Fibroepithelial lesions of the breast: a comprehensive morphological and outcome analysis of a large series.

Mammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3-249 months). Positive final margin (tumor transected), age < 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age > 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.

Validation of the Singapore nomogram for outcome prediction in breast phyllodes tumours in a large patient cohort.

AIMS: To validate the Singapore nomogram for outcome prediction in breast phyllodes tumours in a large cohort of Singaporean patients, as previous validation studies were conducted on small numbers of patients. We also investigate the association of fibroadenomas and phyllodes tumours within a subset of our cohort. METHODS: Histological parameters, surgical margin status and clinical follow-up data of 259 women diagnosed with phyllodes tumours were analysed. Patients with concurrent malignant or premalignant disease were excluded from the validation to minimise confounding influences. Biostatistics modelling was performed, and the concordance between predicted and observed survivals was calculated. The association between fibroadenomas and phyllodes tumours was quantified in a subset of the women. RESULTS: Phyllodes tumours with higher number of mitoses, stromal overgrowth and positive surgical margins were found to be associated with greater risk of clinical recurrence. Patients with a higher nomogram score had a significantly higher risk of developing relapse. Forty out of 78 (51.3%) of the subset of phyllodes cases reviewed showed either fibroadenoma-like areas within the phyllodes tumours or concurrent fibroadenomas in the ipsilateral or contralateral breast. CONCLUSIONS: The Singapore nomogram is useful in predicting outcome in breast phyllodes tumours when applied to a large cohort of Singaporean women.

The Postoperative Immunosuppressive Phenotypes of Peripheral T Helper Cells Are Associated with Poor Prognosis of Breast Cancer Patients.

PURPOSE: T helper cells play essential roles in anti-tumor immune response. However, the postoperative changes of peripheral T cell subsets and their clinical significance in breast cancer patients remain largely unknown. METHODS: We evaluated the perioperative changes of T lymphocyte subsets in invasive breast cancer (IBC) patients and breast fibroadenoma (BF) patients preoperatively (preop) and 6, 24, 72 hours postoperatively (POH6, POH24, and POH72). Proportions of CD3, CD4, CD8, T helper (Th) 1, Th2, Th17 cells, regulatory T cells (Treg), and CD4+/CD8+, Th1/Th2 ratio were detected by flow cytometry. Changes in T helper cell quantity were correlated to clinicopathological parameters. Furthermore, we explored the association between the perioperative variations of T cell subsets and disease-free survival (DFS) of IBC patients. RESULTS: In IBC patients, Th1 cells diminished while Tregs elevated in postoperative 72 hours in the peripheral blood. In contrast, no significant perioperative changes of T cell subsets were observed in BF patients. Postoperative lower Th1 cells at POH 72 of IBC patients were correlated with greater tumor burden, HER2 positive and Ki67 positive. The increased Tregs at POH 72 of IBC patients were correlated with larger tumor size and HER2 positive. Th1 cell decline and Treg increment were both associated with shorter DFS in IBC patients. CONCLUSIONS: The variations of peripheral T helper cell subsets showed postoperative immunosuppression and were associated with poor prognosis in IBC patients.

Significance of TLR4/MyD88 expression in breast cancer.

OBJECTIVE: To investigate the expression of TLR4/MyD88 in breast cancer, and explore the relationship between their expression and breast cancer tumor growth and invasion. METHODS: We examined the protein expression of TLR4 and MyD88 in 60 cases of histologically confirmed breast cancer. The relationship of their protein expressions with clinical features including age at diagnosis, tumor size and stage, lymph node metastasis and distant metastasis were analyzed. RESULTS: The IHC results showed that TLR4 and MyD88 were expressed in 63.3% (38/60) and 58.3% (35/60) of malignant breast tumors respectively. TLR4 expression in breast cancer were significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissues (n = 2, 10.0%) (P < 0.001). MyD88 expression in breast cancer were also significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissue (n = 3, 15.0%) (P < 0.001). The gene expressions of TLR4 and MyD88 were significantly higher in breast cancer than in fibroadenoma and adjacent normal tissues (P < 0.05). The protein expressions of TLR4 and MyD88 were also significantly associated with poor clinical features (P < 0.05). CONCLUSION: TLR4 and MyD88 expression might be associated with breast cancer growth and regional and distant metastases.

