Biochemical and ultrastructural correlations of calreticulin and thioredoxin expression in breast mucinous carcinoma and infiltrating ductal carcinoma non-special type.

Mucinous infiltrating invasive ductal adenocarcinoma consists of 2-4% invasive breast cancer, but is a very interesting type due to its macroscopic similarity to non-special-type (NST) ductal carcinoma. The macroscopic similarity of mucinous and infiltrating ductal carcinoma NST adenocarcinomas consists of a loose and edematous stroma, which is often seen in portions of NST carcinoma and may mimic the mucin pools of mucinous carcinoma. In this study the authors examined the ultrastructural differences between mucinous carcinoma and infiltrating ductal carcinoma NST. They also examined the protein expression of the tissues by 2D electrophoresis due to their belief that from the results of these two levels it is possible to understand the changes that take place both in the ultrastructural and biochemical levels in these two types of breast cancer. The ultrastructural results from mucinous carcinoma have shown many changes in cytoplasmic organelles in comparison to normal samples, depending on the grade and the number of metastatic lymph nodes. At the 2D elecrophoresis level the authors studied two interesting polypeptides, calreticulin and thioredoxin. Both of these proteins were found in patterns of fibroadenoma, mucinous carcinoma, and NST carcinoma, but with different quantitative expression among them. In the future the quantitative differences of these two proteins may provide specific tumor markers for these two types of carcinoma.

Extra-long projections of the cell surface in nonspecial-type ductal carcinoma with vascular invasion under the scanning electron microscope.

In this study, cell surface projections of primary culture cells from tissues of infiltrating ductal carcinoma Non Special Type with vascular invasion are examined by use of the Scanning Electron Microscopy method. In these cases the projections of cell membrane appeared extremely long and bridge-like covering very long distances between the breast cancer cells. Also, the long cell membrane projections, connect cells between them and form a complex. Sometimes, from one edge to another we observed a very long chain of cancer cells reaching sometimes a length of 3, 3 mm. On the other hand the absence of vascular invasion never shows such long projections of the cell membrane even if there are many metastatic nodes. The role of these extra long projections in communication between cancer cells is determinant. Through this communication, these long projections seemed to be responsible for the metastatic process in primary breast cancer with vascular invasion.

Surface topography and ultrastructural changes of mucinous carcinoma breast cells.

Mucinous carcinoma of the breast (MCB) is histologically classified into 2 groups: (1) pure MCB and (2) mixed MCB. Pure MCB carries a better diagnosis than mixed MCB. This research relates to the cell surface topography and ultrastructure of the cells in the above cases and aims to find the differences between them, by means of two methods: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For the SEM examination, it was necessary to initially culture the MCB tissues and then proceed with the usual SEM method. In contrast, for the TEM technique, MCB tissues were initially fixed followed by the classic TEM method. The authors found the topography of pure MCB cases to be without nodes. The cell membrane was smooth, with numerous pores and small ruffles that covered the entire cell. The ultrastructural appearance of the same cases was with a normal cell membrane containing abundant collagen fibers. They also had many small vesicles containing mucin as well as secretory droplets. In contrast the mixed MCB had a number of lymph nodes and their cell surface topography showed stronger changes such as microvilli, numerous blebs, ruffles and many long projections. Their ultrastructure showed very long microvilli with large cytoplasmic inclusions and extracellular mucin collections, electron-dense material vacuoles, and many important cytoplasmic organelles. An important fact is that mixed MCB also contains areas of infiltrating ductal carcinoma. These cells of the cytoplasmic organelles are clearly responsible for the synthesis, storage, and secretion of the characteristic mucin of this tumor type. Evidently, this abnormal mucin production and the abundance of secretory granules along with the long projections observed in the topographical structure might be responsible for transferring tumor cells to neighboring organs, thus being responsible for metastatic disease.

Impact of chemotherapy followed by aromatase inhibitors on bone health of women with ER-positive early breast cancer in real world clinical settings in Greece: Results of the POCHARBI trial conducted by the Hellenic Society of Breast Surgeons.

