Follow-up Of Breast Cancer Patients Research Articles

Axillary ultrasound scanning in the follow-up of breast cancer patients undergoing sentinel node biopsy

In breast cancer patients with negative sentinel node biopsy (SNB), surveillance of the unremoved nodes is recommended. Clinical examination has poor sensitivity. The aim of this study was to evaluate the role of axillary ultrasound scan (AUS) in the follow-up of these patients. AUS was performed every 12 months in a series of 165 patients with negative SNB. During the follow-up (median 45.6 months), in 154 patients, the AUS was carried out as a routine examination and in three cases (1.9%) it showed suspicious nodes, which underwent core biopsy. No evidence of axillary recurrence was found. Conversely, in 11 patients, AUS was performed to clarify a palpable lymphadenopathy; none of them was suspicious at US. We conclude that routine AUS to follow-up patients who have had a negative SNB is unnecessary. However, AUS may be useful in the presence of palpable nodes, to select those patients who do not require biopsy.

Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases

BackgroundIn breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel.MethodsIn 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, ≥ 11 and ≥ 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels.ResultsDistant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off ≥ 11 U/mL, MCA showed the lowest specificity (42%); with cut-off ≥ 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With ≥ 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With ≥ 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel.ConclusionAt both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients.

Metastatic breast cancer: an updating

This article reports on recent advances on metastatic breast cancer. Detection, prognostic factors, predictors of response to therapy and therapy, with particular regard to targeted therapies, were examined. Detection Unlike current guidelines that yet do not routinely recommend intensive clinical-instrumental post-operative follow-up of breast cancer patients, relatively large data collected in the last decades have shown that an intensive post-operative follow-up with ‘dynamic evaluation’ of a suitable tumour marker panel precedes a few months as average the clinical and/or instrumental sign of a pending relapse in most relapsed patients and largely limits the use of the common instrumental examinations. Prognosis and therapy predictors Disease-free interval (DFI) ≤ 24 months, adjuvant chemotherapy, liver and distant soft tissue involvement or DFI > 24 months and disease confined to bony skeleton are prognostic factors more often correlated with relatively poor or prolonged survival, respectively. Estrogen receptor (ER) expression in primary tumour and at the relapse correlates strongly with response to salvage hormone therapy and data from large trials showed that 38–59% of ER and/or PR+ post-menopausal patients had clinical benefit from first line tamoxifen or aromatase inhibitors. An inverse correlation of ER with epidermal growth factor receptor (EGFR) has been found. The co-expression of HER-2/neu and/or elevated serum HER-2/neu protein level were associated with a low rate and shorter duration of response of ER+ patients to first line hormone therapy. Accordingly, ER–EGFR– compared with ER–EGFR+ tumours are usually more responsive to endocrine therapy. High class III beta-tubulin expression or fall in insulin-like growth factor binding protein-3 (IGFBP-3) from baseline levels have been found to significantly predict resistance to chemotherapeutic agents. Therapy Liposomes as carrier of doxorubicin (Caelix, Evacet, Myocet) is one approach to decrease the anthracycline-related cardiac toxicity. Weekly paclitaxel or docetaxel and oral formulation of vinorelbine and 5-fluorouracil (5-FU) (capecitabine) provide new effective and well tolerated options that reach greater dose intensity and cumulative dose than with the conventional schedules. As to the so called ‘tailored’ or targeted therapies, the more potent and highly selective third generation of aromatase inhibitors (letrozole, anastrozole, exemestane) targeting ER+ tumours by estrogen deprivation, challenge tamoxifen as current standard first line therapy in postmenopausals. One pilot study showed that stimulation of cellular immunity by the addition of beta-interferon-interleukin-2 sequence in patients on clinical benefit on first line tamoxifen significantly prolonged median overall survival (OS) and duration of response compared to that observed in similar patients only treated with tamoxifen. Trastuzumab, a humanised monoclonal antibody to extracellular domain of HER-2, plus conventional chemotherapy has become a standard of care for women with overexpressing HER-2 tumours. Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) that in refractory metastatic breast cancer doubled the response rate of capecitabine although it did not affect survival. Finally, the so called ‘oligometastatic’ and a few stage IV diseases are conditions amenable to be rendered with no evidence of disease (NED) after local surgery and/or radiation. In both, as well as in complete responders to chemotherapy, minimal residual disease (m.r.d.) likely continues to be present. Recent data suggest that ‘biological’ therapy (immunomodulators and/or retinoids with or without hormone therapy), might be suitable to be successfully tested in these patients as maintenance treatment given soon after local intervention or chemotherapy.

