Factors influencing return to work: a narrative study of women treated for breast cancer.

The purpose of this qualitative study was to identify factors contributing to a successful return to the labour market after treatment for breast cancer from the women's own perspective. The study is based on 16 narratives - open-ended, in-depth interviews - about women's experiences and thoughts from the period after breast cancer surgery when they focused on their return to work. The women were recruited from participants of a multicentre trial, which allowed comparisons across a range of adjuvant therapies. The narratives of women who worked full time at a cut-off point of 1 year after surgery are analysed separately from the narratives of women still sick-listed at that point of time. The findings show that while all the women strove to belong to the labour market, the study also reveals changes in women's perceptions of the value of employment. The quality of social support received from employers and coworkers differed between women who returned to work and those still sick-listed 1 year after breast cancer treatment. A need to design interventions focusing on the work arena of women treated for breast cancer is pointed out.

Smoking cessation among patients with head and neck cancer: cancer as a 'teachable moment'.

Many cancer patients continue to smoke past diagnosis and treatment, even though smoking in some cases may cause more side effects and increase the risk of treatment failure. We developed and evaluated a nurse-led smoking cessation programme on 50 patients with head and neck (H&N) cancer undergoing radiotherapy (RT) with 1-year follow-up. To evaluate the effectiveness of the programme (proportion of smoke-free patients), smoking status was tested by measuring carbon monoxide in expired air. Thirty-seven patients (74%) were tested smoke-free weekly during the RT period. At the 1-year follow-up visit, 28 patients (68%) were tested smoke-free. The results indicated that even H&N cancer patients with a heavy smoking history and multiple abuses could quit smoking with systematic support but a more sophisticated evaluation including larger study populations and control groups are needed.

Endocrine treatment options for advanced breast cancer--the role of fulvestrant.

For many years, tamoxifen has been the 'gold standard' amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in early, operable breast cancer and is being increasingly used in the adjuvant setting. Generally, the selective oestrogen receptor modulators (SERMs), such as toremifene, droloxifene, idoxifene, raloxifene, and arzoxifene, show minimal activity in tamoxifen-resistant disease and show no superiority over tamoxifen as first-line treatments. In addition to these agents, other treatment options for advanced disease include high-dose oestrogens and progestins. Response rates for high-dose oestrogens and tamoxifen are similar, but the use of oestrogens is limited by their toxicity profile. Consequently, there is a need for new endocrine treatment options for breast cancer, particularly for use in disease that is resistant to tamoxifen or AIs. Fulvestrant ('Faslodex') is a new type of steroidal oestrogen receptor (ER) antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity. This paper reviews the key efficacy and tolerability data for fulvestrant in postmenopausal women in the context of other endocrine therapies and explores the potential role of fulvestrant within the sequencing of endocrine therapies for advanced breast cancer.

Impact of a surgical training programme on rectal cancer outcomes in Stockholm.

BACKGROUND: Total mesorectal excision (TME) and use of adjuvant radiotherapy are major advances in the treatment of rectal cancer that have emerged in the past 20 years. The aim of this study was to evaluate the effects of an initiative to teach the TME technique on outcomes at 5 years after surgery. METHODS: TME-based surgery was introduced in Stockholm in 1994. The study population comprised all 447 patients who underwent abdominal operations for rectal cancer in Stockholm County during 1995 and 1996. Outcomes were compared with those in the Stockholm I (790 patients) and Stockholm II (542 patients) radiotherapy trials. RESULTS: The permanent stoma rate was reduced from 60.3 and 55.3 per cent in the Stockholm I and II trials respectively to 26.5 per cent in the TME project (P < 0.001). Five-year local recurrence rates decreased from 21.9 and 19.1 per cent to 8.2 per cent respectively (P < 0.001). Five-year cancer-specific survival rates increased from 66.0 and 65.7 per cent in the Stockholm trials to 77.3 per cent in the TME project (hazard ratio 0.62 (95 per cent confidence interval 0.49 to 0.80); P < 0.001). CONCLUSION: A surgical teaching programme had a major impact on rectal cancer outcome.

