Survival for clinical stage I lung cancer not surgically treated. Comparison between screen-detected and symptom-detected cases. The Japanese Lung Cancer Screening Research Group.

To assess the extent of overdiagnosis bias in lung cancer screening, clinical Stage I lung cancer cases detected by chest radiograph examination, with histologic or cytologic evidence of malignancy and not treated by surgical operation, were followed up for more than 10 years. Of 1297 screen-detected and 1297 symptom-detected cases collected from 20 institutions, 42 screen-detected and 27 symptom-detected cases satisfied the study criteria. In about half of the cases, the patients had no contraindication for surgical treatment, but they refused surgical procedure. All such patients from the screen-detected and symptom-detected groups died within 122 and 67 months, respectively, of diagnosis. Among the screen-detected and symptom-detected cases, 80% and 81%, respectively, of the patients died of lung cancer. The median survival time was 25 and 13 months for those in the screen-detected and symptom-detected groups, respectively. The difference in survival was statistically significant between the two groups, which indicated the effect of lead time and length-biased sampling. Analysis of the causes of death other than lung cancer showed that there was no difference in the observed cumulative rates of deaths of other causes between the two groups, and these figures were almost the same as those expected from the general population. This indicates that overdiagnosis bias would be minimal in screen-detected lung cancer cases detected by chest radiograph examination.     

Flow cytometric analysis of DNA ploidy and S-phase fraction from prostatic carcinomas: implications for prognosis and response to endocrine therapy

We analysed ploidy and S-phase fraction (SPF) from 78 paraffin-embedded primary prostatic carcinomas by DNA flow cytometry. DNA aneuploidy and above median (4.2%) SPF were both associated with high tumour grade, large size of prostate and presence of distant metastases. Both aneuploidy and high SPF (greater than 4.2%) indicated short 10-year progression-free (P = 0.01 for ploidy and P = 0.0002 for SPF), overall (P = 0.004 and P less than 0.0001) as well as prostate cancer survival (P = 0.002 and P less than 0.0001). Ten-year overall survival rate was 45% in cases with SPF below 4.2% and 0% in those with higher values, whereas the corresponding prostate cancer-specific survival rates were 80% and 11%, respectively. None of the seven tumours with SPF above 12% showed an objective response to endocrine therapy, whereas 26/49 (52%) of those with lower SPF values responded (P = 0.01). DNA ploidy, tumour grade, T-stage or M-stage did not significantly correlate with endocrine responsiveness. SPF was also the best predictor of progression free survival in patients treated hormonally. In conclusion, detection of high SPF in prostate cancer may indicate lack of hormonal responsiveness and poor prognosis.     

Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer.

DNA Ploidy and S phase fraction (SPF) were measured in Stage I and II breast cancers from patients with at least 8 years of follow-up, to assess the prognostic significance of these data. Disaggregated sections of formalin-fixed, paraffin-embedded tumour were analysed by flow cytometry. SPF was calculated using a rectangular model of S phase, after subtraction of background debris using an exponential model. 64% of tumours were DNA aneuploid. The median SPF was 4.5% for DNA diploid, and 10.9% for DNA aneuploid tumours. There were small reductions in survival at 10 years for DNA aneuploid tumours, and for tumours with above median SPF, but these were not statistically significant. The relative hazard for DNA aneuploid tumours was 1.20 (95% CI 0.81-1.76), and for high SPF was 1.31 (95% CI 0.87-1.98). Neither factor was statistically correlated with survival in multivariate analysis. Technical and theoretical factors limit the accuracy and reproducibility of flow cytometric data, and may explain the lack of prognostic information given.     

DNA index, S-phase fraction, histological grade and prognosis in breast cancer

DNA index and S-phase fraction (SPF) were measured by flow cytometry on paraffin embedded tissue from 140 primary breast tumours. The results of DNA analysis were compared with the size, degree of axillary node involvement, histological grade and steroid receptor content of the tumours, as well as with the patients' subsequent clinical course. Forty-four (31.4%) of the 140 tumours were diploid. S-phase fraction was evaluable for 134 (95.7%). The median SPF of the whole population was 7.1%, with diploid tumours having a significantly lower median SPF (3.2%) than aneuploid (10.1%, P less than 0.001). Both aneuploidy (P = 0.002) and high SPF (P less than 0.001) were strongly associated with high histological grade. There was no significant association between either DNA ploidy or SPF and tumour size, nodal status or steroid receptor content. An SPF below the median was strongly associated with better relapse-free survival (P = 0.008), overall survival (P = 0.004) and survival after relapse (P less than 0.001). Ploidy did not correlate significantly with clinical course. Multivariate analysis using the Cox model suggested that, while SPF gave prognostic information independent of tumour size or nodal status, this independent significance was lost when histological grade was included in the analysis.     

Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: review of a series of 271 patients with stage I and II breast cancer]

PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery, radiotherapy+/-systemic therapy was analysed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, N=37), DIP and medium or high SPF (DMH, N=76), ANEUP and low SPF (AL, N=24), ANEUP and medium or high SPF (AMH, N=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.     

Prognostic value of DNA flow cytometry in the locally recurrent, conservatively treated breast cancer patient.

PURPOSE: This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer. METHODS AND MATERIALS: Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale-New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow-cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis. RESULTS: At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P < .02). Patients with low SPF (< 12%) experienced an 83% 5-year survival rate, compared with a 24% 5-year survival rate in patients with high SPF (> or = 12%) (P < .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P < .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence. CONCLUSIONS: DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed.     

Copy number imbalances between screen- and symptom-detected breast cancers and impact on disease-free survival

Screening mammography results in the increased detection of indolent tumors. We hypothesized that screen- and symptom-detected tumors would show genotypic differences as copy number imbalances (CNI) that, in part, explain differences in the clinical behavior between screen- and symptom-detected breast tumors. We evaluated 850 women aged 40 and above diagnosed with stage I and II breast cancer at the University of Texas MD Anderson Cancer Center between 1985 and 2000 with information available on method of tumor detection (screen vs. symptoms). CNIs in screen- and symptom-detected tumors were identified using high-density molecular inversion probe arrays. Cox proportional modeling was used to estimate the effect of method of tumor detection on disease-free survival after adjusting for age, stage, and the CNIs. The majority of tumors were symptom detected (n = 603) compared with screen detected (n = 247). Copy number gains in chromosomes 2p, 3q, 8q, 11p, and 20q were associated with method of breast cancer detection (P < 0.00001). We estimated that 32% and 63% of the survival advantage of screen detection was accounted for by age, stage, nuclear grade, and Ki67 in women aged 50 to 70 and aged 40 to 87, respectively. In each age category, an additional 20% of the survival advantage was accounted for by CNIs associated with method of detection. Specific CNIs differ between screen- and symptom-detected tumors and explain part of the survival advantage associated with screen-detected tumors. Measurement of tumor genotype has the potential to improve discrimination between indolent and aggressive screen-detected tumors and aids patient and physician decision making about use of surgical and adjuvant treatments.     

Flow cytometric S-phase fraction in soft-tissue sarcoma: prognostic importance analysed in 160 patients.

We could determine the S-phase fraction (SPF) by flow cytometric DNA analysis of paraffin archival material in 160 of 260 patients with soft-tissue sarcoma of extremity and trunk wall. The prognostic value of SPF was compared with other clinicopathological factors. The median follow-up time was 16 (6-31) years. In a univariate analysis, deep tumour location, increasing tumour size and histological malignancy grade, microscopic tumour necrosis, vascular invasion, DNA non-diploidy and high SPF (>3.0%) were associated with poor metastasis-free survival. In a multivariate analysis, microscopic tumour necrosis and high SPF were independently prognostic for metastasis. Used in combination with tumour size, microscopic tumour necrosis and vascular invasion, SPF could identify a group of patients with a 5-year metastasis-free survival rate of 0.97. This group constituted one-quarter of all patients. Patients with low SPF who did recur had a prolonged clinical course both as regards metastases and local recurrence. We conclude that SPF is a valuable adjunct in prognostication in soft-tissue sarcoma.     

Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients.

