stickeler  8 , Achim Wöckel  9 , Wolfgang Janni  10 , Volkmar Müller  11 ; AGO Kommission Mamma
Affiliations

AGO Algorithms for the Treatment of Breast Cancer: Update 2021

Andreas Schneeweiss et al. Geburtshilfe Frauenheilkd. 2021 Oct.

Abstract
in English, German

Therapy options shown in the algorithms are based on the current AGO recommendations, but cannot represent all evidence-based treatment options, since prior therapies, performance status, comorbidities, patient preference, etc. must be taken into account for the actual treatment choice. In individual cases, other evidence-based treatment options may also be appropriate and justified. Regardless of approval status, the algorithms only take into account drugs that were available in Germany at the time the algorithm was last updated. Here we present the 2021 update of AGO treatment algorithms for early and metastatic breast cancer, which are intended to intensify structured treatment decision by providing reproducible and evidence-based treatment paths and may be helpful for a broad treatment landscape.

Die in den Algorithmen aufgezeigten Behandlungsoptionen basieren zwar auf den aktuellen AGO-Empfehlungen, können aber nicht alle evidenzbasierten Behandlungsoptionen darstellen, da frühere Therapien, der Patientinnenstatus, Begleiterkrankungen, Patientinnenpräferenzen usw. bei der tatsächlichen Therapiewahl mitberücksichtigt werden müssen. Andere evidenzbasierte Behandlungsoptionen können in Einzelfällen auch angemessen und gerechtfertigt sein. Ungeachtet ihres Zulassungsstatus werden nur die Medikamente in den Algorithmen aufgenommen, die zum Zeitpunkt des letzten Algorithmus-Updates in Deutschland zugelassen waren. Die Aktualisierung der AGO-Behandlungsalgorithmen für die Therapie von frühen und metastasierten Brustkrebserkrankungen von 2021 wird hier vorgestellt. Diese Aktualisierung soll strukturierte Behandlungsentscheidungen durch die Darlegung reproduzierbarer, evidenzbasierter Therapiepfade verstärken und kann für eine breit angelegte Behandlungslandschaft nützlich sein.

Keywords: breast cancer guidelines; evidence-based treatment; therapy algorithms.

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Conflict of interest statement

Conflict of Interest Consultancy: Sanofi-Aventis, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene, Johnson & Johnson, Seagen, MSD, PierreFabre, Amgen, Gilead, DaiichiSankyo. Research Funding: Sanofi-Aventis, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene, Johnson & Johnson, Seagen, MSD, PierreFabre, Amgen, Gilead, DaiichiSankyo. Honoraria: Sanofi-Aventis, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene, Johnson & Johnson, Seagen, MSD, PierreFabre, Amgen, Gilead, DaiichiSankyo.