Tamoxifen and megestrol acetate for postmenopausal breast cancer: diverging effects on liver proteins, androgens, and glucocorticoids.

AIM: To compare the effects of tamoxifen and megestrol acetate on liver proteins, androgens, and glucocorticoids during adjuvant treatment for postmenopausal breast cancer. METHODS: A subgroup of women within a large prospective multicenter trial were followed with blood sampling every 3 mo during 2 yr. Women were randomized to receive either continuous tamoxifen 40 mg/d or repeated sequential treatment with tamoxifen and megestrol acetate (MA) 160 mg/d. RESULTS: We found profound and distinct differences between the two regimens. Tamoxifen increased steroid-binding proteins (SHBG and CBG) and suppressed circulating androgens and IGF-I. In contrast, the metabolic effects of tamoxifen were clearly antagonized by MA. There was a rise in IGF-I and marked suppression of steroid-binding proteins. Levels of free testosterone were reduced by 70%. MA also caused apparent adrenal suppression. CONCLUSION: The different effects on anabolic/catabolic balance and adrenal function may relate to certain clinical effects during treatment.

Bone mineral density among premenopausal women with early breast cancer in a randomized trial of adjuvant endocrine therapy.

PURPOSE: To examine the effects on bone mineral density of 2 years of treatment with a luteinizing hormone-releasing hormone (LHRH) agonist alone or in combination with tamoxifen or tamoxifen alone in premenopausal breast cancer. PATIENTS AND METHODS: We recruited 89 women from two centers in Stockholm participating in a randomized multicenter trial of three different endocrine approaches in the adjuvant setting (Zoladex in Premenopausal Patients Trial). The women were assigned to receive the LHRH agonist goserelin with or without tamoxifen, tamoxifen alone, or no endocrine therapy. The treatment was given for 2 years. We measured total-body bone density before start of treatment and at 12, 24, and 36 months. RESULTS: After 2 years of treatment, there was a significant loss of bone mineral density (mean change, -5%; P <.001) in the women receiving goserelin alone. The combined goserelin and tamoxifen treatment, as well as tamoxifen alone, resulted in a lesser but statistically significant decline in bone mineral density (mean change, -1.4%; P =.02; and -1.5%; P <.001). One year after cessation of treatment, the goserelin group alone showed a partial recovery from bone loss (mean change, 1.5%; P =.02). CONCLUSION: Two years of ovarian ablation from goserelin treatment caused a significant reduction in bone mineral density but there was a partial recovery from the bone loss 1 year after cessation of treatment. The addition of tamoxifen seems to partially counteract the demineralizing effects of goserelin.

Prognostic significance of both surgical and pathological assessment of curative resection for rectal cancer.

BACKGROUND: Information on whether surgery has been 'curative' is essential for prediction of prognosis and for selection of patients for adjuvant treatment. The aim of this study was to analyse the prognostic value of surgeons' and pathologists' assessments of tumour clearance in patients with primary rectal cancer who underwent resection. METHODS: A total of 1550 patients were studied prospectively. Data were collected from reports made by surgeons and pathologists on whether tumour clearance had been 'complete', 'uncertain' or 'incomplete'. The predictive value in relation to outcome after at least 5 years of follow-up was assessed. RESULTS: In patients assessed as having a complete surgical clearance, tumour recurrence developed in 33.3 per cent. For patients with an uncertain or incomplete clearance the recurrence rate was 59.5 and 61 per cent respectively (P < 0.001). The relative risk of recurrence was twice as high when the surgeon and pathologist disagreed than when they both agreed on the complete clearance. Survival in patients with a complete, uncertain or incomplete surgical clearance was 55.3, 23.0 and 10 per cent respectively (P = 0.050). CONCLUSION: Assessments of tumour clearance were of strong prognostic value in relation to outcome. When the surgeon or pathologist was uncertain, or there was disagreement about the completeness of clearance, the risk of recurrence was similar to that among patients in whom an incomplete resection had been performed.

A randomised study of axillary drainage and pectoral fascia preservation after mastectomy for breast cancer.