Paediatric fibroepithelial lesions revisited: pathological insights.

AIM: To review the clinicopathological features of fibroepithelial neoplasms of the breast diagnosed by the paediatric pathology service in a children's hospital. METHODS: Files of the Department of Pathology and Laboratory Medicine, Kandang Kerbau Women's and Children's Hospital, were searched for breast fibroepithelial neoplasms diagnosed between January 2002 and December 2012. Tumour size and macroscopic findings were obtained from surgical pathology reports while clinical features were determined from clinical files. Histological slides were reviewed and microscopic parameters documented. Findings were tabulated and analysed using statistical methods. RESULTS: 68 fibroepithelial neoplasms from 53 female subjects were studied. There were 27 (39.7%) fibroadenomas, 32 (47.1%) juvenile fibroadenomas, 3 (4.4%) cellular fibroadenomas, 3 (4.4%) benign phyllodes tumours with the remaining 3 (4.4%) comprising benign fibroepithelial neoplasms with focal infarction and hybrid features. Half (50%) of the tumours possessed small leaf-like fronds and a majority had at least moderate stromal cellularity (83.8%). Most tumours had no discernible stromal mitoses with only 23.5% (16/68) having ≥1 mitoses per 10 high power fields. Many (79.4%) disclosed positive surgical margins. Recurrences occurred in 8 (11.8%) cases after excision. CONCLUSIONS: Most paediatric fibroepithelial tumours showed increased stromal cellularity which did not correlate with recurrence. Leaf-like fronds were commonly seen in paediatric fibroepithelial tumours apart from phyllodes tumours. Stromal mitoses were rare and may be a better criterion for predicting recurrence.

[Prognostic analysis of benign, borderline and malignant phyllodes tumors of the breast].

OBJECTIVE: To explore the prognosis of benign, borderline and malignant phyllodes tumors of the breast. METHODS: Data from 246 women with phyllodes tumors of the breast treated in the Cancer Hospital, Chinese Academy of Medical Sciences between January 2002 and December 2012, were collected and analyzed retrospectively. The patients were followed-up for a median of 48 months (range 1-138 months). Kaplan-Meier analysis and Cox proportional hazard model were used to analyze the factors affecting the disease-free survival. RESULTS: Among the 246 patients, 65 were dropped out from the follow-up. 56 patients had local recurrence, 5 patients had distant metastasis, while one case had both local recurrence and distant metastasis. The median disease-free survival time was 39 months. Kaplan-Meier survival analysis revealed that fibroadenoma history and type of primary surgery were associated to the disease-free survival of phyllodes tumors of the breast (P<0.001, P=0.043), while histological type and primary tumor size had no significant relationship with the disease-free survival (P=0.083, P=0.974). The multivariate Cox proportional hazard model showed that type of primary surgery, fibroadenoma history and histological types are all independent factors affecting the disease-free survival (P=0.009, P=0.001 and P<0.001). CONCLUSION: Phyllodes tumors of the breast have a relatively good prognosis on the whole. Type of primary surgery, fibroadenoma history and histological type are independent factors predicting the disease-free survival of patients with phyllodes tumors of the breast.

Oncoplastic surgery in breast conservation: a prospective evaluation of the patients, techniques, and oncologic outcomes.

BACKGROUND: The oncologic efficacy of breast-conserving therapies has been established in recent decades. Oncoplastic breast surgery (OBS), as a leap forward in breast conservation, offers concomitant techniques of oncologic and plastic surgeries that grant better esthetic results. The outcomes of our oncoplastic surgeries from 2007 to 2012 are reported. METHODS: A series of 258 cases with breast masses (18 benign and 240 carcinomas) were operated on by OBS techniques and prospectively followed. Neoadjuvant and adjuvant oncologic treatments were also delivered as indicated. RESULTS: Free margins were obtained in 95% of cancer patients. During the 26 months of follow-up, local recurrence happened in 7 (2.9%) patients, of which 1 underwent oncologic therapies and 6 underwent completion mastectomy. Complications postponed adjuvant therapies in 3 (1.2%) patients. Postsurgically, metastases were diagnosed in 8 (3.3%) patients. Two patients (.8%) died of cancer. CONCLUSIONS: Outcomes of OBS are oncologically acceptable with low frequencies of positive margins and recurrence, while cosmetic results are much improved by OBS.

Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats.

BACKGROUND/AIM: This study examines the chemopreventive potential and action of the herb black cohosh on Sprague-Dawley rats. MATERIALS AND METHODS: Female Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 (Group I), 7.14 (Group II), 0.714 (Group III) or 0 mg/kg b.w. for 40 weeks starting from 56 weeks of age and the incidence of benign and malignant mammary tumors was determined at the end of observation. RESULTS: Among female rats treated at 35.7 and 7.14 mg/kg b.w. there was a dose-related reduction (p<0.05) of the incidence of mammary adenocarcinomas when compared to the treatment of 0.714 mg/kg b.w., with a protection index (calculated relative to the group III; PI=[total tumours × 100 animals of group III] - [total tumours × 100 animals of the group I (or group II)]/ [total tumours of group III] × 100) for mammary adenocarcinomas of 87.5 and 48.8%, respectively. Black cohosh reduced Ki-67 and cyclin D1 protein expression in fibroadenomas, by immunohistochemistry. CONCLUSION: Our results suggest that black cohosh may have chemopreventive potential for mammary cancer.

Malignant transformation of breast fibroadenoma to malignant phyllodes tumor: long-term outcome of 36 malignant phyllodes tumors.

BACKGROUND: Malignant phyllodes tumor of the breast is a rare neoplasm for which clinical findings remain insufficient for determination of optimal management. We examined the clinical behavior of these lesions in an attempt to determine appropriate management. We evaluated long-term outcome and clinical characteristics of malignant phyllodes tumors arising from fibroadenomas of the breast. METHODS: A total of 173 patients were given a diagnosis of phyllodes tumor and underwent surgery at the Cancer Institute Hospital in Japan between January 1980 and December 1999. Of these patients, 39 (22.5%) were given a diagnosis of malignant phyllodes tumor; in three of these cases, detailed medical records were lost. Malignant phyllodes tumors were classified into two groups based on history of malignant transformation. Of the 36 malignant cases, 11 (30.6%) were primary and were given a diagnosis of fibroadenoma, experienced recurrence during the follow-up period, and were diagnosed with malignant phyllodes tumor (cases with a history of fibroadenoma). The other group was defined as cases without history of fibroadenoma and in whom lesions initially occurred as malignant phyllodes tumors. Based on differences between the two groups, overall survival curves were plotted using the Kaplan­Meier method, and statistical comparisons were performed using the log-rank test and Peto and Peto's test. RESULTS: The outcome of cases with history of fibroadenoma was significantly better than that of cases without history of fibroadenoma. CONCLUSIONS: Patients with malignant phyllodes tumors but without prior history of malignant transformation who exhibit rapid growth within 6 months require aggressive treatment.

Breast cancer mimicking fibroadenomas in postmenopausal women.

INTRODUCTION: Fibroadenomas (FADs) are benign breast lesions usually seen in late teens less so common in postmenopausal women. This is a case series of postmenopausal patients, where breast cancer looked like fibroadenoma on imaging. The aim of this study was to identify the important role of tissue diagnosis in FAD like lesions on imaging and highlight the deceiving imaging findings. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients at our Breast unit who were treated for breast cancer under one surgeon in the period of Feb 2009 to Jan 2010. Patients underwent triple assessment as per protocol of the breast screening unit. All had fine needle aspiration and core biopsy of the lesions. Appropriate surgery was offered and the size, grade and lymph node status were evaluated and Nottingham Prognostic Index (NPI) used to predict survival. RESULTS: 5 patients were identified with breast cancers that had initial radiological diagnosis of fibroadenoma. All patient lesions were screen detected on NHS screening programme. One patient out of five was discharged after triple assessment and represented with a lump 18 months later. The Median age was 56 years (range 50-66 years). The mammogram showed these to be benign-looking lesions and ultrasound scans suggested fibroadenomas as reported by specialist breast radiologist. Seven lesions were identified in 5 patients. One patient had 3 lesions. Lesions size ranged between 8 mm and 25 mm on mammogram (median 14 mm) and 8-20 mm on ultrasound (range 8-20). Fine needle aspiration cytology was C5 in the two lesions, C4 in 2 and C3 in 1 lesion. Two patients had unifocal grade 3 tumours. One patient had multifocal cancer (3 cancers - in unilateral breast) all were grade 3 cancers with lymph node involvement. One patient had grade 2 cancer and 1 was found to have adenoid cystic adenocarcinoma and therefore the grade and NPI were not assessed. NPI was good in 1, moderate in 2 and poor in 1 patient. CONCLUSION: Our case series suggested that one should have a high index of suspicion for FAD in the postmenopausal ladies and triple assessment should include thorough tissue sampling in the form of FNA and core biopsy.