Figures

Fig. 1
Fig. 1
Format legend for the AGO agorithms.
Fig. 2
Fig. 2
Algorithm (Neo)adjuvant Therapy of HER2-positive Breast Cancer. 1 Gianni L et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25 – 32. 2 Tolaney SM et al. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol 2019; 37: 1868 – 1875. 3 Perez EA et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014; 32: 3744 – 3752. 4 Cameron D et al., Herceptin Adjuvant (HERA) Trial Study Team. 11 yearsʼ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 2017; 389: 1195 – 1205. 5 Martin M et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18: 1688 – 1700. 6 von Minckwitz G et al., APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med 2017; 377: 122 – 131. 7 Piccart M et al. Interim overall survival analysis of APHINITY (BIG 4 – 11): A randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive early breast cancer. SABCS 2019; Abstr. GS01-04. 8 Gianni L et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol 2014; 15: 640. 9 von Minckwitz G et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2019; 380: 617 – 628. 10 Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer 2018; 89: 27 – 35.
Fig. 3
Fig. 3
Algorithm Adjuvant Endocrine Therapy in Premenopausal Patients. 1 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771 – 784. 2 Davies C, Pan H, Godwin J et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013; 381: 805 – 806. 3 Goss PE, Ingle JN, Martino S et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 2005; 97: 1262 – 1271. 4 Francis PA, Regan MM, Fleming GF et al. The SOFT Investigators and the International Breast Cancer Study Group. Adjuvant Ovarian Suppression in Premenopausal Breast Cancer. N Engl J Med 2015; 372: 436 – 446. 5 Pagani O, Regan MM, Walley BA et al. TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 2014; 371: 107 – 118.
Fig. 4
Fig. 4
Algorithm Adjuvant Endocrine Therapy in Postmenopausal Patients. 1 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771 – 784. 2 Davies C, Pan H, Godwin J et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013; 381: 805 – 806. 3 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG): Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341 – 1352. 4 Gray R (EBCTCG) et al. Extended aromatase inhibitor treatment following 5 or more years of endocrine therapy: a metaanalysis of 22 192 women in 11 randomised trials. SABCS 2018; GS3-03.
Fig. 5
Fig. 5
Algorithm HR-positive/HER2-negative Metastatic Breast Cancer: Strategies. 1 Qi WX, Tang LN, He AN et al. Comparison between doublet agents versus single agent in metastatic breast cancer patients previously treated with an anthracycline and a taxane: A meta-analysis of four phase III trials. Breast 2013; 22: 314 – 319. 2 Belfiglio M, Fanizza C, Tinari N et al., Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO). Meta-analysis of phase III trials of docetaxel alone or in combination with chemotherapy in metastatic breast cancer. J Cancer Res Clin Oncol 2012; 138: 221 – 229. 3 Pallis AG, Boukovinas I, Ardavanis A et al. A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol 2012; 23: 1164 – 1169. 4 Dear RF, McGeechan K, Jenkins MC et al. Combination versus sequential single agent chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev 2013; (12): CD008792. doi:10.1002/14651858.CD008792.pub 2. 5 Petrelli F, Ghidini A, Pedersini R et al. Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials. Breast Cancer Res Treat 2019; 174: 597 – 604. doi:810.1007/s10549-019-05133-y. PMID: 30659432. 6 Rossi V, Berchialla P, Giannarelli D et al. Should All Patients With HR-Positive HER2-Negative Metastatic Breast Cancer Receive CDK 4/6 Inhibitor As First-Line Based Therapy? A Network Meta-Analysis of Data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT Trials. Cancers (Basel) 2019; 11; pii: E1661. doi:10.3390/cancers11111661 . 7 Robson M et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523 – 533. 8 Robson ME, Tung N, Conte P et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physicianʼs choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol 2019; 30: 558 – 566. doi:10.1093/annonc/mdz012 . PMID: 30689707. 9 Robson M, Ruddy KJ, Im SA et al. Patient-reported outcomes in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer receiving olaparib versus chemotherapy in the OlympiAD trial. Eur J Cancer 2019; 120: 20 – 30. doi:10.1016/j.ejca.2019.06.023 . PMID: 31446213. 10 Litton J et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753 – 763. doi:10.1056/NEJMoa180290510 . 11 Turner NC, Telli ML, Rugo HS et al., ABRAZO Study Group. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res 2019; 25: 2717 – 2724. doi:10.1158/1078-0432.CCR-18-1891 . PMID: 30563931. 12 Ettl J, Quek RGW, Lee KH et al. Quality of life with talazoparib versus physicianʼs choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol 2018; 29: 1939 – 1947. doi:10.1093/annonc/mdy257 . PMID: 30124753. 13 Hurvitz SA, Gonçalves A, Rugo HS et al. Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial. Oncologist 2020; 25: e439 – e450. doi:10.1634/theoncologist.2019-0493 . PMID: 31767793. 14 Cardoso F, Senkus E, Costa A et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC4). Ann Oncol 2018; 29: 1634 – 1657. 15 Kornblum NS et al. PrECOG 0102: A randomized, double-blind, phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC) resistant to aromatase inhibitor (AI) therapy. SABCS 2016; #S1-02. 16 André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Pápai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D, SOLAR-1 Study Group. Alpelisib for PIK3CA -Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2019; 380: 1929 – 1940.