BACKGROUND: To reduce the risk of seroma after modified radical mastectomy in breast cancer patients, the use of suction axillary drainage is a standard procedure. The optimal time to remove the drain is not established. Whether the removal or preservation of the pectoral fascia influences the risk of seroma formation or loco-regional recurrence rate remains unclear. METHOD: The trial included 247 patients with breast cancer who underwent modified radical mastectomy in five Swedish hospitals 1993-1997. The median follow-up time was 6 years. One hundred and twenty-two and 125 patients, respectively, were randomised between removal versus preservation of the pectoral fascia. Of these 247 patients a total of 198 patients were also randomised to have the drain removed 24 h postoperatively or to keep the drain in until discharge had decreased to less than 40 ml/24 h. RESULTS: Early removal of the axillary drain was associated with significantly more seromas and a shorter average postoperative hospital stay. There were no differences between the two groups regarding the rate of wound infections and/or hematoma formation. Removal or preservation of the pectoral fascia did not influence the formation of seroma or the amount of peroperative bleeding. A trend towards an increased risk for chest wall recurrence was observed in patients with preserved pectoral fascia (16/125 compared with 8/122; hazard ratio=2.0, 95% confidence interval=0.9-4.7). CONCLUSION: Early removal of axillary drain shortened the duration of hospital stay without any increase in wound complications. However, it yielded a significantly higher incidence of seroma. Seroma formation and the chest wall recurrence rate was not significantly influenced by the preservation of the pectoral fascia or not.

The surgeon as a prognostic factor after the introduction of total mesorectal excision in the treatment of rectal cancer.

BACKGROUND: With conventional blunt surgical resection of rectal cancer, local recurrence rates are high and the individual surgeon putatively influences patient outcome. With total mesorectal excision (TME) local recurrence rates have been reduced and intersurgeon variability may be less important. The 'TME project' was a collaborative project that included surgical workshops in Stockholm between 1994 and 1997. The aim of this study was to assess the impact of the project on the practice of rectal cancer surgery in Stockholm and to analyse whether surgeon case volume and participation in the workshops influenced patient outcome. METHODS: All 652 patients who had an abdominal resection for rectal cancer in Stockholm between 1995 and 1997 were included. Outcome was compared in patients operated on by teams that included high-volume surgeons (more than 12 operations per year) with teams that included low-volume surgeons (12 operations or fewer per year), as well as between teams that including workshop participants and non-participants. RESULTS: Forty-six surgeons operated on the 652 patients. Five high-volume surgeons operated on 48 per cent of the patients. In these, outcome was significantly better than in patients treated by low-volume surgeons (local recurrence rate 4 versus 10 per cent (P = 0.02); rate of rectal cancer death 11 versus 18 per cent (P = 0.007)). Twenty-six surgeons were workshop participants and performed 93 per cent of the operations. Radiotherapy, TME and sphincter-preserving surgery were more common among patients treated by workshop participants. CONCLUSION: The TME project has had an impact on rectal cancer surgical practice in Stockholm. Variability in patient outcome was mainly related to case volume, with better results obtained in patients treated by high-volume surgeons.

Prognostic significance of tumor cell proliferation analyzed in fine needle aspirates from primary breast cancer.

The objective of this study was to analyze the role of proliferating fraction (PF) measured with Ki-67/MIB-1 antibody in a large series of preoperative fine-needle aspirate (FNA) biopsies as a prognosticator of disease recurrence. The study comprised 732 patients who all had a conclusive cytological diagnosis of breast cancer. The follow-up time ranged from 1.2 to 10.2 years with a median of 5.7 years. In multivariate analysis Ki-67/MIB-1 value was a strong (p < 0.001) significant, prognosticator of disease recurrence free interval (DRFI) independent of lymph node status, progesterone receptor content, and tumor size. In the subgroup analysis of 430 node-negative patients the distant recurrence-free rate after 5 years was 94.4% in patients with Ki-67/MIB-1 value < 15% compared to 88.7% in patients with Ki-67/MIB-1 value > or = 15% (p = 0.03). Test of the interaction between tumor size and the value of PF revealed a p-value of 0.06. If the patients, in addition, had a tumor size >20 mm the distant recurrence-free rate after 5 years was 93.2% if Ki-67/MIB-1 < 15% compared to 80.7% in patients with Ki-67/MIB-1 value > or = 15%. This difference was statistically significant (p < 0.01). For patients with tumors <20mm Ki-67/MIB-1 value did not add any prognostic information. In the subgroup of 302 node-positive patients the distant recurrence-free rate after 5 years was 86.0% in patients with Ki-67/MIB-1 value < 15% compared to 70.6% in patients with Ki-67/MIB-1 value > or = 15% (p < 0.01). We conclude that PF assessed by Ki-67/MIB-1 antibodies in preoperative FNA biopsies has a significant prognostic value independent of lymph node status, PgR status and tumor size. To our knowledge, this is the first study demonstrating PF, which can contribute prognostic information when analyzed in preoperative smears.

