Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [18F]-fluorodeoxyglucose positron emission tomography.

To determine whether [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) can predict complete pathological response (pCR) in patients achieving a good clinical response to neoadjuvant chemotherapy for primary breast cancer, 10 patients underwent FDG PET scanning prior to definitive breast surgery. Scan reports were compared with histopathological findings. No abnormal uptake at the primary tumour site was visualised in any patient. 9 of the 10 patients had residual invasive carcinoma at operation, ranging from 2 to 20 mm in maximum dimension. One patient achieved a complete pathological response. Of the 5 patients who underwent axillary surgery, no axillary FDG uptake was seen preoperatively although 3 of the 5 were histologically node-positive. FDG PET did not reliably identify residual disease in this series of good clinical responders to neoadjuvant chemotherapy, and its discriminatory power as a tool to predict complete pathological response therefore appears to be inadequate for clinical use in this setting.

Breast cancer after bilateral subcutaneous mastectomy in a female-to-male trans-sexual.

We describe a female-to-male trans-sexual, aged 33, who developed breast cancer 10 years after cosmetic bilateral subcutaneous mastectomy and nipple reimplantation. The complex hormonal pathways involved and the implications for women undergoing prophylactic mastectomy because of a high risk of familial breast cancer are discussed.

Variations in dose and dose intensity of adjuvant CMF chemotherapy for breast cancer throughout the UK.

Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a commonly prescribed regimen for the adjuvant treatment of early breast cancer in the UK and in other countries with a high incidence of breast carcinoma. A number of variations in dose and scheduling of these drugs have been reported in the literature, with all of these being recognized under the generic term 'CMF'. To investigate the extent of differences in CMF regimens used for the adjuvant treatment of early breast cancer we sent a postal questionnaire to all consultant medical and clinical oncologists in the UK seeking details of their practice. CMF drug doses were then converted into dose intensity parameters for comparison. The results showed a wide variation in the number of CMF schedules (n = 36) and CMF dose intensities (n = 33) used. The potential consequences of such variation and the evidence for and against dose intensity as an important parameter in the adjuvant treatment of early breast cancer are discussed.

The role of staging CT scans in the treatment of prostate cancer: a retrospective audit.

A retrospective audit was performed to review the use of diagnostic and planning computed tomographic (CT) scans in the management of patients treated with radical radiotherapy for prostate cancer at Mount Vernon Hospital. All 97 patients had a planning CT scan. In addition, 85 also underwent a diagnostic scan for staging purposes. Fifty-one (60%) had both pelvic and abdominal imaging. Twenty abnormalities were detected in 19 patients. Although 13 of these were 'malignant' abnormalities considered to represent metastatic disease, only four altered the treatment intent. Overall, only 4% of patients were denied radical treatment on the basis of CT findings. Malignant intra-abdominal disease was not identified in the absence of metastatic disease in the pelvis. This study confirms that abdominal CT scans contribute very little useful prognostic information in men with prostate cancer, and are not necessary for routine staging prior to radiotherapy. We propose that a single CT scan of the pelvis in patients who are suitable for radical radiotherapy can provide adequate information for both staging and planning purposes, resulting in significant reductions in cost, radiation exposure and scanner time.

Hyperhomocysteinemia in women with advanced breast cancer.

Patients with malignancy have an increased risk of venous thromboembolic disease but the pathophysiology of this association has not been precisely defined. Hyperhomocysteinemia has become established as one of the commonest conditions associated with venous and arterial thrombosis. We examined the prevalence of hyperhomocysteinemia in women with early (group A, n = 31), metastatic breast cancer (group B, n = 41) and in a group of healthy females (group C, n = 29). Blood samples were collected at diagnosis or prior to treatment. We measured both total plasma homocysteine (tHcy) and red cell folate (RCF). The Mean (SD) tHcy were group A - 9.43 micromol/l (5.6), group B - 11.34 micromol/l (5.1) and group C - 7.9 micromol/l (1.5). A total of 39% of patients with metastatic and 22.6% with early breast cancer had tHcy concentrations above the upper limit of normal. Women with metastatic disease had significantly higher tHcy compared with controls (P < 0.01) but not when compared with women with early breast cancer. Also, no difference was observed when women with early disease were compared with controls. We found no correlation between age and tHcy. Lower RCF levels were identified in group B compared with group A, but this does not fully explain the increased tHcy levels seen within the same group. We conclude that hyperhomocysteinemia is common in women with advanced breast cancer. This observation could explain the high rate of venous thrombosis in women with metastatic breast malignancy.

Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer.

Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2-4 N0-1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (P < 0.0001). Higher Ki-67 proliferation indices were associated with PgR- tumours (median 28.3%, PgR+ 22.9%; P = 0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P = 0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying >75% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P = 0.004).

Massive mediastinal seminoma post-orchidectomy--late relapse with skip-metastases or new primary?

A case of a massive, biopsy-proven, advanced seminoma in the mediastinum 12 years after orchidectomy for a malignant right-sided testicular tumour of unknown histology is presented. The highly unusual nature of this presentation is discussed and may represent either late relapse from skip-metastases or metachronous gonadal and extragonadal tumour development. Immunohistochemical staining was unable to distinguish the site of origin of the lesion.

A systematic review of the role of pulmonary irradiation in the management of primary bone tumours.

INTRODUCTION: Adjuvant therapy in osteosarcoma (OS) and Ewing's sarcoma (ES) is primarily directed towards treatment of subclinical lung disease. Before the advent of modern intensive chemotherapy, lung irradiation was the only available adjuvant treatment. It has proven biological activity and low morbidity. There is, however, a wide variation in its application between centres. This systematic review aims to define the evidence to support the use of lung irradiation in these diseases. DESIGN: A review of trials published between 1966 and 2000 was undertaken to determine the evidence for the use of pulmonary irradiation in OS and ES. RESULTS: Several small series of prophylactic lung irradiation (PLI) have been reported, most from over 20 years ago. These studies support the theoretical basis for the use of PLI in both OS and ES. Few randomised studies have been performed which include PLI. In OS, studies demonstrated a trend in favour of PLI compared with no adjuvant treatment and, subsequently, a level of benefit similar to that achieved with chemotherapy, but no additive effect. No studies have used PLI in addition to current standard chemotherapy regimens, or evaluated its use after successful metastatectomy. In ES, only one randomised study has addressed the role of PLI, in a comparison with vincristine, actinomycin D and cyclophosphamide combination chemotherapy with or without doxorubicin. Prolonged follow-up favoured four-drug chemotherapy. Retrospective reports from large cooperative groups suggest that the addition of whole-lung radiotherapy (WLRT) improves outcome in ES patients presenting with pulmonary metastases. However, there are no randomised study data to support this. CONCLUSIONS: Further randomised studies are necessary to clarify the role of PLI in addition to current standard chemotherapy regimens, or its use after successful metastasectomy in patients with OS. In patients with localised ES adjuvant chemotherapy appears to be superior to PLI alone, while there is little evidence to support treatment with WLRT in patients who present with pulmonary metastases.