Tumour markers in breast carcinoma correlate with grade rather than with invasiveness. (49/1031)

Ductal breast carcinoma in situ (DCIS) is regarded as a precursor to invasive breast cancer. The progression from in situ to invasive cancer is however little understood. We compared some tumour markers in invasive and in situ breast carcinomas trying to find steps in this progression. We designed a semi-experimental setting and compared histopathological grading and tumour marker expression in pure DCIS (n = 194), small invasive lesions (n = 127) and lesions with both an invasive and in situ component (n = 305). Grading was done according to the Elston-Ellis and EORTC classification systems, respectively. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, ER, PR, bcl-2 and angiogenesis. All markers correlated with grade rather than with invasiveness. No marker was clearly associated with the progression from in situ to invasiveness. The expression of tumour markers was almost identical in the 2 components of mixed lesions. DCIS as a group showed a more 'malignant picture' than invasive cancer according to the markers, probably, due to a higher proportion of poorly differentiated lesions. The step between in situ and invasive cancer seems to occur independently of tumour grade. The results suggest that well-differentiated DCIS progress to well-differentiated invasive cancer and poorly differentiated DCIS progress to poorly differentiated invasive cancer.  (+info)

Studies of epidermal growth factor receptor inhibition in breast cancer. (50/1031)

Until recently, there has been little knowledge on the growth control of oestrogen receptor (ER)-negative ductal carcinoma in situ (DCIS) and invasive breast cancer. The recent development of DCIS models, such as transgenic mice, cell-line xenograft models and, importantly, in vivo human DCIS xenograft models has facilitated the investigation and understanding of the control of growth of early pre-invasive breast lesions. Recent studies have shown that ER-negative DCIS, unlike ER-positive DCIS, is hormone independent and does not respond to anti-oestrogen treatment. Moreover, DCIS of the comedo type utilises type I tyrosine kinase growth factors, such as epidermal growth factor receptor (EGFR) and c-erbB-2, in receptor signalling for growth. New data underscore the importance of EGFR as the major modulating growth factor receptor in the control of proliferation in the breast. Pre-clinical studies performed on human DCIS xenografts in nude mice suggest a potential role for EGFR tyrosine kinase inhibitors (EGFR-TKIs). More specifically, ZD1839, a novel orally active and selective EGFR-TKI, has been shown to produce a response in DCIS through a decrease in epithelial proliferation. These findings have enhanced our knowledge of signal transduction pathways in cancer and indicate that tyrosine kinase blockade of EGFR has potential for the treatment and chemoprevention of DCIS. It is hoped that further advances in this area and evaluation of EGFR-TKIs in Phase II/III clinical trials will allow their therapeutic potential as anticancer agents to be appreciated.  (+info)

Correlation of nuclear morphometry with pathologic parameters in ductal carcinoma in situ of the breast. (51/1031)

Morphometric features of nuclear perimeter, nuclear area, feret ratio, and feret circle were studied in a series of 64 cases of ductal carcinoma in situ (DCIS) of the breast in Singapore women. The results were compared with pathologic parameters of tumor size, nuclear grade, necrosis, cell polarization, and architectural pattern. There was statistically significant correlation between nuclear perimeter and area with all the pathologic parameters, with the strongest association observed for nuclear grade (P <.0001). Higher grade nuclei as assessed histologically were associated with larger nuclear area (44.14 microm(2) in low-grade lesions, 47.77 microm(2) in intermediate-grade lesions, and 72.05 microm(2) in high-grade lesions) and perimeter (25.94 microm in low-grade nuclei, 27.12 microm in intermediate-grade nuclei, and 33.66 microm in high-grade nuclei). DCIS lesions with necrosis and absence of polarization also revealed increased nuclear area and perimeter (P <.05). Comedo architecture was associated with larger nuclear area and perimeter (65.97 microm(2), 31.7 microm) than the papillary subtype (42.17 microm(2), 25.29 microm), with the mixed morphologic pattern disclosing intermediate values (54.83 microm(2), 29.43 microm). There was direct correlation for tumor size with nuclear area and perimeter (P <.01). No similar relationship was found between pathologic parameters and feret ratio or circle, indicating that nuclear roundness or lack of it did not factor as a significant component in the pathologic assessment.  (+info)

