Skip to main content

Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma

Abstract

Purpose

Few studies evaluated the prognostic value of the presence of lymphovascular invasion (LVI) after neoadjuvant chemotherapy (NAC) for breast cancer (BC).

Methods

The association between LVI and survival was evaluated in a cohort of BC patients treated by NAC between 2002 and 2011. Five post-NAC prognostic scores (ypAJCC, RCB, CPS, CPS + EG and Neo-Bioscore) were evaluated and compared with or without the addition of LVI.

Results

Out of 1033 tumors, LVI was present on surgical specimens in 29.2% and absent in 70.8% of the cases. Post-NAC LVI was associated with impaired disease-free survival (DFS) (HR 2.54; 95% CI 1.96–3.31; P < 0.001), and the magnitude of this effect depended on BC subtype (Pinteraction = 0.003), (luminal BC: HR 1.83; P = 0.003; triple negative BC: HR 3.73; P < 0.001; HER2-positive BC: HR 6.21; P < 0.001). Post-NAC LVI was an independent predictor of local relapse, distant metastasis, and overall survival; and increased the accuracy of all five post-NAC prognostic scoring systems.

Conclusions

Post-NAC LVI is a strong independent prognostic factor that: (i) should be systematically reported in pathology reports; (ii) should be used as stratification factor after NAC to propose inclusion in second-line trials or adjuvant treatment; (iii) should be included in post-NAC scoring systems.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Abbreviations

AIC:

Akaike information criterion

BC:

Breast cancer

BMI:

Body mass index (kg/m2)

DCIS:

Ductal carcinoma in situ

DFS:

Disease-free survival

ER:

Oestrogen receptor

LVI:

Lymphovascular invasion

MFS:

Metastasis-free survival

NAC:

Neoadjuvant chemotherapy

NPRI:

Nottingham Clinico-Pathological Response Index

NST:

No specific type

OS:

Overall survival

pCR:

Pathological complete response

PR:

Progesterone receptor

RCB:

Residual cancer burden

RFS:

Recurrence-free survival

TNBC:

Triple negative breast cancer

References

  1. Lee AHS, Pinder SE, Macmillan RD et al (2006) Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma. Eur J Cancer 42:357–362. https://doi.org/10.1016/j.ejca.2005.10.021

    CAS  Article  PubMed  Google Scholar 

  2. Rakha EA, Martin S, Lee AHS et al (2012) The prognostic significance of lymphovascular invasion in invasive breast carcinoma. Cancer 118:3670–3680. https://doi.org/10.1002/cncr.26711

    Article  PubMed  Google Scholar 

  3. Freedman GM, Li T, Polli LV et al (2012) Lymphatic space invasion is not an independent predictor of outcomes in early stage breast cancer treated by breast-conserving surgery and radiation. Breast J 18:415–419. https://doi.org/10.1111/j.1524-4741.2012.01271.x

    Article  PubMed  Google Scholar 

  4. Ravdin PM (1996) A computer program to assist in making breast cancer adjuvant therapy decisions. Semin Oncol 23:43–50

    CAS  PubMed  Google Scholar 

  5. Michaelson JS, Chen LL, Bush D et al (2011) Improved web-based calculators for predicting breast carcinoma outcomes. Breast Cancer Res Treat 128:827–835. https://doi.org/10.1007/s10549-011-1366-9

    Article  PubMed  Google Scholar 

  6. Wishart GC, Azzato EM, Greenberg DC et al (2010) PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer. Breast Cancer Res 12:R1. https://doi.org/10.1186/bcr2464

    Article  PubMed  PubMed Central  Google Scholar 

  7. NCCN Evidence Blocks, TM (2016) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) - Breast Cancer., 2016

  8. 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 Off J Eur Soc Med Oncol 26:1533–1546. https://doi.org/10.1093/annonc/mdv221

    CAS  Article  Google Scholar 

  9. Senkus E, Kyriakides S, Ohno S et al (2015) Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26:v8–v30. https://doi.org/10.1093/annonc/mdv298

    Article  PubMed  Google Scholar 

  10. Liu YL, Saraf A, Lee SM et al (2016) Lymphovascular invasion is an independent predictor of survival in breast cancer after neoadjuvant chemotherapy. Breast Cancer Res Treat 157:555–564. https://doi.org/10.1007/s10549-016-3837-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Edge S, Byrd D, Compton C, et al (2009) American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edn

