Randomized phase II placebo-controlled study to evaluate the efficacy of topical pure emu oil for joint pain related to adjuvant aromatase inhibitor use in postmenopausal women with early breast cancer: JUST (Joints Under Study).

PURPOSE: Aromatase inhibitors are standard of care in women with hormone receptor-positive early breast cancer. Published evidence demonstrates that adverse effects may have an impact on drug compliance, with arthralgias being one of the most commonly reported adverse effects. METHODS: Eligible patients were postmenopausal women who had experienced arthralgia following initiation of an aromatase inhibitor. Patients who experienced arthralgias following a minimum of a 3-month treatment on the aromatase inhibitor were randomized to emu oil or placebo oil. The primary endpoint was to assess for a reduction in pain as measured by a visual analogue score after 8 weeks of treatment. RESULTS: Seventy-three patients comprised the intent-to-treat population, and there was no statistically significant benefit with use of EO. However, there was a statistically significant improvement in pain (visual analogue score was -1.28; p < 0.001) and Brief Pain Inventory severity score -0.88 (p < 0.001), as well as functional interference (Brief Pain Inventory interference -1.10 (p < 0.001) for the entire population following an 8-week administration of EO or placebo oil. CONCLUSIONS: Arthralgias, as a result of aromatase inhibitor use, may be ameliorated by the use of topical oil massaged onto the joint. Further research into interventions for this common side effect is needed.

Diagnosis of breast microcalcifications: a comparison of stereotactic FNA and core imprint cytology as adjuncts to core biopsy.

Stereotactic core biopsy (CB) using 14-gauge needles was adopted as the standard method of diagnosis of screen-detected breast microcalcifications (MC) at Sir Charles Gairdner Hospital in 1996. Fine needle aspiration (SFNA) was included as an adjunct, to optimise sensitivity and to provide immediate reporting. Recently, core imprint cytology (CI) has been shown to have a high sensitivity in diagnosing malignancy. The aims of this paper were to evaluate the accuracy of SFNA as an adjunct to CB, and whether CI could replace SFNA for immediate reporting in MC. Part A is a retrospective review of CB/SFNA of screen-detected MC from May 1998 to February 2000. A minimum of five cores was performed. SFNA samples were restricted to a maximum of three needle passes. Part B is a prospective study of CI from May to November 2000. In Part A, there were 406 MC in 353 women and 81 carcinomas were proven on excision. The complete sensitivity of CB for a diagnosis of malignancy was 97.5% and of SFNA was 65%. No false-positive diagnoses were made by either method. No extra carcinomas were detected using SFNA. In Part B, CB/CI were performed on 203 MC from 165 women. There were 38 carcinomas and 30 of these (79%) were diagnosed as malignant on CI. No false-positive diagnoses were made. The predictive value of a benign diagnosis was 95%. SFNA had little value as an adjunct to core biopsy in MC. CI promises to be useful in providing same day diagnosis for counselling purposes and for planning future surgery.

Management of breast cancer in the elderly by complete local excision and tamoxifen alone.

BACKGROUND: Breast cancer in the elderly is a significant problem, with approximately 30% of all breast cancers occurring in women who are aged 70 or more. Treatments such as axillary dissection, radiotherapy and chemotherapy, part of standard therapy in younger women, have a considerable morbidity and may not be well tolerated in the elderly. The authors report their experience with a more conservative approach to breast cancer in the elderly, using complete local excision combined with long-term tamoxifen (CLE and Tam). METHODS: Seventy women aged > or = 70 years (median age: 79.5 years; range: 70-93 years) were treated by CLE and Tam, and were followed for a median of 25 months (range: 1-82 months). The study population of 70 women represented a less fit group, with tumours suitable for a breast-conserving approach and without palpable axillary lymph nodes. Follow-up was by clinical examination and annual mammography. RESULTS: Loco-regional failure occurred in seven women (10%), three of which involved the breast alone, three the axilla alone, and one involved both sites. Five patients had further surgery. Six of the seven patients had high-grade tumours and two of them were oestrogen receptor-negative. Four of the failure group have subsequently died: two with metastatic breast cancer and two from non-malignant disease. Of the whole study group, there have been 12 deaths in the follow-up period: three from metastatic breast cancer and nine from unrelated medical illness. CONCLUSIONS: It is believed that CLE and Tam provide a simple and safe approach for early non-high-grade breast cancers in elderly women. By such an approach, a large number of elderly women can avoid axillary dissection and radiotherapy.

Comparison of radioligand assay and immunostaining for epidermal growth factor receptor in human breast cancer.

Epidermal growth factor (EGF) receptor status is a useful prognostic indicator in women with breast cancer. Lack of standardization and correlation of methodology for the detection of EGF receptor has hampered its further evaluation. EGF receptor status was ascertained by immunohistochemistry and radioligand assay in 120 breast cancers. Of 52 tumours negative for EGF receptor on radioligand assay, 47 were negative on immunohistochemistry and, of 68 tumours positive for the receptor on assay, 52 were positive on immunohistochemistry. If the more widely evaluated radioligand assay is assumed to be the 'gold standard', immunohistochemistry has a sensitivity of 81 per cent and a specificity of 91 per cent.

