Sreekumar Sundara Rajan

The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer

Background:A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour–stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas.Methods:TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed.Results:Tumours with ⩾49% stroma were associated with better survival in female (OS P=0.008, HR=0.2–0.7; RFS P=0.006, HR=0.1–0.6) and male breast cancer (OS P=0.005, HR=0.05–0.6; RFS P=0.01, HR=0.87–5.6), confirmed in multivariate analysis.Conclusions:High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR.

Characterisation of male breast cancer: a descriptive biomarker study from a large patient series

Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.

Pathological evaluation of the staging axillary lymph nodes for breast cancer: a national survey in the United Kingdom

The handling and examination of sentinel lymph nodes (SLNs) to detect metastasis is critical in the assessment of early breast cancer patients. This survey investigates the variation in practise followed by pathology units across the United Kingdom in the staging evaluation of axillary lymph nodes (ALNs).

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12–2.8 and P = 0.035; HR = 1.68, 1.03–2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26–5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P = 0.016; HR = 2.38 (1.18–4.8), eIF5 P = 0.022; HR = 2.55 (1.14–5.7); coexpression P = 0.001; HR = 7.04 (2.22–22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required. Clin Cancer Res; 23(10); 2575–83. ©2016 AACR.

Management of Palpable but Radiologically Occult Breast Abnormalities

Objective: To examine the utility of palpation-guided fine-needle aspiration cytology (pgFNAC) in the context of clinically palpable but radiologically occult breast abnormalities in this era of digital mammography and high sensitivity ultrasound. Methods: Women undergoing pgFNAC from January 2005 to December 2007 were identified from the histopathology database and correlated with clinical and radiological findings recorded prospectively in electronic patient records. Results: 142 cases matching our selection criteria were identified with a mean age of 43 (SD ±13.7) years; 83 patients had focal lumps and 59 had non-focal lumpiness. In the latter, pgFNAC showed C1 cytology in 45 (76.3%), C2 in 13 (22%) and C3 in 1 (1.7%) patient. In 83 patients with a focal discrete lump, pgFNAC revealed C1 cytology in 65 (78.3%), C2 in 14 (16.9%), and 2 patients each had C3 and C4 cytology. Core biopsy was undertaken in the latter 4 patients, invasive cancer was found in 1 patient each with C3 and C4 cytology and benign pathology in the rest. To date, none of the patients discharged has developed pre-malignant or malignant lesions in the ipsilateral breast. Conclusion: In patients presenting with clinically palpable but radiologically occult breast abnormality, pgFNAC can identify those who need further investigation or who can be safely discharged.