Immunization with a P53 synthetic long peptide vaccine induces P53-specific immune responses in ovarian cancer patients, a phase II trial.

The prognosis of ovarian cancer, the primary cause of death from gynecological malignancies, has only modestly improved over the last decades. Immunotherapy is one of the new treatment modalities explored for this disease. To investigate safety, tolerability, immunogenicity and obtain an impression of clinical activity of a p53 synthetic long peptide (p53-SLP) vaccine, twenty patients with recurrent elevation of CA-125 were included, eighteen of whom were immunized 4 times with 10 overlapping p53-SLP in Montanide ISA51. The first 5 patients were extensively monitored for toxicity, but showed no > or = grade 3 toxicity, thus accrual was continued. Overall, toxicity was limited to grade 1 and 2, mostly locoregional, inflammatory reactions. IFN-gamma producing p53-specific T-cell responses were induced in all patients who received all 4 immunizations as measured by IFN-gamma ELISPOT. An IFN-gamma secretion assay showed that vaccine-induced p53-specific T-cells were CD4(+), produced both Th1 and Th2 cytokines as analyzed by cytokine bead array. Notably, Th2 cytokines dominated the p53-specific response. P53-specific T-cells were present in a biopsy of the last immunization site of at least 9/17 (53%) patients, reflecting the migratory capacity of p53-specific T-cells. As best clinical response, stable disease evaluated by CA-125 levels and CT-scans, was observed in 2/20 (10%) patients, but no relationship was found with vaccine-induced immunity. This study shows that the p53-SLP vaccine is safe, well tolerated and induces p53-specific T-cell responses in ovarian cancer patients. Upcoming trials will focus on improving T helper-1 polarization and clinical efficacy.

Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study.

PURPOSE: Breast cancer patients with treatment-induced menopause experience frequent and severe hot flashes (HF). We compared venlafaxine and clonidine for the treatment of HF with regard to side effects, efficacy, quality of life and sexual functioning. METHODS: In a double-blind, cross-over study, 60 breast cancer patients experiencing HF were randomized to 8 weeks venlafaxine followed by 2 weeks wash-out, and 8 weeks clonidine or vice versa. HF frequency and severity, side effects, quality of life and sexuality were assessed. RESULTS: Thirty patients started with venlafaxine and 30 with clonidine. Premature discontinuation for toxicity occurred in 14/59 during venlafaxine and 5/53 during clonidine (P = .038). Venlafaxine induced more side effects. Median reduction in HF score was 49% for venlafaxine and 55% for clonidine (ns). CONCLUSION: Venlafaxine and clonidine are equally, but moderately effective in HF reduction. Side effects are the main reason for drug discontinuation, occurring more often with venlafaxine.

Sexual function in patients with metastatic midgut carcinoid tumours.

BACKGROUND: Sexual dysfunction is a poorly studied aspect of quality of life in patients with midgut carcinoid tumours. We investigated whether carcinoid patients experience sexual problems. METHODS: Patients with metastatic midgut carcinoid tumours filled in a validated questionnaire for sexual dysfunction. The prevalence of dysfunction on the subscales arousal, erection, lubrication, orgasm and dyspareunia was compared to a Dutch reference population. Plasma concentration of gonadal hormones, tryptophan and urinary 5-hydroxyindolacetic acid concentrations were measured. RESULTS: 43 patients were studied, 27 men and 16 women. Sexual dysfunction was present in 29.6% of men and 6.3% of women. The prevalence of sexual dysfunction on the different subscales did not differ from the reference population. Patients with a sexual dysfunction had, compared to those without a sexual dysfunction, a longer duration of disease, 95.3 months (range 5.4-314.5) versus 18.6 months (range 0.6-167.9) (p = 0.024), lower plasma tryptophan concentration (+/-SD) of 31.5 +/- 16.1 and 48.9 +/- 14.5 micromol/l (p = 0.031), and more often used interferon-alpha, 50% of patients versus 10.5% of patients (p = 0.044). CONCLUSION: Patients with metastatic midgut carcinoid tumours do not experience sexual problems more often than a reference population. Male patients with sexual dysfunction are characterised by more long-standing disease and lower tryptophan concentration.

Effect of tamoxifen on the endometrium and the menstrual cycle of premenopausal breast cancer patients.