A randomized controlled trial (RCT) of long-term follow-up for early stage breast cancer comparing family physician to specialist care: A report of secondary outcomes

6003 Background: Breast cancer patients usually receive follow-up in specialist cancer clinics. We have reported that family physician follow-up of breast cancer patients is a safe and acceptable alternative to specialist follow-up as measured by the primary clinical outcome of the rate of serious clinical events (Grunfeld et al, JCO 2006;24(6)). We report here the secondary outcomes of this trial: quality of life domains, patient satisfaction and patients’ costs. Methods: Women with early stage breast cancer who had completed adjuvant therapy (patients may have continued on adjuvant hormonal therapy), who were disease free and between 9 and 15 months after diagnosis, were allocated to receive follow-up in a cancer clinic according to usual practice (CC arm) or follow-up from their own family physician (FP arm). For patients without recurrence, quality of life (QL) measured by the SF36, patient satisfaction, and patients’ costs were measured every 6 months. For patients with recurrence QL measured by the EORTC QLQ C-30 was measured at the time of recurrence. Results: 483 patients were allocated to the FP arm and 485 to the CC arm. Median follow-up was 3.5 years. There were no significant differences between groups on change scores for SF36 subscales to 24 months, or EORTC functional subscale scores at the time of recurrence. Patients’ costs of follow-up (travel costs, out-of-pocket expenses, and lost earnings) were significantly less to 24 months (p < 0.02) in the FP arm. Although costs were less between 36 and 48 months, these were not significant. Conclusions: Family physician follow-up of breast cancer patients does not have a negative impact on clinical or QL outcomes and is less costly for patients. No significant financial relationships to disclose.

Breast cancer follow-up: could primary care be the right venue?

ABSTRACTAims: To identify the elements of a follow-up protocol for treated breast cancer patients in primary care with reference to key stakeholders in one region of the UK.Methods: Stage 1: a survey of 100 consecutive hospital records relating to patients treated for primary breast cancer. The most common problems managed at follow-up and the type and frequency of resources used were identified. Stage 2: focus groups with stakeholders identifying potential barriers to follow-up of breast cancer patients in primary care after successful therapy. Stage 3: a nominal group outlined the elements of a follow-up protocol in primary care.Results: The most frequently recorded problems in 702 patient years of follow-up were anxiety, unrelated medical problems and joint pain. Anxiety and depression tend to present relatively soon and are often enduring whereas concomitant medical problems also present later. Health care professionals considered patients difficult to manage because symptoms of recurrence require investigation for absolute reassurance of the symptomatic patient. However, investigations other than mammograms were seldom necessary.Conclusions: A multidisciplinary panel identified attention to the psychosocial sequelea of breast cancer as a vital aspect of follow-up. Patients and their partners are preoccupied with a fear of recurrence. This may manifest in a variety of guises including mental health problems. These can be addressed in primary care especially with the support of counsellors, with teamwork and agreed protocols for referral back to specialists when indicated.

Quantitative analysis of plasma circulating DNA at diagnosis and during follow-up of breast cancer patients

The aim of the present project was to quantify the level of plasma DNA in patients with malignant or non-malignant breast diseases and in healthy controls, then investigate whether such measurements have diagnostic or prognostic value. Plasma DNA from 121 women (61 patients with breast cancer, 33 control patients with benign breast diseases and 27 healthy control individuals) was quantified by a real-time quantitative polymerase chain reaction (PCR) method. Plasma DNA concentration in the breast cancer patients (median 65 ng/ml) was significantly higher ( P<0.05) than that in the control patients (median 22 ng/ml) or healthy control (median 13 ng/ml). No association was observed between plasma DNA levels and clinicopathological parameters. The data suggest that quantification of plasma circulating DNA may be a valuable complementary diagnostic tool in discriminate breast cancer from unaffected individuals and may be proposed as an early detection test as well as a new, noninvasive assay to follow-up patients.

