Treatment results in patients with ductal carcinoma in situ treated with adjuvant radiotherapy

Background/aim: The aim of this study was to evaluate the treatment results of patients undergoing adjuvant radiotherapy (ART) after breast surgery with the diagnosis of ductal carcinoma in situ (DCIS). Materials and methods: A total of 61 women who had undergone radiotherapy following extensive surgical excision were enrolled. All patients underwent 50 Gy ART. Survival analysis was performed using Kaplan­Meier analysis and SPSS 20.0. Results: The median age was 52 years (range: 28­86). The median follow-up period after RT was 92 months (range: 23­237). The median overall survival and distant and regional recurrence-free and disease-specific survival was 96 months (range: 26­240), while disease-free and local recurrence-free survival was 96 months (range: 22­240). While the 15-year and 20-year overall survival rates were 87% and 87%, respectively, the recurrence-free survival rates were 98% and 98%, respectively; the rates of disease-specific survival were 100% and 100%, respectively. Conclusion: The results of this study with a long follow-up period have shown that ART in DCIS is an effective treatment method to provide local disease control. However, further large studies are needed to identify the prognostic factors.

In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study).

OBJECTIVE: The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1). MATERIAL AND METHOD: 552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative. RESULTS: Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not. CONCLUSION: The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice.

Patients with only 1 positive hormone receptor have increased locoregional recurrence compared with patients with estrogen receptor-positive progesterone receptor-positive disease in very early stage breast cancer.

BACKGROUND: Estrogen receptor (ER) and progesterone receptor (PR) are important prognostic and predictive biomarkers in breast cancer. Patients with tumors positive for either receptor are generally considered hormone receptor-positive for treatment decisions. However, some data suggest that patients with ER(+) /PR(-) or ER(-) /PR(+) tumors may have worse outcomes than those with ER(+) /PR(+) tumors. Few data correlate these biomarkers with locoregional (LR) recurrence. METHODS: The authors retrospectively reviewed records of 635 patients with T1a,bN0 disease who received definitive treatment at their institution between 1997 and 2002 and had archival tissue blocks for prospective assessment of ER/PR expression. They compared clinical outcomes of the 479 patients with ER(+) /PR(+) disease to the 156 patients with ER(+) /PR(-) or ER(-) /PR(+) disease. RESULTS: LR recurrence rates were higher in patients with 1 receptor positive compared with ER(+) /PR(+) (7-year rate: 8.8% vs 2.5%, P = .024). There was no difference between the 2 groups in the rates of distant metastasis (DM) (P = .531) or overall survival (P = .491). One positive receptor predicted for LR recurrence in patients who did not receive hormonal therapy (P = .046), but not in patients who received hormonal therapy (P = .296). On multivariate analysis, 1 positive receptor predicted for LR recurrence in the overall group (hazard ratio, 2.81; 95% confidence interval, 1.06-7.48; P = .038). CONCLUSIONS: Patients with T1a,bN0 breast cancer with only 1 positive hormone receptor have increased rates of LR recurrence compared with patients with ER(+) /PR(+) disease, although this difference may be reduced or eliminated with systemic treatment. In contrast, the authors found no evidence of an increased rate of DM in these patients with favorable disease stage.

Langerhans cell histiocytosis of the cervical spine in an adult: a case report.

We present a case of a 47-year-old-woman with a complaint of cervical pain with paresthetic appearance on her left arm. She was treated with analgetics. Further radiological evaluation because of the persistent pain revealed an osteolytic destruction of the fourth cervical vertebra. The patient underwent anterior cervical corpectomy with total excision of the tumor. Stabilization of the cervical spine was performed. Histology confirmed the diagnosis of Langerhans cell histiocytosis (LCH) of the cervical spine. This case report presents the histopathological evaluation, diagnostic work-up and the treatment procedures because of rarity of cervical spinal LCH cases in the literature.

Papillary carcinoma arising in subhyoid ectopic thyroid gland with no orthotopic thyroid tissue.

Ectopic thyroid gland with no orthotopic thyroid tissue is extremely rare. The authors present a case of a follicular variant of papillary carcinoma developed from an ectopic thyroid gland with no orthotopic thyroid tissue.

Estrogen/progesterone receptor negativity and HER2 positivity predict locoregional recurrence in patients with T1a,bN0 breast cancer.

