The mean age of 490 patients with breast cancer treated with NAC was 48.6 (range: 25–82). Of the patients, 262 (53.5%) were pre-menopausal and 228 (46.5%) were post-menopausal. The initial T stages of the cases (T1, T2, T3, T4) were 68 (13.9%), 269 (54.9%), 115 (23.5%), and 38 (7.7%), respectively. The lymph node was tumor-free in 259 (52.8%) cases and metastatic in 231 (47.2%). Before NAC, the intrinsic subtype was determined according to ER, PR, HER2 status, and Ki67 indices in 470 cases. Among them, 53 (11.3%) cases were luminal A-like subtype, 212 (45.1%) cases were luminal B-like subtype, 123 (26.2%) cases were HER2 overexpression subtype, and 82 (17.4%) cases were triple-negative subtype. The mean regression rate of 490 patients with breast cancer treated with NAC was 79% (range: 10–100). Two hundred (40.8%) cases had pathologic complete response (pCR) in the PCTB in breast. There were 166 (33.9%) cases with RCB class 0 (pCR), 24 (4.9%) cases with RCB class 1, 151 (30.8%) cases with RCB class 2, and 149 (30.4%) cases with RCB class 3.

Of the postchemotherapy cases, 242 (49.4%) and 248 (50.6%) were negative and positive, respectively, for ER in the stromal cells of PCTB (Fig. 1). The mean regression rate was 68.6 and 90% for cases with ER-negative and ER-positive stromal cells in the PCTB, respectively, and the difference was statistically significant (p < 0.001). Of the 200 cases with pCR, 60 (30%) were negative, and 140 (70%) showed positivity for ER in stromal cells of the PCTB, respectively (p < 0.001).

a The tumor bed is an irregular area of vascularized fibrous stroma that exhibits varying degrees of fibroblastic/myofibroblastic proliferation and inflammatory cells and is devoid of normal ducts and lobules. (× 200). b Estrogen receptor positivity in the stromal cells of the tumor bed (× 400). c Estrogen receptor negativity in the stromal cells of the tumor bed (× 400)

According to the threshold value determined by ROC, the mean RCB value was 1.366 and 2.424 for cases with ER-positive and ER-negative stromal cells in PCTB, respectively (p < 0.001). The stromal ER positivity rate was 68.1% in cases with pCR in the RCB system, while the stromal ER positivity rate was 39.8% in those without complete response (p < 0.001) (Table 1).

The average regression rates after NAC were 48.7% in the luminal A-like subtype, 77% in the luminal B-like subtype, 86.2% in the HER2 overexpression subtype, and 88% in the triple negative subtype, respectively (p < 0.001). ER expression in the stromal cells of the PCTB was positive in 18.9, 48.1, 58.5, and 57.3% of cases of luminal A-like, luminal B-like, HER2 overexpression, and triple-negative subtypes, respectively (p < 0.001). When the cases were classified as luminal and non-luminal subtypes, the difference in ER positivity in the stromal cells of the PCTB was statistically significant between the two groups (42.3 vs 58%) (p < 0.001) (Table 1).

According to pre-treatment radiological findings, the mean tumor diameter in cases with pCR according to RCB was 37.7 ± 1.7, while the mean tumor diameter in cases with incomplete response was 40.3 ± 1.4 (p = 0.256). In addition, according to RCB, the mean Ki67 value in cases with pCR was 47.9%, while the mean Ki67 value in cases with incomplete response was 33.7% (p < 0.001). Significant or near significant factors found by univariate test were included in multivariate stepwise logistic regression analysis. In the multivariate logistic analysis performed by selecting stromal ER positivity, subtype, Ki67 index, age, and tumor diameter as covariates for predicting pCR, stromal ER positivity (OR: 3.059; 95% CI [1.947–4.807]; p < 0.001), intrinsic subtype (OR: 1.477; 95% CI [1.102–1.980]; p = 0.009), and Ki67 index (OR: 1.028; 95% CI [1.104–1.041]; p < 0.001) were found to be independent factors (Table 2).

ER expression in the tumor stroma was analyzed in core biopsy before the NAC in 299 cases. Among them, 270 (90.3%) and 29 cases (9.7%) showed ER negativity and positivity in stromal cells, respectively. Of the 270 cases with stromal ER negativity before NAC, 132 cases (48.9%) converted to ER positivity in stromal cells of the PCTB after NAC. The regression rate of those that remained negative for ER (138/270) after NAC was 68.4%, while the regression rate of those that changed to positive was 89.8% (p < 0.001). Pathologic complete response rates were also found to be 23.2 and 56.8% in the ER negative-remaining and ER-positive/conversion groups, respectively (p < 0.001). We also identified five cases in which stromal cells were ER-positive in core biopsy and turned ER-negative after neoadjuvant therapy. However, these 5 cases did not show similarity in either regression rate or intrinsic subtype (Table 3).