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. Electronic supplementary material The online version of this article (10.1007/s10549-018-4987-4) contains supplementary material, which is available to authorized users.

PARP inhibitor (PARPi) sensitivity is related to tumor-specific defects in homologous recombination (HR). Therefore, there is great clinical interest in tests that can rapidly and reliably identify HR deficiency (HRD). Functional HRD tests determine the actual HR status by using the (dis)ability to accumulate RAD51 protein at sites of DNA damage as read-out. In this study, we further improved and calibrated a previously described RAD51-based functional HRD test on 74 diagnostic formalin-fixed paraffin-embedded (FFPE) specimens (RAD51-FFPE test) from endometrial cancer (EC n = 25) and epithelial ovarian cancer (OC n = 49) patients. We established optimal parameters with regard to RAD51 foci cut-off (≥ 2) and HRD threshold (15%) using matched endometrial and ovarian carcinoma specimens for which HR status had been established using a RAD51-based test that required ex vivo irradiation of fresh tissue (RECAP test). The RAD51-FFPE test detected BRCA deficient tumors with 90% sensitivity and RECAP-HRD tumors with 87% sensitivity, indicating that it is an attractive alternative to DNA-based tests with the potential to be applied in routine diagnostic pathology.

Purpose The tumour microenvironment in older patients is subject to changes. The tumour-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoural stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (≥ 70 years). Methods Two retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on haematoxylin and eosin stained tissue slides. Results The intra-tumoural stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006-0.057, p = 0.016 and B 0.034, 95% CI 0.015-0.054, p < 0.001, respectively). Fifty-one per cent of the patients from the Nottingham Breast Cancer series < 40 years had a stroma-high tumour compared to 73% of the patients of ≥ 90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients ≥ 70 years. Conclusions The intra-tumoural stroma increases with age. This might be the result of an activated tumour microenvironment. The TSR did not validate as an independent prognostic parameter in patients ≥ 70 years in contrast to young women with breast cancer as published previously.

distribution of FOLR1 in normal tissues may increase it's diagnostic and therapeutic potential through targeted agents currently under development. We characterized the FOLR1 serum expression in benign and malignant ovarian pathology pre-and postoperatively. Methodology Patients with suspected ovarian cancer treated at our Institution between 2018-2021 were prospectively enrolled. Pre-and/or postoperative (1-8 days after) blood samples were taken. Quantitative measurement of FOLR1 serum concentration was carried out by ELISA. Result(s)* Median age of participating patients was 53 (range 40-78). On definitive pathology 13 (22%) patients had benign adnexal masses and 46 (78%) had serous ovarian cancer. Thirty-seven (63%) patients had FIGO stage III-IV and 15 (25%) received neoadjuvant chemotherapy (NACT). Preoperative FOLR1 was significantly higher in the malignant group versus cases with benign pathology (mean 2190 ng/mL vs 499 ng/mL, p=0.001). NACT patients had a significantly lower preoperative FOLR1 than chemotherapy naïve patients (mean 1001 ng/mL vs 2765 ng/mL, p=0.012). Additionally, the preoperative FOLR1 in chemotherapy naïve patients was significantly higher in advanced-stage disease FIGO III-IV versus early-stage disease FIGO I-II (3317 ng/mL vs 1179 ng/mL, p=0.023). In paired pre-and postoperative samples no significant FOLR1 difference was noted (n=19, p=0.64), however for paired samples taken up to 3 days postoperatively a significant increase was seen in the postoperative value (1547 ng/ mL vs 1768 ng/mL, p=0.047, n=7). Interestingly, 1/7 (14%) cases demonstrated a decrease in postoperative FOLR1 in the first 3 days while 8/12 (66.6%) cases had a decrease in postoperative FOLR1 4-8 days after (p=0.027). Conclusion* Elevated serum FOLR1 values correlated with malignancy and advanced stage while NACT significantly reduced FOLR1 values, in correlation with disease burden. We describe here a significant postoperative surge of FOLR1 that decreases >3 days after surgery that requires subsequent investigation. The full diagnostic and therapeutic potential of FOLR1 is yet to be explored and further analysis in corresponding tissue samples is ongoing.

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