Real‑world Data Indicated That Neoadjuvant Chemotherapy Alone Was Associated with a Higher Risk of Tumor Recurrence in High‑risk Breast Cancer Subgroup Patients

Overview

Journal Oncol Lett

Specialty Oncology

Date 2023 Apr 28

PMID 37113400

Authors

Zhensheng Li

Yue Li

Yunjiang Liu

Yuguang Shang

Yarong Zhou

Xiaohui Ji

Huina Han

Kaiye Du

Jun Zhang

Affiliations

Soon will be listed here.

Abstract

Numerous clinical trials have reported equal effects of tumor control between neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) in patients with breast cancer (BC). However, this conclusion has not been verified in practice. The present retrospective study evaluated if there were different risk profiles for NAC, AC and their combinative modes on disease-free survival (DFS) in patients with BC using real-world data. All women with primary unilateral Stage I-III BC and first recurrence in 2008-2018 at The Fourth Hospital of Hebei Medical University were retrospectively identified for enrollment. The four modes of chemotherapy administered for primary BC were classified as 'None', 'NAC only', 'NAC+AC' and 'AC only'. One multivariate Cox model was used to estimate the adjusted Hazard Ratio (HR) and P-value. Covariates included age, Easter Cooperative Oncology Group grade, T stage, N stage, pathology, grade, lymphovascular invasion (LVI), BC subtype, number of chemotherapy cycles and other therapies. Amongst 637 patients, who had a mean age of 48.2 years at BC diagnosis and 50.9 years at recurrence, the median DFS by the 'None' (n=27), 'NAC only' (n=47), 'NAC+AC' (n=118) and 'AC only' (n=445) modes were 31.4, 16.6, 22.6 and 28.4 months (P<0.001), respectively. Compared with the 'AC only', adjusted HR (P-value) of the 'None', 'NAC only' and 'NAC+AC' modes on tumor recurrence were 1.182 (0.551), 1.481 (0.037) and 1.102 (0.523), respectively. The adjusted HR of 'NAC only' vs. 'AC only' modes were 1.448 (P=0.157) for locoregional recurrence and 2.675 (P=0.003) for distant recurrence. Stratified analyses further indicated that the 'NAC only' mode was associated with a higher recurrence risk in T3-4, N2-3, LVI-positive, or HER2-negative subgroup patients. In conclusion, NAC alone was associated with a higher risk of tumor recurrence in high-risk BC subgroup patients in real-world data. Patient selection of chemotherapy mode was involved in practice but could not fully explain this finding. The 'inadequate' NAC was highly likely to have accounted for this observation.

References

Mougalian S, Soulos P, Killelea B, Lannin D, Abu-Khalaf M, DiGiovanna M . Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015; 121(15):2544-52. DOI: 10.1002/cncr.29348. View

Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S . American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007; 25(33):5287-312. DOI: 10.1200/JCO.2007.14.2364. View

Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese R . 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. 1997; 15(7):2483-93. DOI: 10.1200/JCO.1997.15.7.2483. View

Caparica R, Brandao M, Piccart M . Systemic treatment of patients with early breast cancer: recent updates and state of the art. Breast. 2019; 48 Suppl 1:S7-S20. DOI: 10.1016/S0960-9776(19)31115-4. View

Reyal F, Hamy A, Piccart M . Neoadjuvant treatment: the future of patients with breast cancer. ESMO Open. 2018; 3(4):e000371. PMC: 5976132. DOI: 10.1136/esmoopen-2018-000371. View

Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher E . Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998; 16(8):2672-85. DOI: 10.1200/JCO.1998.16.8.2672. View

Bagegni N, Tao Y, Ademuyiwa F . Clinical outcomes with neoadjuvant versus adjuvant chemotherapy for triple negative breast cancer: A report from the National Cancer Database. PLoS One. 2019; 14(9):e0222358. PMC: 6752843. DOI: 10.1371/journal.pone.0222358. View

. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol. 2009; 35 Suppl 1:1-22. DOI: 10.1016/j.ejso.2009.01.008. View

Edge S, Compton C . The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010; 17(6):1471-4. DOI: 10.1245/s10434-010-0985-4. View

10.

Cooke T, Reeves J, Lanigan A, Stanton P . HER2 as a prognostic and predictive marker for breast cancer. Ann Oncol. 2001; 12 Suppl 1:S23-8. DOI: 10.1093/annonc/12.suppl_1.s23. View

11.

Mauri D, Pavlidis N, Ioannidis J . Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005; 97(3):188-94. DOI: 10.1093/jnci/dji021. View

12.

Sparano J, Paik S . Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol. 2008; 26(5):721-8. DOI: 10.1200/JCO.2007.15.1068. View

13.

Rastogi P, Anderson S, Bear H, Geyer C, Kahlenberg M, Robidoux A . Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008; 26(5):778-85. DOI: 10.1200/JCO.2007.15.0235. View

14.

Poggio F, Bruzzone M, Ceppi M, Ponde N, La Valle G, Del Mastro L . Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol. 2018; 29(7):1497-1508. DOI: 10.1093/annonc/mdy127. View

15.

Ponde N, Zardavas D, Piccart M . Progress in adjuvant systemic therapy for breast cancer. Nat Rev Clin Oncol. 2018; 16(1):27-44. DOI: 10.1038/s41571-018-0089-9. View

16.

Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E . Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 Suppl 5:v8-30. DOI: 10.1093/annonc/mdv298. View

17.

. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019; 393(10179):1440-1452. PMC: 6451189. DOI: 10.1016/S0140-6736(18)33137-4. View

18.

Murphy B, Day C, Hoskin T, Habermann E, Boughey J . Neoadjuvant Chemotherapy Use in Breast Cancer is Greatest in Excellent Responders: Triple-Negative and HER2+ Subtypes. Ann Surg Oncol. 2018; 25(8):2241-2248. DOI: 10.1245/s10434-018-6531-5. View

19.

. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005; 365(9472):1687-717. DOI: 10.1016/S0140-6736(05)66544-0. View

20.

. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2017; 19(1):27-39. PMC: 5757427. DOI: 10.1016/S1470-2045(17)30777-5. View