Clinical tools to monitor treatment response and metastatic risk could improve early-stage triple-negative breast cancer (TNBC) care. Although molecular residual disease assays show promise, their use in the neoadjuvant setting requires rapid turnaround times. Tissue-informed approaches may be challenging for patients with limited biopsy samples. The objectives were to determine the surveillance sensitivity for detecting metastatic recurrence and evaluate the ctDNA response to neoadjuvant therapy (NAT) using a tissue-free epigenomic assay.

Patients with stage II or III TNBC undergoing neoadjuvant docetaxel and carboplatin chemotherapy on a clinical trial (NCT02124902) followed by surgery with or without adjuvant therapy were included in this study. Blood samples were prospectively collected before, during, and after completion of NAT and after surgery at prespecified surveillance time points. Plasma samples were analyzed by Guardant Reveal.

A total of 119 patients with TNBC were included in the analysis. ctDNA was detected in the postsurgical setting in 8.9% (7/79) of patients, with an 83% (5/6) patient-level surveillance sensitivity for metastatic recurrence and 99.5% (197/198) sample-level specificity. Postsurgical ctDNA detection was prognostic for the shorter recurrence-free interval (HR, 37.7; P < 0.0001). ctDNA detection at the post-NAT presurgical time point was also associated with a shorter recurrence-free interval in patients with residual disease at surgery (HR, 28.2; P < 0.0001).

In patients with early-stage TNBC, a tissue-free, epigenomic assay demonstrated high specificity and sensitivity for metastatic recurrence. ctDNA detection in the neoadjuvant setting indicated poor prognosis, highlighting its potential role across breast cancer care.

Breast cancer (BC) is a complex heterogenous disease that is a leading cause of death in women. For patients with early stage disease following primary BC therapy, approximately 30% will develop metastatic BC (MBC). The median survival of MBC patients is ~ 2-3 yr. While the early detection and monitoring of BC progression have improved prognosis and reduced BC-related mortality, there is a lack of long-term surveillance strategies for monitoring patients for recurrence of MBC. The aim of our study was to identify non-invasive urinary biomarkers for detection and monitoring of MBC.

We have conducted a comparative label-free LC-MS/MS analysis of the urinary proteome of patients with MBC and healthy age-matched, sex-matched controls (HC). A hybrid quadrupole time of flight (Q-Tof™) mass spectrometer was used for urine analysis via liquid chromatography (LC) with tandem mass spectrometry (MS/MS). Retrospective analysis of urine samples from MBC and locally invasive breast cancer (IBC) patients as well as HC was conducted. Diagnostic accuracies of candidate markers were validated using independent training and validation sets according to the REMARK criteria.

Using this approach, we have identified 212 urinary proteins of which 83 and 25 were unique to the MBC and HC groups, respectively. Upregulated proteins in the MBC cohort were associated with angiogenesis, Ca2+ homeostasis, apoptosis, proteolysis, extracellular matrix regulation, cell adhesion and protein synthesis pathways. A specific non-invasive metastasis signature comprised of candidate biomarkers (urinary CALB1, S100A8, ZAG, VTN and TN) were validated and analyzed via monospecific ELISA assays. Urinary vitronectin (uVTN) levels correlated with disease status and were significantly higher in samples from MBC compared to those from IBC patients and HC. uVTN alone (cutoff > 500 ng/ml) could discriminate between HC and MBC groups (AUC = 0.782, P < 0.001). Longitudinal analysis of samples from MBC patients indicated a strong correlation between uVTN levels and disease status.

Our findings suggest that uVTN is a promising and non-invasive biomarker for the diagnosis and monitoring of MBC. While future validation in larger cohorts should be done, these results identify a novel urinary protein that represents the first non-invasive diagnostic test for monitoring BC progression and recurrence.