  12. Symmans WF, Peintinger F, Hatzis C et al (2007) Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25:4414–4422. https://doi.org/10.1200/JCO.2007.10.6823

    Article  PubMed  Google Scholar 

  13. Jeruss JS, Mittendorf EA, Tucker SL et al (2008) Combined use of clinical and pathologic staging variables to define outcomes for breast cancer patients treated with neoadjuvant therapy. J Clin Oncol 26:246–252. https://doi.org/10.1200/JCO.2007.11.5352

    CAS  Article  PubMed  Google Scholar 

  14. Mittendorf EA, Vila J, Tucker SL et al (2016) The neo-bioscore update for staging breast cancer treated with neoadjuvant chemotherapy: incorporation of prognostic biologic factors into staging after treatment. JAMA Oncol 2:929–936. https://doi.org/10.1001/jamaoncol.2015.6478

    Article  PubMed  PubMed Central  Google Scholar 

  15. R Development Core Team (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing

  16. Abdel-Fatah TM, Ball G, Lee AHS et al (2015) Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer. Clin Cancer Res 21:1052–1062. https://doi.org/10.1158/1078-0432.CCR-14-0685

    CAS  Article  PubMed  Google Scholar 

  17. Choi MK, Park YH, Kil WH et al (2014) Clinicopathological features of early failure of neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Chemother Pharmacol 74:521–529. https://doi.org/10.1007/s00280-014-2542-5

    CAS  Article  PubMed  Google Scholar 

  18. Ejlertsen B, Jensen M-B, Rank F et al (2009) Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer. J Natl Cancer Inst 101:729–735. https://doi.org/10.1093/jnci/djp090

    Article  PubMed  Google Scholar 

  19. Ragage F, Debled M, MacGrogan G et al (2010) Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer? Cancer 116:3093–3101. https://doi.org/10.1002/cncr.25137

    Article  PubMed  Google Scholar 

  20. Guarnieri A, Neri A, Correale PP et al (2001) Prediction of lymph node status by analysis of prognostic factors and possible indications for elective axillary dissection in T1 breast cancers. Eur J Surg Acta Chir 167:255–259. https://doi.org/10.1080/110241501300091381

    CAS  Article  Google Scholar 

  21. Ugras S, Stempel M, Patil S, Morrow M (2014) Estrogen receptor, progesterone receptor, and HER2 status predict lymphovascular invasion and lymph node involvement. Ann Surg Oncol 21:3780–3786. https://doi.org/10.1245/s10434-014-3851-y

    Article  PubMed  PubMed Central  Google Scholar 

  22. Talmadge JE, Fidler IJ (2010) AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res 70:5649–5669. https://doi.org/10.1158/0008-5472.CAN-10-1040

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Aleskandarany MA, Sonbul SN, Mukherjee A, Rakha EA (2015) Molecular mechanisms underlying lymphovascular invasion in invasive breast cancer. Pathobiology 82:113–123. https://doi.org/10.1159/000433583

    CAS  Article  PubMed  Google Scholar 

  24. Provenzano E, Bossuyt V, Viale G, et al (2015) Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol 28:1185–201. https://doi.org/10.1038/modpathol.2015.74

  25. Masuda N, Lee S-J, Ohtani S et al (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376:2147–2159. https://doi.org/10.1056/NEJMoa1612645

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Roche* France for financial support for construction of the Institut Curie neoadjuvant database (NEOREP). The funding source had no role in data analysis and interpretation neither in writing the manuscript. AS Hamy was supported by an ITMO-INSERM-AVIESAN cancer translational research grant.

Funding

This work was supported by the Site de Recherche Intégrée en Cancérologie/Institut National du Cancer (INCa-DGOS-4654); and Grant ARC Fundation 2013 (SL220130607090).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fabien Reyal.

Ethics declarations

Conflict of interest

This report describes an original work and is not under consideration by any other journal. All authors approved the manuscript and this submission. There are no conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1270 kb)

Supplementary material 2 (XLSX 59 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hamy, AS., Lam, GT., Laas, E. et al. Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma. Breast Cancer Res Treat 169, 295–304 (2018). https://doi.org/10.1007/s10549-017-4610-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-017-4610-0

Keywords

  • Breast carcinoma
  • Lymphovascular invasion
  • Neoadjuvant chemotherapy
  • Prognostic scores