Tumours from 336 breast cancer patients under the age of 50 were analysed for hormone receptor content and by DNA flow cytometry. Sixty-six percent of the tumours were positive for estrogen receptors (ER), 60% were progesterone receptor (PR) positive and 42% showed DNA diploid profiles. DNA hypodiploid tumours were relatively frequent (7%), especially in patients aged 40 years or less (11%). S-phase fraction (SPF), with a mean of 10%, correlated significantly with receptor status, DNA ploidy, lymph node status, tumour size and age. With a median follow-up period of 34 months, the distant recurrence-free interval was independently predicted by lymph node status, tumour size, SPF and PR content. Amongst the 212 patients who had not received adjuvant systemic treatment, receptor status was, in addition to lymph node status and SPF, independently related to distant recurrence rate. A high SPF identified a subgroup with high recurrence rate, comprising approximately one third of the node-negative patients. Similarly, the one third of node-positive patients who had PR-positive tumours with a low S-phase fraction formed a subgroup with low recurrence rate. We conclude that hormone receptor assays and DNA flow cytometry should be useful tools in the management of breast cancer patients less than 50 years of age.     

DNA flow cytometric analysis indicates that many breast cancers detected in the first round of mammographic screening have a low malignant potential

An organized mammographic screening program covered 8,690 women from selected birth cohorts (aged 50-59) in the Tampere University Central Hospital district. Forty-four breast cancer cases were detected in the first round of mammographic screening, which is 3.7 times the expected annual number of new cases in this population. To evaluate the proliferative kinetics and biological properties of these cancers, DNA flow cytometric analysis was carried out in 37 of the screen detected cancers (SDCs) using 60 clinically detected stage I-II cancers and 30 screen-detected benign lesions as reference. DNA aneuploidy was observed in 17/37 (46%) of the SDCs as compared to 41/60 (68%) in the clinical controls (p less than 0.05), while all the benign lesions were DNA-diploid. The median S-phase fraction (SPF) in the SDCs was significantly (p less than 0.001) lower (3.5%) than in the clinical controls (9.6%). Differences in SPF persisted in subgroups defined by DNA ploidy and histological type. In stage-I SDCs the median SPF value (2.5%) approached that of benign tumors (1.9%). Our epidemiological and biological data indicate that the first round of mammography predominantly detects prevalent preclinical lesions, some of which are of very low malignant potential. At present such patients may often receive too extensive treatment. DNA flow cytometry could help in the identification of cases which could be treated, for example, by breast-conserving methods.     

Tumour growth rate and DNA flow cytometry parameters as prognostic factors in metastatic melanoma.

The prognostic value of flow cytometric parameters and tumour growth rate of melanoma metastases under the mouse renal capsule was investigated for tumours from 117 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. DNA flow cytometry (FCM) was interpretable for the tumours of 114 patients, and growth rate analysis for 82 patients, both results being available from 79 patients. Thirty-six percent of the tumours were DNA diploid and 64% DNA aneuploid. Tumour ploidy and S-phase fraction were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Patients with DNA diploid or aneuploid tumours survived a median 16 and 27 months, respectively. A high growth rate of tumour sample in vivo under the mouse renal capsule tended to be a sign of poor prognosis, although not reaching statistical significance. Combining the results of FCM, tumour growth rate and TNM stage, we propose a highly efficient prognostic scoring method. Patients with a score above 0.75 had a median survival of 11 months compared to 30 months among patients scoring under 0.75 (P less than 0.0001). This score was the most significant (P less than 0.0001) prognostic factor in the Cox model when TNM stage, age, ploidy, SPF, and tumour growth rate were analysed as covariates.     

Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: analysis of a series of 271 patients with stage I and II breast cancer

Purpose. To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer.Patients and methods. A series of 271 patients, treated by surgery, radiotherapy ± systemic therapy was analyzed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, n=37), DIP and medium or high SPF (DMH, n=76), ANEUP and low SPF (AL, n=24), ANEUP and medium or high SPF (AMH, n=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model).Results. On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N(–) patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N(–) stage I and II breast cancer.     

Breast cancer proliferation measured on cytological samples: a study by flow cytometry of S-phase fractions and BrdU incorporation