After radical surgery for breast cancer, screening to diagnose recurrence in asymptomatic patients is not recommended. We retrospectively evaluated quality-adjusted survival. Included were fifty-seven recurrent breast cancer patients who died. Survival was partitioned into 3 health states by two different definitions: definition a) time with toxicities due to chemotherapy before progression (TOX1), time from the diagnosis of recurrence to progression without toxicities (TWiST1), and time from progression to death (REL1); definition b) time from the diagnosis of recurrence to death with toxicities (TOX2), without toxicities or hospitalization (TWiST2), and with hospitalization (REL2). Q-TWiST was calculated by multiplying the time in each health state by its utility (uTOX, uTWiST, and uREL). In threshold analyses, uTOX and uREL ranged from 0.0 to 1.0 whereas uTWiST was maintained at 1.0. We compared the patients with (n=32) and without (n=25) symptoms at the time of the diagnosis of recurrence. There was no difference in overall survival after primary surgery, although survival after the diagnosis of recurrence was significantly longer in the asymptomatic patients (p<0.01). Q-TWiST1 and Q-TWiST2 from the diagnosis of recurrence in the asymptomatic patients were significantly longer. Q-TWiST2 from primary surgery in the asymptomatic patients was significantly longer with some combinations of higher uTOX2 and lower uREL2. In conclusion, the asymptomatic detection of recurrence was associated with significantly longer quality-adjusted survival in comparison to symptomatic detection with some combinations of uTOX2 and uREL2. A prospective evaluation would clarify adequate follow-up methods after radical surgery for breast cancer.

The purpose of this study was to assess advanced imaging (bone scan, CT, or PET/CT) and serum tumor biomarker use in asymptomatic breast cancer survivors during the surveillance period.

Cancer registry records for 2,923 women diagnosed with primary breast cancer in Washington State between January 1, 2007, and December 31, 2014, were linked with claims data from 2 regional commercial insurance plans. Clinical data including demographic and tumor characteristics were collected. Evaluation and management codes from claims data were used to determine advanced imaging and serum tumor biomarker testing during the peridiagnostic and surveillance phases of care. Multivariable logistic regression models were used to identify clinical factors and patterns of peridiagnostic imaging and biomarker testing associated with surveillance advanced imaging.

Of 2,923 eligible women, 16.5% (n=480) underwent surveillance advanced imaging and 31.8% (n=930) received surveillance serum tumor biomarker testing. Compared with women diagnosed before the launch of the Choosing Wisely campaign in 2012, later diagnosis was associated with lower use of surveillance advanced imaging (odds ratio [OR], 0.68; 95% CI, 0.52-0.89). Factors significantly associated with use of surveillance advanced imaging included increasing disease stage (stage III: OR, 3.65; 95% CI, 2.48-5.38), peridiagnostic advanced imaging use (OR, 1.76; 95% CI, 1.33-2.31), and peridiagnostic serum tumor biomarker testing (OR, 1.35; 95% CI, 1.01-1.80).

Although use of surveillance advanced imaging in asymptomatic breast cancer survivors has declined since the launch of the Choosing Wisely campaign, frequent use of surveillance serum tumor biomarker testing remains prevalent, representing a potential target for further efforts to reduce low-value practices.

Most cancer survivors receive follow-up care after completion of treatment with the primary aim of detecting recurrence. Traditional follow-up consisting of fixed visits to a cancer specialist for examinations and tests are expensive and may be burdensome for the patient. Follow-up strategies involving non-specialist care providers, different intensity of procedures, or addition of survivorship care packages have been developed and tested, however their effectiveness remains unclear.

The objective of this review is to compare the effect of different follow-up strategies in adult cancer survivors, following completion of primary cancer treatment, on the primary outcomes of overall survival and time to detection of recurrence. Secondary outcomes are health-related quality of life, anxiety (including fear of recurrence), depression and cost.

We searched CENTRAL, MEDLINE, Embase, four other databases and two trials registries on 11 December 2018 together with reference checking, citation searching and contact with study authors to identify additional studies.

