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Aspirin use is associated with improvement in distant metastases outcome in patients with residual disease after neoadjuvant chemotherapy

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Abstract

Purpose

Aspirin (ASA) use has been correlated with improved outcomes in high-risk patients at risk for distant metastases. Breast cancer (BC) patients with residual disease, particularly nodal disease (ypN +) after neoadjuvant chemotherapy (NAC), are high-risk patients portending worse outcomes. We hypothesized that ASA use can reduce distant metastases and improve outcomes in these patients.

Methods

Patients at our institutions from 2005 to 2018, with BC who did not achieve complete response (pCR) after NAC were reviewed (IRB protocol STU- 052012–019). Data, including evidence of ASA use, and clinico-pathologic parameters were analyzed. Survival outcomes were obtained (Kaplan Meier analysis) and univariate (UVA) and multivariable (MVA) Cox proportional hazards regression analyses were performed.

Results

637 did not achieve pCR (ypN+ = 422). 138 were ASA users. Median follow-up for the control and ASA group were 3.8 (IQR 2.2–6.3) and 3.8 (IQR 2.5–6.4) years, respectively. Majority were stage II/III. 387 were hormone receptor positive, 191 HER2 +, and 157 triple negative. On UVA, ASA use, PR status, pathologic and clinical stage showed significance for DMFS, and disease-free survival (DFS). On MVA, ASA use associated with improved 5-year DFS (p = .01, 87.0% vs 79.6%, adjusted HR = 0.48) and improved 5-year DMFS (p = .04, 92.8% vs 89.2%, adjusted HR = 0.57). In the ypN + patients, ASA use associated with improved 5-year DMFS (p = .008, 85.7% vs 70.7%, adjusted HR = 0.43) and DFS (p = .02, 86.8% vs 74.3%, adjusted HR = 0.48).

Conclusion

For non-responders, particularly ypN + patients, ASA use associated with improved outcome. These hypotheses-generating results suggest for development of prospective clinical trials of augmented ASA use in selected very high-risk BC patients.

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Fig. 1
Fig. 2

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ASA:

Aspirin

BC:

Breast cancer

pCR:

Pathologic complete response

ypN + :

Residual nodal disease

NAC:

Neoadjuvant chemotherapy

OS:

Overall survival

DFS:

Disease-free survival

DMFS:

Distant metastasis free survival

UVA:

Univariate analysis

MVA:

Multivariable analysis

HR + :

Hormone receptor positive

IQR:

Interquartile range

ER/PR:

Estrogen receptor/Progesterone receptor

LVI:

Lymphovascular invasion

pT:

Pathologic tumor stage

pN:

Pathologic nodal stage

References

  1. Breastcancer.org. U.S. Breast Cancer Statistics. 2021 [cited 2021 March 18]; Available from: https://www.breastcancer.org/symptoms/understand_bc/statistics.

  2. Institute, N.C. Cancer Stat Facts: Female Breast Cancer. 2020 [cited 2021 March 18]; Available from: https://seer.cancer.gov/statfacts/html/breast.html.

  3. Montemurro F, Nuzzolese I, Ponzone R (2020) Neoadjuvant or adjuvant chemotherapy in early breast cancer? Expert Opin Pharmacother 21:1071–1082. https://doi.org/10.1080/14656566.2020.1746273

    Article  PubMed  Google Scholar 

  4. Cortazar P, Geyer CE Jr (2015) Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol 22:1441–1446. https://doi.org/10.1245/s10434-015-4404-8

    Article  PubMed  Google Scholar 

  5. von Minckwitz G 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 

  6. Mamounas EP et al (2012) Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of national surgical adjuvant breast and bowel project B-18 and B-27. J Clin Oncol 30:3960–3966. https://doi.org/10.1200/JCO.2011.40.8369

    Article  PubMed  PubMed Central  Google Scholar 

  7. Spring L et al (2017) Pathologic complete response after neoadjuvant chemotherapy and long-term outcomes among young women with breast cancer. J Natl Compr Canc Netw 15:1216–1223. https://doi.org/10.6004/jnccn.2017.0158

    Article  PubMed  Google Scholar 

  8. Tsuruo T, Fujita N (2008) Platelet aggregation in the formation of tumor metastasis. Proc Jpn Acad Ser B Phys Biol Sci 84:189–98. https://doi.org/10.2183/pjab.84.189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lucotti S et al (2019) Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2. J Clin Invest 129:1845–1862. https://doi.org/10.1172/JCI121985

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dai X et al (2017) Aspirin inhibits cancer metastasis and angiogenesis via targeting heparanase. Clin Cancer Res 23:6267–6278. https://doi.org/10.1158/1078-0432.CCR-17-0242