OBJECTIVE: Tamoxifen, a nonsteroidal antiestrogen, is the agent of choice in the treatment of premenopausal receptor-positive breast cancer. This study aimed to investigate the influence of tamoxifen on the menstrual cycle and serum hormone levels and the subsequent endometrial response in premenopausal breast cancer patients. METHODS: In tamoxifen-using breast cancer patients aged 55 years or younger, the last menstrual period was registered, serum hormone levels measured, and the endometrial response visualized by transvaginal ultrasonography every 6 months. Premenopausal status was defined as serum levels of estradiol (E2) 0.10 nmol/L or more and follicle-stimulating hormone 30 IU/L or less. Premenopausal patients with an endometrial response of greater than 12 mm were offered a hysteroscopy and curettage. RESULTS: In 121 patients, a total of 241 measurements were performed. Amenorrhea predicted menopausal status incorrectly in 85 (35%) of the 241 measurements in 47 patients. In 8 of 47 endocrinologic premenopausal patients, transvaginal ultrasonography showed an endometrial response of greater than 12 mm (range,15-29 mm). Histopathology in women with an endometrial thickness of greater than 12 mm showed no malignancy. No relation between E2 levels and endometrial thickness was found. CONCLUSIONS: Tamoxifen leads to a disconnection between clinical and endocrinologic menopause in breast cancer patients aged 55 years or less. In premenopausal patients, tamoxifen has a predominantly antiestrogenic effect on the endometrium without a correlation between E2 levels and endometrial response.

Distinguishing benign and malignant pelvic masses: the value of different diagnostic methods in everyday clinical practice.

OBJECTIVE: To optimize referral to specialized gynaecologists for surgical treatment of ovarian cancer by improving preoperative discrimination between benign and malignant pelvic tumours. STUDY DESIGN: In a prospective multicentre study 143 patients with a pelvic mass were included. At several occasions during the diagnostic work-up the gynaecologist estimated the chance of malignancy (educated guess/expert opinion). MRI in the local setting was suggested for uncertain cases. All MRI images were reviewed by an expert radiologist. The datasheet designed for the study further allowed for determining the risk of malignancy index (RMI). RESULTS: The diagnostic accuracy of the gynaecologist's final estimation of the chance of malignancy and the calculated RMI were comparable (area under the ROC curve of 0.87 and 0.86). MRI did not improve the accuracy of the diagnostic work-up for the study population as a whole. Subgroup analysis did however show improved diagnostic accuracy in cases with an estimated chance of malignancy between 20 and 80% when the MRI was read by an expert radiologist. CONCLUSION: Patient selection for surgery of a pelvic mass should be based on the chance of malignancy as assigned by the referring gynaecologists. In case of uncertainty MRI improves diagnostic accuracy, when judged by an expert.

Persistent low urinary excretion of 5-HIAA is a marker for favourable survival during follow-up in patients with disseminated midgut carcinoid tumours.

Survival of patients with disseminated midgut carcinoid tumours varies. We investigated which factors predict survival at referral and during follow-up, with emphasis on urinary 5-hydroxyindolacetic acid (5-HIAA) levels. Between 1992 and 2003, 76 patients were studied; urine was prospectively collected over a 24 h period every 3 months in order to measure 5-HIAA levels. Uni- and multivariate analyses were performed. Median follow-up was 55 months with a median survival of 54 months. Prognostic factors for poor survival were high age, high gamma-glutamyltransferase levels and greatly increased 5-HIAA levels (>20 mmol/mol creatinine) The Hazard Ratio (HR) of a greatly increased 5-HIAA level was 3.33 (95% confidence interval (CI) 1.66-6.66, p=0.001). In a multivariate survival analysis with the 5-HIAA level as time dependent covariable, the HR for the 5-HIAA level was 1.007 (95% CI 1.004-1.010, p=0.000). In conclusion, patients with persistent moderately increased urinary 5-HIAA levels (< or =20 mmol/mol creatinine) have favourable outcome.

Hot flushes in breast cancer patients.