We included all randomised trials comparing different follow-up strategies for adult cancer survivors following completion of curatively-intended primary cancer treatment, which included at least one of the outcomes listed above. We compared the effectiveness of: 1) non-specialist-led follow-up (i.e. general practitioner (GP)-led, nurse-led, patient-initiated or shared care) versus specialist-led follow-up; 2) less intensive versus more intensive follow-up (based on clinical visits, examinations and diagnostic procedures) and 3) follow-up integrating additional care components relevant for detection of recurrence (e.g. patient symptom education or monitoring, or survivorship care plans) versus usual care.

We used the standard methodological guidelines by Cochrane and Cochrane Effective Practice and Organisation of Care (EPOC). We assessed the certainty of the evidence using the GRADE approach. For each comparison, we present synthesised findings for overall survival and time to detection of recurrence as hazard ratios (HR) and for health-related quality of life, anxiety and depression as mean differences (MD), with 95% confidence intervals (CI). When meta-analysis was not possible, we reported the results from individual studies. For survival and recurrence, we used meta-regression analysis where possible to investigate whether the effects varied with regards to cancer site, publication year and study quality.

We included 53 trials involving 20,832 participants across 12 cancer sites and 15 countries, mainly in Europe, North America and Australia. All the studies were carried out in either a hospital or general practice setting. Seventeen studies compared non-specialist-led follow-up with specialist-led follow-up, 24 studies compared intensity of follow-up and 12 studies compared patient symptom education or monitoring, or survivorship care plans with usual care. Risk of bias was generally low or unclear in most of the studies, with a higher risk of bias in the smaller trials. Non-specialist-led follow-up compared with specialist-led follow-up It is uncertain how this strategy affects overall survival (HR 1.21, 95% CI 0.68 to 2.15; 2 studies; 603 participants), time to detection of recurrence (4 studies, 1691 participants) or cost (8 studies, 1756 participants) because the certainty of the evidence is very low. Non-specialist- versus specialist-led follow up may make little or no difference to health-related quality of life at 12 months (MD 1.06, 95% CI -1.83 to 3.95; 4 studies; 605 participants; low-certainty evidence); and probably makes little or no difference to anxiety at 12 months (MD -0.03, 95% CI -0.73 to 0.67; 5 studies; 1266 participants; moderate-certainty evidence). We are more certain that it has little or no effect on depression at 12 months (MD 0.03, 95% CI -0.35 to 0.42; 5 studies; 1266 participants; high-certainty evidence). Less intensive follow-up compared with more intensive follow-up Less intensive versus more intensive follow-up may make little or no difference to overall survival (HR 1.05, 95% CI 0.96 to 1.14; 13 studies; 10,726 participants; low-certainty evidence) and probably increases time to detection of recurrence (HR 0.85, 95% CI 0.79 to 0.92; 12 studies; 11,276 participants; moderate-certainty evidence). Meta-regression analysis showed little or no difference in the intervention effects by cancer site, publication year or study quality. It is uncertain whether this strategy has an effect on health-related quality of life (3 studies, 2742 participants), anxiety (1 study, 180 participants) or cost (6 studies, 1412 participants) because the certainty of evidence is very low. None of the studies reported on depression. Follow-up strategies integrating additional patient symptom education or monitoring, or survivorship care plans compared with usual care: None of the studies reported on overall survival or time to detection of recurrence. It is uncertain whether this strategy makes a difference to health-related quality of life (12 studies, 2846 participants), anxiety (1 study, 470 participants), depression (8 studies, 2351 participants) or cost (1 studies, 408 participants), as the certainty of evidence is very low.

Evidence regarding the effectiveness of the different follow-up strategies varies substantially. Less intensive follow-up may make little or no difference to overall survival but probably delays detection of recurrence. However, as we did not analyse the two outcomes together, we cannot make direct conclusions about the effect of interventions on survival after detection of recurrence. The effects of non-specialist-led follow-up on survival and detection of recurrence, and how intensity of follow-up affects health-related quality of life, anxiety and depression, are uncertain. There was little evidence for the effects of follow-up integrating additional patient symptom education/monitoring and survivorship care plans.

