Like Frying Multiple Eggs in One Pan: a Qualitative Study Exploring the Understanding of Inter-speciality Training in Cancer Care.

H igh-quality cancer care is a key priority worldwide. Caring for people affected by cancer requires a range of specific knowledge, skills and experience to deliver the complex care regimens both within the hospital and within the community environment. In June 2022, the European Cancer Organisation along with 33 European cancer societies began working together to develop a curriculum for inter-speciality training for healthcare professionals across Europe. As part of the project, this research consisted of a qualitative survey distributed to the European Union societies via email. The aim of this paper is to disseminate the qualitative findings from healthcare professionals across Europe. Questionnaires were sent out to a convenience sample of 219 healthcare professionals and patient advocates with a response rate of 55% (n = 115). The findings identified that there were four key themes: 'What is inter-speciality training?', 'Barriers and challenges', 'Support throughout the cancer journey' and 'New ways of working'. These results are part of a larger needs analysis and scoping review to inform the development of a core competency framework which will be part of an inter-speciality curriculum for specialist cancer doctors, nurses and other healthcare professionals across Europe. Healthcare professionals will be able to access education and training through the virtual learning environment and workshops and by clinical rotations to other specialties.

Estrogen receptor-beta mRNA is associated with adverse outcome in patients with breast cancer.

BACKGROUND/AIMS: Estrogen receptor (ER) is the prototype therapy predictive marker in oncology. The ER is now known to exist in two main forms with similar overall structure: ER-alpha and ER-beta. Both forms may be expressed in breast cancer. The aim of this study was to examine breast cancer outcome in relation to expression of ER-beta. METHODS: In this investigation, we measured the expression of ER-alpha protein and ER-beta mRNA in 121 extracts of invasive breast cancer. Association of expression with clinical outcome was examined using Kaplan-Meier and Cox regression analyses. RESULTS: While ER-alpha expression was associated with good patient outcome [hazard ratio (HR) for death from breast cancer 0.37; 95% confidence interval (CI) 0.17-0.84; p = 0.017], ER-beta predicted poor outcome (HR for death from breast cancer 2.49; 95% CI 1.10-5.63; p = 0.028). CONCLUSION: Based on these findings, we conclude that ER-beta may have a different biological role from that of ER-alpha in breast cancer.

Acute colonic obstruction due to benign prostatic hypertrophy.

A seventy two year old man presented to the Emergency Department with clinical features of colonic obstruction. Subsequent radiological investigations confirmed this impression and revealed the aetiology to be compression of the sigmoid colon against the sacrum by a massively distended urinary bladder. Chronic urinary retention due to benign prostatic hypertrophy is an extremely unusual cause of large bowel obstruction. Little in this patient's clinical findings suggested this aetiology. We reviewed the literature in this area and highlight the benefits of CT scanning over contrast studies.

ADAM-17 predicts adverse outcome in patients with breast cancer.

ADAM-17 is a matrix metalloproteinase-like enzyme involved in the release of several ligands that have been shown to promote both cancer formation and progression. These ligands include transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, epiregulin and tumor necrosis factor-alpha. In this investigation, we measured the expression of total ADAM-17 by enzyme-linked immunosorbent assay in 153 invasive breast cancers. We also measured the precursor and active forms by western blotting in 140 invasive breast cancers. Expression of ADAM-17 was significantly increased in high-grade compared with low-grade tumors and was independent of tumor size, lymph node metastasis and estrogen receptor status. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for breast cancer. Our results are further evidence that ADAM-17 is involved in breast cancer progression and thus provides further impetus for exploiting ADAM-17 as new target for cancer treatment.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

Sentinel lymph node biopsy in elderly irish patients with malignant melanoma.

