Background: Hürthle cell thyroid carcinoma (HCTC) is a rare disease. It is believed that it is more aggressive than follicular thyroid carcinoma. The aim of our study was to identify factors associated with disease-specific and disease-free survival. Methods: Altogether, 108 patients with HCTC (26 male, 82 female; median age 62 years; range 19-87 years) treated at our Institute from 1972 to 2011 were included in the present retrospective study. Data on age, clinical and histopathological factors, tumor stage, recurrence, disease-free and disease-specific survival were collected. Univariate analysis was used to identify factors associated with disease-specific survival. Cox%s multivariate regression model was used to identify independent prognostic factors for disease-specific survival. Results: The follow-up period was 1 to 337 (median 105) months. Of 108 patients, 12 (11%) had distant and 8 (7%) had locoregional metastases before primary treatment. Recurrence was diagnosed in 26 cases (24%): locoregional, distant, and both locoregional and distant in 12, 11, and 3 cases, respectively. The 5-year, 10-year, and 20-year disease-specific survival were 96%, 88%, and 67%, respectively. Independent prognostic factors for disease-specific survival were: age of patients at diagnosis, distant metastases and residual tumor after surgery. Conclusion: Long disease-specific survival was found in patients with HCTC younger than 45 years of age without distant metastases and without residual tumor after surgery.
COBISS.SI-ID: 1899643
BACKGROUND: Sentinel node biopsy (SNB) is the "gold standard" in axillary staging in clinically node-negative breast cancer patients. However, axillary treatment is undergoing a paradigm shift and studies are being conducted on whether SNB may be omitted in low-risk patients. The purpose of this study was to evaluate the risk factors for axillary metastases in breast cancer patients with negative preoperative axillary ultrasound. METHODS: A total of 1,395 consecutive patients with invasive breast cancer and SNB formed the original patient series. A univariate analysis was conducted to assess risk factors for axillary metastases. Binary logistic regression analysis was conducted to form a predictive model based on the risk factors. The predictive model was first validated internally in a patient series of 566 further patients and then externally in a patient series of 2,463 patients from four other centers. All statistical tests were two-sided. RESULTS: A total of 426 of the 1,395 (30.5 %) patients in the original patient series had axillary lymph node metastases. Histological size (P ( 0.001), multifocality (P ( 0.001), lymphovascular invasion (P ( 0.001), and palpability of the primary tumor (P ( 0.001) were included in the predictive model. Internal validation of the model produced an area under the receiver operating characteristics curve (AUC) of 0.731 and external validation an AUC of 0.79. CONCLUSIONS: We present a predictive model to assess the patient-specific probability of axillary lymph node metastases in patients with clinically node-negative breast cancer. The model performs well in internal and external validation. The model needs to be validated in each center before application to clinical use.
COBISS.SI-ID: 1937531
BACKGROUND: The population of elderly people is increasing and so is the population of breast cancer patients aged )=80 years. The aim of our retrospective study was to identify independent prognostic factors for the duration of breast cancer-specific survival of surgically treated patients aged )=80 years. The secondary aim was to determine the appropriate surgical treatment of breast cancer in patients aged )=80 years. METHODS: We reviewed the medical records of 154 patients aged )=80 years with early-stage breast cancer (mean age 83 years) who underwent surgery at the tertiary cancer center in the period from 2000 to 2008. Tumor stage was pT1/pT2 and pT3/pT4 in 75% and 25%, respectively. Surgical treatment comprised: quadrantectomy (in 27%), mastectomy (in 73%), axillary dissection (in 57%), and sentinel lymph node biopsy (in 18%), while 25% of patients had no axillary surgery. RESULTS: During a median follow-up of 5.3 years, 31% of patients died of breast cancer, while 28% of patients died of other causes. Half of our patients with poorly differentiated breast cancer or estrogen receptor-negative tumor died of breast cancer. Multivariate statistical analysis showed that the pathological T-stage, pathological N-stage and estrogen receptors were independent prognostic factors for the duration of breast cancer-specific survival of patients. CONCLUSION: Short breast cancer-specific survival indicates that, in patients aged )=80 years, breast cancer with metastases in axillary lymph nodes can be an aggressive disease.
COBISS.SI-ID: 1871227
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy in women under 40 years of age. We sequenced the exomes of six individuals from three families with SCCOHT. After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we tested DNA from a fourth affected family, which also carried a segregating SMARCA4 germline mutation. All the familial tumors sequenced harbored either a somatic mutation or loss of the wild-type allele. Immunohistochemical analysis of these cases and additional familial and non-familial cases showed loss of SMARCA4 (BRG1) protein in 38 of 40 tumors overall. Sequencing of cases with available DNA identified at least one germline or somatic deleterious SMARCA4 mutation in 30 of 32 cases. Additionally, the SCCOHT cell line BIN-67 had biallelic deleterious mutations in SMARCA4. Our findings identify alterations in SMARCA4 as the major cause of SCCOHT, which could lead to improvements in genetic counseling and new treatment approaches.
COBISS.SI-ID: 1744251
Metformin may exhibit inhibitory effects on cancer cells by inhibiting mTOR signaling pathway. The aim of our retrospective study was to examine if patients with breast carcinoma (BC) and diabetes mellitus (DM) receiving metformin have a lower stage of carcinoma in comparison to patients not receiving metformin, and if the use of metformin correlates with the molecular subtype of BC. METHODS: A chart review of 253 patients with invasive BC and DM (128 on metformin and 125 not on metformin) was performed. Control group consisted of 320 consecutive patients with invasive BC without DM. BC subtypes were classified by immunohistochemical surrogates as luminal A (estrogen receptor [ER] + and/or progesterone receptor [PR]+, HER-2-), luminal B (ER + and/or PR+, HER-2+), HER-2 (ER-, PR-, HER-2+), triple-negative/basal (ER-, PR-, HER-2-). RESULTS: Patients on metformin had a lower proportion of T3 or T4 tumors than patients who were not receiving metformin (16% vs. 26%; p = 0.035). No statistical difference was found between the two study groups in N stage. Patients with DM on metformin, with DM not on metformin and the control group had different molecular subtypes of BC (p = 0.01): the luminal A subtype was found in 78%, 83% and 71%, the luminal B in 12.6%, 9% and 11%, HER-2 in 0.8%, 1.6% and 8%, and the triple-negative/basal-like subtype in 8.6%, 6.4% and 10%, respectively. CONCLUSION: Our data indicate that long-term use of metformin use correlates with molecular subtype of BC in diabetics on metformin in comparison to diabetics not on metformin and patients without DM. However, most likely, different distribution of the molecular subtypes of BC in these three groups of patients was caused by other risk factors for breast carcinoma, such as age of patients or obesity.
COBISS.SI-ID: 1767803