Evaluation of tumor-infiltrating lymphocytes and mammographic density as predictors of response to neoadjuvant systemic therapy in breast cancer

Abstract

Background

Response rates vary among breast cancer patients treated with neoadjuvant systemic therapy (NAST). Thus, there is a need for reliable treatment predictors. Evidence suggests tumor-infiltrating lymphocytes (TILs) predict NAST response. Still, TILs are seldom used clinically as a treatment determinant. Mammographic density (MD) is another potential marker for NAST benefit and its relationship with TILs is unknown. Our aims were to investigate TILs and MD as predictors of NAST response and to study the unexplored relationship between TILs and MD.

Material and methods

We studied 315 invasive breast carcinomas treated with NAST between 2013 and 2020. Clinicopathological data were retrieved from medical records. The endpoint was defined as pathological complete response (pCR) in the breast. TILs were evaluated in pre-treatment core biopsies and categorized as high (≥10%) or low (<10%). MD was scored (a–d) according to the breast imaging reporting and data system (BI-RADS) fifth edition. Binary logistic regression and Spearman’s test of correlation were performed using SPSS.

Results

Out of 315 carcinomas, 136 achieved pCR. 94 carcinomas had high TILs and 215 had low TILs. Six carcinomas had no available TIL data. The number of carcinomas in each BI-RADS category were 37, 122, 112, and 44 for a, b, c, and d, respectively. High TILs were independently associated with pCR (OR: 2.95; 95% CI: 1.59–5.46) compared to low TILs. In the univariable analysis, MD (BI-RADS d vs. a) showed a tendency of higher likelihood for pCR (OR: 2.43; 95% CI: 0.99–5.98). However, the association was non-significant, which is consistent with the result of the multivariable analysis (OR: 2.51; 95% CI: 0.78–8.04). We found no correlation between TILs and MD (0.02; p = .80).

Conclusion

TILs significantly predicted NAST response. We could not define MD as a significant predictor of NAST response. These findings should be further replicated.

Keywords:

• Breast cancer
• tumor-infiltrating lymphocytes
• mammographic density
• neoadjuvant therapy
• pathological complete response

Prior presentation

Preliminary results were presented at the Swedish conference ‘Kirurgveckan’ in Stockholm, Sweden on 25 August 2022.

Acknowledgements

We thank the mammographic department at our institution for their assistance with the collection and evaluation of mammograms.

Author contributions

AL, KC, EH, AST, and PK conceived the study. KC provided study participants. AL, KC, AK, and EM assembled and collected data. AL and EH analyzed the data. AL, EH, AST, and PK interpreted the results. AL drafted the manuscript. KC, EH, AST, and PK revised the manuscript. All authors read and approved the manuscript.

Disclosure statement

PK and EH report interests not related to the current study: contract with PFS Genomics/Exact Sciences regarding genomic profiling; co-inventor on patent applications; contract with Prelude Dx. AST reports interest not related to the current study: co-inventor on patent applications; contract with Prelude Dx. No disclosures were reported by the other authors.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author.

Additional information

Funding

This work was supported by the Swedish Cancer Society [Grant No. 21 1889 S], the Swedish Research Council [Grant No. 2021-0138], and the Swedish governmental ALF agreement [Grant No. ALFGBG-965020].