IgG immune response to tumor-associated carbohydrate antigens (TF, Tn, alphaGal) in patients with breast cancer: impact of neoadjuvant chemotherapy and relation to the survival.

AIM: To study the humoral immune response to tumor-associated carbohydrate epitopes (TF, Tn and alphaGal) in patients with breast cancer and healthy donors, the putative impact of the chemotherapy and to evaluate if the level of antibody to these epitopes might be beneficial or detrimental for the patients with breast cancer. MATERIALS AND METHODS: The humoral immune response to TF, Tn and alphaGal was studied in 133 patients with breast cancer, including the patients at stage II-III (n = 44) before and after neoadjuvant chemotherapy (10 patients received cyclophosphamide/methotrexate/fluorouracyl (CMF) chemotherapy regimens, 34 patients received cyclophosphamide/doxorubicin/fluorouracil (CAF)), and in controls (healthy donors and patients with fibroadenoma). Fully synthetic carbohydrate hapten-polyacrylamide conjugates were used as antigens in ELISA for anti-carbohydrate antibody determination. The correlation analysis between the level of anti-carbohydrate antibodies and the stage of cancer, histological grade, expression of TF and alphaGal epitopes in tumor tissue, patient's survival was performed. RESULTS: The level of anti-carbohydrate antibodies varied between individuals with no significant correlation between IgG immune response to the three epitopes. Lower levels of antibodies were observed at advanced stages of cancer. Neoadjuvant chemotherapy stimulated antibody production to Tn and alphaGal epitopes (increase > 50%) in about one third of patients. Immunosuppression, decrease in antibody levels, was observed only in 4.5-13.6% of cases. High levels of TF-antigen specific IgG antibody before surgery were associated with a better survival time of stage II breast cancer patients. CONCLUSION: The widely used regimens of neoadjuvant chemotherapy (such as CMF, CAF) can stimulate the immune response to tumor-associated carbohydrate epitopes in some patients. The high levels of anti-TF antibody before surgery are associated with a better survival of stage II breast cancer patients. This may indicate that the selection of immunopotentiating regimens of neoadjuvant chemotherapy might be beneficial for the host.

Apoptotic index: use in predicting recurrence in breast cancer patients.

Apoptosis maintains tissue homeostasis through its ability to control cell population and has been extensively studied in human cancers. Relation of apoptosis to prognosis is still controversial. In this study, we analyzed the prognostic significance of apoptotic and mitotic indices (AI & MI) using hematoxylin and eosin stained slides by light microscopy in breast cancer patients. In our study, apoptotic index was significantly associated with predicting relapse free survival (RFS), distant recurrence free survival (DRFS) and overall survival (OS) with lesions having higher apoptotic index showing poor prognosis. Our results also point out that quantitation of apoptotic index by simple light microscopy as a routine practice along with histological diagnosis, could provide additional prognostic information in patients who are at high risk of developing recurrence with breast cancers.

p53 expression in phyllodes tumours is associated with histological features of malignancy but does not predict outcome.

