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De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer

Cancer Chemotherapy and Pharmacology volume 83, pages 1099–1104 (2019)Cite this article

Abstract

Purpose

Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse.

Methods

We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted.

Results

Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low.

Conclusion

This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.

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References

  1. Hudis CA (2007) Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med 357:39–51

    CAS  Article  Google Scholar 

  2. Buzdar AU, Valero V, Ibrahim NK et al (2007) Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res 13:228–233

    CAS  Article  Google Scholar 

  3. Gianni L, Eiermann W, Semiglazov V et al (2010) Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 375:377–384. https://doi.org/10.1016/S0140-6736(09)61964-4

    CAS  Article  PubMed  Google Scholar 

  4. Suter TM, Procter M, van Veldhuisen DJ et al (2007) Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol 25:3859–3865

    CAS  Article  Google Scholar 

  5. Tolaney SM, Barry WT, Dang CT et al (2015) Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 372:134–141. https://doi.org/10.1056/NEJMoa1406281

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Coates AS, Winer EP, Goldhirsch A et al (2015) Tailoring therapies–improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 26:1533–1546. https://doi.org/10.1093/annonc/mdv221

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Pegram MD, Lopez A, Konecny G, Slamon DJ (2000) Trastuzumab and chemotherapeutics: drug interactions and synergies. Semin Oncol 27:21–25; discussion 92–100

  8. Inoue K, Nakagami K, Mizutani M (2010) Randomized phase III trial of trastuzumab monotherapy followed by trastuzumab plus docetaxel versus trastuzumab plus docetaxel as first-line therapy in patients with HER2-positive metastatic breast cancer: the JO17360 trial group. Breast Cancer Res Treat 119:127–136. https://doi.org/10.1007/s10549-009-0498-7

    CAS  Article  PubMed  Google Scholar 

  9. Perez EA, Suman VJ, Davidson NE et al (2011) Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol 29:4491–4497. https://doi.org/10.1200/JCO.2011.36.7045

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Untch M, Jackisch C, Schneeweiss A et al (2016) Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol 17:345–356

    CAS  Article  Google Scholar 

  11. Cortazar P, Zhang L, Untch M et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172. https://doi.org/10.1016/S0140-6736(13)62422-8

    Article  PubMed  Google Scholar 

  12. von Minckwitz G, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804. https://doi.org/10.1200/JCO.2011.38.8595

    Article  Google Scholar 

  13. Tanaka S, Iwamoto M, Kimura K et al (2015) Phase II study of neoadjuvant anthracycline-based regimens combined with nanoparticle albumin-bound paclitaxel and trastuzumab for human epidermal growth factor receptor 2-positive operable breast cancer. Clin Breast Cancer 15:191–196. https://doi.org/10.1016/j.clbc.2014.12.003

    CAS  Article  PubMed  Google Scholar 

  14. Valachis A, Mauri D, Polyzos NP et al (2011) Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: a systematic review and meta-analysis. Breast 20:485–490. https://doi.org/10.1016/j.breast.2011.06.009

    Article  PubMed  Google Scholar 

  15. Buzdar AU, Suman VJ, Meric-Bernstam F et al (2013) Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol 14:1317–1325. https://doi.org/10.1016/S1470-2045(13)70502-3

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684

    CAS  Article  Google Scholar 

  17. Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283. https://doi.org/10.1056/NEJMoa0910383

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ et al (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 382:1021–1028. https://doi.org/10.1016/S0140-6736(13)61094-6

    CAS  Article  PubMed  Google Scholar 

  19. Niraula S, Gyawali B (2018) Optimal duration of adjuvant trastuzumab in treatment of early breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat 173:103–109. https://doi.org/10.1007/s10549-018-4967-8

    CAS  Article  PubMed  Google Scholar 

  20. Nagayama A, Hayashida T, Jinno H et al (2014) Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis. J Natl Cancer Inst 106:dju203. https://doi.org/10.1093/jnci/dju203

    CAS  Article  PubMed  Google Scholar 

  21. Clavarezza M, Puntoni M, Gennari A et al (2016) Dual block with lapatinib and trastuzumab versus single-agent trastuzumab combined with chemotherapy as neoadjuvant treatment of HER2-positive breast cancer: a meta-analysis of randomized trials. Clin Cancer Res 22:4594–4603. https://doi.org/10.1158/1078-0432.CCR-15-1881