Ultrasonography of the axilla in the follow-up of breast cancer patients who have a negative sentinel node biopsy and who avoid axillary clearance

The clinical value of ultrasonography of the axilla in detection of breast cancer recurrence is not known among patients who have a negative sentinel node biopsy and avoid axillary clearance. We studied a cohort of 205 such patients using ultrasonography one and three years after breast surgery. A recurrent tumour was found in the axilla in only two (0.5%) of the total of 383 ultrasound examinations performed during the study, and only one (0.3%) of the 369 examinations performed at the scheduled study visits revealed cancer. None of the ultrasound examinations was false positive, and no study participant was subjected to unnecessary surgery due to ultrasound monitoring. We conclude that the rate of breast cancer recurrence in the ipsilateral axilla is low following sparing of the axillary contents, and that monitoring of such patients with repeated ultrasound examinations is unlikely to be cost-effective.

Follow-up after treatment of primary breast cancer.

This study evaluates the usefulness of routine follow-up of breast cancer patients. In all, 416 patients who were treated with curative intent for breast cancer were followed according to a fixed follow-up schedule for a minimum of 2.5 years and a maximum of 13.5 years (mean about 5 years). During the 4533 routine out-patient visits, 4116 chest radiographs, 3889 pelvic radiographs and about 17,000 laboratory tests were carried out routinely. In the follow-up period, 148 patients were found to have distant recurrence of whom 34 (23 per cent) had asymptomatic metastases and 114 symptomatic metastases. Of the 8005 routinely performed radiographs, 24 (0.3 per cent) revealed asymptomatic metastases, and the 17,000 laboratory tests led to the discovery of six asymptomatic bone and four asymptomatic liver recurrences. Screening for metastases did not result in a reduction of the lead time to the diagnosis of asymptomatic metastases; the disease-free interval was equal in both symptomatic and asymptomatic patients. Of the 46 locoregional recurrences 42 were found by physical examination during a routine follow-up visit and 37 had not been noticed by the patient. Seventeen second primary breast cancers were diagnosed, six of which were in stage I (less than 2 cm). Mammography was not a part of the routine follow-up scheme. It is concluded that routine follow-up of breast cancer patients by history and physical examination is sufficient to detect local recurrence and a second primary tumour as well as giving the opportunity to track signs and symptoms of distant recurrence at an early stage. Performing annual or biannual mammography is advisable, but the use of other costly routine investigations in the follow-up is not justifiable, as no therapeutic advantages can be expected.

Lymphödem bei Mammakarzinom: Regionale Konsensus-Empfehlungen zum postoperativen Management, Prävention, Therapie und Nachsorge

Fragestellung: Das Lymphödem ist eine der häufigsten Komplikationen der lokalen operativen und strahlentherapeutischen Behandlung bei Mammakarzinom und betrifft bis zu 30 % aller Brustkrebspatientinnen. Die Schädigungen des Lymphgefäßsystems führen dabei zu progressiven und chronischen Funktionsstörungen, die mit physischer Behinderung und Beeinträchtigungen bei Alltagsaktivitäten einhergehen und die Lebensqualität betroffener Frauen in nahezu allen Lebensbereichen einschränkt. Bei zunehmender Überlebenschance ist der Bedarf, langfristige Nebenwirkungen durch eine patientinnenorientierte Versorgung zu verbessern, Ausgangspunkt für die Entwicklung einer Handlungsempfehlung zum Management bei Lymphödem für Ärzte und Patientinnen. Methode: Es wurde ein systematisches Konsensusverfahren und eine Ergebnisabstimmung mit allen regionalen Behandlungspartnern unter Berücksichtigung der relevanten Studien und existierenden Leitlinien durchgeführt. Ergebnisse: Eine praxisorientierte und indikationsbezogene Handlungsempfehlung zur Untersuchung und Verlaufsdokumentation des Lymphödems bei Mammakarzinom wurde entwickelt, die die Messung relevanter Lebensqualitätsparameter durch die Patientin selbst mit anerkannten Messinstrumenten einschließt. Konsensusempfehlungen zum postoperativen Management, zur Prävention, Behandlung und Nachsorge entsprechend dem klinischen Algorithmus wurden verabschiedet. Schlussfolgerung: Mit erhöhten Heilungschancen stellen langfristige Folgestörungen, mit Auswirkungen auf die Lebensqualität der Patienten, zunehmend einen wichtigen Faktor zur Beurteilung onkologischer Therapiekonzepte dar. Die vorliegende Handlungsempfehlung begegnet den Defiziten der sektor- und fachübergreifenden Versorgung bei sekundärem Lymphödem bei Mammakarzinom. Die Untersuchungsmodalitäten und ihre Dokumentation zu festgelegten Zeitpunkten erlaubt eine longitudinale, dem individuellen Krankheitsverlauf angepasste Unterstützung von Ärzten und Patientinnen bei der Entscheidung zur Einleitung von therapeutischen Maßnahmen. Patientencompliance zur Behandlung und Prävention sind ebenso wichtig wie die Gewährleistung der Versorgungskontinuität. Die Implementierung der Handlungsempfehlung wird durch eine wissenschaftliche Untersuchung zur Effektivität und Effizienz begleitet.