Although not guideline recommended, studies suggest 50% of locoregional breast cancer patients undergo systemic imaging during follow-up, prompting its inclusion as a Choosing Wisely measure of potential overuse. Most studies rely on administrative data that cannot delineate scan intent (prompted by signs/symptoms vs. asymptomatic surveillance). This is a critical gap as intent is the only way to distinguish overuse from appropriate care.

Our aim was to assess surveillance systemic imaging post-breast cancer treatment in a national sample accounting for scan intent.

A stage-stratified random sample of 10 women with stage II-III breast cancer in 2006-2007 was selected from each of 1217 Commission on Cancer-accredited facilities, for a total of 10,838 patients. Registrars abstracted scan type (computed tomography [CT], non-breast magnetic resonance imaging, bone scan, positron emission tomography/CT) and intent (cancer-related vs. not, asymptomatic surveillance vs. not) from medical records for 5 years post-diagnosis. Data were merged with each patient's corresponding National Cancer Database record, containing sociodemographic and tumor/treatment information.

Of 10,838 women, 30% had one or more, and 12% had two or more, systemic surveillance scans during a 4-year follow-up period. Patients were more likely to receive surveillance imaging in the first follow-up year (lower proportions during subsequent years) and if they had estrogen receptor/progesterone receptor-negative tumors.

Locoregional breast cancer patients undergo asymptomatic systemic imaging during follow-up despite guidelines recommending against it, but at lower rates than previously reported. Providers appear to use factors that confer increased recurrence risk to tailor decisions about systemic surveillance imaging, perhaps reflecting limitations of data on which current guidelines are based. ClinicalTrials.gov Identifier: NCT02171078.

Overuse of surveillance imaging in patients after curative treatment for early breast cancer (ebc) was recently identified as one of the Choosing Wisely Canada initiatives to improve the quality of cancer care. We undertook a population-level examination of imaging practices in Ontario as they existed before the launch of that initiative.

Patients diagnosed with ebc between 2006 and 2010 in Ontario were identified from the Ontario Cancer Registry. Records were linked deterministically to provincial health care databases to obtain comprehensive follow-up. We identified all advanced imaging exams [aies: computed tomography (ct), bone scan, positron-emission tomography] and basic imaging exams (bies: ultrasonography, chest radiography) occurring within the first 2 years after curative treatment. Poisson regression was used to assess associations between patient or provider characteristics and the rate of aies.

Of 30,006 women with ebc, 58.6% received at least 1 bie, and 30.6% received at least 1 aie in year 1 after treatment. In year 2, 52.7% received at least 1 bie, and 25.7% received at least 1 aie. The most common aies were chest cts and bone scans. The rate of aies increased with older age, higher disease stage, comorbidity, chemotherapy exposure, and prior staging investigations (p < 0.001). Imaging was ordered mainly by medical oncologists (38%), followed by primary care physicians (23%), surgeons (13%), and emergency room physicians (7%).

Despite recommendations against its use, imaging is common in ebc survivors. Understanding the factors associated with aie use helps to identify areas for further research and is required to lower imaging rates and to improve survivorship care.

Advanced imaging and serum biomarkers are commonly used for surveillance in patients with early-stage breast cancer, despite recommendations against this practice. Incentives to perform such low-value testing may be less prominent in integrated health care delivery systems. The purpose of the current study was to evaluate and compare the use of these services within 2 integrated systems: Kaiser Permanente (KP) and Intermountain Healthcare (IH). The authors also sought to distinguish the indication for testing: diagnostic purposes or routine surveillance.