PURPOSE: Data have suggested that the molecular features of breast cancer are important determinants of outcome; however, few studies have correlated these features with locoregional recurrence (LRR). In the present study, we evaluated estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as predictors of LRR in patients with lymph node-negative disease and tumors < or = 1cm, because these patients often do not receive adjuvant chemotherapy or trastuzumab. METHODS AND MATERIALS: The data from 911 patients with stage T1a,bN0 breast cancer who had received definitive treatment at our institution between 1997 and 2002 were retrospectively reviewed. We prospectively analyzed ER/PR/HER2 expression from the archival tissue blocks of 756 patients. These 756 patients represented the cohort for the present study. RESULTS: With a median follow-up of 6.0 years, the 5- and 8-year Kaplan-Meier LRR rate was 1.6% and 5.9%, respectively, with no difference noted in those who underwent breast conservation therapy vs. mastectomy (p=.347). The 8-year LRR rates were greater in the patients with ER-negative (10.6% vs. 4.2%, p=.016), PR-negative (9.0% vs. 4.2%, p=.009), or HER2-positive (17.5% vs. 3.9%, p=0.009) tumors. On multivariate analysis, ER-negative and PR-negative disease (hazard ratio, 2.37; p=.046) and HER2-positive disease (hazard ratio, 3.13, p=.016) independently predicted for LRR. CONCLUSION: Patients with ER/PR-negative or HER2-positive T1a,bN0 breast cancer had a greater risk of LRR. Therapeutic strategies, such as the use of chemotherapy and/or anti-HER2 therapies, should be considered for future clinical trials for these patients.

High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller.

PURPOSE: To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer. METHODS: We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. RESULTS: Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor-positive tumors. CONCLUSION: Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

Identification and biologic significance of micrometastases in axillary lymph nodes in patients with invasive breast cancer.

CONTEXT: The presence or absence of metastases in axillary lymph nodes is one of the most important prognostic factors for patients with breast cancer. During the past decade sentinel lymph node (SLN) biopsy has been increasingly adopted as a minimally invasive staging alternative to complete axillary node dissection. OBJECTIVE: Sentinel lymph nodes are more likely to contain metastases than non-SLNs. In routine clinical practice SLNs are assessed by diverse methodologies including multiple sectioning, immunohistochemical staining, and molecular diagnostic tests. Despite the lack of standard histopathologic protocols during the years detailed evaluation of SLNs has resulted in an increased detection of small (micro) metastases. DATA SOURCES: Breast cancer with micrometastases constitutes a heterogenous group of tumors with variable clinical outcome regarding the risk of additional metastases in the remaining axillary lymph nodes and to patients' survival. CONCLUSION: The clinical significance of micrometastases has been subject to great controversy in patients with breast cancer. In this review we highlight controversies regarding micrometastases especially in relation to SLNs.

Prognostic significance of occult axillary lymph node metastases after chemotherapy-induced pathologic complete response of cytologically proven axillary lymph node metastases from breast cancer.

BACKGROUND: Primary systemic chemotherapy has been a standard of care for the management of locally advanced breast cancer (LABC) patients and has increasingly been used for patients with large operable breast cancer. Pathologic complete response (pCR) of axillary lymph node metastases predicted an excellent probability of long-term disease-free and overall survival. Although the clinical significance of occult lymph node metastases in patients with breast cancer was extensively studied, their prognostic value in patients with LABC after primary chemotherapy was not known. This study evaluated the detection rate and clinical significance of occult lymph node metastases in lymph nodes that contained metastatic carcinoma at the time of initial diagnosis and converted to negative based on routine pathologic examination after primary systemic chemotherapy. METHODS: Fifty-one patients with LABC and cytologically involved axillary lymph nodes that converted to negative after preoperative chemotherapy were identified from 2 prospective clinical trials. All lymph node sections were reviewed, 1 deeper level hematoxylin and eosin-stained section of each lymph node was obtained and immunohistochemical staining for cytokeratin (CK) was performed. A total of 762 lymph nodes were evaluated for occult metastases. Kaplan-Meier survival curves were used for calculating disease-free and overall survival times. RESULTS: Occult axillary lymph node metastases were identified in 8 of 51 (16%) patients. In 6 patients, occult metastases were found in only 1 lymph node. In 7 patients, only isolated CK-positive cells were identified. In all cases, occult carcinoma cells were embedded within areas of fibrosis, foreign body giant cell reaction, and extensive histiocytosis. Patients with occult lymph node metastases tended to have a higher frequency of residual primary breast tumors than those without occult metastases (4 of 8 vs 7 of 43, respectively). There was no statistically significant difference in disease-free or overall survival times between patients with and without occult metastases after a median follow-up 63 months. CONCLUSIONS: Persistent occult axillary lymph node metastases were not uncommon in patients with axillary lymph node-positive LABC who experienced a pCR in involved lymph nodes after preoperative chemotherapy. However, such occult metastases did not adversely affect the good prognosis associated with axillary lymph node pCR. Therefore, routine lymph node CK evaluation was not recommended after primary chemotherapy.

Breast myxoma: Radiologic and histopathologic features.