Systematische oder symptomorientierte Nachsorge bei Frauen mit Mammakarzinom

Nearly all national (AGO, DKG) and international guide lines (e. g. ASCO) for follow-up of breast cancer patients do not explicitly recommend regular laboratory and radiological/ultrasound screening procedures. According to these guide lines, follow-up should be focused on the breast, only patients with possibly tumour related symptoms should be screened for metastatic disease. The rejection of more time-consuming and costlier follow-up examinations remains a contradiction to established follow-up guide lines for other solid tumours. In addition, treatment options for metastatic breast cancer disease have improved continuously over the last years. However, treatment options are considerably limited in advanced disease, if e. g. symptoms like dyspnoea or jaundice are already present at first diagnosis of metastatic disease. Therefore we will review available data of older studies as well as discuss arguments for a systematic surveillance in high-risk breast cancer patients. Overall, symptom guided follow-up seems to be adequate for patients with small primary tumours, no lymph node involvement and therefore a high curative probability, whereas in the authors' opinion systematic surveillance should be recommended for high risk patients even in the absence of symptoms. All patients, however, should be fully informed about the possibility of metastatic disease development and should be enabled to select the quality of their postoperative follow-up.

Implementing a clinical pathway for quality-of-life diagnostics and therapy in follow-up of breast cancer patients

758 Background: In order to integrate DRQL diagnostics into the guideline-based treatment of breast cancer patients a logistically refined clinical pathway was developed and implemented in the regional tumor center (population 2,3 millions) to diagnose and treat DRQL in breast cancer patients. Methods: Implementation from June 2003- Sept. 2004 included a prospective trial with 218 female patients (age 34–86 years), a multifaceted strategy (outreach visits, opinion leaders, CME in a quality circle) (Med Care 39, Suppl. 2, 85, 2000). The clinical pathway has been developed using the clinical algorithm methodology (Med. Dec. Mak. 12, 149,1992) and is here presented in narrative terms. Results: The clinical pathway starts in the clinic with DRQL questionnaire and health status by the physician. They are sent to the quality of life unit for producing the visual QL profiles and the expert report. The letter is sent to coordinating practitioners who decide either not to accept or to apply one or more of 5 therapeutic options (physiotherapy, psychotherapy, social support, pain therapy or nutrition/sports) or to send the patient to special health care providers for these options. A loop is built between quality of life unit and coordinating physician to ensure adherence to the system and initiating re-admission in 3,6,9 and 12 moths. The system was applied in 218 patients within 15 months. Structurally it included 5 clinical centers, the DRQL unit, 38 practitioners, 12 opinion leaders and 72 health care providers (specialists) for 5 therapeutic options. The complete clinical pathway can be depicted in the form of a clinical algorithm (not shown here), including 3 decision modes, 7 action boxes and one loop. Conclusion: DRQL was implemented successfully into standard follow up of breast cancer patients via a clinical pathway. The pathway guarantees state-of-the art therapy of all breast cancer patients treated within the tumor centre. The effectiveness of the clinical pathway is currently being evaluated by a randomized clinical trial. No significant financial relationships to disclose.

