Zoledronate for patients with invasive residual disease after anthracyclines-taxane-based chemotherapy for early breast cancer - The Phase III NeoAdjuvant Trial Add-oN (NaTaN) study (GBG 36/ABCSG 29).
Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer.



Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival.



After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified.



Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.
German Breast Group, Martin Behaim Strasse 12, 63263 Neu-Isenburg, Germany. Electronic address: gunter.vonminckwitz@gbg.de.
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von Minckwitz
Luisenkrankenhaus Düsseldorf, Hans-Günther-Sohl-Straße 6-10, 40235 Düsseldorf, Germany. Electronic address: dr.mahdi.rezai@luisenkrankenhaus.de.
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Rezai
Hämatologisch-Onkologische Gemeinschaftspraxis Bethanien, Im Prüfling 17-19, 60389 Frankfurt/Main, Germany. Electronic address: Hans.Tesch@chop-studien.de.
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Tesch
Universitäts-Frauenklinik Ulm, Prittwitzstraße 43, 89081 Ulm, Germany. Electronic address: jens.huober@uniklinik-ulm.de.
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Huober
Universitäts-Frauenklinik Rostock, Südring 81, 18059 Rostock, Germany. Electronic address: bernd.gerber@med.uni-rostock.de.
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Gerber
SRH Wald-Klinikum Gera GmbH, Straße des Friedens 122, 07548 Gera, Germany. Electronic address: dirk-michael.zahm@wkg.srh.de.
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Zahm
Eilenriede Krankenhaus, Uhlemeyerstraße 16, 30175 Hannover, Germany. Electronic address: j.hilfrich@eilenriedeklinik.de.
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Hilfrich
Universitäts-Frauenklinik Magdeburg, Gerhart-Hauptmann-Straße 35, 39108 Magdeburg, Germany. Electronic address: serban-dan.costa@med.ovgu.de.
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Costa
Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Wien, Austria. Electronic address: peter.dubsky@meduniwien.ac.at.
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Dubsky
Charité-Universitätsmedizin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: jens.blohmer@charite.de.
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Blohmer
Charité-Universitätsmedizin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: carsten.denkert@charite.de.
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Denkert
Rotkreuzklinikum München, Taxisstr. 3, 80637 München, Germany. Electronic address: claus.hanusch@swmbrk.de.
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Hanusch
Klinikum Offenbach, Starkenburgring 66, 63069 Offenbach, Germany. Electronic address: christian.jackisch@sana.de.
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Jackisch
Brustzentrum, Kliniken Essen-Mitte, Henricistr. 92, 45136 Essen, Germany. Electronic address: s.kuemmel@kliniken-essen-mitte.de.
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Kümmel
Universitätsfrauenklinik Erlangen, Universitätsstr. 21-23, 91054 Erlangen, Germany. Electronic address: Peter.Fasching@uk-erlangen.de.
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Fasching
Nationales Centrum für Tumorerkrankungen (NCT), Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany. Electronic address: Andreas.Schneeweiss@med.uni-heidelberg.de.
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Schneeweiss
Universitäts-Frauenklinik rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany. Electronic address: stefan.paepke@lrz.tu-muenchen.de.
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Paepke
Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany. Electronic address: michael.untch@helios-kliniken.de.
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Untch
German Breast Group, Martin Behaim Strasse 12, 63263 Neu-Isenburg, Germany. Electronic address: nicole.burchardi@gbg.de.
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Burchardi
German Breast Group, Martin Behaim Strasse 12, 63263 Neu-Isenburg, Germany. Electronic address: Keyur.mehta@gbg.de.
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Mehta
German Breast Group, Martin Behaim Strasse 12, 63263 Neu-Isenburg, Germany. Electronic address: Sibylle.loibl@gbg.de.
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Loibl
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008875:Middle Aged; D018365:Neoplasm, Residual; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
Adjuvant treatment; Early breast cancer; Postneoadjuvant; Zoledronate