OBJECTIVES: A literature search was conducted to gather information concerning the pathophysiologic mechanisms leading to hot flushes, their prevalence and severity in breast cancer patients, their influence on quality of life, and the best therapeutic option. METHODS: Relevant studies in English were selected from Medline. RESULTS AND CONCLUSION: Pathophysiologic mechanisms leading to hot flushes are poorly understood. Estrogen withdrawal is considered to have a central role. Also, serotonin and norepinephrine seem to be involved in hot flush induction. Menopause induced by chemotherapy or ovarian ablation, is accompanied by an abrupt decrease in estrogen level, causing vasomotor symptoms. Hot flushes are also a side effect of tamoxifen and aromatase inhibitors. Quality of life in breast cancer patients may be negatively influenced by hot flushes, and therefore, adequate treatment is important. Currently, of the several non-hormonal options, the selective serotonin-reuptake inhibitor (SSRI) venlafaxine is the most effective in breast cancer patients. However, studies on interaction between SSRIs and tamoxifen may influence future recommendations.

Quality of life versus prolongation of life in patients treated with chemotherapy in advanced colorectal cancer: A review of randomized controlled clinical trials.

Oncologists disagree if chemotherapy in advanced cancer can improve quality of life (QoL), to prolong duration of life, or both. The objective of this study was to clarify the main treatment intention of palliative chemotherapy (PCT): the prolongation of life (PoL); or QoL. Randomized controlled clinical trials of PCT in advanced colorectal cancer that included HRQoL assessment were selected from PubMed and reviewed. Authors' conclusions were based on both PoL- and QoL-related outcomes. However, if PoL and QoL outcomes of the experimental arm were opposite, which was the case in 13 out of 28 trials, the authors generally based their conclusion on PoL outcomes. Authors' conclusions focused mainly on PoL-related outcomes, while QoL-related outcomes were of overriding importance in only 1/28 case. QoL can therefore not be considered as the main outcome of PCT. The review shows that in the context of chemotherapy in advanced colorectal cancer, 'palliative' refers to a life-prolonging intention, whereas within palliative care it refers to an improvement in QoL.

Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery.

PURPOSE: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. METHODS AND MATERIALS: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. RESULTS: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). CONCLUSIONS: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery.

Irritability rather than depression during interferon treatment is linked to increased tryptophan catabolism.

OBJECTIVE: Treatment with recombinant interferon is associated with high rates of psychiatric comorbidity. We investigated the relation between catabolism of the essential amino acid tryptophan, being rate-limiting of peripheral and cerebral serotonin formation, and psychiatric symptoms in patients undergoing combination treatment with interferon-alpha and ribavirin. PATIENTS AND METHODS: Eighteen patients with viral hepatitis C who received interferon were included. A psychiatrist screened patients before and while on interferon-alpha treatment for 2 months, using a structured diagnostic interview. Fasting plasma tryptophan and platelet serotonin levels were measured at each visit. RESULTS: At baseline no evident psychopathology was observed. After 2 months of interferon treatment, 10 patients experienced increased irritability. No other structural psychopathology was observed. Decreased plasma tryptophan level correlated with the presence of irritability (p = .047). Platelet serotonin levels were found to be decreased during treatment (p = .002). CONCLUSIONS: Aggressive impulse dysregulation is highly prevalent in patients receiving interferon treatment. This is associated with decreased plasma tryptophan levels which may lead to attenuated peripheral and central serotonergic neurotransmission.

Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment.

PURPOSE: To analyze whether serum squamous cell carcinoma (SCC) antigen and cytokeratin-19 fragments (CYFRA) levels can assist in selecting patients with locally advanced cervical cancer who will benefit from combined treatment or additive surgery. METHODS AND MATERIALS: Of 114 patients with cervical cancer Stage IB-IV, the first 39 patients received radiotherapy, the following 75 patients received identical radiotherapy plus concomitant chemotherapy (3 cycles of carboplatin and 5-fluorouracil). SCC antigen and CYFRA 21-1 serum levels were measured before treatment, after therapy, and during follow-up. Baseline tumor markers were related to tumor stage and size and clinical outcome. RESULTS: Before treatment, SCC antigen was elevated (>1.9 microg/L) in 60% and CYFRA 21-1 (>2.2 microg/L) in 46% of patients. For all patients, disease-free survival (DFS) was better after combined treatment (67% vs. 43%, p < 0.0005). For patients with elevated baseline SCC antigen, DFS was better after combination therapy (67% vs. 27%, p = 0.001) which resulted more frequently in a normal SCC antigen (93% vs. 65%, p = 0.004). In contrast, in those with a normal baseline CYFRA 21-1, combined therapy resulted in a better DFS (p = 0.04). Patients who achieved a normal SCC antigen or CYFRA 21-1 after treatment had a better DFS (respectively 63 vs. 17% and 64 vs. 30%). Elevated SCC antigen posttreatment indicated residual tumor in 11/12 patients (92%), elevated CYFRA 21-1 in 7/10 patients (70%). Forty-seven patients had a tumor recurrence. At recurrence, SCC antigen was raised in 70% and CYFRA 21-1 in 69%. CONCLUSIONS: In patients with an elevated pretreatment SCC antigen, SCC antigen normalized more frequently with combined treatment and those patients had a better DFS. Elevated SCC antigen or CYFRA 21-1 levels after treatment completion indicated residual tumor in respectively 92% and 70%. The presence of elevated posttreatment levels of SCC antigen or CYFRA 21-1 indicates the need for additional salvage surgery. SCC antigen proved to be superior to CYFRA 21-1 in predicting DFS and disease recurrence.

