Skip to main content

Advertisement

SpringerLink
Log in

Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within breast cancer subtypes and stages among older women: a SEER-Medicare analysis

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

This study aimed to compare survival outcomes of neoadjuvant (NAC) and adjuvant chemotherapy (AdC) within each breast cancer subtype and stage among older women.

Methods

Older (≥ 66 years) women newly diagnosed with stage I–III invasive ductal breast cancer during 2010–2017 and treated with both chemotherapy and surgery within one year were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Analyses were performed within each of six groups, jointly defined based on subtype (hormone receptor [HR]-positive/human epidermal growth factor receptor 2 [HER2]-negative, HER2 + , and triple-negative) and stage (I–II and III). Kaplan–Meier curves and multivariable Cox models were used to compare overall and recurrence-free survival between NAC and AdC, with optimal full matching performed for confounding adjustment.

Results

Among 8,495 included patients, 8,329 (20.6% received NAC) remained after matching. Before multiple testing adjustment, Cox models showed that NAC was associated with a lower hazard for death among stage III HER2 + patients (hazard ratio = 0.347, 95% confidence interval CI 0.161–0.745) but a higher hazard for death among triple-negative patients (stage I–II: hazard ratio = 1.558, 95% CI 1.024–2.370; stage III: hazard ratio = 2.453; 95% CI 1.254–4.797). A higher hazard for death/recurrence was associated with NAC among stage I–II HR + /HER2– patients (hazard ratio = 1.305, 95% CI 1.007–1.693). No significant difference remained after multiple testing adjustment.

Conclusions

The opposite trends (before multiple testing adjustment) of survival comparisons for advanced HER2 + and triple-negative disease warrant further research. Caution is needed due to study limitations such as cancer stage validity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data that support the findings of this study are available from the National Cancer Institute but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.

References

  1. Murphy BL, Day CN, Hoskin TL, Habermann EB, Boughey JC. Neoadjuvant chemotherapy use in breast cancer is greatest in excellent responders: Triple-negative and HER2+ subtypes. Ann Surg Oncol. 2018;25:2241–8.

    Article  PubMed  Google Scholar 

  2. Mougalian SS, Soulos PR, Killelea BK, Lannin DR, Abu-Khalaf MM, DiGiovanna MP, et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer Wiley. 2015;121:2544–52.

    Article  Google Scholar 

  3. Puig CA, Hoskin TL, Day CN, Habermann EB, Boughey JC. National trends in the use of neoadjuvant chemotherapy for hormone receptor-negative breast cancer: A national cancer data base study. Ann Surg Oncol. 2017;24:1242–50.

    Article  PubMed  Google Scholar 

  4. Hoskin TL, Boughey JC, Day CN, Habermann EB. Lessons learned regarding missing clinical stage in the national cancer database. Ann Surg Oncol. 2019;26:739–45.

    Article  PubMed  Google Scholar 

  5. Zeidman M, Alberty-Oller JJ, Ru M, Pisapati KV, Moshier E, Ahn S, et al. Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a national cancer database (NCDB) study. Breast Cancer Res Treat. 2020;184:203–12.

    Article  CAS  PubMed  Google Scholar 

  6. Zeidman M, Schmidt H, Alberty-Oller JJ, Pisapati KV, Ahn S, Mazumdar M, et al. Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer DataBase (NCDB). Breast Cancer Res Treat. Springer Science and Business Media LLC; 2021;187:177–85.

  7. Wang M, Hou L, Chen M, Zhou Y, Liang Y, Wang S, et al. Neoadjuvant chemotherapy creates surgery opportunities for inoperable locally advanced breast cancer. Sci Rep. 2017;7:44673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Asselain B, Barlow W, Bartlett J, Bergh J, Bergsten-Nordström E, Bliss J, et al. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol Elsevier BV. 2018;19:27–39.

    Article  Google Scholar 

  9. Mamounas EP, Fisher B. Preoperative (neoadjuvant) chemotherapy in patients with breast cancer. Semin Oncol Elsevier BV. 2001;28:389–99.

    Article  CAS  Google Scholar 

  10. von Minckwitz G, Huang C-S, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med Massachusetts Medical Society. 2019;380:617–28.

    Article  Google Scholar 

  11. Masuda N, Lee S-J, Ohtani S, Im Y-H, Lee E-S, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med New England Journal of Medicine (NEJM/MMS); 2017;376:2147–59.

  12. Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. J Clin Oncol. 2021; JCO2003399.

  13. Mauri D, Pavlidis N, Ioannidis JPA. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst: Oxford University Press (OUP); 2005.

    Google Scholar 

  14. Mieog JSD, van der Hage JA, van de Velde CJH. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev. Wiley; 2007; CD005002.

  15. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 2018 19:27–39.

  16. Sedrak MS, Freedman RA, Cohen HJ, Muss HB, Jatoi A, Klepin HD, et al. Older adult participation in cancer clinical trials: a systematic review of barriers and interventions. CA Cancer J Clin. 2021;71:78–92.

    Article  PubMed  Google Scholar 

  17. Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341:2061–7.

    Article  CAS  PubMed  Google Scholar 

  18. Mislang AR, Biganzoli L. Adjuvant systemic therapy in older breast cancer women: can we optimize the level of care? Cancers. 2015;7:1191–214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chubak J, Yu O, Pocobelli G, Lamerato L, Webster J, Prout MN, et al. Administrative data algorithms to identify second breast cancer events following early-stage invasive breast cancer. J Natl Cancer Inst: Oxford University Press (OUP); 2012.

    Book  Google Scholar 

  20. Andersen RM. Revisiting the behavioral model and access to medical care: does it matter? J Health Soc Behav. 1995;36:1–10.

