Follow-up Of Breast Cancer Patients Research Articles

Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

IntroductionDetection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients.MethodsWe used a microarray platform of 60mer MUC1 glycopeptides, to confirm the presence of autoantibodies to cancer associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans at specific sites. Based on these results, larger amounts of an extended repertoire of defined MUC1 glycopeptides were synthesised, printed on microarrays, and screened with sera from a large cohort of breast cancer patients (n = 395), patients with benign breast disease (n = 108) and healthy controls (n = 99). All sera were collected in the 1970s and 1980s and complete clinical follow-up of breast cancer patients is available.ResultsThe presence and level of autoantibodies was significantly higher in the sera from cancer patients compared with the controls, and a highly significant correlation with age was observed. High levels of a subset of autoantibodies to the core3MUC1 (GlcNAcβ1-3GalNAc-MUC1) and STnMUC1 (NeuAcα2,6GalNAc-MUC1) glycoforms were significantly associated with reduced incidence and increased time to metastasis.ConclusionsAutoantibodies to specific cancer associated glycoforms of MUC1 are found more frequently and at higher levels in early stage breast cancer patients than in women with benign breast disease or healthy women. Association of strong antibody response with reduced rate and delay in metastases suggests that autoantibodies can affect disease progression.

Professionals’ opinion on follow-up in breast cancer patients; perceived purpose and influence of patients’ risk factors

AimTo provide insight into professionals’ opinions on breast cancer follow-up to facilitate implementation of new follow-up strategies. The study focuses on current practice, purpose and perceived effects, and preferred frequency and duration of follow-up. DesignA 29-item questionnaire on professionals’ demographics, current practice, opinion on the current guideline, preferences in frequency and duration of tailored follow-up, and the purpose and perceived effects of follow-up was sent to 633 Dutch professionals. ResultsThe current national guideline is followed by 81% of respondents. All different specialists are involved in follow-up. Sixty-nine percent of respondents’ report nurse practitioners to be involved in follow-up. When asked for tailored follow-up, professionals indicate more factors for increased follow-up (age<40 years, pT3-4 tumour, pN2-3, treatment related morbidity, and psychosocial support), than for reduced schedules (age >70 years and DCIS histology). Alternative forms of follow-up are not endorsed by >90% of respondents. Detection of a new primary tumour of the breast is considered the most important purpose of follow-up (98%), 57% still indicates detecting metastases as a goal. ConclusionsProfessionals tend towards longer and more intensive follow-up than the current guideline for a large group of patients. Limitations and developments in follow-up need to be considered to facilitate alternative follow-up strategies.

Economic evaluation of four follow-up strategies after curative treatment for breast cancer: Results of an RCT

BackgroundAn economic evaluation was performed alongside a randomised controlled trial (ISRCTN 74071417) investigating the cost-effectiveness of nurse-led telephone follow-up instead of hospital visits, and of a short educational group programme (EGP) in the first year after breast cancer treatment. MethodThis economic evaluation (n=299) compared the one-year costs and the effects of four follow-up strategies: (1) hospital follow-up; (2) nurse-led telephone follow-up; (3) hospital follow-up plus EGP; and (4) nurse-led telephone follow-up plus EGP. Costs were measured using cost diaries and hospital registrations. Quality-adjusted life years (QALYs) were measured using the EQ-5D. Outcomes were expressed in incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves. ResultsHospital follow-up plus EGP yielded most QALYs (0.776), but also incurred the highest mean annual costs (€4914). The ICER of this strategy versus the next best alternative, nurse-led telephone follow-up plus EGP (0.772 QALYs and €3971), amounted to €235.750/QALY. Hospital and telephone follow-up without EGP both incurred higher costs and less QALYs than telephone follow-up plus EGP and were judged inferior. Hospital follow-up plus EGP was not considered cost-effective, therefore, telephone follow-up plus EGP was the preferred strategy. The probability of telephone follow-up plus EGP being cost-effective ranged from 49% to 62% for different QALY threshold values. Secondary and sensitivity analyses showed that results were robust. ConclusionNurse-led telephone follow-up plus EGP seems an appropriate and cost-effective alternative to hospital follow-up for breast cancer patients during their first year after treatment.