The epidermal growth factor receptor as a prognostic marker: results of 370 patients and review of 3009 patients.

Epidermal growth factor receptor (EGFR) and estrogen receptor (ER) were assayed by ligand binding in tumors from 370 patients with primary breast carcinoma with a median follow up of 18 months. Forty seven percent (175/370) and 57% (210/370) of tumors had > 20 fmol/mg and > 10 fmol/mg of EGFR and ER respectively. There was a highly significant inverse relationship between EGFR and ER (p = 0.0032). There was also a significant association between EGFR and patient age (p = 0.0006) but not correlation between EGFR and lymph node status, tumor grade, or tumor size (p = 0.104, p = 0.198, and p = 0.085 respectively). In a univariate analysis of all patients, EGFR expression was not associated with a significant reduction in overall survival (OS). However, there was a significant decrease in relapse-free survival (RFS) and OS in node negative EGFR positive patients (p = 0.03 and p = 0.05 respectively). In a multivariate analysis (Cox proportional hazard model) of all patients, lymph node status was an independent prognostic indicator for OS and RFS (p < 0.00005) and p = 0.00005 respectively), ER status for RFS (p = 0.0006), and EGFR (in the node negative model) for RFS (p = 0.03). When all patients were stratified for EGFR and ER, there was a significant difference in RFS and OS such that EGFR positive and ER negative had the worst prognosis (p = 0.0034 and p = 0.005 respectively).

Correlation between p53 mutations and antibody staining in breast carcinoma.

Abnormalities of the p53 gene and protein were examined in 81 primary breast carcinoma samples. Using a polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis, mutations in p53 exons 5-8 were identified in 13 of 81 tumours (16 per cent) and confirmed by DNA sequencing. Positive staining for p53 protein was detected in ten of 77 (13 per cent) of these tumours using polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR-SSCP analysis were more common in grade III tumours (P = 0.015), but no correlation was found with tumour size, node status or level of epidermal growth factor receptor expression. A p53 mutation was associated with positive antibody staining in only two patients. Positive immunohistochemical staining using a p53 antibody may detect p53 protein expression, but this may not correlate directly with an underlying mutation in the hot spot region examined.

Epidermal growth factor receptor determination on tumour imprints.

Epidermal growth factor receptor (EGFR) is a sensitive prognostic indicator in women with breast cancer. A new technique for the detection of EGFR on breast cancer imprints is described and evaluated in relation to immunohistochemistry on frozen sections. The standard streptavidin-biotin method using the R1 antibody on frozen sections was modified for use on tumour imprints. In the first group (group 1 imprints) 43 tumours were assessed by frozen section and imprint staining. The group 1 imprint method had a sensitivity of 50% and a specificity of 89% compared with the frozen sections. Further modifications were made for the following 32 tumours (group 2) and this method had a much improved sensitivity of 94% while specificity was preserved. This method is simple and could be performed in any hospital histopathology department.

Delay in the diagnosis of breast cancer: the effect of the introduction of fine needle aspiration cytology to a breast clinic.

Fine needle aspiration cytology (FNAC) was introduced to a District General Hospital Breast Clinic in 1984 and since that time the rate of surgical excision biopsy for benign breast disease has halved. The rate of benign to malignant breast operations fell from 2.0 to 0.7 over a 7-year period from 1982 to 1988. During this period the diagnosis of breast cancer was made at the first clinic appointment in 85% of women. However, a delay in diagnosis of more than 50 days occurred in 33 patients (6.9%) and there was little difference in the annual rate of delayed diagnosis despite the addition of FNAC as an extra diagnostic tool in the later years of the study. Eighty-five per cent of patients with a delayed diagnosis were under the age of 55 (mean and median age 47) years. FNAC is a useful adjunct in the management of patients with diagnostic breast problems, but even in combination with mammography is not always sufficiently sensitive to exclude malignancy, particularly in young women.

Diagnostic and therapeutic aspects of fine-wire localization biopsy for impalpable breast cancer.

During the first 2 years (July 1989 to July 1991) of the Avon Breast Screening Service, fine-wire localization biopsy was indicated in 213 impalpable breast lesions. A total of 144 lesions were benign and 69 malignant. Only four of 213 lesions (1.9 per cent) were not excised at the first localization. Factors influencing reoperation in the 69 patients with malignant impalpable lesions were examined. There was a significant association (P < 0.001) between parenchymal disturbances on mammography and invasive carcinoma, and between non-invasive carcinoma and microcalcification (P < 0.001). In 31 patients the localization biopsy was the only surgical procedure. Thirty-eight patients required further surgery: 12 underwent further local excision and 26 mastectomy. Reoperation was more frequent in patients with calcification than in those with parenchymal disturbance (P < 0.001). The most frequent indications for mastectomy were inadequate excision of widespread comedo ductal carcinoma in situ or invasive ductal carcinoma combined with extensive ductal carcinoma in situ. Fine-wire localization biopsy was a combined therapeutic and diagnostic procedure in 31 of 69 women with impalpable screen-detected lesions. The majority of patients required further surgery because radiological abnormalities underestimated the extent of disease.