Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study.

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm(2) and 18% of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2- subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2- subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.

Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

Spontaneous changes in tumour cell dissemination to bone marrow in colorectal cancer.

AIM: The study aimed to evaluate the incidence of disseminated tumour cells (DTCs) in bone marrow (BM) preoperatively and during follow up and to correlate these with established risk factors in patients with colorectal cancer. METHOD: We prospectively studied BM in 57 patients using the anti-cytokeratin antibody A45-B/B3. RESULTS: The overall detection rate of DTCs was 23% with a similar detection rate through all stages of the disease. No significant association was found between the presence of DTCs and clinicopathological parameters. After a median follow up of 35.4 months, no differences were found in relapse and overall survival between patients with and without DTC preoperatively. In 31 of 45 patients with local disease, we performed a follow-up BM examination after 1 year. In 26% of the patients, the BM status had changed as compared with the preoperative finding. CONCLUSION: This is the first study to report the follow up of DTC in BM in colorectal cancer using the A45-B/B3 antibody. The presence of tumour cells in the preoperative BM had no impact on outcome. The BM status had changed after 12 months in a quarter of patients.

Practice of HER-2 immunohistochemistry in breast carcinoma in Austria.

Practice and accuracy of immunohistochemistry is known to vary highly. Reliability of HER-2 immunohistochemistry is critical because of its role in patient selection for therapeutical options in breast cancer. Therefore reliability of HER-2 immunohistochemistry in pathology laboratories in Austria was assessed. Ten tissue specimens of invasive ductal breast carcinomas and three cell line samples were tested. Presence/absence of gene amplification was determined by FISH to be used as a gold standard. Laboratories were asked to stain and assess slides using their routine immunohistochemical staining protocol. Overall the study consisted of 311 tests on tissue specimens and 142 on cell lines. In all cases manual scoring was performed. Participation was voluntary and was 94%. Overall sensitivity was 90.5% and specificity 99.2%. Overscoring including true false positive results were found in 6.7% and 6.3% in tissue specimens and cell lines, respectively. False negative determinations were obtained in 1.9% and 2.8% of tissue specimens and cell lines, respectively. HercepTest showed slightly higher reliability in comparison with individualized staining methods. By manual scoring inaccurate scoring affected 12.3% of test results and 62% of the laboratories. In conclusion participation rate and accuracy of HER-immunohistochemistry was high all over the country. Manually performed scoring demonstrated some limitations.

The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma.

BACKGROUND: Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients. OBJECTIVE: To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma. METHODS: The value of IHC, the types of metastasis found by this method, and the involvement of non-sentinel lymph nodes were analysed in a multi-institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis. RESULTS: 189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non-sentinel-node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general. CONCLUSIONS: IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.

[Lesions of the male breast]. / Mammaläsionen beim Mann. Man(n) denkt daran.

Lesions of the male breast are rather rare. The most frequent lesion is gynecomastia followed by breast cancer. Gynecomastia is well known but male breast cancer is a rather rare tumor. It occurs in less than 1% of all cancers in men and of breast cancers. The mean age is high with a median of 68 years. Predisposing factors appear to be associated with hyperestrogenism such as testicular factors including maldescensus, orchitis and infertility. Other factors are Klinefelter, adipositas, diabetes mellitus and liver disease. In recent years an increased risk of male breast cancer has been reported in families with positive family history and in which BRCA2 mutations have been identified. Diagnostic procedures for male breast lesions should be the same as for the female breast. Underdiagnosis of male breast lesions is a frequently reported problem. Histology of male breast cancer differs in some aspects from female breast cancer. Male breast cancers are more frequently invasive ductal, G3 and steroid hormone receptor positive. In case of intraductal cancer male lesions are more frequently papillary. Lobular carcinomas almost never occur. Prognostic factors for male breast cancer are similar to female breast cancer. For male breast cancer no randomised therapy studies are described. Therefore all therapy strategies are extrapolated from female breast cancer. The existing main therapeutic problem is undertreatment.