Prognostic importance of the uPa/PAI-1 complex in breast cancer.

The complex between urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor 1) has been prognostically evaluated in patients with breast cancer. The concentrations of uPA antigen, PAI-1 antigen and the uPA/PAI-1 complex were analysed in extracts from breast cancer tumours from 233 patients (median follow-up of patients: 71months). The uPA/PAI-1 complex typically constituted about 5% of the uPA antigen (total uPA). The concentration of complex was found to correlate more strongly to the concentration of PAI-1 (r = 0.72; p < 0.0001) than to the concentration of uPA (r = 0.55: p < 0.0001). Interestingly, in this material the uPA/PAI-1 complex (using an optimised cutoff level of 0.22 ng microg(-1) DNA) had a stronger prognostic value than optimised cut-off valuesfor uPA or PAI-1. The data suggest that activation of prourokinase within the tumour, which is a prerequisite for the formation of the uPA/PAI-1 complex, is of better prognostic value than the production of prourokinase or PAI-1 in the breast cancer tumour.

The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study.

BACKGROUND: The Stockholm II trial is a population-based prospective randomized trial on preoperative radiotherapy in rectal carcinoma. METHODS: Eligibility criteria were age younger than 80 years and biopsy-proven adenocarcinoma of the rectum judged resectable for cure with an abdominal procedure. Between 1987 and 1993, 557 patients were included. Patients were randomized to preoperative radiotherapy (RT+) followed by surgery within a week (n = 272) or surgery alone (RT-; n = 285). Radiotherapy was given with 25 grays in 1 week to the rectum and pararectal tissues. Curative resection was performed in 481 patients (86%). Median follow-up was 8.8 years. RESULTS: Among patients who underwent curative surgery, the incidence of pelvic recurrence was 12% (RT+) and 25% (RT-), respectively (P < 0.001). The overall survival rate in irradiated patients who underwent curative surgery was improved (46%) versus (39%; P < 0.03). For all included patients, the difference was 39% (RT+) compared with 36% (RT-; P = 0.2). Within 6 months of surgery, 13 of 272 (5%) of the irradiated patients died of intercurrent disease versus 4 of 285 (1%) of the nonirradiated (P = 0.02). Cardiovascular death was the main cause of intercurrent death and occurred in 35 of 272 (13%) of the irradiated patients compared with 20 of 285 (7%) among the nonirradiated (P = 0.07). CONCLUSIONS: Preoperative short-term radiotherapy reduces the risk of pelvic recurrence and can improve survival after curative surgery for rectal carcinoma. An increased risk of intercurrent death may reduce the benefit especially in elderly patients.

Partial irradiation of the heart.

Radiation-induced heart disease (RIHD) includes pericarditis, ischemic heart disease, and myocardial infarction and leads in some cases to fatal complications. It has been shown that the increased survival due to radiotherapy could be negated by excess deaths from RIHD in breast cancer radiotherapy for left-sided tumors. Subclinical effects following irradiation have been detected in several studies both of breast cancer and Hodgkin's irradiation. The dose-volume response relationships describing cardiac complications have been studied for pericarditis and cardiac mortality by means of biologic models, including the well-known Lyman-Kutcher-Burman (LKB) model and Källman's relative seriality model. Studies by Martel and coworkers on pericarditis and by Gagliardi and coworkers on cardiac mortality are reviewed. The anatomical and functional definition of the heart represents a key issue in modeling, as it affects strongly the dosimetrical data to be used as input data in the models. Several treatment strategies to decrease heart irradiation, based on models and/or based on dose-distribution evaluations, are reviewed. It is concluded that left-sided breast cancer patients should always be 3-dimensional (3D) dose planned.