    Article  CAS  PubMed  Google Scholar 

  21. National Cancer Institute, Division of Cancer Control & Population Sciences. SEER-Medicare: Comorbidity SAS Macros [Internet]. [cited 2021 Oct 1]. Available from: https://healthcaredelivery.cancer.gov/seermedicare/considerations/calculation.html

  22. Imai K, Ratkovic M. Covariate balancing propensity score. J R Stat Soc Series B Stat Methodol Wiley. 2014;76:243–63.

    Article  Google Scholar 

  23. Stuart EA. Matching methods for causal inference: a review and a look forward. Stat Sci. 2010;25:1–21.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Austin PC, Stuart EA. Optimal full matching for survival outcomes: a method that merits more widespread use. Stat Med Wiley. 2015;34:3949–67.

    Article  Google Scholar 

  25. Xie J, Liu C. Adjusted Kaplan-Meier estimator and log-rank test with inverse probability of treatment weighting for survival data. Stat Med Wiley. 2005;24:3089–110.

    Article  Google Scholar 

  26. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Wiley. 1995;57:289–300.

    Google Scholar 

  27. Zhang H, Barner JC, Moczygemba LR, Rascati KL, Park C, Kodali D. Neoadjuvant chemotherapy use trends among older women with breast cancer: 2010–2017. Breast Cancer Res Treat. 2022;193:695–705.

    Article  CAS  PubMed  Google Scholar 

  28. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from national surgical adjuvant breast and bowel project B-18. J Clin Oncol Am Soc Clin Oncol. 1997;15:2483–93.

    Article  CAS  Google Scholar 

  29. Rubin M. When to adjust alpha during multiple testing: a consideration of disjunction, conjunction, and individual testing. Synthese. Springer Science and Business Media LLC; 2021;199:10969–1000.

  30. Laas E, Bresset A, Féron J-G, Le Gal C, Darrigues L, Coussy F, et al. HER2-Positive breast cancer Patients with Pre-treatment axillary involvement or postmenopausal status benefit from neoadjuvant rather than adjuvant chemotherapy plus trastuzumab regimens. Cancers . Multidisciplinary Digital Publishing Institute; 2021; 13:370.

  31. Pomponio MK, Burkbauer L, Goldbach M, Nazarian SM, Xie F, Clark AS, et al. Refining the indications for neoadjuvant chemotherapy for patients with HER2+ breast cancer: a single institution experience. J Surg Oncol Wiley. 2020;121:447–55.

    Article  CAS  Google Scholar 

  32. Zheng S, Li L, Chen M, Yang B, Chen J, Liu G, et al. Benefits of neoadjuvant therapy compared with adjuvant chemotherapy for the survival of patients with HER2-positive breast cancer: a retrospective cohort study at FUSCC. Breast Elsevier BV. 2022;63:177–86.

    Google Scholar 

  33. Xia L-Y, Hu Q-L, Zhang J, Xu W-Y, Li X-S. Survival outcomes of neoadjuvant versus adjuvant chemotherapy in triple-negative breast cancer: a meta-analysis of 36,480 cases. World J Surg Oncol Springer Science and Business Media LLC; 2020; 18:129.

  34. Giacchetti S, Hamy A-S, Delaloge S, Brai.n E, Berger F, Sigal-Zafrani B, et al. Long-term outcome of the REMAGUS 02 trial, a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status. Eur J Cancer. 2017;75:323–32.

    Article  CAS  PubMed  Google Scholar 

  35. Amiri-Kordestani L, Wedam S, Zhang L, Tang S, Tilley A, Ibrahim A, et al. First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer. Clin Cancer Res. American Association for Cancer Research (AACR); 2014;20:5359–64.

  36. The Food and Drug Administration. FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer [Internet]. [cited 2022 Mar 3]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer

  37. Ruhl J, Adamo M, Dickie L. SEER Program Coding and Staging Manual 2016: Section V [Internet]. National Cancer Institute, Bethesda, MD; 2020 Feb. Available from: https://seer.cancer.gov/archive/manuals/2016/SPCSM_2016_SectionV.pdf

  38. Wu DY, Spangler AE, de Hoyos A, Vo DT, Seiler SJ. Quality of anatomic staging of breast carcinoma in hospitals in the United States, With focus on measurement of Tumor Dimension. Am J Clin Pathol. 2021;156:356–69.

    Article  PubMed  Google Scholar 

  39. Byrd DR, Brierley JD, Baker TP, Sullivan DC, Gress DM. Current and future cancer staging after neoadjuvant treatment for solid tumors. CA Cancer J Clin Wiley. 2021;71:140–8.

    Article  Google Scholar 

  40. Fisher B, Gunduz N, Saffer EA. Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 1983;43:1488–92.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the National Cancer Institute; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results Program tumor registries in the creation of the SEER-Medicare database.

Funding

This study was funded by the PhRMA Foundation (2021 Predoctoral Fellowship Health Outcomes Research PDDS 846487).

Author information

Authors and Affiliations

  1. College of Pharmacy, The University of Texas at Austin, Austin, TX, USA

    Hanxi Zhang, Jamie C. Barner, Leticia R. Moczygemba, Karen L. Rascati & Chanhyun Park

  2. Texas Oncology, Deke Slayton Cancer Center, Webster, TX, USA

    Dhatri Kodali

Authors
  1. Hanxi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jamie C. Barner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leticia R. Moczygemba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karen L. Rascati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chanhyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dhatri Kodali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jamie C. Barner.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 76 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, H., Barner, J.C., Moczygemba, L.R. et al. Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within breast cancer subtypes and stages among older women: a SEER-Medicare analysis. Breast Cancer 30, 489–496 (2023). https://doi.org/10.1007/s12282-023-01441-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-023-01441-w

Keywords

Search

Navigation