Fig. 6
Fig. 6
Algorithm HR-positive/HER2-negative Metastatic Breast Cancer: Endocrine-based First Line Treatment. 1  Turner N et al. Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209 – 219. 2 Loibl S et al. Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results. Oncologist 2017; 22: 1028 – 1038. 3 Layman RM et al. Comparative effectiveness of palbociclib plus letrozole vs. letrozole for metastatic breast cancer in US-real world clinical practises. ESMO 2019; #329P. 4 Tripathy D et al. First-line ribociclib vs. placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. SABCS2017; GS-26. 5 Im SA, Lu YS, Bardia A et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019; 381: 307 – 316. doi:10.1056/NEJMoa1903765 . PMID:31166679. 6 Sledge GW jr., Toi M, Neven P et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol 2019. doi:10.1001/jamaoncol.2019.4782 [Epub ahead of print]. PMID:31 563 959. 7 Klijn JG, Blamey RW, Boccardo F et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol 2001; 19: 343 – 353. 8 Rugo HS et al. Endocrine Therapy for Hormone Receptor-Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline. J Clin Oncol 2016; 34: 3069 – 3103. 9 Forward DP, Cheung KL, Jackson L et al. Clinical and endocrine data for goserelin plus anastrozole as second-line endocrine therapy for premenopausal advanced breast cancer. Br J Cancer 2004; 90: 590 – 594. 10 Park IH, Ro J, Lee KS et al. Phase II parallel group study showing comparable efficacy between premenopausal metastatic breast cancer patients treated with letrozole plus goserelin and postmenopausal patients treated with letrozole alone as first-line hormone therapy. J Clin Oncol 2010; 28: 2705 – 2711. 11 Carlson RW et al. Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor-positive, metastatic carcinoma of the breast in premenopausal women. J Clin Oncol 2010; 28: 3917 – 3921. 12 Bartsch R, Bago-Horvath Z et al. Ovarian function suppression and fulvestrant as endocrine therapy in premenopausal women with metastatic breast cancer. Eur J Cancer 2012; 48: 1932 – 1938. 13  Taylor CW, Green S, Dalton WS et al. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 1998; 16: 994 – 999. 14 Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339: 1609 – 1618. 15 Crump M, Sawka CA, DeBoer G et al. An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer. Breast Cancer Res Treat 1997; 44: 201 – 210. 16 Finn RS et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375: 1925 – 1936. 17 Finn RS et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015; 16: 25 – 35. 18 Im SA, Mukai H, Park IH et al. Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. J Glob Oncol 2019; 5: 1 – 19. doi:10.1200/JGO.18.00173 . PMID: 31125276. 19 Rugo HS, Finn RS, Diéras V et al. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat 2019; 174: 719 – 729. doi:10.1007/s10549-018-05125-4 . PMID: 30632023. 20 Hortobagyi GN et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med 2016; 375: 1738 – 1748. 21 Yardley DA, Hart L, Favret A et al. Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study. Clin Breast Cancer 2019; 19: 268 – 277.e1. doi:10.1016/j.clbc.2019.02.007 . 22 Goetz MP et al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol 2017; 35: 3638 – 3646. 23 Johnston S, Martin M, Di Leo A et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer 2019; 5: 5. doi:10.1038/s41523-018-0097-z . PMID: 30675515. 24 Bonneterre J et al. Anastrozole versus Tamoxifen as First-Line Therapy for Advanced Breast Cancer in 668 Postmenopausal Women: Results of the Tamoxifen or Arimidex Randomized Group Efficacy and tolerability Study. J Clin Oncol 2000; 18: 3748 – 3757. 25 Thürlimann B et al. Anastrozole (Arimidex) versus tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer: results of the double-blind cross-over SAKK trial 21/95 – a substudy of the TARGET (Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability) trial. Breast Cancer Res Treat 2004; 85: 247 – 254. 26 Bonneterre J et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma Cancer 2001; 92: 2247 – 2258. 27 Mouridsen H et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group Journal of Clinical Oncology. J Clin Oncol 2003; 21: 2101 – 2109. 28 Paridaens R et al., European Organization for the Research and Treatment of Cancer (EORTC) – Investigational Drug Branch for Breast Cancer (IDBBC). Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Ann Oncol 2003; 14: 1391 – 1398. 29 Gibson L, Lawrence D, Dawson C et al. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 2009; (4): CD003370. 30 Fulvestrant 500 mg plus Palbociclib (vs. Fulvestrant alone). 31 Turner NC, Ro J, André F et al., PALOMA3 Study Group. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209 – 219. 32 Turner NC et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med 2018; 379: 1926 – 1936. doi:10.1056/NEJMoa1810527 . 33 Slamon DJ, Neven P, Chia S et al. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol 2018; 36: 2465 – 2472. doi:10.1200/JCO.2018.78.9909 . PMID: 29860922. 34 Slamon DJ, Neven P, Chia S et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med 2020; 382: 514 – 524. doi:10.1056/NEJMoa1911149 . 35 Sledge GW jr. et al. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol 2017; 35: 2875 – 2884. 36 Sledge GW jr., Toi M, Neven P et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol 2020; 6: 116 – 124. doi:10.1001/jamaoncol.2019.4782 . PMID: 31563959. 37 Ellis MJ et al. Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study. J Clin Oncol 2015; 33: 3781 – 3787. 38 Robertson JF et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet 2016; 388: 2997 – 3005. 39 Di Leo A et al. Final overall survival: fulvestrant 500 mg vs. 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst 2014; 106: djt337.
