Discordant expression of hormone receptors and HER2 in breast cancer. A retrospective comparison of primary tumors with paired metachronous recurrences or metastases.

PURPOSE: Expression of biomarkers in breast cancer, such as the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), can impact therapeutic decisions; however, it has been reported that their expression may change with disease progression. The aim of this retrospective study was to investigate the expression of these biomarkers in primary breast cancer and in its metachronous recurrences or metastases, and to estimate the percentage of cases with discordant expression. METHODS: Paired primary and metastatic tumor samples were collected from patients with primary breast cancer and subsequent metachronous distant metastases, diagnosed at the Metaxa Cancer Hospital, Piraeus, Greece, from 1988 to 2008. Two cases of local recurrence were also included. ER, PR and HER2 expression were assessed by immunohistochemistry (IHC) according to ASCO-CAP 2007 guidelines. Statistical comparisons were made using McNemar's exact test and Bowker's test for symmetry. RESULTS: Tumor samples from 110 patients were analysed. In the primary tumor, ER, PR and HER2 were positively expressed in 64.5%, 58.2% and 32.7% of cases, respectively, and expression of these biomarkers was lost in 18.2%, 21.8% and 10.9% of the corresponding metastases, respectively. Overall, a change of ER, PR and HER2 expression from positive to negative and vice versa occurred in 27.3% (p = 0.0987), 25.5% (p < 0.001) and 18.2% (p = 0.5034) of the cases, respectively. CONCLUSION: The expression of ER, PR and HER2 in metachronous recurrences or metastases can be discordant from that observed in the primary tumor. As such changes can occur during disease progression, the evaluation of biomarkers in metastatic sites should be mandatory, whenever possible, to ensure that patients are receiving the most effective treatment at all times.

Triple-negative phenotype is of adverse prognostic value in patients treated with dose-dense sequential adjuvant chemotherapy: a translational research analysis in the context of a Hellenic Cooperative Oncology Group (HeCOG) randomized phase III trial.

PURPOSE: It is well recognized that breast cancer is a heterogeneous disease. The purpose of the current study was to classify patients according to the immunohistochemical phenotype of their tumors in an effort to evaluate the outcome of the respective groups of patients and specifically of those with triple-negative breast cancer (TNBC) following dose-dense sequential adjuvant chemotherapy. METHODS: A total of 595 patients with high-risk breast cancer were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy with or without paclitaxel in the context of a randomized study. ER, PgR, HER2, Ki67, EGFR, and CK5 protein expression were evaluated in 298 formalin-fixed paraffin-embedded tumor samples by immunohistochemistry (IHC). HER2 was also evaluated by chromogen in situ hybridization (CISH). HER2 status and Ki67 protein expression differentiated luminal IHC subtypes (luminal B tumors being HER2 and/or Ki67-positive). RESULTS: Among the 298 tumors, the immunohistochemical panel classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2 enriched, and 36 (12%) as TNBC. The median follow-up time was 97 months. Patients with luminal A tumors had the best prognosis, with improved disease-free survival (log-rank, P = 0.033) and overall survival (P = 0.006) compared with the other three tumor subtypes. The three subtypes had an increased risk for relapse and death compared with luminal A in multivariate analysis, as well. No benefit from paclitaxel treatment was detected in any of the four subtypes or the total cohort. Hierarchical clustering based on mRNA expression of ER, PgR, and HER2 by quantitative RT-PCR identified patient groups that were comparable to the subtypes identified by IHC. CONCLUSIONS: The results of this study confirm that triple negative, luminal B and HER2-enriched phenotypes identified by IHC are of adverse prognostic value in high-risk breast cancer patients treated with dose-dense sequential adjuvant chemotherapy.

Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy.

PURPOSE: To assess the prognostic and predictive significance of p53 and Bcl-2 protein expression in high risk patients with breast cancer treated with dose-dense sequential chemotherapy. PATIENTS AND METHODS: From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (P) 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and 397 patients respectively. RESULTS: Positive expression of p53 was detected in 104 (26.5%) patients and was significantly associated with negative hormonal status, worse histologic grade, higher incidence of disease relapse and higher rate of death. p53 positive expression was a significant negative predictor of overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001). Negative expression of Bcl-2 was detected in 203 (51%) patients and was significantly associated with negative hormonal status. Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS. CONCLUSIONS: For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident.

Gastrointestinal tract metastasis as first presentation of breast cancer.

Gastrointestinal metastases of breast cancer are a rare occurrence. It is even rarer to be the first manifestation of an unknown breast cancer. We present 2 cases of metastatic breast cancer of the lobular type to the stomach and large bowel in 2 women, initially considered as primary disease. The establishment of diagnosis required experienced histopathologic and immunohistochemical examination. The management follows the principles of the primary disease. Surgery is spared for complications. Mean survival is one year. Prognosis is better for patients with positive hormonal receptors.

Multiple dermoid cysts within the same ovary: our experience of a rare case with review of the literature.

OBJECTIVE: Ovarian dermoid cysts are relatively frequent ovarian lesions that can be easily diagnosed by transvaginal ultrasonography. However, the recognition of multiple dermoid cysts, separated by normal ovarian tissue, within a single ovary is rare. CASE: We present a case with bilateral dermoid cysts, four dermoid cysts within the right ovary and one in the contralateral ovary. Transvaginal ultrasonography showed hyperechogenic areas in the right ovary with a hypoechogenic area in front of them; the hyperechogenic areas were separated by areas with the echogenicity of normal ovarian tissue and indentation, suggesting the presence of multiple dermoid cysts within the same ovary. CONCLUSION: Preoperative ultrasonographic suspicion of multiple dermoid cysts within the same ovary might contribute to a better decision about the surgical approach.