Reduced rates of cancer-related worries and mortality associated with guideline surveillance after breast cancer therapy

Guidelines have been developed for appropriate post-therapy surveillance for breast cancer recurrence. Two objectives of post-therapy surveillance are to support and counsel patients and to detect potentially curable local recurrences and new cancers in the opposite breast. The objective of this investigation was to assess the impact of guideline surveillance (history, physical examination, and annual mammography) on cancer-related worries and all-cause mortality. We collected data on a cohort of 303 Massachusetts women with stages I or II breast cancer diagnosed between 1992 and 1994. Cases were women with increasing cancer-related worries or decedents. We used risk-set sampling to match five controls to each case on follow-up time. Cases and members of their matched risk set were characterized with respect to receipt of guideline surveillance and covariates preceding the date of their outcomes. The adjusted odds ratio associating guideline surveillance in the preceding year with an increase in cancer-related worries equaled 0.37 (95% CI = 0.14-0.99). The adjusted odds ratio associating continuous guideline surveillance with all-cause mortality equaled 0.66 (95% CI = 0.51-0.86). The results are consistent with the stated objectives of surveillance follow-up of breast cancer patients after the completion of their primary therapy.

Intensive post-operative follow-up of breast cancer patients with tumour markers: Accuracy of serum MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels for early detection of relapse

753 Background: In breast cancer serum CEA-TPA-CA15.3 tumour marker panel is a cheap tool with high accuracy for the early detection of relapse (A Nicolini, Br J Cancer 1997); serum MCA and CA15.3 are also reported among the most useful serum tumour markers. However the most suitable cut-off of MCA has not yet been defined. The aims were to compare the MCA-CA15.3 with the CEA-TPA-CA15.3 tumour marker panel and to assess the effect of two different MCA cut-off values on this comparison. Methods: From May 2000 to February 2003, 264 breast cancer patients every 6 or 4 months, according to whether they were at low or high risk of relapse, were monitored with serial serum MCA, CEA, CA15.3, and TPA levels besides history and routine lab examinations. Cut-off value was 4.3 ng/mL (CEA), 32 U/mL (Ca15.3), 95 U/L (TPA), 11 and 16 U/mL (MCA). Tumour marker increase was dynamically evaluated according to a previously described method (A Nicolini, Br J Cancer 2000) Bone scintigraphy, liver echography and chest x-ray...

A randomized controlled trial (RCT) of routine follow-up for early stage breast cancer: A comparison of primary care versus specialist care

665 Background: Breast cancer patients usually receive follow-up in cancer centers. From the results of preliminary research (Grunfeld, BMJ 1996;313:665), we hypothesized that routine follow-up in primary care is a safe and acceptable alternative to follow-up in specialist care. Methods: Women with early stage breast cancer who had completed adjuvant therapy (patients may have continued on adjuvant hormonal therapy), who were disease free and between 9 and 15 months after diagnosis, were allocated to receive follow-up in a cancer center according to usual practice (CC arm) or follow-up from their family physician (FP arm). Patients in the FP arm were referred back to the cancer center if diagnosed with recurrence or a new primary cancer. The primary outcome was a comparison of the rate of ‘serious clinical events’ (SCE) defined as any one of the following: spinal cord compression, pathological fractures, hypercalcaemia, uncontrolled local recurrence, brachial plexopathy, or poor functional status (Karnofsky ≤ 70). Secondary outcome was quality of life (QL). Results: 483 patients were allocated to the FP arm and 485 to the CC arm. Median follow-up was 3.5 years. The average age was 61 years; 69% were node negative; 73% had a lumpectomy; 77% had radiation. The FP arm had 54 (11.2%) recurrences and 29 deaths (6.0%). The CC arm had 63 (13.0%) recurrences and 30 (6.2%) deaths. In the FP arm 16 patients (3.3%) experienced a SCE compared to 18 (3.7%) in the CC arm (0.4% difference; 95%CI –2.02 to +2.83). There were no differences between groups in QL as measured by the SF36 Physical and Mental Component Scales and the HADS anxiety and depression scales. Conclusions: Primary care follow-up of breast cancer patients is a safe and acceptable alternative to specialist follow-up. No significant financial relationships to disclose.