AIMS: To study p53 protein expression in phyllodes tumours of the breast, with particular attention to its prevalence and to its relationship with histological features and clinical outcome. METHODS AND RESULTS: Stromal and epithelial p53 immunohistochemical expression was studied in 57 phyllodes tumours (27 benign, 17 borderline, 13 malignant) using an avidin-biotin peroxidase method. High levels of expression (> 30% of stromal nuclei) were found in eight phyllodes tumours (14%). p53 expression was associated with tumour grade (P = 0.001), prominent stromal overgrowth (P = 0.0003), prominent stromal nuclear pleomorphism (P = 0.006), high stromal mitotic count (P = 0.05), and an infiltrative tumour margin (P = 0. 05). Six patients were lost to follow-up after surgery. Mean follow-up time of the remaining 51 patients was 7.3 years (median 4. 3, range 0.5-25) or until death. Sixteen patients (31%) experienced tumour recurrence. Recurrence was more likely if there was an infiltrative tumour margin (P = 0.006) or prominent stromal overgrowth (P = 0.04) but not p53 expression (P = 0.55). A minority of recurrences expressed p53 more extensively than their primary counterparts. There were five tumour-related deaths (10% of patients). Death was associated with high grade (P = 0.0002), prominent stromal overgrowth (P = 0.0001), an infiltrative margin (P = 0.0002), prominent nuclear pleomorphism (P = 0.005), a high mitotic count (P = 0.01) and tumour size (P = 0.03). Again, p53 expression was not associated with tumour-related survival (P = 0. 13). CONCLUSIONS: p53 abnormalities occur in a minority of borderline and malignant phyllodes tumours. p53 expression is associated with known negative prognostic factors, but does not appear to be a useful determinant of tumour recurrence or long-term survival.

Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in F344/N rats.

A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in rats. Groups of 100 male and 100 female F344/N rats were exposed continuously to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female F344/N rats received intermittent (1 hr on/1 hr off) exposure to 10 G fields. Mortality patterns, body weight gains throughout the study, and the total incidence and number of malignant and benign tumors in all groups exposed to magnetic fields were similar to those found in sex-matched sham controls. Statistically significant increases in the combined incidence of C-cell adenomas and carcinomas of the thyroid were seen in male rats chronically exposed to 20 mG and 2 G magnetic fields. These increases were not seen in male rats exposed continuously or intermittently to 10 G fields or in female rats at any magnetic field exposure level. No increases in the incidence of neoplasms, which have been identified in epidemiology studies as possible targets of magnetic field action (leukemia, breast cancer, and brain cancer), were found in any group exposed to magnetic fields. There was a decrease in leukemia in male rats exposed to 10 G intermittent fields. The occurrence of C-cell tumors at the 2 lower field intensities in male rats is interpreted as equivocal evidence of carcinogenicity; data from female rats provides no evidence of carcinogenicity in that sex. These data, when considered as a whole, are interpreted as indicating that chronic exposure to pure linearly polarized 60 Hz magnetic fields has little or no effect on cancer development in the F344/N rat.

Global DNA hypomethylation in breast carcinoma: correlation with prognostic factors and tumor progression.

BACKGROUND: The global DNA methylation of 136 breast lesions (117 primary invasive carcinomas, 5 benign phyllodes tumors, 11 fibroadenomas, and 3 sclerosing adenosis) and their respective adjacent parenchyma was analyzed using an in vitro enzyme assay. METHODS: In the group of patients with breast carcinoma, DNA hypomethylation was correlated with clinical and pathologic parameters known to affect disease prognosis. Histopathologic type, disease stage, and tumor grade were evaluated according to the World Health Organization classification, the TNM system, and the criteria of Elston and Ellis' criteria, respectively. DNA flow cytometry was performed in fresh/frozen samples stained with propidium iodide. Hormone receptor (estrogen and progesterone receptor) status was determined by immunocytochemistry. RESULTS: The comparative study of DNA methylation showed that the DNA of breast carcinomas was statistically significantly less methylated than the DNA of the respective adjacent parenchyma (P=0.0001), the DNA of breast benign lesions (P=0.0002), and the DNA of normal parenchyma (P < 0.0001). A statistically significant correlation was found between the global DNA hypomethylation and the disease stage (P=0.0009), tumor size (P=0.0026), and histologic grade (P=0.0097) of malignant neoplasms. A trend for DNA from breast carcinomas with positive axillary lymph nodes (N1) to be more hypomethylated than those without nodal involvement (NO) (P=0.055) was verified. In contrast, no significant association was found between DNA methylation and histologic type of tumors, hormone receptors, DNA ploidy, and S-phase fraction. CONCLUSIONS: The current shows that DNA hypomethylation is increased in breast carcinomas, playing a potentially important role in tumor development. These findings also suggest that DNA methylation status may be a biologic marker with prognostic significance in this group of neoplasms.