Abstract P4-09-05: Long Term Follow-Up of Breast Cancer Patients of the Swedish Cancer Institute Breast Cancer Research Registry

Abstract Background: Since 1990 the Swedish Cancer Institute Breast Cancer Research Registry has accrued over 10,900 cases with a 92% follow-up rate. We analyzed the incidence of recurrence over time to evaluate the appropriate duration of our long term follow-up. Methods: Patients with stages 1-3 disease were selected for study. Stages 0 and 4 disease, and neo-adjuvant treatment patients were excluded. The incidence and time to recurrence was compared with tumor grade [Bloom Richardson (BR) score], hormone receptor, HER2 status, stage, number of positive lymph nodes, surgery, radiation therapy, chemotherapy, hormone therapy and menopausal status. Results: The recurrence rate was 7.8% (740/9455) of which 68% (500) occurred in the first 5 years, 24% (179) occurred between 5 and 10 years, and 8% (61) occurred after 10 years. Factors that had a significant (P&amp;lt;0.05) relationship with the incidence of and time to recurrence were: stage, grade, hormone receptor status, number of positive lymph nodes, hormone therapy and radiation therapy. In the hormone receptor negative group, 15% (181/1205) recurred - 86% within 5 years, 12% between 5 and 10 years and 1.7% over 10 years. In the hormone receptor positive group, 7.3% (522/7201) recurred - 62% within 5 years, 28% between 5 and 10 years and 10% over 10 years. Of the patients with negative nodes, 4.7% (255/5405) recurred - 65% within 5 years, 27% within 5 to 10 years and 7.5% over 10 years. For the patients with 1 - 3 nodes positive, 12.6% (222/1769) recurred - 67% within 5 years, 24% between 5 and 10 years and 10% over 10 years. For 4-9 nodes positive, 25.3% (121/478) recurred - 79% within 5 years, 20% between 5 and 10 years and 6.6% over10 years. For greater than 10 nodes positive, 40.9% (92/225) recurred - 75% within the first 5 years, 20% between 5 and 10 years and 5.4% over 10 years. A BR score of 3-5 resulted in 2.0% (32/1574) recurrences - 63% within 5 years, 25% between 5 and 10 years and 13% over 10 years. A BR score of 6-7 resulted in 5.1% (131/2559) recurrences - 73% within 5 years, 26% between 5 and 10 years and 1.5% over 10 years. A BR score of 8-9 resulted in 11.3% (179/1581) recurrences - 89% within 5 years, 10% between 5 and 10 years and 0.6% over 10 years. Conclusion: The incidence of recurrence and the rate of recurrence of breast cancer was greatest for tumors that were hormone receptor negative, had a high number of positive lymph nodes and were high grade (BR 8-9). The incidence of recurrence after 10 years was under 0.5% overall and under 1.0% for most groups. The exception was patients with over 10 nodes positive (2.2%). However, patients with low grade (BR 3-5), hormone receptor positive or 1-3 positive lymph nodes, or patients treated with total mastectomy without irradiation or hormone therapy had over 10% of their recurrences occur after 10 years. The old adage that after ten years one is cured does not apply to these low risk patients. Nor does it apply to the high risk patients although their outlook is markedly improved by 10 years. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-05.

307 Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastases. Interim analysis of the Spanish multicenter clinical trial. AATRM 048/13/2000

307 Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastases. Interim analysis of the Spanish multicenter clinical trial. AATRM 048/13/2000

Consequences of the expression of sialylated antigens in breast cancer

Changes in cell surface glycosylation are common modifications that occur during oncogenesis, leading to the over-expression of tumour-associated carbohydrate antigens (TACA). Most of these antigens are sialylated and the increase of sialylation is a well-known feature of transformed cells. In breast cancer, expression of TACA such as sialyl-Lewis x or sialyl-Tn is usually associated with a poor prognosis and a decreased overall survival of patients. However, the specific role of these sialylated antigens in breast tumour development and aggressiveness is not clearly understood. These glycosylation changes result from the modification of the expression of genes encoding specific glycosyltransferases involved in glycan biosynthesis and the level of expression of sialyltransferase genes has been proposed to be a prognostic marker for the follow-up of breast cancer patients. Several human cellular models have been developed in order to explain the mechanisms by which carbohydrate antigens can reinforce breast cancer progression and aggressiveness. TACA expression is associated with changes in cell adhesion, migration, proliferation and tumour growth. In addition, recent data on glycolipid biosynthesis indicate an important role of G D3 synthase expression in breast cancer progression. The aim of this review is to summarize our current knowledge of sialylation changes that occur in breast cancer and to describe the cellular models developed to analyze the consequences of these changes on disease progression and aggressiveness.

Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer

The choice of adjuvant systemic therapy is based on targeted therapy in line with the St. Gallen Consensus meeting. In addition to the traditional parameters, the panel recommended the use of proliferation markers and multigene assays. The purpose of the present study was to evaluate the clinical significance of proliferative activity using the Ki-67 index as a prognostic marker and as a predictor of recurrence time in breast cancer patients. The Ki-67 index was measured in 3,652 cases with primary breast cancer from 1987 to 2009. Out of these patients, 2,638 cases were evaluated simultaneously for estrogen receptor, progesterone receptor and HER2 from 1997, and these were analyzed as a prognostic factor according to their subtypes. The Ki-67 index exhibited a wide range of 1-99%, with a median of 20%, and cases were divided into 2 or 3 index groups; <20% and ≥20% (and ≥50%). The median Ki-67 index of tumors with luminal A was 17%, and that of luminal B type tumors was 29%. The Ki-67 index of HER2 tumors was 40% and that of triple negative tumors was 50%. A higher Ki-67 index significantly correlated with a higher grade of malignancy. Patients with a higher Ki-67 index had significantly lower disease-free survival (DFS) and overall survival rates. Moreover, there was a significant difference in the recurrence time. Multivariate analysis revealed that the Ki-67 index was a significant factor for DFS, irrespective of nodal status, and that Ki-67 was a significant marker only in luminal A type tumors. Furthermore, luminal A type cases with high Ki-67 had a similar DFS as the luminal B type cases. A higher Ki-67 index (≥20%) significantly correlated with other biological markers, poorer prognosis and early recurrence, particularly in luminal A type tumors. It is important to take the Ki-67 index into consideration in the treatment and follow-up of breast cancer patients.

Multiple 18f-fdg, pet-ct for postoperative monitoring of breast cancer patients

Positron emission tomography (PET)-computed tomography (CT) may be useful in the post-treatment follow-up of breast cancer patients. To assess the usefulness of (18)F-fluorodeoxyglucose (FDG) PET-CT (PET-CT) for postoperative monitoring of breast cancer patients. One hundred twenty-nine PET-CT studies performed on 55 female postoperative breast cancer patients (median age 56 years, range 36-86 years) were analyzed. The median interval between the PET-CT studies was 6 months (range 1-15 months). In order to determine the usefulness of serial PET-CT examinations in the postoperative follow-up of breast cancer patients, the PET-CT findings were compared with the physical findings, findings obtained by other imaging modalities, and the (18)F-FDG-PET (PET) findings. The PET findings were negative in 4 metastatic bone lesions with a positive bone scan. The PET findings were also negative in 6 of 9 osteogenic bone metastases and one of 64 osteolytic bone lesions. There were 5 cases with false-positive of PET, which were determined to be areas of soft-tissue hyperactivity. All false-positive/-negative findings were corrected by the addition of CT. The results of this study lend support to the clinical role of PET-CT in the postoperative follow-up/monitoring of breast cancer patients.

The value of surveillance mammography of the contralateral breast in patients with a history of breast cancer

Purpose To determine the contribution of surveillance mammography to the early detection of metachronous contralateral breast cancer (MCBC) and to assess its impact on the survival of breast cancer patients with relation to compliance. Method Breast cancer patients (5589) were identified using files from the regional cancer registry of the Comprehensive Cancer Centre North Netherlands (CCCN Groningen, The Netherlands). The programme sensitivity and the impact on prognosis of follow-up mammography with relation to compliance were evaluated in 114 patients who developed MCBC during hospital follow-up. Results The cumulative MCBC incidence rate at year 10 was 3.4% (95% CI: 2.8–4.0%). The programme sensitivity of surveillance mammography was 59.6% (95% CI: 50.6–68.7). In patients who complied with annual mammography, sensitivity was increased to 70.8% (95% CI: 61.7–80.0). Patients with MCBCs detected by routine mammography have better survival rates than patients with MCBCs detected by other means (HR: 3.18; 95% CI: 1.59–6.34). Though there was a trend towards improved survival in patients being compliant with regular clinical follow-up (HR: 1.69; 95% CI: 0.72–3.96), this was not the case for patients being compliant with annual mammography (HR:1.02; 95% CI:0.50–2.09). Conclusion Mammography is a valuable tool for the early detection of MCBC during hospital follow-up of breast cancer patients and is probably beneficial to survival. The utilisation of follow-up surveillance in breast cancer patients and its potential impact on survival deserve further investigation.

5051 Follow-up of breast cancer patients – the meaning of cardiovascular disorders

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.