In patients with malignant melanoma, Breslow depth increases with age. However, studies suggest that the frequency of sentinel lymph node metastases in malignant melanoma decreases with age. We investigated whether this applied to the cohort of patients undergoing sentinel lymph node biopsy (SLNB) in our institution. In a prospectively accrued database we identified 149 patients undergoing SLNB from 1997 to 2005. Tumour thickness as measured by Breslow depth was assessed in stratified age groups. We assessed the relationship between SLNB positivity and age using the Chi-square for trend. We directly examined the relationship between SLNB positivity in patients aged less than 65 and aged 65 years of age and over. Disease-free and overall survival in patients aged less than 65 and aged 65 years of age and over were also assessed. Comparing the age groups, there was no significant difference identified in Breslow depth (<65 years, median Breslow > or = 1.2 mm (range 0.2-9.7); > or =65 years, median Breslow > or = 1.4 mm (range 0.12-8.5); p > or = 0.06, Mann-Whitney U). Chi-square for trend identified no significant relationship between SLNB positivity and age. We found n=120 patients <65 had SLNB, of which 26 (21.7%) were positive. In patients =65, n=29 had SLNB of which 3 (10.3%) were positive. These differences were not statistically significant (Fisher's exact test, p > or = 0.2). There was no difference in disease-free or overall survival between patients aged <65 or > or =65 who had SLNB (median follow-up 37.5 months (range 5-70); disease-free survival, p > 0.08; overall survival, p > or = 0.3, Logrank test). We did not find that elderly patients with malignant melanoma had a demonstrable difference in tumour thickness when compared to younger patients. In those patients who underwent SLNB there was no significant difference in node positivity between the age groups. Disease-free and overall survival were not significantly different between the age groups. Further study and longer follow-up will help establish the relationship between age and SLNB positivity.

Ets2 transcription factor in normal and neoplastic human breast tissue.

The Ets family of transcription factors regulate the expression of multiple genes involved in tumour formation and progression. The aim of this work was to test the hypothesis that the expression of Ets2 in breast cancers was associated with parameters of tumour progression and metastasis. Using reverse-transcriptase polymerase chain reaction (RT-PCR), Ets2 mRNA was detected in 69% of 181 breast carcinomas, 63% of 43 fibroadenomas and 47% of 43 specimens of normal breast tissue. Levels were significantly higher in carcinomas compared with normal breast tissue (P = 0.006). Using Western blotting, Ets2 protein was found to migrate as two bands with molecular masses of 52 kDa (p52) and 54kDa (p54). Levels of both proteins were significantly higher in the carcinomas compared with both fibroadenomas (P = 0.0001) and normal breast tissue (P = 0.0001). In the carcinomas, a significant relationship was found between the p52 and p54 form of Ets2 (r = 0.51, P < 0.0001; Spearman correlation). Also, in the carcinomas, a significant correlation was found between both forms of Ets2 protein and urokinase plasminogen activator (uPA) (for p52, r = 0.43, P = 0.0005, n = 68; for p54, r = 0.50, P = 0.0001, n = 68). As Ets2 binding sites are present on the uPA promoter, Ets2 may be one of the transcription factors regulating uPA expression in human breast cancer.

Diagnostic accuracy of core biopsy for ductal carcinoma in situ and its implications for surgical practice.

BACKGROUND: Core biopsy is considered to be a highly accurate method of gaining a preoperative histological diagnosis of breast cancer. Ductal carcinoma in situ (DCIS) is often impalpable and is a more subtle form of breast cancer. AIM: To investigate the accuracy of core biopsy in the diagnosis of cancer in patients with DCIS. METHODS: All patients who had invasive cancer (n = 959) or DCIS (n = 92) that was confirmed by excision between 1999 and 2004 were identified. The diagnostic methods, histology of the core biopsy specimen and excision histology were reviewed in detail. RESULTS: Core biopsy was attempted in 88% (81/92) of patients with DCIS and in 91% (874/959) of those with invasive disease. Of those patients who underwent core biopsy, a diagnosis of carcinoma on the initial core was made in 65% (53/81) of patients with DCIS compared with 92% (800/874) of patients with invasive disease (p<0.0001). Smaller lesion size (p = 0.005) and lower grade (p = 0.03) were associated with increased risk for a negative or non-diagnostic core in patients with DCIS. The nature of the mammographic lesion or the method of biopsy did not affect the probability of an accurate core biopsy. Patients who had a preoperative diagnosis of DCIS by core biopsy had a reoperation rate of 36% compared with 65% of those that did not have a preoperative diagnosis (p = 0.007). CONCLUSION: Although core biopsies are highly accurate forms of obtaining a preoperative diagnosis in patients with invasive breast cancer, this is not the case in DCIS. As the number of surgical procedures can be reduced by core biopsy, it is still of considerable value in the management of DCIS.

Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer.

Urokinase plasminogen activator (UK-PA) is a serine protease implicated in cancer invasion and metastasis. In this investigation, patients with breast cancers containing high levels of UK-PA antigen had significantly higher risk of early disease recurrence and shorter overall survival than did patients with low levels of the protein. In univariate analysis, UK-PA was a more powerful discriminator for disease-free interval than axillary node status, tumor size, or estradiol receptor. For overall survival, UK-PA as a prognostic marker, was of similar magnitude to axillary node status but stronger than that of tumor size or estradiol receptor. In multivariate analysis, for both disease-free interval and survival, UK-PA was an independent risk factor, being independent of tumor size, axillary node status, and estradiol receptor. UK-PA appears to be a new and independent prognostic marker in breast cancer.

Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration.

The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR in breast cancer tissue are associated with poor prognosis, while high levels of tPA or PAI-2 correlate with good prognosis. In this study, pre-operative plasma levels of uPA, PAI-1, uPAR, tPA, uPA-PAI-1 complex, and tPA-PAI-1 complex were measured in patients with benign (n=103) and malignant breast disease (n=113) by immunoenzymatic assays (ELISA). While plasma antigen levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR were not significantly different in the 2 groups, antigen levels of tPA and tPA-PAI-1 complex were significantly higher in patients with breast carcinoma compared to the control group. In plasma from the breast cancer patients, uPA levels correlated weakly but significantly with those of tPA (r=0.20, p=0.035) and uPAR (r=0.208, p=0.028). tPA levels correlated strongly with tPA-PAI-1 complex (r=0.972, p=0.0001) while uPA-PAI-1 levels were significantly associated with PAI-1 levels (r=0.534, p<0.0001), tPA levels (r=0.348, p=0.0003) and tPA-PAI-1 levels (r=0.356, p=0.002). However, no significant correlation was found between plasma and tumor tissue levels of uPA, PAI-1, uPA-PAI-1 complex, tPA or tPA-PAI-1. Our findings indicate that determination of these factors in plasma do not reflect their concentration in tumor tissue. Therefore, measurement of PA components in blood cannot be recommended for assessing prognosis in breast cancer.

Adjuvant therapies in the treatment of stage II and III malignant melanoma.

BACKGROUND: The incidence of cutaneous melanoma has increased during the past three decades. The development of sentinel lymph node biopsy has facilitated better staging. Despite these improvements, 5-year survival rates for American Joint Committee on Cancer stage II and III disease range from 50%-90%. METHODS: A review of the current literature concerning adjuvant therapies in patients with stage II and III malignant melanomas was undertaken. RESULTS: The focus of adjuvant therapies has shifted from radiotherapy, BCG and levamisole to newer biological agents. Interferon, interleukin and vaccines have been evaluated but none of these agents have demonstrated an increase in overall survival in patients with stage II and III melanoma. Interferon can prolong disease-free interval. CONCLUSION: At present, no adjuvant therapy improves overall survival in patients with stage II and III melanoma. New staging allows more accurate stratification of patients for clinical trials.

A direct relationship between thyroid enlargement and breast cancer.

Despite extensive study, evidence to support a direct relationship between diseases of the thyroid and breast has not been established. In this study thyroid volume was assessed by ultrasound in 200 patients with breast cancer and 354 with benign breast disease. Results were compared to appropriate female control groups. Both mean thyroid volume (21.1 +/- 1.4 mL) and the percentage of individual patients with enlarged (> 18.0 mL) thyroid glands (41.5%) were significantly greater in the breast cancer group than equivalent values (13.2 +/- 0.5 mL and 10.5%, respectively) in age-matched controls (P < 0.01 in both cases). The mean thyroid volume of 14.5 +/- 0.34 mL in patients with benign breast disease was also significantly greater than that of 12.5 +/- 0.38 mL in younger controls (P < 0.01). The results support a direct association between breast cancer and increased thyroid volume as mean thyroid volumes and the percentage of individual patients with enlarged thyroid glands were similar in those studied both before (20.8 +/- 1.3 mL and 43.0%) and after (21.4 +/- 1.6 mL and 40.0%) therapies for breast cancer. Although there is no evidence that thyroid enlargement represents a risk factor for breast cancer, the results emphasize the importance of raising the consciousness of the coincidence of both disorders.