Cell kinetics have been shown to be an important predictor of clinical evolution of operated breast cancer. We established a method for the estimation of the proliferative activity of tumour cells obtained by fine needle sampling without aspiration (FNS), using simultaneously S-phase fractions (SPF) measured on DNA histograms and 5-bromodeoxyuridine (BrdU) labelling index (BLI) measured by flow cytometry. Biparametric BrdU/DNA flow cytometry could be performed in 122 of 189 (65%) consecutive patients. The mean BLI of the cytologically malignant FNS (118) was of 3.0 and the median of 2.2%. One hundred and forty-eight DNA histograms (78%) were suitable for SPF analysis, of which 141 presented malignant cells, showing a mean of 4.5 and a median of 3.5%, comparable to BLIs. These results were obtained from fluorescence peak area histograms with doublet discrimination and background subtraction allowing the measurements of SPFs as low as 0.4%. An excellent correlation was thus observed between BLIs and SPFs, for the 94 cases for which both results were available (r = 0.85). Infrequent discordances (9%) were noted with SPFs considerably higher than BLIs. Seven patients had three consecutive FNS of their tumour at weekly intervals before treatment. Some variability in the proportions of multiple subpopulations of tumour cells was observed on the DNA histograms. In contrast, proliferation indices (SPF or BLI) were reproducible, suggesting homogeneous growth rates. We conclude that an estimation of the proliferative activity of breast tumours at any stage of the disease is possible routinely by SPF and/or BLI analysis of FNS. At least one quantitative proliferation index could be obtained for 91% of patients.     

乳腺癌细胞DNA含量分析及其预后关系

本实验应用流式细胞检测技术对53例乳腺癌石蜡包理组织标本DNA含量进行了测定,并分析了DNA倍体性、合成期细胞百分比与其他临床病理指标及患者5年存活率的关系,其中43例获得可供分析的结果.结果表明:(1)合成期细胞百分比(SPF)与患者5年存活率及腋淋巴结转移有显著相关性.(2)SPF和腋淋巴结转移与否结合可更准确地评估乳腺癌患者的预后.(3)DNA倍体性SPF、乳腺癌组织学类型之间无显著关系.作者认为:SPF反映了乳腺癌细胞的增殖活性和侵袭能力,可做为评估乳腺癌患者预后的指标.     

DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens

Breast cancer proliferative capacity as determined by the DNA thymidine labeling index, along with estrogen and progesterone receptor status, is highly predictive for risk of relapse and overall survival. Recently, DNA ploidy and proliferative capacity (S-phase fraction [SPF]) as determined by flow cytometry have also shown significant prognostic value. The authors have developed a technique which allows a 50 to 100 mg aliquot of the same frozen breast tumor specimen routinely employed in steroid receptor assays, to be assayed for both DNA ploidy and SPF by flow cytometry. Of the 1331 tumors examined, DNA histograms were evaluable for ploidy in 89% (1184) of specimens examined; 57% of these were aneuploid. Adapting a trapezoidal model to estimate SPF in both diploid and aneuploid tumors, the authors found 81% (1084) to be evaluable for SPF, with a median SPF of 5.8% for the entire population. The median SPF was significantly lower in diploid tumors (2.6%) than in aneuploid tumors (10.3%, P less than 0.0001). Both aneuploidy and high SPF were strongly associated with absence of steroid receptors. Aneuploid tumors showed more striking differences in the frequency of high S-phase values with respect to receptor status and age or menopausal status, whereas diploid but not aneuploid tumors showed lower SPF in node-negative versus node-positive patients. Because it is particularly important to identify the high-risk minority of node-negative patients, the authors examined the node-negative group separately. High SPF subgroups appeared in each category of receptor status and age or menopausal status within the node-negative group, suggesting that SPF will be an independent prognostic factor. With the DNA flow cytometric methods used here, it is now practical to determine ploidy and SPF for nearly every breast cancer patient. These factors, which show associations with established prognostic factors, such as receptor status can now be fully evaluated for their prognostic significance in broad patient populations.     

Predicting outcome for patients with node negative breast cancer: a comparative study of the value of flow cytometry and cell image analysis for determination of DNA ploidy.

This study was aimed at determining whether tumour DNA content measured by cell image analysis could provide additional prognostic information when compared to that provided by flow cytometry. Sections cut from paraffin blocks of tumours from 101 patients with node negative breast cancer were analysed by both methods and the results related to other prognostic variables and to patient relapse and overall survival. DNA ploidy measured by flow cytometry classified 46 tumours as diploid and 55 as aneuploid, whereas by cell image analysis 30 were diploid and 71 aneuploid (P less than 0.002). There were 20 tumours with discrepancies between the two methods; 18 of these were tumours with only one peak in flow analysis, but determined to be aneuploid with image analysis. DNA content as measured by both methods was significant for predicting relapse and survival by log-rank test, as were tumour histological grade, c-erbB-2 expression and tumour size. Multivariate analysis showed DNA ploidy measured by flow cytometry to be the only variable of independent significance (P less than 0.02) for both relapse and overall survival. Compared with cell image analysis, flow cytometry demonstrated a significantly higher proportion of diploid tumours, which may be related to differences in the internal standards applied to each method. We suggest that cell image analysis techniques can provide more sensitive information on the DNA content of tumour cells by direct measurement of nuclear DNA density of both normal lymphocytes and tumour cells in the same section. However, although image analysis appears to be more sensitive than flow cytometry in detecting DNA aneuploidy, the image technique appears to lack the specificity of flow cytometry in correlation with clinical outcome.     

