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R R Millis

Publications and source records attributed to R R Millis.

At least 73 records · Page 4Linked to original sources
PubMed1991

Sclerosing lymphocytic lobulitis of the breast--evidence for an autoimmune pathogenesis.

We describe 13 cases of inflammatory lesion of breast lobules in young and middle-aged women, presenting as breast lumps, with, in five cases, associated breast pain. The patient with the most florid bilateral disease subsequently developed Hashimoto's thyroiditis. This prompted us to consider an autoimmune pathogenesis for all the breast lesions. We confirm a previously documented association of such breast lesions with diabetes mellitus and review the evidence for a possible HLA association. Increased HLA-DR expression by breast epithelial cells was observed in cases available for study. Of the seven patients screened for circulating autoantibodies, three had none, one had smooth muscle antibodies, one parietal cell, one parietal cell and thyroid microsomal, and the seventh had the thyroid autoantibodies expected in Hashimoto's disease. Five of seven patients whose HLA-status was determined were HLA-DR3, 4 or 5 positive, either singly or in combination. Immunophenotypic analysis of the mammary lymphoid infiltrate showed that the majority of infiltrating lymphocytes were B-cells.

Autoantibodies↗
PubMed1990

S100 protein in human mammary tissue--immunoreactivity in breast carcinoma, including Paget's disease of the nipple, and value as a marker of myoepithelial cells.

The expression of S100 protein, as assessed by immunohistochemistry, has been evaluated in 101 mammary carcinomas of various histological types, including Paget's disease of the nipple. S100 immunoreactivity was seen in 44 of 101 primary carcinomas, including in situ lesions. It was present in all histological types, with the exception of mucoid carcinoma. In the 33 cases with associated Paget's disease of the nipple, S100 expression was seen in the Paget's cells in six cases. S100 immunoreactivity has been suggested as a marker of myoepithelial cells, but in our hands staining of these cells is less consistent using the S100 antibody than with antibodies to actin. Furthermore, S100 protein is also expressed by some luminal epithelial cells. Therefore, in contrast to actin immunoreactivity, S100 immunoreactivity is not a reliable means of differentiating between luminal epithelial and myoepithelial cells. The possibility that staining with antibody to S100 protein may be affected by methods of fixation and immunohistochemical technique is discussed.

Biomarkers, Tumor↗
PubMed1990

Immunohistochemical demonstration of c-erbB-2 protein in mammary ductal carcinoma in situ.

The presence of the c-erbB-2 protein, demonstrated immunohistochemically with antibody 21N, has been studied in 72 cases of pure mammary ductal carcinoma in situ. Sixty-one percent of cases showed positive staining. The protein was always present in large-cell comedo type of ductal carcinoma in situ, and never in small-cell cribriform/micropapillary type of ductal carcinoma in situ. When nuclear size was measured, staining was associated with tumors containing cells with large nuclei measuring up to 20 mu, and was never present in lesions containing cells with small nuclei measuring 10 mu or less. In tumors of mixed histopathologic type of ductal carcinoma in situ, variable staining was seen; the cells with small nuclei never stained, while the majority of cells with large nuclei reacted positively. The possible relevance of these findings to the biologic behavior of DCIS is discussed.

Breast Neoplasms↗
PubMed1990

Proliferative activity, histological grade and benefit from adjuvant chemotherapy in node positive breast cancer.

The influence of S-phase fraction (SPF), measured by DNA flow cytometry, and histological grade on outcome following adjuvant chemotherapy was analysed for 214 patients with node positive breast cancer treated at Guy's Hospital who were entered into the Guy's/Manchester trial of combination chemotherapy with cyclophosphamide/methotrexate/5-fluorouracil (CMF) vs. no adjuvant treatment. Adjuvant CMF significantly improved relapse-free survival (RFS) for premenopausal patients whose tumours had an SPF of 10% or less (control vs. CMF, P = 0.05) and premenopausal patients whose tumours had an SPF over 10% (control vs. CMF, P = 0.003). No significant improvement in RFS attributable to CMF was seen for either subgroup of postmenopausal patients. When patients were divided into subgroups based on histological grade of tumour, an improvement in RFS attributable to CMF was seen for premenopausal patients with well differentiated (grade 1 or 2) tumours (control vs. CMF, P = 0.03) and premenopausal patients with poorly differentiated (grade 3) tumours (control vs. CMF, P = 0.006). Again, no improvement in RFS was noted for any subgroup of postmenopausal patients defined by tumour grade.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

DNA index, S-phase fraction, histological grade and prognosis in breast cancer.