A randomized controlled trial (RCT) of routine follow-up for early stage breast cancer: A comparison of primary care versus specialist care

665 Background: Breast cancer patients usually receive follow-up in cancer centers. From the results of preliminary research (Grunfeld, BMJ 1996;313:665), we hypothesized that routine follow-up in primary care is a safe and acceptable alternative to follow-up in specialist care. Methods: Women with early stage breast cancer who had completed adjuvant therapy (patients may have continued on adjuvant hormonal therapy), who were disease free and between 9 and 15 months after diagnosis, were allocated to receive follow-up in a cancer center according to usual practice (CC arm) or follow-up from their family physician (FP arm). Patients in the FP arm were referred back to the cancer center if diagnosed with recurrence or a new primary cancer. The primary outcome was a comparison of the rate of ‘serious clinical events’ (SCE) defined as any one of the following: spinal cord compression, pathological fractures, hypercalcaemia, uncontrolled local recurrence, brachial plexopathy, or poor functional status (Karnofsky ≤ 70). Secondary outcome was quality of life (QL). Results: 483 patients were allocated to the FP arm and 485 to the CC arm. Median follow-up was 3.5 years. The average age was 61 years; 69% were node negative; 73% had a lumpectomy; 77% had radiation. The FP arm had 54 (11.2%) recurrences and 29 deaths (6.0%). The CC arm had 63 (13.0%) recurrences and 30 (6.2%) deaths. In the FP arm 16 patients (3.3%) experienced a SCE compared to 18 (3.7%) in the CC arm (0.4% difference; 95%CI –2.02 to +2.83). There were no differences between groups in QL as measured by the SF36 Physical and Mental Component Scales and the HADS anxiety and depression scales. Conclusions: Primary care follow-up of breast cancer patients is a safe and acceptable alternative to specialist follow-up. No significant financial relationships to disclose.

Intensive post-operative follow-up of breast cancer patients with tumour markers: Accuracy of serum MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels for early detection of relapse

Intensive post-operative follow-up of breast cancer patients with tumour markers: Accuracy of serum MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels for early detection of relapse

Advantages and limitations of FDG PET in the follow-up of breast cancer.

18F-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has been evaluated in breast cancer for the characterisation of primary tumours, lymph node staging and the follow-up of patients after surgery, chemotherapy and/or external radiotherapy. In contrast to both the low sensitivity and moderate specificity of FDG PET in the initial detection and characterisation of breast cancer and the low lesion-based sensitivity for lymph node staging, the results from use of FDG PET in re-staging breast cancer patients are very promising. A major advantage of FDG PET imaging compared with conventional imaging is that it screens the entire patient for local recurrence, lymph node metastases and distant metastases during a single whole-body examination using a single injection of activity, with a reported average sensitivity and specificity of 96% and 77%, respectively. In most studies the sensitivity of FDG PET is higher than that of a combination of conventional imaging methods. Limitations of FDG PET in the follow-up of breast cancer patients include the relatively low detection rate of bone metastases, especially in case of the sclerotic subtype, and the relatively high rate of false positive results. The rather low specificity of FDG PET can be improved/increased by utilising combined anatomical-molecular imaging techniques, such as a PET/CT tomograph. First results using PET/CT imaging in the follow-up of breast cancer patients demonstrate increased specificity compared with FDG PET alone. Both imaging modalities, however, offer to detect recurrent and metastatic breast cancer disease at an early stage and thus continue to demonstrate the efficacy of molecular imaging in patient management, despite the limited therapeutic options in recurrent and metastatic breast cancer.

Utility of a Serum Tumour Marker Panel in the Post-Operative Follow-Up of Breast Cancer Patients with Equivocal Conventional Radiological Examinations