Association of breast cancer with meningioma: report of a case and review of the literature. (52/1031)

We report a case of meningioma subsequently developed in a patient with primary breast carcinoma. A 53-year-old woman received a left modified radical mastectomy because of stage IIA breast carcinoma. Histologically, the tumor was a predominantly intraductal carcinoma with negative lymph node metastasis. Estrogen receptor (ER) was negative but progesterone receptor (PR) of the left tumor was positive by immunohistochemistry. Four years later, cranial bone and/or brain metastasis was suspected from a routine follow-up bone scintigram. The patient showed no symptoms or signs at that time. Magnetic resonance imaging (MRI) and angiography revealed that the right parasagittal mass was suspicious of meningioma. A complete tumor removal was performed. On histological examination, this brain tumor was a transitional-type meningioma (meningotheliomatous and fibrous type) without malignant findings. ER was negative but PR was positive also in this tumor. She is currently well 6 years after the initial surgery. A review of the literature is presented with emphasis on the association between breast cancer and meningioma, which indicates a possible hormonal relationship. The knowledge of this association is important in the differential diagnosis of patients with breast cancer who develop central nervous manifestations.  (+info)

Surfactant protein A expression in human normal and neoplastic breast epithelium. (53/1031)

We studied the presence of surfactant protein A (Sp-A) immunoreactivity and messenger RNA in 62 normal and abnormal breast samples. Sections were immunostained with polyclonal anti-Sp-A antibody. The association between Sp-A immunoreactivity and histologic grade of 32 invasive ductal carcinomas was assessed by 3 pathologists who scored the intensity of Sp-A immunoreactivity times the percentage of tumor immunostained; individual scores were averaged, and the final scores were correlated with tumor grade, proliferative index, and expression of estrogen and progesterone receptors. Strong Sp-A immunoreactivity was present at the luminal surface of ductal epithelial cells in normal breast samples and in benign lesions; carcinomas displayed variable immunoreactivity, inversely proportional to the degree of differentiation. Sp-A messenger RNA was detected by reverse transcriptase-polymerase chain reaction in 3 of 3 normal breast samples and 9 of 9 carcinomas. The significance of Sp-A expression in breast epithelium requires further study; possibly it has a role in native host defense or epithelial differentiation.  (+info)

Breast carcinoma in situ: risk factors and screening patterns. (54/1031)

BACKGROUND: Risk factors associated with invasive breast cancer are well documented, but those associated with breast carcinoma in situ are not well defined. METHODS: We conducted a population-based, case-control study among female residents of Connecticut to identify risk factors for breast carcinoma in situ. Case patients, diagnosed with ductal carcinoma in situ (DCIS) (n = 875) or lobular carcinoma in situ (LCIS) (n = 123), were matched by 5-year age groups with control subjects (n = 999). Case patients were diagnosed between September 15, 1994, through March 14, 1998, and all subjects were between the ages of 20 and 79 years. Information on risk factors and cancer-screening history was collected by telephone interviews. Conditional logistic regression was used to determine odds ratios (ORs) for the association of these factors with the risk of DCIS and LCIS. RESULTS: Case patients with DCIS were more likely than control subjects to report a family history of breast cancer (OR = 1.48; 95% confidence interval [CI] = 1.19 to 1.85) or previous breast biopsy (OR = 3.56; 95% CI = 2.86 to 4.43). They also had fewer full-term pregnancies (OR = 0.86; 95% CI = 0.80 to 0.93) and were older at first full-term pregnancy (OR for being 20-29 years old relative to being <20 years old = 1.68; 95% CI = 1.17 to 2.43) and at menopause (OR for being > or =55 years old relative to being <45 years old = 1.71; 95% CI = 1.05 to 2.77). DCIS case patients were more likely than control subjects to have had a mammographic examination (OR = 2.46; 95% CI = 1.78 to 3.40) or an annual clinical breast examination (OR = 1.83; 95% CI = 1.48 to 2.26). DCIS patients and control subjects did not differ with respect to oral contraceptive use, hormone replacement therapy, alcohol consumption or smoking history, or breast self-examination. Associations for LCIS were similar. CONCLUSIONS: The risk factors associated with DCIS and LCIS are similar to those associated with invasive breast cancer. Diagnosis of DCIS is associated with increased mammography screening.  (+info)

Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma. (55/1031)

Overexpression of the HER-2/neu oncogene appears to have prognostic significance in breast cancer. Recently, some have reported a relationship between increased immunohistochemical expression in osteosarcoma and poor clinical outcome. Despite limited data, a pilot trial of Herceptin, which targets the oncogene product, has been initiated for the therapy of some metastatic osteosarcomas (CCG-P9852). Archival formalin-fixed, paraffin-embedded tissue obtained from 41 patients diagnosed with osteosarcoma was examined immunohistochemically by 2 antibodies against the HER-2/neu oncogene product: CB-11 (monoclonal, 1/100) and Oncor (polyclonal, 1/200). All but one tumor (case of recurrent dedifferentiated parosteal osteosarcoma) represented primary tumor samples; when applicable, only prechemotherapy biopsies were analyzed. The study sample included the full spectrum of histologic subtypes and grades of osteosarcoma (25 conventional high grade; 3 telangiectatic; 1 small cell; 6 parosteal; 1 periosteal; and 5 low-grade intramedullary). A case of metastatic breast cancer with known overexpression of the HER-2/neu oncogene served as the positive control. Complete membranous positivity, considered prognostically significant in breast cancer, was not seen in any of our osteosarcoma cases. At least focal cytoplasmic positivity was documented in 40 (98%) tumors using the CB11 antibody and in 34 (83%) using the Oncor antibody. The intensity of the cytoplasmic staining (0, 1-3+) did not correlate with histologic subtype/grade, response to chemotherapy (<90% versus > or = 90% necrosis), metastasis, or survival. Immunohistochemical overexpression of the HER-2/neu oncogene, defined as complete membranous positivity, is not present in our series of osteosarcomas. Cytoplasmic positivity is observed in most osteosarcomas, irrespective of histologic subtype/grade, and is not associated with response to preoperative chemotherapy or disease progression.  (+info)

Nipple aspirate cytology and pathologic parameters predict residual cancer and nodal involvement after excisional breast biopsy. (56/1031)

We previously demonstrated that abnormal nipple aspirate fluid (NAF) cytology predicted residual breast cancer (RC) and tumour size after excisional biopsy (EB), although normal NAF cytology did not exclude RC. Tumour size correlates with the risk of lymph node (LN) metastases. LN metastases provide prognostic information allowing medical and radiation oncologists to determine the need for adjuvant therapy. We hypothesized that pathologic factors known after EB, combined with NAF cytology, would predict with a high degree of accuracy the presence of RC and LN spread. NAF cytology and pathologic parameters: tumour distance from biopsy margins, multifocal and multicentric disease, sub-type of ductal carcinoma in situ (DCIS) or invasive cancer (IC), grade of DCIS or IC, tumour and specimen size, tumour and biopsy cavity location, presence or absence of extensive DCIS, and biopsy scar distance from the nipple were evaluated bivariately and then by logistic regression (LR) for their association with RC and involved LN (> or = 1 (+) LN, useful to determine chemotherapy need, and > or = 4 (+) LN, useful to determine radiation need to the chest and axilla). Data were analysed using NAF cytology alone, pathologic parameters alone, and NAF cytology and pathologic parameters combined. The combined LR model was superior in predicting residual cancer (94%) to LR models using NAF cytology (36%) or pathologic parameters (75%) alone. When only subjects with normal NAF cytology were evaluated by LR, the model was 92% sensitive in predicting RC. Tumour size and NAF cytology predicted which patients had > or = 1 (+) LN, whereas tumour and specimen size predicted which patients had > or = 4 (+) LN. We propose an algorithm which, if confirmed in a larger study, may allow clinicians to be more selective in their recommendations of re-excision breast biopsy or mastectomy.  (+info)