INTRODUCTION: The aim of this observational study was to assess the combined impact of chemotherapy (CT) and aromatase inhibitors (AI) therapy on bone mineral density (BMD) in postmenopausal women with estrogen receptor (ER)-positive early breast cancer. METHODS: Patients were treated with a third generation AI, either as adjuvant therapy (HT cohort, n = 166) or as subsequent endocrine therapy after initial treatment with chemotherapy (CT cohort, n = 124), and were followed up for a 12-month period. BMD was evaluated at lumbar spine (LS) and total hip (HP) before CT, before AI therapy and after 12 months of AI therapy. The primary study objective was changes in LS BMD between pre CT treatment and post 12 months AI therapy in the CT cohort. RESULTS: There were no statistically significant changes in LS BMD, either within CT or HT cohort. In the CT cohort, the mean LS BMD change was -0.72% (95% CI: -2.97%, +1.53%, p = 0.5526) between CT start and month 12 of AI therapy, while it was -0.19% (95% CI: -2.12%, +1.74%, p = 0.8309) and -0.59% (95% CI: -3.18%, +2.00%, p = 0.4759) between CT start and AI start and AI start and month 12 of AI therapy respectively. The mean change in LS BMD in the HT cohort (i.e. after 12 months of AI treatment) was +1.51% (95% CI: -0.96%, +3.98%, p = 0.7420). CONCLUSIONS: The results of this study indicate that, under routine clinical practice, most postmenopausal patients who receive CT before AI therapy do not experience debilitating BMD consequences during the first year of AI treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01298362.

Clinical experience of using Oncotype DX as an additional treatment decision tool in early breast cancer - a retrospective analysis from 5 Greek institutions.

AIMS: The objective of this retrospective study was to describe the results from five institutions' experience of using Oncotype DX(®) to identify patients who need chemotherapy despite the presence of primarily favorable characteristics. PATIENTS AND METHODS: Oncotype DX was performed in 106 pre- and postmenopausal patients with estrogen receptor-positive, HER2-negative, early breast cancer with a combination of favorable prognostic factors or favorable prognostic factors with at least one unfavorable characteristic (tumor size >2 cm, tumor grading of II-III, Ki-67 ≥ 10%, presence of lymph node micrometastases) in which it was unclear whether hormonal therapy only or chemotherapy plus hormonal therapy was the optimal adjuvant treatment. RESULTS: Sixty-four (60.4%) women had Recurrence Score (RS) values <18, 29 (27.4%) intermediate RS values of 18-30, and 13 (12.3%) high RS values of ≥31. Tumor size, grading and presence of micrometastases were not associated with the RS. There was a significant association between Recurrence Score and the number of unfavorable characteristics as a categorical but not as a continuous variable. High Recurrence Scores were predictive of high Ki-67 but the converse was not true. Overall, 29 of 106 (27.4%) patients received chemotherapy because of an intermediate or a high Recurrence Score. CONCLUSION: The Recurrence Score helped in treatment decision-making for estrogen receptor-positive, HER2-negative patients with favorable characteristics or an intermediate risk of recurrence due to the presence of at least one unfavorable factor. The results of the 21-gene assay increased the likelihood for patients with intermediate clinical and histopathological risk factors receiving chemotherapy.

Effect of exemestane on the lipidemic profile of post-menopausal operable breast cancer patients following 5-7 years of adjuvant tamoxifen: preliminary results of the ATENA substudy.

Long-term endocrine therapy for breast cancer may have clinical implications as drugs that potentially alter the lipid profile may increase the risk of developing cardiovascular disease. In this study, a companion subprotocol to the ATENA (Adjuvant post-Tamoxifen Exemestane versus Nothing Applied) trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of post-menopausal women with operable breast cancer in the adjuvant setting to that of observation alone following deprivation of 5-7 years primary treatment with tamoxifen. In this open-label, randomized, parallel group study, 340 post-menopausal patients with operable breast cancer who had been treated with tamoxifen for 5-7 years were randomized to either 5 additional years of exemestane (25 mg/day; n=172) or observation alone (n=168). Assessments of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total serum triglycerides (TRG) were performed at baseline, and at 6 and 12 months. Total TRG levels were significantly reduced compared with baseline for the exemestane and the observational arm. Both total cholesterol and LDL levels were significantly increased above that of baseline values by 6 months, maintained through to 12 months, with no significant difference between the two treatment arms. There was no significant alteration observed for HDL over time or between the two arms. We conclude that sequential adjuvant treatment with exemestane in post-menopausal operable breast cancer patients following cessation of 5-7 years of tamoxifen does not appear to significantly alter the lipidemic profile for at least 12 months compared with an observational arm.