Bone metastases in carcinoid tumors: clinical features, imaging characteristics, and markers of bone metabolism.

UNLABELLED: The purpose of this study was to describe the clinical presentation of bone metastases in patients with carcinoid tumors and to determine the diagnostic value of imaging techniques and markers of bone metabolism. METHODS: This retrospective study was performed on the entire group of patients with carcinoid tumors treated in our hospital from January 1992 to May 1999. Only patients with metastasized tumors were included. RESULTS: Eleven of 90 patients (12%) (95% confidence interval [CI], 5%-19%) with a metastasized carcinoid tumor had symptomatic bone metastases. All bone metastases occurred in 55 patients with midgut carcinoids (20%; 95% CI, 9%-31%). Plain radiography had a sensitivity of 44% (95% CI, 12%-76%); MRI, 100% (95% CI, 61%-100%); bone scintigraphy, 90% (95% CI, 72%-100%); and octreotide scintigraphy, 60% (95% CI, 35%-93%). In 9 patients, both octreotide scintigraphy and bone scintigraphy were performed. Of 45 bone lesions, 22 (49%) were visualized by both modalities, 13 (29%) were visualized with octreotide scintigraphy but not with bone scintigraphy, and 10 (22%) were visualized with bone scintigraphy but not with octreotide scintigraphy. In 2 patients, octreotide scintigraphy and bone scintigraphy provided complementary results. Markers of bone metabolism could not discriminate carcinoid patients from those without bone metastases. The markers of bone metabolism did not reflect the osteolytic or osteoblastic appearance of metastases. CONCLUSION: Pain is the principal symptom of bone metastases in patients with carcinoid tumors. Plain radiography and markers of bone metabolism do not contribute to the diagnosis of bone metastases. MRI has a high sensitivity for bone metastases. Both bone scintigraphy and octreotide scintigraphy have acceptable sensitivity and can provide complementary results.

Patients with carcinoid syndrome exhibit symptoms of aggressive impulse dysregulation.

OBJECTIVE: Carcinoid tumors can produce excessive amounts of biogenic amines, notably serotonin. We assessed psychiatric symptoms in carcinoid patients and peripheral metabolism of tryptophan, the precursor of serotonin. METHODS: Twenty consecutive patients with carcinoid syndrome underwent a structured psychiatric interview applying DSM-IV (Diagnostical Statistical Manual) criteria. Tumor activity was measured by determination of 24-hour urine excretion of 5-hydroxyindoleacetic acid (5-HIAA) and platelet serotonin levels. Plasma tryptophan levels were measured and compared with sex- and age-matched references. RESULTS: Fifteen patients (75%) fulfilled diagnostic DSM-IV criteria for a disorder of impulse control. Tryptophan plasma levels were lower in patients compared with controls (p =.031) and were correlated negatively with urinary 5-HIAA excretion (p =.001). CONCLUSIONS: Impulse control disorders are prevalent in patients with carcinoid syndrome. The serotonin production by the tumor possibly decreases the tryptophan pool in the cerebrospinal fluid, which is the essential substrate for the production of brain serotonin as a pivotal neurotransmitter.

Tryptophan as a link between psychopathology and somatic states.