Myxomas are benign mesenchymal tumors, which rarely develop in the breast. Histologically, stellate, round, and spindle-shaped cells with vesicular nuclei and scant cytoplasm are scattered in the myxoid stroma. We present a case of this rare type of breast tumor with sonographic and mammographic findings.

Benign breast diseases: classification, diagnosis, and management.

Benign breast diseases constitute a heterogeneous group of lesions including developmental abnormalities, inflammatory lesions, epithelial and stromal proliferations, and neoplasms. In this review, common benign lesions are summarized and their relationship to the development of subsequent breast cancer is emphasized.

Hypertrophic cardiomyopathy: pathological features and molecular pathogenesis.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic cardiac disorder with various genotypic and phenotypic manifestations, and is often a diagnostic challenge. Although more than forty years have passed since the first description of HCM, a variety of mutations in genes encoding sarcomeric proteins, that cause the disease have been defined by laboratory and clinical studies over the past few years. The fact that HCM is the most common cause of sudden death in young competitive athletes and that, it is actually an important cause of morbidity and mortality in people of all ages, has made the researchers to concentrate more on the molecular basis and treatment strategies of the disease. This study aims to summarize both pathological features and rapidly evolving molecular genetics of HCM, and so to understand this not infrequently seen, complex disorder better.

Antinociceptive and neurotoxicologic screening of chronic intrathecal administration of ketorolac tromethamine in the rat.

UNLABELLED: Many drugs are tested intrathecally to investigate alternatives to opioids. We aimed to explore the analgesic and possible neurotoxic effects of chronic intrathecally-administered ketorolac tromethamine in rats. Catheters were placed via atlantoaxial interval in 28 Wistar rats under anesthesia of intraperitoneally-injected thiopental 30 mg/kg. Rats were randomized into 4 groups and administered 4 repeated intrathecal doses of therapy with 5-day intervals. The control group received 10 microL of saline, and the other groups received 50, 150, and 400 microg of ketorolac tromethamine respectively. The formalin test, behavioral test, and histopathological examination of four different spinal cord levels were performed. Neither behavioral testing nor histopathological examination revealed abnormalities that would suggest neurotoxicity. Formalin tests showed that both phase I and phase II responses of ketorolac tromethamine groups were significantly less than those of the control group. Although phase I responses did not differ during comparisons among ketorolac tromethamine-administered groups, phase II responses decreased significantly in groups that received 150 and 400 microg of ketorolac tromethamine. Intrathecally administered ketorolac tromethamine reduced nociceptive responses and exhibited no untoward neurological effect even at large doses. However, its intrathecal use as a safe alternative drug for chronic pain remains to be investigated in other species. IMPLICATIONS: The present study is unique because it has demonstrated that chronic intrathecal administration of ketorolac tromethamine in rats, even at considerably large doses, showed a potent analgesic effect during the formalin test without exhibiting any neurotoxic side effect.

Expression of p53 and mdm2 and their significance in recurrence of superficial bladder cancer.

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.

Expression of Bcl-2, Bax and p53 proteins in pituitary adenomas: an immunohistochemical study.

AIMS AND BACKGROUND: Although pituitary adenomas are usually benign lesions, their growth rate is highly variable and unpredictable. Apoptosis appears to be an important process in neoplastic lesions. The purpose of this study was to investigate the expression of apoptosis-related proteins including Bcl-2, bax and p53 in pituitary adenomas and its correlation with hormone function, tumor size, local control, and proliferative activity. STUDY DESIGN: The expression of Bcl-2, Bax and p53 proteins and hormonal function were determined in formalin-fixed, paraffin-embedded tissue from 41 untreated pituitary adenomas using immunohistochemistry. The patients were followed for a median of 60 months (range, 12 to 95). Patient charts were reviewed to record tumor recurrence and size. Tumor proliferative activity was assessed by immunohistochemistry using Ki-67 antibody. RESULTS: Of 41 pituitary adenomas, 26 (63%) were hormone-secreting and 15 (37%) non-functioning, 34 (83%) were macroadenoma and 7 (17%) microadenoma, and 15 (37%) showed local relapse. Six (14%) adenomas were of low proliferative activity, whereas the others (86%) were non-proliferative. Immunohistochemically, 31 adenomas (75%) showed bcl-2 positivity, 37 (90%) bax positivity, and 7 (17%) p53 positivity. Statistical analysis revealed that Bcl-2 protein expression significantly diminished in prolactin-secreting and non-functioning adenomas (P = 0.005 and P = 0.006, respectively), and increased in growth hormone-secreting adenomas (P = 0.003). In addition, expression of bax protein significantly decreased in recurrent tumors, in contrast to p53 protein, which showed a significant increase (P = 0.03 and P = 0.002, respectively). CONCLUSIONS: We think that apoptosis-related proteins such as Bcl-2, Bax and p53 may be significantly related to hormone function and local control in pituitary adenomas.