Tissue iodine content and serum-mediated 125I uptake-blocking activity in breast cancer.

In the thyroid, active transport of iodide is under control of the TSH-dependent Na+/I- symporter (NIS), whereas in the breast such control is less well understood. In this study, NIS expression was demonstrated by RT-PCR in 2 of 2 fibroadenomata and 6 of 7 breast carcinoma messenger ribonucleic acid isolates. In addition, mean total tissue iodine levels of 80.9 +/- 9.5 ng I/mg protein in 23 benign tumors (fibroadenomata) were significantly higher than those in 19 breast cancers taken from either the tumor (18.2 +/- 4.6 ng I/mg) or morphologically normal tissue taken from within the tumor-bearing breast (31.8 +/- 4.9 ng I/mg; P < 0.05 in each case). Inhibition of 125I uptake into NIS-transfected CHO cells was observed in serum from 20 of 105 (19.0%) breast carcinoma, 8 of 49 (16.3%) benign breast disease, and 27 of 86 (31.4%) Graves' patients, but in only 1 of 33 (3.0%) age-matched female controls. IgG purified from serum of patients showing positive 125I uptake inhibition also inhibited iodide uptake, suggesting that such inhibition was antibody mediated. 125I uptake inhibition was significantly associated with thyroid peroxidase antibody positivity (P < 0.05) in sera from breast cancer patients, but not in those with benign breast disease, once again suggesting an association between thyroid autoimmunity and breast carcinoma.

Serum thyroid peroxidase autoantibodies, thyroid volume, and outcome in breast carcinoma.

The prevalence of thyroid peroxidase autoantibodies (TPO.Ab) was assessed in patients with either breast carcinoma or benign breast disease, and its association with disease outcome in breast carcinoma was studied. TPO.Ab were detected by direct RIA in serum from 121/356 (34.0%) of patients with breast carcinoma, compared with 36/194 (18.5%) of controls (P < 0.001); and in 31/108 (28.7%) with benign breast disease, compared with 12/88 (13.6%) of controls (P < 0.05). Survival analysis in a group of 142 women with breast carcinoma demonstrated that TPO.Ab titres > or = 0.3 U/mL were associated with a significantly better disease-free [relative risk (RR) = 1.84, P < 0.05] and overall survival (RR = 3.46, P < 0.02), compared with those who were TPO.Ab-negative. Better outcome associated with higher TPO.Ab titres was confined to those who had thyroid volumes within the intermediate range (10.1-18.8 mL) and did not further enhance the good outcome recorded when volumes were < or = 10.0 mL or > 18.8 mL. Multivariate survival analysis showed that both TPO.Ab and thyroid volume were independently associated with prognosis in breast carcinoma and that RRs for disease-free survival were of a similar order of magnitude to well-established prognostic indices such as axillary nodal status or tumor size. These findings supply evidence that manifestations of thyroid autoimmunity are associated with a beneficial effect on disease outcome in breast carcinoma and provide the strongest evidence to date of a biological link between breast carcinoma and thyroid disease.

Towards a high standard of surgical oncology throughout Europe.

To retain their role in co-ordinating the multidisciplinary management of cancer, surgeons must adapt to new developments in oncology. In addition to technical skill in operative surgery, all surgeons treating cancer patients must add new information in tumour biology, chemotherapy and radiotherapy to their range of knowledge. Such a broad approach is needed nowadays in order to give a valid clinical opinion and is indispensable in the planning of operative strategies. Although considerable differences in cancer treatment exist within Europe, centres of excellence can be defined. The European Society of Surgical Oncology is planning, with the co-operation of national surgical oncology groups, to devise Guidelines for Good Practice in Surgical Oncology which will be acceptable throughout Europe. Identification of centres for training, registration and accreditation of trainees and a system of continuing education for established surgical oncologists will be proposed. The aims of these proposals are (i) to promote excellence in treatment, (ii) to facilitate an exchange of information, (iii) to encourage participation in clinical trials, (iv) to improve education of medical and para-medical personnel about oncology and (v) to point the way to research opportunities. In medical practice abundant evidence exists that (a) a high standard of clinical care promotes educational activity, (b) good education stimulates research and (c) research in turn activates improvements in service and care. Because of its complexity and the need to involve many disciplines in its management, the treatment of patients with cancer requires a high standard of professional training and competence. Moreover, because of rapid developments in cancer research and treatment, mechanisms for continuing medical education for oncologists are essential.