    CAS  Article  PubMed  Google Scholar 

  22. Guarneri V, Dieci MV, Frassoldati A et al (2015) Prospective biomarker analysis of the randomized CHER-LOB study evaluating the dual anti-HER2 treatment with trastuzumab and lapatinib plus chemotherapy as neoadjuvant therapy for HER2-positive breast cancer. Oncologist 20:1001–1010. https://doi.org/10.1634/theoncologist.2015-0138

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Nitz UA, Gluz O, Christgen M et al (2017) De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel. Ann Oncol 28:2768–2772. https://doi.org/10.1093/annonc/mdx494

    CAS  Article  PubMed  Google Scholar 

  24. de Azambuja E, Holmes AP, Piccart-Gebhart M et al (2014) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 15:1137–1146. https://doi.org/10.1016/S1470-2045(14)70320-1

    CAS  Article  PubMed  Google Scholar 

  25. Gianni L, Pienkowski T, Im YH et al (2016) 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol 17:791–800. https://doi.org/10.1016/S1470-2045(16)00163-7

    CAS  Article  PubMed  Google Scholar 

  26. von Minckwitz G, Huang CS, Mano MS et al (2019) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380:617–628. https://doi.org/10.1056/NEJMoa1814017

    Article  Google Scholar 

  27. Peng L, Bu Z, Ye X, Zhou Y, Zhao Q (2017) Incidence and risk of peripheral neuropathy with nab-paclitaxel in patients with cancer: a meta-analysis. Eur J Cancer Care. https://doi.org/10.1111/ecc.12407

    Article  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the participating patients, their families, and study investigators for their invaluable contributions. Data from this study were previously presented at the 2016 39th San Antonio Breast Cancer Symposium.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Affiliations

  1. Department of Breast Surgery, National Hospital Organization, Osakaminami Medical Center, 2-1 Kidohigashi-cho, Kawachinagano-shi, Osaka, 586-8521, Japan

    Satoru Tanaka & Ayana Ikari

  2. Department of Breast Surgery, Osaka Rosai Hospital, 1179-3 Kita-Ku Nagasone-cho, Sakai-shi, Osaka, 591-8025, Japan

    Nobuki Matsunami, Hirotaka Morishima & Naofumi Oda

  3. Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Tsutomu Takashima, Satoru Noda, Shinichiro Kashiwagi, Yukie Tauchi & Yuka Asano

  4. Department of Breast and Endocrine Surgery, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki-shi, Osaka, 569-8686, Japan

    Kosei Kimura, Hiroya Fujioka, Risa Terasawa, Kanako Kawaguchi & Mitsuhiko Iwamoto

  5. Department of Breast Surgery, Yao Municipal Hospital, 1-3-1 Ryuge-cho, Yao-shi, Osaka, 581-0069, Japan

    Takashi Morimoto & Shintaro Michishita

  6. Department of Breast Surgery, Red Cross Takatsuki Hospital, 1-1-1 Abuno-cho, Takatsuki-shi, Osaka, 569-1045, Japan

    Toshihiro Kobayashi & Junna Sakane

  7. Department of Breast Surgery, Shiroyama Hospital, 2-8-1 Habikino, Habikino-shi, Osaka, 583-0872, Japan

    Toshikatsu Nitta

  8. Department of Breast Surgery, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita-shi, Osaka, 564-0133, Japan

    Nayuko Sato

  9. Department of Surgery, Red Cross Kochi Hospital, 2-13-51 Shinhon-machi, Koci-shi, Kochi, 780-8562, Japan

    Norihiro Hokimoto

  10. Department of Breast Surgery, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-ku, Osaka, 550-0006, Japan

    Yukihiro Nishida

Authors
  1. Satoru Tanaka
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  2. Nobuki Matsunami
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  3. Hirotaka Morishima
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  14. Ayana Ikari
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  15. Takashi Morimoto
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  16. Shintaro Michishita
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  17. Toshihiro Kobayashi
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  18. Junna Sakane
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  19. Toshikatsu Nitta
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  20. Nayuko Sato
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  21. Norihiro Hokimoto
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  22. Yukihiro Nishida
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  23. Mitsuhiko Iwamoto
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Corresponding author

Correspondence to Satoru Tanaka.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Tanaka, S., Matsunami, N., Morishima, H. et al. De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer. Cancer Chemother Pharmacol 83, 1099–1104 (2019). https://doi.org/10.1007/s00280-019-03836-z

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Keywords

  • Human epidermal growth factor receptor 2
  • Estrogen receptor negative
  • Neoadjuvant chemotherapy
  • Nanoparticle albumin-bound paclitaxel
  • Pathological complete response