DNA aneuploidy and low S-phase fraction as favourable prognostic signs in metastatic melanoma

The prognostic value of cellular DNA content in melanoma metastases was investigated by flow cytometric analysis of fresh or paraffin-embedded tumour blocks from 95 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. Thirty-three per cent of the tumours were DNA diploid and 67% DNA aneuploid. S-phase fractions were lower in DNA diploid than in DNA aneuploid tumours (10.7% and 17.6%). Tumour ploidy and S-phase fraction were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Surprisingly, patients with DNA aneuploid tumours and with tumours with low SPF survived significantly longer than those with DNA diploid or high SPF tumours. This exceptional finding of favourable prognosis for DNA aneuploid tumours was more prominent among patients receiving intensive systemic therapy and among patients with stage IV disease, probably indicating a tendency for DNA aneuploid tumours to have higher sensitivity to systemic therapy.     

Primary Care Continuity and Wait Times to Receiving Breast Cancer Chemotherapy: A Population-Based Retrospective Cohort Study Using CanIMPACT Data

(1) Background: Wait times to chemotherapy are associated with morbidity and mortality in breast cancer patients; however, it is unclear how primary care physician (PCP) continuity impacts these wait times, or whether this association is different in immigrants, who experience cancer care inequities. We assessed the association between PCP continuity and the contact-to-chemotherapy interval (wait time from when a patient first presents to healthcare to the first day of receiving breast cancer chemotherapy), with a specific look at the immigrant population. (2) Methods: Population-based, retrospective cohort study of women who were diagnosed with stage I–III breast cancer in Ontario who received surgery and adjuvant chemotherapy. We used quantile regression at the median and 90th percentile to quantify the effect of PCP continuity on the contact-to-chemotherapy interval, performing a separate analysis on the immigrant population. (3) Results: Among 12,781 breast cancer patients, including 1706 immigrants, the median contact-to-chemotherapy interval (126 days) was 3.21 days shorter (95% confidence interval (CI) 0.47–5.96) in symptom-detected patients with low PCP continuity, 10.68 days shorter (95% CI 5.36–16.00) in symptom-detected patients with no baseline PCP visits and 17.43 days longer (95% CI 0.90–34.76) in screen-detected immigrants with low PCP continuity compared to the same groups with high PCP continuity. (4) Conclusions: Higher PCP continuity was not associated with a change in the contact-to-chemotherapy interval for most of our study population, but was associated with a marginally longer interval in our symptom-detected population and a shorter contact-to-chemotherapy interval in screen-detected immigrants. This highlights the importance of PCP continuity among immigrants with positive screening results. Additionally, having no PCP visits at baseline was associated with a shorter contact-to-chemotherapy interval in symptom-detected patients.     

Screen-detected vs symptomatic breast cancer: is improved survival due to stage migration alone?

This paper examines whether screen-detected breast cancer confers additional prognostic benefit to the patient, over and above that expected by any shift in stage at presentation. In all, 5604 women (aged 50-70 years) diagnosed with invasive breast cancer between 1998 and 2003 were identified by the Eastern Cancer Registration and Information Centre (ECRIC) and mammographic screening status was determined. Using proportional hazards regression, we estimated the effect of screen detection compared with symptomatic diagnosis on 5-year survival unadjusted, then adjusted for age and Nottingham Prognostic Index (NPI). A total of 72% of the survival benefit associated with screen-detected breast cancer can be accounted for by age and shift in NPI. Survival analysis by continuous NPI showed a small but systematic survival benefit for screen-detected cancers at each NPI value. These data show that although most of the screen-detected survival advantage is due to a shift in NPI, the mode of detection does impact on survival in patients with equivalent NPI scores. This residual survival benefit is small but significant, and is likely to be due to differences in tumour biology. Current prognostication tools may, therefore, overestimate the benefit of systemic treatments in screen-detected cancers and lead to overtreatment of these patients.