Low neutrophil-lymphocyte ratio correlates with extended survival in patients with metastatic breast cancer who achieved clinically complete response following multidisciplinary therapy: A retrospective study

Takuwa,Haruko; Tsuji,Wakako; Yamamoto,Yoshihiro; Shintaku,Masayuki; Yotsumoto,Fumiaki

doi:10.3892/ol.2018.8145

Low neutrophil-lymphocyte ratio correlates with extended survival in patients with metastatic breast cancer who achieved clinically complete response following multidisciplinary therapy: A retrospective study

Authors:
- Haruko Takuwa
- Wakako Tsuji
- Yoshihiro Yamamoto
- Masayuki Shintaku
- Fumiaki Yotsumoto
View Affiliations

Affiliations: Department of Breast Surgery, Shiga Medical Center for Adults, Moriyama‑shi, Shiga 524‑8524, Japan, Department of Pathology, Shiga Medical Center for Adults, Moriyama‑shi, Shiga 524‑8524, Japan
Published online on: March 1, 2018 https://doi.org/10.3892/ol.2018.8145
Pages: 6681-6687

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The prognosis of patients with metastatic or recurrent breast cancer (MBC) is improving as novel treatments are developed. The present study compared the clinical characteristics of patients with MBC with or without a complete clinical response (cCR) and identified the survival‑associated factors. This was a retrospective study, which included 171 patients treated for MBC between 2011 and 2017 at the Shiga Medical Center for Adults. Neutrophil to lymphocytes ratios (NLRs) were determined in blood samples. The median follow‑up period following diagnosis of MBC was 44 months (range, 0‑217 months). A total of 32 patients (18.7%) achieved a cCR. Compared with the non‑cCR group, the cCR group had significantly fewer metastases or recurrences (P<0.001), significantly fewer visceral metastases (P<0.001), a significantly lower NLR (P<0.001) and were diagnosed with primary breast cancer at a significantly earlier stage (P=0.003). Prognosis was significantly improved in the cCR group compared with the non‑cCR group (P<0.001) and a high NLR (≥19) independently predicted worse survival in a multivariate analysis (P=0.0218; hazard ratio, 1.75; 95% confidence interval, 1.09‑2.85). In conclusion, the present study determined that achieving a cCR and having a low NLR are important for the long‑term survival of patients with MBC.

