Purpose
Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor–stroma ratio (TSR) and the immune ...status of tumors in breast cancer patients was evaluated.
Methods
A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs).
Results
TSR (
P
< .001) and immune status of tumors (
P
< .001) were both statistically significant for recurrence free period (RFP) and both independent prognosticators (
P
< .001) in which tumors with a high stromal content behave more aggressively as well as tumors with a low immune status. Ten years RFP for patients with a stroma-low tumor and high immune status profile was 87% compared to 17% of patients with a stroma-high tumor combined with low immune status profile (
P
< .001). Classical HLA class I is the most prominent immune marker in the immune status profiles.
Conclusions
Determination of TSR is a simple, fast and cheap method. The effect on RFP of TSR when combined with immune status of tumors or expression of classical HLA class I is even stronger. Both are promising for further prediction and achievement of tailored treatment for breast cancer patients.
Purpose
There is a strong need to improve the prognostication of breast cancer patients in order to prevent over- and undertreatment, especially when considering adjuvant chemotherapy. Tumour stroma ...characteristics might be valuable in predicting disease progression.
Methods
Studies regarding the prognostic value of tumour–stroma ratio (TSR) in breast cancer are evaluated.
Results
A high stromal content is related to a relatively poor prognosis. The most pronounced prognostic effect of this parameter seems to be observed in the triple-negative breast cancer (TNBC) subtype.
Conclusions
TSR assessment might represent a simple, fast and reproducible prognostic factor at no extra costs, and could possibly be incorporated into routine pathological diagnostics. Despite these advantages, a robust clinical validation of this parameter has yet to be established in prospective studies.
The tumor–stroma ratio (TSR) was evaluated as a promising parameter for breast cancer prognostication in clinically relevant subgroups of patients. The TSR was assessed on hematoxylin and ...eosin‐stained tissue slides of 1,794 breast cancer patients from the Nottingham City Hospital. An independent second cohort of 737 patients from the Netherlands Cancer Institute to Antoni van Leeuwenhoek was used for evaluation. In the Nottingham Breast Cancer series, the TSR was an independent prognostic parameter for recurrence‐free survival (RFS; HR 1.35, 95% CI 1.10–1.66, p = 0.004). The interaction term was statistically significant for grade and triple‐negative status. Multivariate Cox regression analysis showed a more pronounced effect of the TSR for RFS in grade III tumors (HR 1.89, 95% CI 1.43–2.51, p < 0.001) and triple‐negative tumors (HR 1.86, 95% CI 1.10–3.14, p = 0.020). Comparable hazard ratios and confidence intervals were observed for grade and triple‐negative status in the ONCOPOOL study. The prognostic value of TSR was not modified by age, tumor size, histology, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status or lymph node status. In conclusion, patients with a stroma‐high tumor had a worse prognosis compared to patients with a stroma‐low tumor. The prognostic value of the TSR is most discriminative in grade III tumors and triple‐negative tumors. The TSR was not modified by other clinically relevant parameters making it a potential factor to be included for improved risk stratification.
What's new?
A tumor does not exist in isolation, and evaluation of its microenvironment or “stroma” could help determine clinical outcome in breast cancer. Here, the authors show that women with a stroma‐high tumor had a worse prognosis compared to women with a stroma‐low tumor. The prognostic value of the tumor‐stroma ratio was most discriminative in patients with grade III or triple negative breast cancer, thus making it a potential valuable factor to improve risk stratification for these patients.
The tumor–stroma ratio (TSR) has previously been found to be a strong prognostic parameter in primary breast cancer tumors. Since the presence of tumor cells in lymph nodes is important for clinical ...decision making, the influence of TSR in the primary breast tumor combined with the TSR in tumor‐positive lymph nodes on prognosis was evaluated. Women with invasive breast cancer without distant metastasis who underwent an axillary lymph node dissection between 1985 and 1994 at the Leiden University Medical Center were retrospectively analyzed. TSR assessment was performed on hematoxylin and eosin stained tissue slides. In total, 87 (45.5%) primary tumors were scored as stroma‐low and 104 (54.5%) as stroma‐high. Patients with a high stromal percentage in the primary tumors had a statistically significant worse relapse free period (RFP) compared to stroma‐low tumors (HR 1.97, 95% CI 1.37–2.82, p < 0.001). A total number of 915 lymph nodes were assessed for TSR. In 101 (52.9%) patients, heterogeneity was observed between stroma percentage category in primary tumor and lymph nodes. The combination of TSR of the primary tumor combined with TSR of tumor‐positive lymph nodes strengthened each other as independent prognostic parameter for RFP (p = 0.019). Patients with primary tumor stroma‐low/lymph nodes stroma‐low tumors showed strongly improved RFP rates compared to patients with primary tumor stroma‐high/lymph node stroma‐high tumors with 10‐year percentages of 58 versus 8%, respectively. Assessing the TSR on tumor‐positive lymph nodes can provide additional prognostic information. Stromal activation strongly differs between primary tumors and lymph node metastasis.
What's new?
Measuring the amount of stroma in tumor‐ positive lymph nodes, not just only in the primary tumor, can better predict breast cancer relapse. In recent years, researchers have increasingly looked to the tumor microenvironment for prognostic clues. Here, the authors compared the prognostic value of the TSR in primary breast tumors alone with TSR from both primary tumor and tumor‐positive lymph nodes. Risk of relapse for patients with high amount of stroma at the primary tumor was 75%, while a combination of stroma‐high primary tumor and stroma‐high lymph nodes correlated with 92% relapse rate after 10 years of follow‐up.
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