Assay of E-cadherin by ELISA in human breast cancers.

E-cadherin is a membrane-bound adhesion glycoprotein. Loss of E-cadherin has been correlated with invasion and metastasis in model systems. Using a new ELISA, we found higher levels of E-cadherin in fibroadenomas than in primary breast cancers. Levels in primary cancers showed no significant relationship with either tumour size, nodal status or oestrogen receptor levels. Patients with breast cancers containing low levels of the adhesion protein had a significantly shorter disease-free interval than patients with high levels (P = 0.041). The prognostic value of E-cadherin, for disease-free interval, was also found in node-negative patients as well as in patients presenting with small tumors (< or = 2 cm). In conclusion, loss of E-cadherin expression in human breast cancers is associated with increased metastatic potential as has previously been found in model systems. Loss of E-cadherin is thus likely to contribute to breast cancer progression.

Continuing medical education in oncology in Europe.

A European Conference on Continuing Medical Education (CME) in Oncology was designed and organised in Dublin (Ireland), on 12th and 13th October 1995 by the European School of Oncology in collaboration with University College Dublin and with the financial support of the European Commission (Europe Against Cancer Programme). Two experts were invited from each Member State and all attended the Conference with the sole exception of the representatives of Luxembourg, who did not attend due to unexpected important commitments. Observers were invited to contribute to the discussion as representatives of organisations that were involved either directly or indirectly in CME. The Conference took the format of a plenary session coupled with the identification of five discussion groups formed to debate key areas in CME at a European level in oncology (Table 1). As a result of these discussions and subsequent consultations, an agreement was reached on the following statements: (a) Continuing Medical Education (CME) is an ethical duty and an individual responsibility for each doctor. Although CME should remain voluntary at the present time, it is nevertheless a professional obligation since almost 50% of medical knowledge becomes obsolete after ten years. It should be organised with clear guidelines for medical personnel working in hospitals, in primary health care and in private practice. (b) The CME system within the European Union (EU) should remain self-directed without the necessity for interval examinations: it should be interdisciplinary and must be driven and controlled by the profession itself. (c) A common concept and system within a CME framework may have a considerable impact on EU integration. It should certainly be developed, maintained and monitored at national level but on the basis of a common European model to ensure scientific and cultural interchange among Member States. (d) It was agree that a credit system is needed to help doctors keep track of their CME activities: the system should be based on the accumulation of credit points (one credit equalling one hour of continuing medical education) and monitored at a national level. Credit transfer among Member States is vital to facilitate exchange between Member States. (e) Oncology provides a very useful model of CME within which guidelines can be proposed and tested. Harmonisation of CME systems among the different European cancer organisations and scientific societies within this model system may represent a useful basis that other specialities can follow.

Audit of complete axillary dissection in early breast cancer.

The role of complete axillary dissection (CAD) in the management of breast cancer is controversial and largely unresolved. Acceptance of the results of trials incorporating CAD assumes that the axillary dissection is truly complete. To address this point, and also to define quality control criteria for this operation within our unit, we audited 100 consecutive axillary dissections as follows: the primary surgeon performed what he/she felt to be a thorough CAD and submitted separately the contents of level I, II and III for pathological evaluation; a second surgeon then independently assessed the dissection and arbitrarily labelled any further excised tissue as level IV. Level IV nodes were retrieved in 38% of cases. Tumour involvement of level IV nodes was noted in 5% (2/38) of dissections where lymph nodes were retrieved, but in neither instance was pathological staging altered. There was a significant decrease in the incidence of level IV node retrieval from 47% (28/60) in the first 6 months of audit to 20% (8/40) subsequently. This novel approach to our continuing audit identified quality control criteria for this procedure in our unit and suggested that audit of this kind benefits training.