Immunohistochemical assessment of hormone receptor status of breast carcinoma : Interobserver variation of the quick score

Background: Immunohistochemical (IHC) assessment of estrogen receptor (ER) and progesterone receptor (PR) status has become a routine practice to predict the likely outcome of Tamoxifen therapy. Aims: To assess the interobserver variation in scoring hormone receptor status of breast carcinoma, using the Quick Score. Materials and Methods: IHC-stained slides of breast carcinomas reported by the two authors during a 28-month period were included in the study. Both authors independently reassessed all the tumors. Both were blinded to each other′s assessment. The Quick score with a 0-8 point scale was used to score the hormone receptor status. Weighted Kappa was calculated to assess the interobserver variation. Results: A total of 210 breast carcinomas were included in this study. There was a substantial to almost perfect agreement between the two observers in scoring the hormone receptor status (kappa values; ER = 0.856, PR = 0.711). Both ER and PR showed an almost perfect agreement in assessing the intensity of staining (kappa value; ER = 0.882, PR = 0.840), while the scoring of proportion of cells gave lower Kappa values (kappa value; ER = 0.778, PR = 0.592). Interobserver agreement was less in scoring hormone receptor status of breast carcinomas after mastectomies compared with excision biopsies, wide local excisions and metastatic deposits in lymph nodes. Suboptimal fixation resulting in background staining has contributed to the variation. Conclusion: A substantial to almost perfect interobserver agreement was seen in assigning an overall Quick score. Detection of complete negative and strong expression had a moderate to substantial agreement

Experts' opinion: Recommendations for retesting breast cancer metastases for HER2 and hormone receptor status

Abstract The human epidermal growth factor receptor 2 (HER2) and hormone receptor status of recurrent breast cancer may change between the tumor and metastases from negative to positive and vice versa, potentially affecting the treatment regimen. Retesting of metastases may therefore be crucial to allow appropriate selection of patients for whom targeted therapy is indicated; however, retesting is not routinely performed. This article recommends that metastases be retested for HER2 and hormone receptor status and provides practical guidance on when and how to retest, as agreed by a panel of expert pathologists with extensive experience of HER2 and hormone receptor testing

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR 12]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I\u2013III invasive early BC at age 6440 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60\u20130.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94\u20132.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients\u2019 counseling on treatment, prevention, and surveillance strategies

Pathological Assessment of Response to Neoadjuvant Chemotherapy among Carcinoma Breast Patients in a Tertiary Level Hospital

Background: The role of the pathologist reporting a case of post-chemotherapy carcinoma breast involves not just looking for residual carcinoma, but also classifying the patient into a response category, based on histological findings, and thus, analyzing the efficacy of treatment. Therapy related changes are well described in carcinoma breast. This study aims at classifying post-chemotherapy specimens based on response to chemotherapy according to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 system and also identifying important associations between morphology, lymph node metastases and hormone receptor status with response.Methods: The study classified thirty-one cases of carcinoma breast who had undergone neoadjuvant chemotherapy in our institution into three categories based on the NSABP B18 system, and analyzed the association of changes in morphology, hormone receptor status and metastases to lymph nodes with presence or absence of response.Results: The commonest response category was partial response (pPR) (17 cases), followed by pathological non-response (pNR) (11 cases) and pathological complete response (pCR) (3 cases). Statistically significant associations were found between presence of residual mass on gross assessment and presence of lymph node metastases with a poor response to treatment. Histopathological features and change in hormone receptor status did not show a significant association with response.Conclusion: The majority of patients showed a partial response to therapy. Presence of a residual mass and presence of metastases to lymph nodes signified poor response

Prediction of Treatment Response to Neoadjuvant Chemotherapy for Breast Cancer via Early Changes in Tumor Heterogeneity Captured by DCE-MRI Registration.