View Figures

View References

1	Tsuji W, Teramukai S, Ueno M, Toi M and Inamoto T: Prognostic factors for survival after first recurrence in breast cancer: A retrospective analysis of 252 recurrent cases at a single institution. Breast Cancer. 21:86–95. 2014. View Article : Google Scholar : PubMed/NCBI
2	Giordano SH, Buzdar AU, Smith TL, Kau SW, Yang Y and Hortobagyi GN: Is breast cancer survival improving? Cancer. 100:44–52. 2004. View Article : Google Scholar : PubMed/NCBI
3	Gennari A, Conte P, Rosso R, Orlandini C and Bruzzi P: Survival of metastatic breast carcinoma patients over a 20-year period: A retrospective analysis based on individual patient data from six consecutive studies. Cancer. 104:1742–1750. 2005. View Article : Google Scholar : PubMed/NCBI
4	Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK and Buzdar AU: Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol. 14:2197–2205. 1996. View Article : Google Scholar : PubMed/NCBI
5	Falkson G, Gelman RS, Leone L and Falkson CI: Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of eastern cooperative group and cancer and leukemia group B studies. Cancer. 66:1621–1629. 1990. View Article : Google Scholar : PubMed/NCBI
6	Rahman ZU, Frye DK, Smith TL, Asmar L, Theriault RL, Buzdar AU and Hortobagyi GN: Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: A reference. Cancer. 85:104–111. 1999. View Article : Google Scholar : PubMed/NCBI
7	Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R and Winer EP: Trastuzumab plusvinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: The trastuzumab and vinorelbine or taxane study. Cancer. 110:965–972. 2007. View Article : Google Scholar : PubMed/NCBI
8	Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, et al: Pertuzumab plus trastumab plus docetaxel for metastatic breast cancer. N Engl J Med. 366:109–119. 2012. View Article : Google Scholar : PubMed/NCBI
9	Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga M, Pegram M, Oh DY, Diéras V, Guardino E, et al: Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 367:1783–1791. 2012. View Article : Google Scholar : PubMed/NCBI
10	Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Prineri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, et al: The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International tils working group 2014. Ann Oncol. 26:259–271. 2015. View Article : Google Scholar : PubMed/NCBI
11	Hida AI and Ohi Y: Evaluation of tumor-infiltrating lymphocytes in breast cancer; proposal of a simpler method. Ann Oncol. 26:23512015. View Article : Google Scholar : PubMed/NCBI
12	Jia W, Wu J, Jia H, Yang Y, Zhang X, Chen K and Su F: The peripheral blood neutrophl-to-lymphocyte ratio is superior to the lymphocyte-to-monocyte ratio for predicting the long-term survival of triple-negative breast cancer patients. PLoS One. 10:e01430612015. View Article : Google Scholar : PubMed/NCBI
13	Orditura M, Galizia G, Diana A, Saccone C, Cobellis L, Ventriglia J, Iovino F, Romano C, Morgillo F, Mosca L, et al: Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: A propensity score-matched analysis. ESMO Open. 1:e0000382016. View Article : Google Scholar : PubMed/NCBI
14	Iwase T, Sangai T, Sakakibra M, Sakakibra J, Ishigami E, Hayama S, Nakagawa A, Masuda T, Tabe S and Nagashima T: An increased neutrophil-to-lymphocyte ratio predicts poorer survival following recurrence for patients with breast cancer. Mol Clin Oncol. 6:266–270. 2017. View Article : Google Scholar : PubMed/NCBI
15	Ethier JL, Desautels D, Templeton A, Shah PS and Amir E: Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer. A systematic review and meta-analysis. Breast Cancer Res. 19:22017. View Article : Google Scholar : PubMed/NCBI
16	Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC and Clarke SJ: The systemic inflammation-based neutrophil-lymphocyte ratio: Experience in patients with cancer. Crit Rev Oncol Hematol. 88:218–230. 2013. View Article : Google Scholar : PubMed/NCBI
17	Acharyya S and Massague J: Arresting supporters: Targeting neutrophils in metastasis. Cell Res. 26:273–274. 2016. View Article : Google Scholar : PubMed/NCBI
18	Bird L: Tumour immunology: Neutrophils help tumours spread. Nat Rev Immunol. 16:74–75. 2016. View Article : Google Scholar : PubMed/NCBI
19	Wculek SK and Malanchi I: Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature. 528:413–417. 2015. View Article : Google Scholar : PubMed/NCBI
20	Dieci MV, Mathieu MC, Guarneri V, Conte P, Delaloge S, Andre F and Goubar A: Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol. 26:1698–1704. 2015. View Article : Google Scholar : PubMed/NCBI
21	Castaneda CA, Mittendorf E, Casavilca S, Wu Y, Castillo M, Arboleda P, Nunez T, Guerra H, Barrionuevo C, Dolores-Cerna K, et al: Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy. World J Clin Oncol. 7:387–394. 2016. View Article : Google Scholar : PubMed/NCBI
22	Hida AI, Sagara Y, Yotsumoto D, Kaemitsu S, Kawano J, Baba S, Rai Y, Oshiro Y, Aogi K, Sagara Y and Ohi Y: Prognostic and predictive impacts of tumor-infiltrating lymphocytes differ between Triple-negative and HER2-positive breast cancers treated with standard systemic therapies. Breast Cancer Res Treat. 158:1–9. 2016. View Article : Google Scholar : PubMed/NCBI
23	Lambert AW, Pattabiraman DR and Weinberg RA: Emerging biological principles of metastasis. Cell. 168:670–691. 2017. View Article : Google Scholar : PubMed/NCBI
24	Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, et al: Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 45:1446–1451. 2013. View Article : Google Scholar : PubMed/NCBI
25	Zardavas D, Phillips WA and Loi S: PIK3CA mutations in breast cancer: Reconciling findings from preclinical and clinical data. Breast Cancer Res. 16:2012014. View Article : Google Scholar : PubMed/NCBI