Surgical treatment for skeletal breast cancer metastases: a population-based study of 641 patients.

BACKGROUND: The objective of this article was to assess the occurrence of symptomatic bone metastases in a defined population of patients with breast carcinoma and to characterize the clinical outcome with reference to surgical treatment for pathologic fracture or neurologic deficit. METHODS: The authors identified all patients in the Stockholm Breast Cancer Database (population base 1.8 million) with a diagnosis of bone metastases during 1989--1994. These cases were linked with the Stockholm County Council Hospital Discharge Diagnosis Registry that includes information on in-patient care and discharge diagnoses. This enabled us to identify patients who had undergone surgical treatment for their bony metastases at any of the six departments of orthopedics in the region, or who had been treated at the one department of neurosurgery. RESULTS: Six hundred forty-one patients with breast carcinoma presented with symptomatic skeletal metastasis during 1989--1994, and 107 (17%) were operated on. Metastases were located in long bones (77), spine (14), and pelvis (6). The median survival postoperatively was 6 months. The total reoperation rate was 0.12. Hip screws and glide-screw plates were associated more often with failure as was location in the distal femur. Pain decreased postoperatively in 77% of the patients, and function improved in 65%. CONCLUSIONS: One in 10 patients with breast carcinoma developed symptomatic bone metastases, and one-fifth of these patients required surgery for pathologic fracture or neurologic deficit. There was a high failure rate in those hospitals in which few patients were operated on.

Tumour location and the effects of preoperative radiotherapy in the treatment of rectal cancer.

BACKGROUND: Preoperative radiotherapy improves local control and survival in rectal cancer, but may also increase postoperative morbidity and mortality rates. Establishing selection criteria for preoperative radiotherapy is crucial. The tumour level above the anus may be one such criterion. The effect of preoperative radiotherapy in relation to the distance between the tumour and the anus was therefore assessed. METHODS: In 457 patients operated for cure included in the Stockholm II Trial the local recurrence rate in irradiated and non-irradiated patients was analysed in relation to the tumour location (low, mid or upper rectum). RESULTS: Radiotherapy reduced the local recurrence rate from 30 to 20 per cent in low rectal cancer, from 25 to 11 per cent in mid rectal cancer and from 21 to 5 per cent for tumours in the upper rectum. CONCLUSION: With conventional surgical techniques preoperative radiotherapy plays an important role in rectal cancer irrespective of the location of the tumour. To irradiate only patients with tumours in the lower rectum and to omit this treatment for patients with tumours in the mid and upper rectum cannot be recommended. Whether this statement is valid with standardized total mesorectal excision (TME) surgery is not known. Until this knowledge is available the current indications for preoperative radiotherapy should probably also be used with TME surgery.

Radiation therapy in the management of brain metastases from breast cancer.

A retrospective analysis of 99 patients treated at Radiumhemmet, Karolinska Hospital 1979-1990 with palliative radiotherapy for brain metastases from breast cancer was performed. A relief of symptoms was obtained in 45% of patients. Median time from diagnosis of breast cancer until CNS metastases was 33 months. Median survival time with CNS metastases after diagnosis was 5 months. Prognostic indicators for survival were studied. Patients operated for a singular brain metastasis and irradiated postoperatively had a mean survival of 21 months while patients with multiple brain metastases and meningeal spread displayed a short median survival. Extracranial disease status influenced prognosis significantly. Radiation dose (CRE) did not correlate with survival.

Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm.

BACKGROUND: Large, prospective, randomized trials with long term follow-up are required to obtain an unbiased evaluation of the significance of resection margins in patients with cutaneous melanoma. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized, multicenter study of patients with primary melanoma located on trunk or extremities and with a tumor thickness > 0.8 mm and 0.8 mm thick and