DNA index and S-phase fraction (SPF) were measured by flow cytometry on paraffin embedded tissue from 140 primary breast tumours. The results of DNA analysis were compared with the size, degree of axillary node involvement, histological grade and steroid receptor content of the tumours, as well as with the patients' subsequent clinical course. Forty-four (31.4%) of the 140 tumours were diploid. S-phase fraction was evaluable for 134 (95.7%). The median SPF of the whole population was 7.1%, with diploid tumours having a significantly lower median SPF (3.2%) than aneuploid (10.1%, P less than 0.001). Both aneuploidy (P = 0.002) and high SPF (P less than 0.001) were strongly associated with high histological grade. There was no significant association between either DNA ploidy or SPF and tumour size, nodal status or steroid receptor content. An SPF below the median was strongly associated with better relapse-free survival (P = 0.008), overall survival (P = 0.004) and survival after relapse (P less than 0.001). Ploidy did not correlate significantly with clinical course. Multivariate analysis using the Cox model suggested that, while SPF gave prognostic information independent of tumour size or nodal status, this independent significance was lost when histological grade was included in the analysis.

Adult↗
PubMed1990

Radiation and other pathological changes in breast tissue after conservation treatment for carcinoma.

Histological changes in breast tissue after radiotherapy were evaluated. Changes in tissue from 17 patients previously treated for breast cancer by surgery and radiotherapy were compared with those seen in a control group treated with surgery alone. Vascular and epithelial changes were seen only in tissue from patients who had received radiotherapy and, therefore, seemed to be relatively specific; stromal changes were seen in both groups and seemed, therefore, to be non-specific. Epithelial atypia is of particular importance as it may be severe and be confused with recurrent malignancy. The presence of other changes associated with radiotherapy, particularly those in vessels, should help to avoid such misdiagnosis.

Blood Vessels↗
PubMed1990

Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry.

Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy.

Breast Neoplasms↗
PubMed1989

Ductal adenoma of the breast--a review of fifteen cases.

The term ductal adenoma has been recently introduced to describe a solid benign lesion of breast ducts. This study describes the clinical, morphologic, and immunohistochemical features of 15 cases of ductal adenoma. Ductal adenomas are usually single, occasionally multiple, lesions occupying medium- and large-sized breast ducts. They may occur in women of all ages, although the majority of patients are 60 years of age or greater. Ductal adenomas usually present clinically as breast lumps which may mimic carcinoma; less commonly, they are associated with nipple discharge. Patients in this series showed no family or previous history of breast disease and had uneventful follow-up after local excision. Despite often showing worrying pseudoinfiltration and cytologic atypia, the immunohistochemical demonstration of a myoepithelial layer and intact basement membrane around the tubules was clear evidence of the benign nature of the lesions. We conclude that most ductal adenomas evolve by sclerosis of benign intraduct papillary lesions, although processes similar to sclerosing adenosis and, possibly, duct ectasia may contribute to the pathogenesis of a proportion of cases. It is hoped that a wider appreciation of the entity of ductal adenoma will reduce the diagnostic uncertainty that continues to surround these and related lesions.

Adult↗
PubMed1989

An immunohistochemical study of the presence of c-erbB-2 protein in Paget's disease of the nipple.

Tumours from 45 patients with Paget's disease of the nipple have been stained with antibody 21N which was raised against a peptide from the C-terminus of the predicted c-erbB-2 protein. Positive staining was observed in 41 cases (91%). In 42 cases the underlying mammary carcinoma was also available for study. In all but two cases staining was similar in the Paget's cells and the underlying carcinoma whether the latter was purely in situ ductal (35%) or in situ associated with infiltrating carcinoma (65%); the malignant cells in both components were large and pleomorphic and the in situ ductal carcinoma was of the comedo type. In the two exceptions the underlying carcinoma showed different histological features. The significance of the high levels of c-erbB-2 protein in this pattern of mammary carcinoma is considered.