Objective: To assess the value of the serum carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and breast cancer-associated antigen CA15.3 (CEA-TPA-CA15.3) tumour marker panel in selecting from a group of patients with equivocal bone scintigraphy, chest X-ray or liver echography, those with skeletal, thoracic or liver metastases. Clinical data of 427 breast cancer patients submitted to an intensive follow-up after mastectomy between January 1986 and December 2000 were retrospectively reviewed. Methods: Among the 427 patients operated on for breast cancer, 221 patients with a total of 332 equivocal instrumental examinations (bone scintigraphy, n = 286; chest X-ray, n = 29; liver echography, n = 17) were reviewed. All 221 patients were followed up clinically, biochemically and instrumentally until there was a clear definition of their condition, metastatic or not, for an average time of 35 months. Positive and negative predictive values of the tumour marker panel in patients with equivocal bone scintigraphy, chest X-ray and liver echography were evaluated; concomitant clinical symptoms were also taken into consideration. Results: Among the 221 patients with equivocal bone scintigraphy, chest X-ray and liver echography, tumour markers showed a positive predictive value of 69, 93 and 83% and a negative predictive value of 98, 86 and 91%, respectively, for the indication of the metastatic or benign origin of the equivocal instrumental imaging. Clinical symptoms were not helpful in predicting metastatic disease (sensitivity, specificity and accuracy of 60, 53 and 54%, respectively). Conclusions: These data suggest that a short monitoring with the CEA-TPA-CA15.3 tumour marker panel is an important tool to confirm or exclude metastatic disease in those patients who are suspected to have metastases following common instrumental investigations, and it is particularly important to avoid false positive diagnoses.

Proteolytic imbalance is reversed after therapeutic surgery in breast cancer patients.

The occurrence of metastasis severely affects prognosis and survival of breast cancer patients. In order to metastasize, breast cancer cells need to cross the basement membrane (BM) tissue boundaries. Matrix metalloproteases (MMPs) are enzymes with proteolytic activity towards extracellular matrix components (ECM) of the BM, that are blocked by physiological tissue inhibitors (TIMPs). Cancer metastasis occurs as a result of an imbalance between MMPs, in particular MMP-2 and MMP-9, and TIMPs, in particular TIMP-2 and TIMP-1. This is the first study to report that pro-MMP-9 and TIMP-1 serum concentrations are inversely correlated in breast cancer patients. In the same patients, we determined the pro-MMP-9, the TIMP-1, the pro-MMP-2 and TIMP-2 before and after surgical eradication of the breast cancer. Our results show that after surgery, when the breast cancer tissue was removed, pro-MMP-9 concentrations dramatically decreased and TIMP-1 concentrations strongly increased, with statistically significant differences, so that a new balance was established. No statistically significant differences were observed regarding pro-MMP-2 and TIMP-2. Also, no correlation was found between pro-MMP-2, pro-MMP-9, TIMP-1 and TIMP-2 and a number of clinical and pathological parameters. In conclusion, our study suggests that pro-MMP-9 and TIMP-1 could be used as markers of disease during the follow-up of breast cancer patients and possibly as prognostic markers, although more studies are needed to address this issue.

The prognostic value of the soluble urokinase-type plasminogen activator receptor (s-uPAR) in plasma of breast cancer patients with and without metastatic disease

Elevated levels of soluble uPAR (s-uPAR) and other fibrinolytic parameters functionally related to the urokinase-type plasminogen activator system might indicate the presence of cancer cells. In 25 breast cancer patients with metastases s-uPAR was significantly increased compared with 25 patients without metastases and with 25 healthy controls: 420 pg mL-1 vs. 145 pg mL-1 (P = 0.005) and 190 pg mL-1 (P = 0.003). Plasmin-alpha2-antiplasmin (PAP) complexes and d-dimers were significantly increased in breast cancer patients with metastases compared with patients without metastases and with healthy controls. The levels of plasminogen activator inhibitor (PAI)-1 activity, uPA antigen and factor (F)XIIa did not significantly differ between the patient groups and healthy controls. PAP complexes (529 microg L-1 vs. 420 microg L-1; P = 0.03), d-dimers (278.5 ng mL-1 vs. 79.0 ng mL-1; P = 0.005) and FXIIa (1.64 ng mL-1 vs. 1.19 ng mL-1; P = 0.01) were significantly higher in patients with metastases not surviving compared with patients with metastases surviving the 3-year follow-up period. Plasma s-uPAR levels in the patients with metastases did not discriminate between patients surviving and patients not surviving after 3-year follow-up. No significant differences in s-uPAR or any of the other parameters were found in the five patients developing metastases during follow-up. A single value of s-uPAR is of limited value in the follow-up of breast cancer patients with and without metastatic disease and does not predict survival or future metastases.