Tumor‐stroma ratio is associated with Miller‐Payne score and pathological response to neoadjuvant chemotherapy in HER2‐negative early breast cancer

Abstract

The tumor-stroma ratio (TSR) has proven to be a strong prognostic factor in breast cancer, demonstrating better survival for patients with stroma-low tumors. Since the role of the TSR as a predictive marker for neoadjuvant chemotherapy outcome is yet unknown, this association was evaluated for HER2-negative breast cancer in the prospective DIRECT and NEOZOTAC trials. The TSR was assessed on 375 hematoxylin and eosinstained sections of pre-treatment biopsies. Associations between the TSR and chemotherapy response according to the Miller-Payne (MP) grading system, and between the TSR and pathological response were examined using Pearson's chi-square, Cochran-Armitage test for trend and regression analyses. A stroma-low tumor prior to neoadjuvant chemotherapy was significantly associated with a higher MP score (P = .005). This relationship remained significant in the estrogen receptor (ER)-negative subgroup (P = .047). The univariable odds ratio (OR) of a stroma-low tumor on pathological complete response (pCR) was 2.46 (95% CI 1.34-4.51, P = .004), which attenuated to 1.90 (95% CI 0.85-4.25, P = .119) after adjustment for relevant prognostic factors. Subgroup analyses revealed an OR of 5.91 in univariable analyses for ER-negativity (95% CI 1.19-29.48, P = .030) and 1.48 for ER-positivity (95% CI 0.73-3.01, P = .281). In conclusion, a low amount of stroma on pre-treatment biopsies is associated with a higher MP score and pCR rate. Therefore, the TSR is a promising biomarker in predicting neoadjuvant treatment outcome. Incorporating this parameter in routine pathological diagnostics could be worthwhile to prevent overtreatment and undertreatment.

Standardization of the tumor-stroma ratio scoring method for breast cancer research

“…However, to evaluate the effect of neoadjuvant treatment on the TSR or the predictive power of the TSR for a specific type of neoadjuvant treatment, it is necessary to make use of biopsy material acquired before the start of treatment. Biopsies have demonstrated to be of clinical importance in TSR scoring, not only to determine the prognostic value of the TSR in terms of survival (disease-free and overall) [ 38 , 39 ] and relapse risk, but also to evaluate the predictive value of treatment outcomes with regard to histological parameters for pathological response [ 16 , 40 , 41 ].…”

Combined Assessment of the Tumor–Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer

“…Tumors with a high stromal content were previously shown to have a poor patient outcomes in a variety of epithelial malignancies [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. In addition, the TSR was found to be a predictor of pathologic response to neoadjuvant therapy in breast and esophageal cancer [ 12 , 13 , 14 ].…”

The Stroma Liquid Biopsy Panel Contains a Stromal-Epithelial Gene Signature Ratio That Is Associated with the Histologic Tumor-Stroma Ratio and Predicts Survival in Colon Cancer

“…Indeed, the histologic tumor-stroma ratio (TSR), a stroma-derived biomarker developed by our group, has been validated as an independent predictor of patient survival in various primary tumor types [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Moreover, the TSR was found to be associated with pathologic response to neoadjuvant therapy in esophageal and breast cancer, supporting the notion that the TME modulates therapeutic response [ 6 , 14 , 15 ].…”