Adult↗
PubMed1988

Perioperative bromocriptine adjuvant treatment for operable breast cancer.

Blood levels of prolactin are consistently raised in women who have undergone mastectomy for breast cancer, probably because of the stress of surgery. Since this increase in concentration of a known breast epithelial growth promoter might stimulate proliferation in micrometastatic cells shed at the time of surgery, a pilot study was conducted to try to abolish this effect. 38 patients with suspected operable breast cancer were given either bromocriptine (18) or placebo (20) tablets for 5 days preoperatively and thereafter for 3-10 days. Bromocriptine-treated patients showed significant reductions in prolactin levels and in S-phase fraction of tumour cells within the primary infiltrating carcinoma. There were no major side-effects. Perioperative bromocriptine may provide another approach to adjuvant therapy, possibly combined with endocrine or cytotoxic treatment for patients with axillary nodal metastases.

Breast Neoplasms↗
PubMed1988

New lumps in the breast following conservation treatment for early breast cancer.

A new lump in the breast following conservation treatment for early breast cancer may represent a recurrence of the disease or may be a benign lesion. Clinical evaluation of these lumps is often extremely difficult and, potentially, mammography would seem to be of great importance in the assessment. Between November 1981 and March 1986, 214 patients with operable breast cancers of 4 cm or less in diameter underwent conservative treatment. The conservation technique comprised synchronous excision of the primary tumour without a wide margin, axillary clearance, interstitial irradiation with iridium 192 (2000 cGy), and subsequent external beam radiotherapy to the breast (4600 cGy). After an average follow-up of 26 months, 17 patients developed a new lump in the treated breast necessitating further biopsy. Seven of these were malignant and 10 benign. In the latter category the most frequent finding was fat necrosis. Clinically, the lesions were indistinguishable from each other. The mammographic signs, which best predicted malignancy, were either of a mass or of a malignant type of microcalcification. This study illustrates the problems associated with deciding the nature of a new lump in the breast following conservation treatment. Mammography is complementary to physical examination, and a base-line mammogram six months after completion of therapy is helpful. Despite the use of mammography, biopsy is the only definitive way of excluding recurrence.

Adult↗
PubMed1988

Cellular aspects of breast cancer: workshop report.

It has not been possible in this review to cover all the submitted posters nor indeed all the points discussed during the workshop session. It is hoped, however, that major points of interest have been presented and that areas where there is consensus and areas where controversy remains concerning the clinical value of particular investigations have been highlighted. It is also hoped that some new potential growth areas for investigation of tumour biology have been defined.

Animals↗
PubMed1988

An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma.

The c-erbB-2 gene codes for a putative transmembrane protein, similar in structure to the epidermal growth factor (EGF) receptor. Amplification of the gene has been described in a variety of human adenocarcinomas and is particularly well documented in breast carcinoma. It has been suggested that amplification is indicative of poor prognosis and, as such, is comparable with lymph node status as a predictor of clinical outcome. This study examines the suggestion indirectly by an immunohistochemical technique. Archival tissue from 195 patients with primary breast carcinoma was stained with the polyclonal antibody 21N, raised to amino acids 1243-1255, the C-terminus of the predicted amino acid sequence of the c-erbB-2 protein. Up to 10 year verified follow-up data were available on all patients. Staining compatible with significant amplification was observed in 17 patients. Using the chi-squared test for trend a significant correlation was found between staining and grade (P = 0.04) but not with either node or receptor status. No significant association was found between staining and clinical outcome although there was a tendency for patients with stained tumours to have a worse prognosis. A Cox regression analysis was used to adjust for node status and grade and still no correlation was revealed between staining and prognosis. However a study of this size in which only a small number of patients have been found to have stained tumours does have wide confidence limits. Comparable staining observed in in situ and infiltrating components of tumours suggests that amplification is an early event in carcinogenesis. Similar staining in primary and subsequent metastatic lesions was also noted. It is considered that further studies at both the DNA/mRNA and protein levels are required to confirm the significance of c-erbB-2 amplification in human breast carcinoma.

Adult↗