    Article  CAS  PubMed  Google Scholar 

  11. Choe KS et al (2012) Aspirin use and the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy. J Clin Oncol 30:3540–3544. https://doi.org/10.1200/JCO.2011.41.0308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jacobs CD et al (2014) Aspirin improves outcome in high risk prostate cancer patients treated with radiation therapy. Cancer Biol Ther 15:699–706. https://doi.org/10.4161/cbt.28554

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chan AT, Ogino S, Fuchs CS (2009) Aspirin use and survival after diagnosis of colorectal cancer. JAMA 302:649–58. https://doi.org/10.1001/jama.2009.1112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Holmes MD et al (2010) Aspirin intake and survival after breast cancer. J Clin Oncol 28:1467–1472. https://doi.org/10.1200/JCO.2009.22.7918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Murray LJ et al (2014) Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK clinical practice research datalink. Breast Cancer Res 16:R34. https://doi.org/10.1186/bcr3638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen WY, Holmes MD (2017) Role of aspirin in breast cancer survival. Curr Oncol Rep. https://doi.org/10.1007/s11912-017-0605-6

    Article  PubMed  Google Scholar 

  17. Huang XZ et al (2015) Aspirin and nonsteroidal anti-inflammatory drugs after but not before diagnosis are associated with improved breast cancer survival: a meta-analysis. Cancer Causes Control 26:589–600. https://doi.org/10.1007/s10552-015-0539-y

    Article  PubMed  Google Scholar 

  18. Zhong S et al (2015) Association between aspirin use and mortality in breast cancer patients: a meta-analysis of observational studies. Breast Cancer Res Treat 150:199–207. https://doi.org/10.1007/s10549-015-3300-z

    Article  CAS  PubMed  Google Scholar 

  19. Blair CK et al (2007) NSAID use and survival after breast cancer diagnosis in post-menopausal women. Breast Cancer Res Treat 101:191–197. https://doi.org/10.1007/s10549-006-9277-x

    Article  CAS  PubMed  Google Scholar 

  20. Fraser DM et al (2014) Aspirin use and survival after the diagnosis of breast cancer: a population-based cohort study. Br J Cancer 111:623–627. https://doi.org/10.1038/bjc.2014.264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Elwood PC et al (2016) Aspirin in the treatment of cancer: reductions in metastatic spread and in mortality: a systematic review and meta-analyses of published studies. PLoS One 11:e0152402. https://doi.org/10.1371/journal.pone.0152402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shiao J et al (2017) Aspirin/antiplatelet agent use improves disease-free survival and reduces the risk of distant metastases in Stage II and III triple-negative breast cancer patients. Breast Cancer Res Treat 161(3):463–471

    Article  CAS  PubMed  Google Scholar 

  23. Johns C et al (2020) Aspirin use is associated with improvement in overall survival and recurrence free survival in inflammatory breast cancer patients. Int J Radiat Oncol Biol Phys 108:e27. https://doi.org/10.1016/j.ijrobp.2020.07.1048

    Article  Google Scholar 

  24. Chen W et al (2022) A randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (A011502): the aspirin after breast cancer (ABC) Trial. J Clin Oncol. https://doi.org/10.1200/JCO.2022.40.36_suppl.360922

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shiao J et al (2017) Aspirin/antiplatelet agent use improves disease-free survival and reduces the risk of distant metastases in Stage II and III triple-negative breast cancer patients. Breast Cancer Res Treat 161:463–471. https://doi.org/10.1007/s10549-016-4081-8

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We wish to thank the University of Texas Southwestern Department of Radiation Oncology for providing support in this research endeavor.

Funding

None to declare.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Christopher Johns, Steven K. Montalvo, M’Kay Cauble, Sean All, Asal S. Rahimi, Prasanna G. Alluri & Chika Nwachukwu

  2. Department of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Marilyn Leitch, Rachel Wooldridge & Deborah Farr

  3. Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Yu-Lun Liu

  4. Department of Medical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Nisha Unni

  5. Department of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, Suite B-1003, Nashville, TN, 37232-5671, USA

    D. W. Nathan Kim

Authors
  1. Christopher Johns
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  2. Steven K. Montalvo
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  3. M’Kay Cauble
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  4. Yu-Lun Liu
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  5. Sean All
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  9. Nisha Unni
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  13. D. W. Nathan Kim
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Christopher Johns, MKC, Y-LL, and DWNK. The first draft of the manuscript was written by CJ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to D. W. Nathan Kim.

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Conflict of interest

The authors have no relevant financial interests to disclose. Non-financial interests: Dr. Unni has served on advisory boards for Pfizer, Eli Lilly, Novartis, Macrogenics, Biotheranostics, and Eisai.

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Johns, C., Montalvo, S.K., Cauble, M. et al. Aspirin use is associated with improvement in distant metastases outcome in patients with residual disease after neoadjuvant chemotherapy. Breast Cancer Res Treat 199, 381–387 (2023). https://doi.org/10.1007/s10549-023-06920-4

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  • DOI: https://doi.org/10.1007/s10549-023-06920-4

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