# Estrogen receptor positivity in stromal cells of the tumor bed predicts the response to neoadjuvant chemotherapy for breast carcinoma

## TL;DR

This study shows that estrogen receptor positivity in tumor stromal cells after chemotherapy is linked to better treatment response in breast cancer patients.

## Contribution

This is the first study to show that stromal ER positivity in post-chemotherapy tumor beds predicts response to treatment and tumor subtypes.

## Key findings

- ER-positive stromal cells correlate with higher tumor regression rates and lower residual cancer burden.
- Stromal ER positivity is more common in non-luminal tumors and is a strong predictor of pathologic complete response.
- Many ER-negative stromal cells before chemotherapy converted to ER-positive afterward, showing improved regression.

## Abstract

This study aimed to determine estrogen receptor (ER) expression in stromal cells in postchemotherapy tumor bed (PCTB) and its relationship with tumor regression and tumor characteristics.

The study included 490 breast cancer patients who received neoadjuvant chemotherapy (NAC). We performed ER in stromal cells in all resection specimens and available pre-treatment core biopsy materials of 299 patients immunohistochemically.

Two hundred and forty-two (49.4%) cases were negative for ER in the stromal cells of the PCTB, and 248 (50.6%) cases were positive. ER-positive stromal cells in the PCTB correlated with a higher regression rate (90.2 vs 68.6%) and lower mean residual cancer burden value (1.366 vs 2.424) compared to ER-negative cases (p < 0.001). Stromal ER positivity was more prevalent in cases achieving pathologic complete response (pCR) (68.1%) compared to those without pCR (39.8%, p < 0.001). ER positivity in stromal cells was more common in non-luminal tumors than in luminal ones. Multivariate analysis identified stromal ER positivity (OR: 3.059, 95% CI [1.947–4.807], p < 0.001), intrinsic subtype (Odds ratio (OR): 1.477, 95% confidence interval (CI) [1.102–1.980], p = 0.009), and Ki67 index (OR: 1.028, 95% CI [1.104–1.041], p < 0.001) as independent predictors of pCR. In core biopsies before NAC, 270 cases (90.3%) and 29 cases (9.7%) were negative and positive in stromal cells, respectively. Out of the cases with ER-negativity in stromal cells before NAC, 132 (48.9%) converted to ER positivity in stromal cells of PCTB and displayed a high regression rate (89.8%).

This is the first study regarding ER expression in the stroma of breast carcinoma that compares treatment response after NAC. We showed that the increase in ER positivity in the stromal cells of the PCTB is correlative with the complete response and tumor subtypes. In this manner, ER positivity in stromal cells will soon serve as a cornerstone for individualized treatment options.

The online version contains supplementary material available at 10.1007/s10549-024-07601-6.