Experimental studies on the long-term effects of methylphenidate hydrochloride.

Toxicology and carcinogenesis studies of methylphenidate hydrochloride, a drug used in the treatment of attention-deficient disorders, were performed in F344 rats and B6C3F1 mice. In these studies, methylphenidate hydrochloride was administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats and at doses of 0, 50, 250, 500 ppm to mice in groups that consisted of 50 animals/dose/sex/species. The average amount of methylphenidate consumed per day was estimated to be 4-47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival was similar in dosed and control groups. An increase in benign tumors of the liver and increased liver weights were observed in male and female mice at the high dose. An increase in hepatoblastomas was also seen in high dose male mice. Methylphenidate was not mutagenic in the Salmonella assay system, and it is hypothesized that this tumorigenic effect might be due to nongenotoxic effects of the chemical such as an increase in cell proliferation. Increased incidences of neoplasms were not seen in rats. However, there was a notable decrease in mammary gland fibroadenomas in female rats and a marginal decrease in benign pheochromocytomas in male rats. Epidemiology studies of methylphenidate have found no evidence of a carcinogenic effect in humans and like our findings in rats, report a less than expected rate of cancers in patients taking methylphenidate.

Non-operative management of breast masses diagnosed as fibroadenoma.

A 7-9-year study was undertaken in 99 female patients (median age 20 years), 56 of whom had single and 43 multiple fibroadenomas (total 279). Thirty-four women with 58 masses (21 per cent) were lost to follow-up. Twenty-eight women with 73 masses (26 per cent) subsequently underwent excision at a median of 10 (range 3-59) months for single and 38 (1-110) months for multiple fibroadenomas (P = 0.03), with histological confirmation in 71 and other benign disease in two cases. There was resolution of 107 masses (38 per cent of those entered into the study, 72 per cent of those not lost or excised), leaving 41 persisting masses (15 per cent of those entered into the study, 28 per cent of those not lost or excised). The actuarial probability of disappearance was 0.46 at 5 years and 0.69 at 9 years (Kaplan-Meier analysis). There was no difference in the rate of resolution when 56 single lesions were compared with 223 multiple lesions, or when 192 lesions measuring 2 cm or less in diameter were compared with 87 greater than 2 cm. Resolution was significantly more frequent in women aged 20 years or less than in those who were older (P < 0.01). Non-operative management remains a safe approach in selected women and should be followed by resolution of half of fibroadenomas at 5 years.

Effect of surgical removal of subcutaneous tumors on survival of rats.

Mammary and other subcutaneous tumors were surgically removed from aged Sprague-Dawley rats in an attempt to extend survival. The surgical technique was straightforward, and survival following mastectomy was good (17/21). The number of mammary and pituitary tumors in sexually intact rats and those that had previously undergone ovariectomy were compared. The frequency of mammary tumors was significantly lower in ovariectomized vs sexually intact rats (2/47 vs 24/49), as was the frequency of pituitary adenomas (2/46 vs 27/41). Survival to 630 days of age was higher in ovariectomized than in sexually intact rats (42/47 vs 29/49), although tumors did not contribute significantly to mortality.

[Tumoral vascular density in breast tumors and their effect on recurrence-free survival]. / Tumorale Gefässdichte bei Mammatumoren und ihr Einfluss auf das rezidivfreie Uberleben.

Angiogenesis quantitation of 106 patients with primary breast cancer and 35 patients with adenofibroma of the breast was compared and examined to its prognostic relevance for five-years disease-free survival in breast cancer patients. Immunocytochemical staining for Factor VIII-related antigen was performed to outline vascular endothelium. We found a significant higher vessel density in breast cancer patients who experienced recurrence (17.4) than in those with no recurrence (9.4) or with adenofibroma (8.7) [p < 0.0001]. The probability of five-years recurrence-free survival for patients with a primary tumor of high vessel density was at 52.3% and 86.4% for tumors of low microvessel density (p < 0.0011). Microvessel density proved to be an independent prognostic factor for breast cancer recurrence in the Cox-Model (relative risk 2.047, p = 0.0002).