Patients with American Joint Committee on Cancer stage 0 to II breast cancer diagnosed between 2009 and 2010 were identified and the use of imaging and biomarker tests over an 18-month period were quantified, starting at 1 year after diagnosis. Chart abstraction was performed on a random sample of patients who received testing to identify the indication for testing. Multivariate regression was used to explore associations with the use of nonrecommended care.

A total of 6585 patients were identified; 22% had stage 0 disease, 44% had stage I disease, and 34% had stage II disease. Overall, 24% of patients received at least 1 imaging test (25% at KP vs 22% at IH; P = .009) and 28% of patients received at least 1 biomarker (36% at KP vs 13% at IH; P<.001). Chart abstraction revealed that 84% of imaging tests were performed to evaluate symptoms or signs. Virtually all biomarkers were ordered for routine surveillance. Stage of disease, medical center that provided the services, and provider experience were found to be significantly associated with the use of biomarkers.

Advanced imaging was most often performed for appropriate indications, but biomarkers were used for nonrecommended surveillance. Distinguishing between inappropriate use for surveillance and appropriate diagnostic testing is essential when evaluating adherence to recommendations.

Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors.

By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs.

We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors.

Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed.

The number of breast cancer survivors in our ageing population continues to rise. Policy makers internationally are seeking to identify alternatives to follow-up care in an acute setting.

The National Cancer Control Programme set out to develop a new policy for long-term follow-up of breast cancer survivors in Ireland.

Policy development was informed by analysis of current attendances at breast surgical clinics for routine follow-up, extraction of the necessary components of follow-up from international guidelines and focus group research with Irish patients.

Intensive follow-up investigations, other than mammography, do not confer additional survival benefit or improved quality of life. Provision of routine follow-up care of breast cancer survivors by GPs has been shown to be equivalent to follow-up by specialist clinics, in terms of clinical outcomes, patient quality of life and patient satisfaction. In Ireland, routine follow-up accounted for 15.4% (95% CI: 13.8-17.0%) of clinic appointments. A third were at least 5 years post-operative. Women highlighted issues such as attachment to specialist services, importance of communication and need for clarity as to where responsibility of care lies. Reassurance, confidence in the primary care practitioner, and coordination of multiple appointments were also identified as important issues.

A significant proportion of breast cancer survivors attending hospital surgical clinics for long-term follow-up could be safely discharged at 5 years, with the hospital maintaining responsibility for annual mammography. Successful implementation will depend on informed patients, clinicians' acceptance and communication between primary and secondary care.

The American Society of Clinical Oncology (ASCO) recently released a "Top Five" list of opportunities to improve the quality of cancer care. Item 4 on the list advises against using advanced imaging and biomarkers for surveillance in patients with breast cancer who are treated with curative intent. This study examined concordance with ASCO follow-up care guidelines for breast cancer survivors treated at an academic medical center.

Claims data and medical records were reviewed and abstracted for early stage breast cancer survivors starting 1 year post diagnosis. A trained abstractor classified imaging tests as diagnostic or surveillance. Proportions and frequencies were generated for receipt of services. Multilevel logistic regression was used to estimate factors associated with receiving recommended and nonrecommended services and biomarker tests.

Records were available for 258 patients. Mean age at diagnosis was 58 years (standard deviation of 13 years), mean time since diagnosis was 6 years (standard deviation of 2 years), and 71% were stage 0/1. Only 47% of the sample received a mammogram within 1 year of diagnosis, and 55% of the sample received at least 1 nonrecommended imaging service for surveillance purposes. Seventy-seven percent of the sample received at least 1 nonrecommended biomarker test. Regression results indicate that main treating physician, advanced disease stage, younger age at diagnosis, and greater number of years since diagnosis were associated with receiving nonrecommended services for surveillance.

Use of nonrecommended services for surveillance occurs frequently among early-stage breast cancer survivors. There are opportunities to increase use of guideline concordant posttreatment care for breast cancer survivors.

Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted.

To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors.

We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected.

The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million.

Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation.

There is growing evidence that follow-up for patients with early breast cancer (ebc) can be effectively carried out by the primary health care provider if a plan is in place. Here, we present data from a recent survey conducted in Ontario indicating that a shared-care model could work if communication between all health professionals involved in the care of ebc patients were to be improved. Patients and primary care providers benefit when the specialist provides written information about what their roles are and what to expect. Primary care providers need to have easy access to the specialist to discuss areas of concern. Patients also need to share responsibility for their care, ensuring that they attend follow-up visits on a regular basis and that they discuss areas of concern with their primary health care provider. A shared-care model has the potential to provide the best care for the least cost to the health system.

We studied the cost of follow-up of 472 breast cancer patients without distant metastasis after primary treatment in four different schedules in a randomized trial. The mean follow-up was 4.2 years. The four schedules differed in frequency of follow-up visits (every third or sixth month) and in intensity of diagnostic examinations (routine or on clinical grounds). Neither the frequency of visits nor the intensity of diagnostic examinations had any effect on disease-free or overall survival of patients. The total costs of follow-up, however, were different in the four follow-up schedules and varied between arms per patient from 1050 to 2269 euros and per detected recurrence from 4166 to 9149 euros. Outpatient visits every third month compared to every sixth month and routine examinations in the follow-up of asymptomatic primary breast cancer patients do not improve patient disease-free or overall survival, but increase the costs of follow-up 2.2 times.

Follow-up services for patients with localised cutaneous melanoma are widely discussed but there is no international consensus. Our aim was to discuss frequency and duration of follow-up, type of health professional involved, optimum intensity of routine investigation, and patients' satisfaction with follow-up. Searches of the published work were directed at publications between January, 1985, and February, 2004 on recurrences, subsequent primary melanoma, routine tests, and patients' satisfaction. In a selection of 72 articles, 2142 (6.6%) recurrences were reported, 62% of which were detected by the patients themselves. 2.6% of patients developed a subsequent primary melanoma. Most investigators do not support high-intensity routine follow-up investigations. Of the various follow-up investigations requested by physicians, only medical history and physical examination seem to be cost effective. Lymph-node sonography seems to be a promising method for detection, although survival benefit remains to be proven. Patients were found to be anxious about follow-up visits, although other research showed that provision of information to patients was much appreciated. Published work on the follow-up of patients with cutaneous melanoma has mainly been retrospective and descriptive. Recommendations can be given with only a low grade of evidence. For meaningful guidelines to be developed, prospective, high-quality methodological research is needed.

Although metastatic breast cancer is widely believed to carry a grim prognosis, treatment developments over the past 25 years have greatly improved survival outcomes in these patients. In selected cases, aggressive treatment approaches may occasionally result in long-term survival of 15 years or more. This review considers the role of surgery in the treatment of single or multiple metastatic lesions restricted to one site. For each site, available literature from 1992-2002 was assessed to determine the role of surgery on survival outcomes and to determine appropriate criteria for selecting the best candidates for surgery. For lung, liver, brain, and sternum metastases, the use of surgery with or without adjuvant therapy resulted in greater median survival times and 5-year survival rates. The best candidate for surgery had no evidence of additional metastatic disease, good performance status, and a long disease-free interval after treatment of the primary tumor. Current treatment standards for breast cancer follow-up do not include imaging studies other than mammography. The addition of chest x-rays as part of routine follow-up should be considered as a cost-effective approach for early assessment of metastases to the lung or sternum that may be appropriate for surgical excision.

