Serum lipid ratios as novel prognostic biomarkers for patients with locally advanced breast cancer treated with neoadjuvant therapy

ABSTRACT

Objectives

To investigate the association between lipid ratios and survival outcomes in patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy.

Method

This retrospective study included patients with LABC receiving neoadjuvant chemotherapy. Serum lipid levels were prospectively measured at baseline. Associations of triglyceride to total cholesterol (TG/TC), triglyceride to high-density lipoprotein (TG/HDL) and triglyceride to low-density lipoprotein (TG/LDL) ratios with prognosis were evaluated.

Results

Patients with high TG/TC (adjusted hazard ratio [aHR] = 2.47, 95% CI: 1.10, 5.56, p = 0.029), TG/HDL (aHR = 2.73, 95% CI: 1.16, 6.41, p = 0.021) and TG/LDL (aHR = 2.50, 95% CI: 1.11, 5.65, p = 0.027) ratios were more likely to experience disease-free survival (DFS) events. Subgroup analysis suggested that the prognostic impact of lipid ratios was more pronounced in patients with negative HER2 status or those at a high risk of recurrence (e.g. clinical stage III, Ki67 > 30%). Additionally, higher lipid ratios tended to indicate early DFS events (0 ~ 2 years) (TG/TC p = 0.021, TG/HDL p = 0.046, TG/LDL p < 0.001), and the TG/LDL ratio demonstrated the best predictive efficacy (TG/TC vs. TG/HDL vs. TG/LDL, 1-year AUC: 0.724 vs. 0.676 vs. 0.846, 2-year AUC: 0.653 vs. 0.638 vs. 0.708).

Conclusion

Baseline serum TG/TC, TG/HDL and TG/LDL ratios were independent prognostic factors in patients with LABC undergoing neoadjuvant therapy. However, their utility in predicting the early DFS events warrants further investigation.

Clinical trial registration

NCT05621564.

KEYWORDS:

• Locally advanced breast cancer
• neoadjuvant chemotherapy
• lipid ratios
• prognosis
• early relapse

Abbreviations

LABC	=	Locally advanced breast cancer
ER	=	Estrogen receptor
PR	=	Progesterone receptor
HER2	=	Human epidermal growth factor receptor 2
TG	=	Triglyceride
TC	=	Total cholesterol
HDL	=	High-density lipoprotein
LDL	=	Low-density lipoprotein
Non-HDL	=	Non-high-density lipoprotein
TG/TC	=	Triglyceride to total cholesterol
TG/HDL	=	Triglyceride to high-density lipoprotein
TG/LDL	=	Triglyceride to low-density lipoprotein
DFS	=	Disease-free survival
RFS	=	Relapse-free survival
DRFS	=	Distant-recurrence-free survival
LRFS	=	Locoregional-recurrence-free survival
OS	=	Overall survival
RCS	=	Restricted cubic spline
HR	=	Hazard ratio
CI	=	Confidence interval
ROC	=	Receiver operating characteristic
AUC	=	Area under the ROC curve
BMI	=	Body mass index
pCR	=	Pathological complete response
TNBC	=	Triple negative breast cancer

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

XC wrote the original draft of the manuscript. XC and YZ: data curation, formal analysis, investigation, methodology, software and visualization. YZ, YW and WY: data curation and validation. SX, LZ, YL and YY: investigation and project administration. YW, JL and WY: funding acquisition. JL and WY: conceptualization, supervision and writing-review and editing. XC and YZ: contributed equally to this manuscript. All authors contributed to the final version of the manuscript.

Ethics statement

This study was conducted in accordance with REMARK statement and the protocol was approved by the Independent Ethics Committee of Renji Hospital (Approval number: LY2022–028-B). This study was registered with ClinicalTrials.gov (NCT05621564). The informed consent was waived under the provisions of the Independent Ethics Committee of Renji Hospital.

Data availability statement

The data generated and/or analyzed in this study are available upon reasonable written request from the corresponding author.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/00325481.2024.2370235

Additional information

Funding

This work was supported by the [National Natural Science Foundation of China] under Grant [No. 82173115 and 82103695]; [Science and Technology Commission of Shanghai Municipality] under Grant [No. 20DZ2201600]; [Shanghai Municipal Key Clinical Specialty]; [Shanghai Rising-Star Program] under Grant [No. 22QC1400200]; [Innovative Research Team of High-level Local Universities in Shanghai] under Grant [SHSMU-ZLCX20212601]; [Shanghai Municipal Health Commission Health Industry Clinical Research Special Project] under Grant [No. 202340085]; and [Nurturing Fund of Renji Hospital] under Grant [No. PYIII20-09 and RJPY-LX-002].