OBJECTIVE: Several somatic illnesses are associated with psychiatric comorbidity. Evidence is provided that availability of the essential amino acid tryptophan, which is the precursor of serotonin, may cause this phenomenon. METHODS: We performed a database search to find relevant articles published between 1966 and 2002. For our search strategy, we combined several diseases from the categories hormonal, gastrointestinal, and inflammatory with the search terms "tryptophan" and "serotonin." RESULTS: The catabolism of tryptophan is stimulated under the influence of stress, hormones and inflammation by the induction of the enzymes tryptophan pyrrolase (in the liver) and IDO (ubiquitous). Because of the reduction in blood levels of tryptophan under these circumstances the formation of cerebral serotonin is decreased. CONCLUSIONS: It is argued that the coupling of peripheral tryptophan levels and cerebral serotonin levels has physiological significance. The clinical implications and therapeutic consequences of changes in tryptophan and consequently serotonin metabolism are discussed.

Quality of adjuvant CMF chemotherapy for node-positive primary breast cancer: a population-based study.

PURPOSE: Adjuvant 'classical' oral cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) has long been the mainstay of adjuvant chemotherapy for premenopausal breast cancer patients. The Comprehensive Cancer Center North Netherlands (CCCN) breast cancer working group performed a retrospective audit of treatment guideline adherence and quality of CMF in hospitals in the CCCN area. METHODS: The CMF treatment data of 251 consecutive axillary lymph node-positive breast cancer patients <50 years old, diagnosed between 1993 and 1996, were analyzed. RESULTS: Ninety-four patients (42%) completed adjuvant CMF without dose adjustment or delay. Overall median relative dose intensity (RDI) was 92.6 (IQR 85.5-97.7). Sixty patients (24%) had an RDI <85, and 7% had an RDI <65. Myelotoxicity was the main reason for reductions and delays. Of 176 irradiated patients, 96% received radiotherapy simultaneously with CMF. Median CMF dose intensity nor median duration differed between patients who underwent mastectomy, mastectomy and radiotherapy, or breast-conserving therapy. Radiotherapy did not influence the median RDI (94 without versus 92 with radiotherapy). G-CSF, administered at least once to 76 patients, did not result in a higher median RDI. Median RDI was slightly higher when >3 patients/year (P=0.014) were treated by one specialist or >10 patients classified for adjuvant chemotherapy yearly in a hospital (P=0.037). CONCLUSION: The adherence to CMF treatment guidelines was generally good. Simultaneous radiotherapy did not affect the median RDI of CMF. G-CSF had no impact on the median RDI but patient volume did influence the RDI.

Cost-benefit analysis of capecitabine versus 5-fluorouracil/leucovorin in the treatment of colorectal cancer in the Netherlands.

BACKGROUND: Capecitabine is an oral prodrug of 5-fluorouracil and has been studied for the treatment of colorectal cancer. In 2 Phase III trials, capecitabine was at least as effective as 5-fluorouracil plus leucovorin and had a more favorable toxicity profile. OBJECTIVE: A cost-benefit analysis was used to assess the pharmacoeconomic profile of capecitabine compared with 5-fluorouracil/leucovorin, given according to the Mayo regimen, for colorectal cancer patients treated in the Netherlands. METHODS: The medical files of patients treated for colorectal cancer at a single center from 1999 to 2002 were examined to determine the numbers of outpatient visits for 5-fluorouracil/leucovorin administration, health care use and medication to manage adverse effects, and travel distance to and from the hospital. The costs of capecitabine treatment were simulated by assuming that the same patients were treated with capecitabine instead of 5-fluorouracil/leucovorin. Toxicity data for capecitabine were derived from 2 Phase III studies that compared capecitabine and 5-fluorouracil/leucovorin. RESULTS: The files of 65 patients were reviewed. Thirty-two patients received adjuvant treatment and 33 patients were treated palliatively for metastatic disease. The mean total costs of palliative treatment were Euro 4004 with capecitabine and Euro 5614 with 5-fluorouracil/leucovorin. These results were robust in sensitivity analyses. The cost savings were primarily related to the number of outpatient visits for capecitabine versus the number of day-care treatment days for 5-fluorouracil/leucovorin, despite the higher acquisition costs of capecitabine. CONCLUSIONS: Based on this analysis, treatment of colorectal cancer with oral capecitabine is cost saving in the Netherlands compared with 5-fluorouracil plus leucovorin administered according to the Mayo regimen. Baseline savings were estimated at Euro 1610 for palliative treatment and Euro 934 for adjuvant treatment.