Fig. 7
Fig. 7
Algorithm HER2-positive Metastatic Breast Cancer: 1st–3rd-line. 1 Swain SM, Baselga J, Kim SB et al.; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372: 724 – 734. 2 Perez EA, López-Vega JM, Petit T et al. Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer: VELVET Cohort 1 final results. Breast Cancer Res 2016; 18: 126. 3 Verma S, Miles D, Gianni L et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367: 1783 – 1791. 4 Krop IE, Lin NU, Blackwell K et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol 2015; 26: 113 – 119. 5 Murthy RK, Loi S, Okines A et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2020; 382: 597 – 609. 6 Lin NU, Borges V, Anders C et al. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol 2020; 38: 2610 – 2619. 7 Cameron D, Casey M, Press M et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 2008; 112: 533 – 543. 8 Geyer CE, Forster J, Lindquist D et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355: 2733 – 2743. 9 Saura C, Oliveira M, Feng Y-H et al. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol 2020; 38: 3138 – 3149. 10 Modi S, Saura C, Yamashita T et al. Trastuzumab-Deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2020. doi:10.1056/NEJMoa1914510 . 11 von Minckwitz G, Schwedler K, Schmidt M et al.; GBG 26/BIG 03 – 05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3 – 05 phase III study in HER2-positive breast cancer. Eur J Cancer 2011; 47: 2273 – 2281. 12 Rimawi M, Ferrero J – M, de La Haba-Rodriguez J et al. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial. J Clin Oncol 2018; 36: 2826 – 2828. 13 Blackwell KL, Burstein HJ, Storniolo AM et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol 2012; 30: 2585 – 2592. 14 Blackwell KL, Burstein HJ, Storniolo AM et al. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol 2010; 28: 1124 – 1130. 15 Giordano SH, Temin S, Kirshner JJ et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2014; 32: 2078 – 2099. 16 Kaufman B, Mackey JR, Clemens MR et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 2009; 27: 5529 – 5537. 17 Huober J, Fasching PA, Barsoum M et al. Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer – results of the eLEcTRA trial. Breast 2012; 21: 27 – 33. 18 Johnston S, Pippen J jr., Pivot X et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 2009; 27: 5538 – 5546. 19 Burstein HJ, Cirrincione CT, Barry WT et al. Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer-CALGB 40 302 (Alliance). J Clin Oncol 2014; 32: 3959 – 3966. 20 Rimawi M, Ferrero JM, de la Haba-Rodriguez J et al.; PERTAIN Study Group. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial. J Clin Oncol 2018; 36: 2826 – 2835. doi:10.1200/JCO.2017.76.7863 . PMID:30106636.
Fig. 8
Fig. 8
Algorithm Triple-negative Metastatic Breast Cancer. 1 Cardoso F, Senkus E, Costa A et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC4). Ann Oncol 2018; 29: 1634 – 1657. 2 Condorelli R, Mosele F, Verret B et al. Genomic alterations breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 2019; 30: 365 – 373. 3 Hu XC, Zhang J, Xu BH et al. Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2015; 16: 436 – 446. 4 Litton JK, Rugo HS, Ettl J et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753 – 763. 5 Miles DW, Diéras V, Cortés J et al. First-line bevacizumab in combination with chemotherapy for HER2-negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients. Ann Oncol 2013; 24: 2773 – 2780. 6 Miller K, Wang M, Gralow J et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357: 2666 – 2676. 7 Miller KD, Chap LI, Holmes FA et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23: 792 – 799. 8 Robson M, Im S-A, Senkus E et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523 – 533. 9 Robson M, Tung N, Conte P et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physicianʼs choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol 2019; 30: 558 – 566. 10 Schmid P, Adams S, Rugo HS et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018; 379: 2108 – 2121. 11 Cortes J, Cescon DW, Rugo HS et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 2020; 396: 1817 – 1828. 12 Tutt A, Tovey H, Cheang MCU et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med 2018; 24: 628 – 637. 13 Twelves C, Cortes J, Vahdat L et al. Efficacy of eribulin in women with metastatic breast cancer: a pooled analysis of two phase 3 studies [published correction appears in Breast Cancer Res Treat 2015; 149: 313. Breast Cancer Res Treat 2014; 148: 553 – 561. 14 Yardley DA, Coleman R, Conte P et al. nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial. Ann Oncol 2018; 29: 1763 – 1770. 15 Zielinski C, Láng I, Inbar M et al., TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, noninferiority, phase 3 trial. Lancet Oncol 2016; 17: 1230 – 1239. 16 Bardia A, Hurvitz SA, Tolaney SM et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med 2021; 384: 1529 – 1541. 17 Bardia A, Mayer IA, Vahdat LT et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med 2019; 380: 741 – 751
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References

    1. Thill M, Friedrich M, Kolberg-Liedtke C. AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer (MBC): Update 2021. Breast Care. 2021 doi: 10.1159/00051620. - DOI - PMC - PubMed
    1. Ditsch N, Kolberg-Liedtke C, Friedrich M. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer (EBC): Update 2021. Breast Care. 2021 doi: 10.1159/00051619. - DOI - PMC - PubMed
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