We analyzed DCE-MR images from 132 women with locally advanced breast cancer from the I-SPY1 trial to evaluate changes of intra-tumor heterogeneity for augmenting early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) after neoadjuvant chemotherapy (NAC). Utilizing image registration, voxel-wise changes including tumor deformations and changes in DCE-MRI kinetic features were computed to characterize heterogeneous changes within the tumor. Using five-fold cross-validation, logistic regression and Cox regression were performed to model pCR and RFS, respectively. The extracted imaging features were evaluated in augmenting established predictors, including functional tumor volume (FTV) and histopathologic and demographic factors, using the area under the curve (AUC) and the C-statistic as performance measures. The extracted voxel-wise features were also compared to analogous conventional aggregated features to evaluate the potential advantage of voxel-wise analysis. Voxel-wise features improved prediction of pCR (AUC = 0.78 (±0.03) vs 0.71 (±0.04), p &lt; 0.05 and RFS (C-statistic = 0.76 ( ± 0.05), vs 0.63 ( ± 0.01)), p &lt; 0.05, while models based on analogous aggregate imaging features did not show appreciable performance changes (p &gt; 0.05). Furthermore, all selected voxel-wise features demonstrated significant association with outcome (p &lt; 0.05). Thus, precise measures of voxel-wise changes in tumor heterogeneity extracted from registered DCE-MRI scans can improve early prediction of neoadjuvant treatment outcomes in locally advanced breast cancer

Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC

Prognostic value of morphology and hormone receptor status in breast cancer - a population based study

We analysed the 5-year relative survival among 4473 breast cancer cases diagnosed in 1990-1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, 'special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the 5-year relative survival ranged from 66% (95% CI 61-71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriform, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis

Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study.

PurposeThe KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE.MethodsPatients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery).ResultsOf patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment.ConclusionCompared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment

Evaluation of a Novel Anti-Mucin 1 (MUC1) Antibody (PankoMab) as a Potential Diagnostic Tool in Human Ductal Breast Cancer; Comparison with Two Established Antibodies

Aim: PankoMab is a novel antibody that recognizes a tumor-specific epitope of Mucin 1 (MUC1). The aim of this study was the evaluation of PankoMab as a potential diagnostic tool and its comparison with two established antibodies against MUC1 in human ductal breast cancer. Materials and Methods: Breast carcinomas were obtained from 82 patients. MUC1 expression and hormone receptor status were determined by immunohistochemistry of paraffin-embedded material. Results: PankoMab revealed strong correlation to hormone receptor expression. DF3 showed no correlation with grading, lymph node involvement and/or estrogen receptor (ER) expression. In the subgroup of lymph node-positive and ER-negative tumors, we saw a significantly reduced DF3 staining in G3 tumors compared to G2 tumors. VU-4-H5 showed increased staining intensity in correlation with increased grading. In addition, we also identified a significantly higher expression of the VU-4-H5 epitope in lymph node-positive carcinomas compared to carcinomas without lymph node involvement. Conclusion: PankoMab revealed strong correlation to hormone receptor expression in ductal carcinoma of the breast. VU-4-H5 showed increased staining intensity in correlation with increased grading and lymph node involvement. PankoMab and VU-4-H5 staining could be a useful combination in ductal breast cancer prognosis by immunohistochemistry

Study of epidemiological aspects and hormone receptor status of meningiomas

Background: Meningiomas account for about a third of all central nervous system tumours worldwide. Though very common, quite less is known about its epidemiology. This study aims to establish the epidemiological parameters and hormone receptor status (Progesterone Receptor-PR) involved in the development of Meningiomas.Methods: This observational study included 50 patients. Epidemiological parameters studied included age, sex, symptoms, history of hormone intake, smoking, recurrence, family history, history of other hormone related tumours and radiological assessment of tumour site. Surgical samples were grossed and typed according to the WHO standards. Immunohistochemical staining was done using PR to establish the role of hormonal receptors in the development of meningiomas.Results: The mean age was 46.84±13.54 years. The ratio of male and female (Male:Female) was 1.0:2.3. 48.5% of females had history of hormonal pill intake and 28.6% had hormone related tumours, of which fibroid was most common. Amongst the sites involved cerebral convexity was most common (56%). Chi-square (χ2) test showed that there was a significant association between histological grade and PR expression of the patients (p=0.0002).Conclusions: Positivity for hormone receptors like PR, increased intake of hormonal pills by females and association of meningioma with hormone related tumours indicates that hormonal milieu plays a significant role in the growth of meningiomasχχ. This could thus provide an insight to the pathogenesis of meningiomas. In addition, mifepristone, an anti-progestin could be a player in the medical management of meningiomas