Attending the breast screening programme after breast cancer treatment: a population-based study.

INTRODUCTION: In the Netherlands, breast cancer patients are treated and followed at least 5 years after diagnosis. Furthermore, all women aged 50-74 are invited biennially for mammography by the nationwide screening programme. The relation between the outpatient follow-up (follow-up visits in the outpatient clinic for 5 years after treatment) and the screening programme is not well established and attending the screening programme as well as outpatient follow-up is considered undesirable. This study evaluates potential factors influencing women to attend the screening programme during their outpatient follow-up (overlap) and the (re-)attendance to the screening programme after 5 years of outpatient follow-up. METHODS: Data of breast cancer patients aged 50-74 years, treated for primary breast cancer between 1996 and 2007 were selected from the Netherlands Cancer Registry and linked to the National Breast Cancer Screening Programme in the Northern region. Cox regression analyses were used to study women (re-)attending the screening programme over time, possible overlap with the outpatient follow-up and factors influencing this. RESULTS: In total 11227 breast cancer patients were included, of whom 19% attended the screening programme after breast cancer treatment, 4.4% within 5 years and 15.4% after more than 5 years. Factors that independently influenced attendance within 5 years as well as more than 5 years after treatment were: interval tumours (HR 0.77; 95%CI 0.61-0.97 and HR 0.69; 95%CI 0.53-0.88, ref: screen-detected tumours), receiving adjuvant radiotherapy (HR 0.65; 95%CI 0.47-0.90 and HR 0.66; 95%CI 0.47-0.93; ref: none) and diagnosis of in situ tumours (HR 1.67; 95%CI 1.25-2.23 and HR 1.39; 95%CI 1.05-1.85; ref: stage I tumours). Non-screen related tumours (HR 0.41; 95%CI 0.29-0.58) and recent diagnosis (HR 0.89 per year; 95%CI 0.86-0.92) were only associated with attendance within 5 years after treatment. CONCLUSION: The interrelation between outpatient follow-up and screening should be improved to avoid overlap and low attendance to the screening programme after outpatient follow-up. Breast cancer patients should be informed that attending the screening programme during the outpatient follow-up is not necessary.

Do screen-detected breast cancers have positive margins less often than clinically detected breast cancers?

Positive tumour margins after breast-conserving surgery (BCS) have been selected as one of the major quality criteria for the surgical treatment of localized primary breast cancer. The national guideline states that the rate of positive margins should not exceed 30% in ductal carcinoma in situ and 20% in invasive cancers. We aimed to determine whether BCS in women with screen-detected breast cancer (SDBC) will have positive margins less often compared with women with clinically detected breast cancer (CDBC). Furthermore, the choice of subsequent therapy is studied when margins were positive after initial BCS. Women 50-75 years of age who underwent BCS for invasive breast cancer between July 2008 and December 2009 were selected from the Netherlands Cancer Registry. Data were merged with the National Cancer Screening Program, regions North and East, to identify women with SDBC. The relation to screening history, clinical and pathological factors was evaluated for correlation with margin status using multilevel analysis. Of 1537 women with an invasive breast cancer, 873 (57%) were diagnosed through the screening programme. SDBCs were significantly smaller (87 vs. 69% T1 tumours, i.e. ≤2 cm), more often well differentiated (33 vs. 26%), preoperatively confirmed (98 vs. 96%), diagnosed in a nonteaching hospital (60 vs. 66%) and more often had negative lymph nodes (LNs) (80 vs. 68%). In 170 out of 1537 women, the resection margins were positive. Multivariable analysis showed that hospital, tumour size, multifocality, positive LNs and absent preoperative confirmation were predictors of positive margins. No difference was found between women with SDBC and CDBC. Of women with positive margins, 90% underwent additional surgery. Women diagnosed with SDBC do not have a lower risk of having positive margins after BCS than women with CDBC. Although positive margins may occur in 11% of women with invasive tumours, well below the percentage recommended by the national guideline, the presence of encouraging factors by SDBC such as a smaller tumour size, unifocality, negative LNs and the presence of preoperative confirmation should not lead to performing a more sparing excision than is considered usual for comparable CDBC.