Between May 1991 and December 1995, follow-up after primary therapy for 472 consecutive patients with localized breast cancer was randomly assigned to assess the efficacy of routine chest X-ray in detecting intrathoracic relapse as the first metastatic event. One group had regular chest X-rays while the other group had chest radiographs only when clinically needed (spontaneous). Patients were followed up until December 1999 or death. In the routine group, 243 patients had 1429 chest X-rays (mean 5.9 chest X-rays per patient). In the spontaneous group, 229 patients had 411 chest X-rays (mean 1.8 chest X-rays per patient). Both sensitivity and specificity were somewhat higher in the spontaneous arm compared to the routine arm. Patient sensitivity was 30% in the regular arm and 36% in the spontaneous arm. Film sensitivity was 11% in the regular arm and 20% in the spontaneous arm. Patient specificity was 85% in the regular arm and 86% in the spontaneous arm. The predictive values were practically the same in both arms. Patient positive predictive values were 22% in both arms and film positive predictive values were 21% in the regular and 22% in the spontaneous arm. Patient negative predictive values were 90% in the regular and 92% in the spontaneous arm. Film negative predictive values were 93% in the regular and 89% in the spontaneous arm. The differences in accuracy were not statistically significant between the arms. There were no significant differences in disease free survival or overall survival. The 5-year disease free survival was 86% in the regular and 89% in the spontaneous arm and the overall survival was 88 and 85% in the regular versus spontaneous arm, respectively. Routine chest X-ray in the follow-up of breast cancer patient is evidently of little use and is not likely to be of benefit to the patient in terms of disease free survival or overall survival as compared to the spontaneous schedule.

Elderly patients affected by solid tumours are frequently encountered on the surgical ward. Prejudice regarding operative risks and long term outcomes may alter their surgical management. Large series of elderly cancer subjects have been analysed and conclusive data are now available, to better tailor their management. Specific epidemiological data are presented in this review, screening programs critically considered, treatment procedures discussed, and the effectiveness of follow-up protocols is analysed together with cost effectiveness issues. Quality of life issues should not be neglected, and a continuous educational endeavour targeted at specialists and general practitioners is desirable.

Controversies over the frequency and intensity of the follow-up care of breast cancer patients exist. Some physicians have adopted an intensive approach to follow-up care that consists of frequent laboratory tests and routine imaging studies, including chest radiographs, bone scans, and CT scans, whereas others have established a minimalist approach consisting of only history, physical examinations, and mammograms.

Our objective was to evaluate the role of intensive follow-up on detection of breast cancer recurrence and to examine the impact of follow-up on overall survival.

During a 10-year period (1986-1996), 129 patients with recurrent disease were identified from a prospective database of 1898 breast cancer patients. The patients with recurrent disease were divided into minimalist or intensive groups according to method of detection.

Twenty-seven of 126 (21%) patients were assigned to the intensive method of detection group (LFT, CEA, CA 15-3, chest radiograph, CT scan, and bone scan); 99 of 126 (79%) patients were assigned to the minimal detection group (history, physical examination, and mammography). Distant disease to the bone was the most common initial tumor recurrence, at 27%. History, physical examination, and mammography detected recurrent cancer in approximately the same amount of time as LFTs, tumor markers, CT scans, and chest radiographs (P = .960). When the recurrent patients were divided into intensive and minimalist groups and analyzed by time to detection of recurrence, there was no significant difference between the time to detection in those recurrences detected by intensive methods and those recurrences detected by minimalist methods (P = .95). The independent variables age, tumor size, type of surgery, number of positive nodes, time to recurrence, method of detection, and site of recurrence (regional or distant) were subject to univariate and multivariate analysis by the Cox proportional hazards model. Only two variables had an impact on survival by multivariate analysis: early timing of the recurrence (P = .0011) and the site of the recurrence (P = .02). Timing was defined as early (< or =365 days from the time of diagnosis to recurrence) or late (> or =365 days from the time of diagnosis to recurrence). Early recurrence was the first variable found to be significant on stepwise forward regression analysis. The primary site of recurrence was significant at step two. The method of detection--intensive or minimal--did not significantly affect survival (P = .18).

There is no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer. Expensive diagnostic tests such as bone scans, CT scans, and serial tumor markers are best used for detection of metastasis in symptomatic patients.