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Annals of Surgical Oncology

, Volume 22, Issue 8, pp 2517–2525 | Cite as

The Effect of Adjuvant Trastuzumab on Locoregional Recurrence of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Treated with Mastectomy

  • Ryan M. Lanning
  • Monica Morrow
  • Nadeem Riaz
  • Heather L. McArthur
  • Chau Dang
  • Tracy-Ann Moo
  • Mahmoud El-Tamer
  • Kate Krause
  • Chun Siu
  • Meier Hsu
  • Zhigang Zhang
  • Xin Pei
  • Beryl McCormick
  • Simon N. Powell
  • Alice Ho
Breast Oncology

Abstract

Background

Human epidermal growth factor receptor 2 (HER2) overexpression was associated with locoregional recurrence (LRR) in the preadjuvant trastuzumab era. This study aimed to examine the effect of trastuzumab on LRR in mastectomy patients and whether it varied with postmastectomy radiation (PMRT).

Methods

From the authors’ institutional database, 501 women with stages I–III HER2-positive breast cancer who underwent mastectomy from 1998 to 2007 were identified. A landmark analysis was performed to compare two cohorts: 170 women who received trastuzumab and 281 who did not. Kaplan–Meier methods were used to estimate locoregional recurrence-free survival (LRRFS). A propensity score analysis was used to balance the treatment groups with respect to multiple covariates. Analogous methods were used to study the effect of PMRT.

Results

The women in the trastuzumab group were more likely to be node positive and to receive systemic therapy or PMRT (p < 0.01). The 5-year LRRFS was 98 % in the trastuzumab troup versus 94 % in the no trastuzumab group [hazard ratio (HR) 0.31; 95 % confidence interval (CI) 0.091.09; p = 0.07]. After adjustment for multiple covariates, including receipt of chemotherapy and PMRT, trastuzumab decreased LRR rates (HR 0.21; 95 % CI 0.04–0.94; p = 0.04). Among the women who received PMRT, trastuzumab reduced the 5-year LRR rate (0 vs 5 %; p = 0.06). Among those who did not receive PMRT, trastuzumab did not significantly decrease LRR (3 vs 6 %; p = 0.26).

Conclusion

High rates of locoregional control (5-year rate, 98 %) were observed among patients who received trastuzumab and mastectomy ± PMRT. Trastuzumab decreased LRR in HER2-positive women who received mastectomy and PMRT, suggesting that the largest benefit is seen in a higher-risk subset of patients.

Keywords

Overall Survival Trastuzumab Hormone Receptor Status Pertuzumab Propensity Score Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

There is no conflict of interest.

References

  1. 1.
    Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2009;27:5838–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12.PubMedCrossRefGoogle Scholar
  3. 3.
    Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382:1021–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Perez EA, Romond EH, Suman VJ, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29:3366–73.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–83.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Kiess AP, McArthur HL, Mahoney K, et al. Adjuvant trastuzumab reduces locoregional recurrence in women who receive breast-conservation therapy for lymph node-negative, human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2012;118:1982–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Kim MM, Dawood S, Allen P, et al. Hormone receptor status influences the locoregional benefit of trastuzumab in patients with nonmetastatic breast cancer. Cancer. 2012;118:4936–43.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Panoff JE, Hurley J, Takita C, et al. Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation. Breast Cancer Res Treat. 2011;128:899–906.PubMedCrossRefGoogle Scholar
  9. 9.
    Wu SG, He ZY, Li Q, et al. Predictive value of breast cancer molecular subtypes in Chinese patients with four or more positive nodes after postmastectomy radiotherapy. Breast. 2012;21:657–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat. 2012;133:831–41.PubMedCrossRefGoogle Scholar
  11. 11.
    Tendulkar RD, Rehman S, Shukla ME, et al. Impact of postmastectomy radiation on locoregional recurrence in breast cancer patients with 1–3 positive lymph nodes treated with modern systemic therapy. Int J Radiat Oncol Biol Phys. 2012;83:e577–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Balduzzi A, Leonardi MC, Cardillo A, et al. Timing of adjuvant systemic therapy and radiotherapy after breast-conserving surgery and mastectomy. Cancer Treat Rev. 2010;36:443–50.PubMedCrossRefGoogle Scholar
  13. 13.
    Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Haffty BG, Brown F, Carter D, Flynn S. Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: a case-control study. Int J Radiat Oncol Biol Phys. 1996;35:751–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Muss HB, Thor AD, Berry DA, et al. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994;330:1260–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Press MF, Bernstein L, Thomas PA, et al. HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 1997;15:2894–904.PubMedGoogle Scholar
  17. 17.
    Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12:236–44.PubMedCrossRefGoogle Scholar
  18. 18.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.PubMedCrossRefGoogle Scholar
  19. 19.
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.PubMedCrossRefGoogle Scholar
  20. 20.
    Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007;369:29–36.PubMedCrossRefGoogle Scholar
  21. 21.
    Peterson DJ, Truong PT, Sadek BT, et al. Locoregional recurrence and survival outcomes by type of local therapy and trastuzumab use among women with node-negative, HER2-positive breast cancer. Ann Surg Oncol. 2014;21:3490–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Kyndi M, Sorensen FB, Knudsen H, et al. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008;26:1419–26.PubMedCrossRefGoogle Scholar
  23. 23.
    Pietras RJ, Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res. 1999;59:1347–55.PubMedGoogle Scholar
  24. 24.
    Pirollo KF, Tong YA, Villegas Z, Chen Y, Chang EH. Oncogene-transformed NIH 3T3 cells display radiation resistance levels indicative of a signal transduction pathway leading to the radiation-resistant phenotype. Radiat Res. 1993;135:234–43.PubMedCrossRefGoogle Scholar
  25. 25.
    Gianni L, Pienkowski T, Im YH, 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.PubMedCrossRefGoogle Scholar
  26. 26.
    Swain SM, Kim SB, Cortes J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461–71.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Ryan M. Lanning
    • 1
  • Monica Morrow
    • 2
  • Nadeem Riaz
    • 1
  • Heather L. McArthur
    • 3
  • Chau Dang
    • 3
  • Tracy-Ann Moo
    • 2
  • Mahmoud El-Tamer
    • 2
  • Kate Krause
    • 1
  • Chun Siu
    • 1
  • Meier Hsu
    • 4
  • Zhigang Zhang
    • 4
  • Xin Pei
    • 1
  • Beryl McCormick
    • 1
  • Simon N. Powell
    • 1
  • Alice Ho
    • 1
  1. 1.Department of Radiation OncologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Department of Biostatistics & EpidemiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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