Surrounding rim formation and reduction in size after radiofrequency ablation for primary breast cancer

Radiofrequency ablation (RFA) has recently been used to treat small breast cancer. However, there are no data on the long-term morphological features after the procedure. The present study attempts to clarify the characteristics of and changes in the ablated lesion. A total of 17 breast cancer patients underwent RFA using a single needle featuring an internally cooled electrode; this was followed by whole-breast irradiation and adjuvant systemic therapy. Magnetic resonance imaging (MRI) using a 1.5-T system was performed before and 1, 3, 6, and 12 months after ablation, and the morphological characteristics and the size of the ablated lesion were evaluated. Mammography was also performed for a comparison with the MRI measurement. MRI displayed no residual enhancement of the tumor after RFA; there was an altered signal intensity with peripheral enhancement, however, and the area decreased in size gradually at a rate of 3.3% per month. Mammography showed a ring surrounding a roundish area whose size was equal to that seen with MRI. Our current series demonstrated the morphological characteristics on breast imaging after RFA plus radiation therapy. The size of the ablated area decreased over time. These findings are valuable for clinical follow-up of breast cancer patients undergoing RFA.

Follow-up of breast cancer patients: Preliminary findings from nurse-patient consultations and patient surveyst

BACKGROUND: Although clinicians in both primary and tertiary care settings are involved in the care of breast cancer patients following the active treatment phase, few studies report how patients interact with health care providers.METHODS: Participants in this breast cancer follow-up study were recruited from a hospital based nurse-led follow-up clinic in Western Australia. Methods included audio taped, transcribed consultations with Specialist Breast Nurses (SBNs) and patient self-completed surveys.RESULTS: Preliminary data suggest that SBNs play an important role in supporting women to deal with the impact of breast cancer in the years following active treatment. The data suggest that the process of adjustment to a diagnosis of cancer continues for many years after the treatment has ceased. In many cases the women require on-going support to recalibrate their response to normal physical changes that may or may not be a consequence of surgery, radiotherapy and chemotherapy.

Optimizing follow-up after breast cancer treatment

This review focuses on studies that help elucidate the optimum approach to posttreatment follow-up of breast cancer patients. The re-conceptualization of follow-up under the rubric of survivorship care and the benefit of survivorship care plans, studies on the elements of follow-up care including surveillance mammograms, alternative models of follow-up care including primary care based follow-up, and patterns of care studies that involve population-based samples are discussed. Posttreatment follow-up of breast cancer patients continues to be controversial despite almost two decades of research. The research does show that surveillance mammograms are beneficial and guidelines recommend routine surveillance mammograms annually. Other routine surveillance tests are not beneficial and are not recommended. The precise frequency and duration of clinical visits is not known and recommendations vary; but most do support continued clinical assessment. Alternative models, such as nurse-led follow-up or less frequent follow-up, show good patient satisfaction and quality-of-life outcomes. Primary care based followup results in similar clinical and quality-of-life outcomes as specialist-based follow-up. Instead of trying to find a one-size-fits-all approach, the focus should be on an individualized tailored approach in which the patient makes an informed decision on the basis of evidence of actual benefits and risks.

Introduction to the sessions on 'Debate: Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors'

Introduction to the sessions on 'Debate: Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors'

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case against.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case against.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case for

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case for

Shared responsibility for follow-up of breast cancer patients. Experience of the Institut Curie

Routine follow-up of breast cancer patients in specialist clinics is standard practice. This follow-up involves regularly scheduled breast cancer check-ups during the disease-free period, in order to detect recurrence. However, demands on specialist resources rise with the increase in the prevalence of diagnosed breast cancer. Since September 2004, it was proposed in our Institut an alternative routine follow-up schedule. Some patients who are in remission for more than 5 years will be deferred to their general practitioner or gynaecologist for follow-up schedule, alternatively with their referent practitioner from the institut (oncologist, radiation oncologist, or surgeon). We herein present the preliminary results of this strategy, and demonstrate that partially transferring primary responsibility for follow-up does not compromise its quality.

Second primary small cell carcinoma of the trachea in a breast cancer survivor: a case report and literature review

Small cell carcinoma of the trachea is a rare entity and only a few cases have been described, none as a second malignant neoplasm. This is the first report of a metachronous second primary of the trachea with small cell histology in a breast cancer survivor. A 25-year-old woman was diagnosed initially with an infiltrating ductal carcinoma of the breast, and was treated with modified radical mastectomy followed by adjuvant chemo-radiotherapy. 10 years later, she presented with breathlessness and central airway obstruction. Bronchoscopy revealed an intraluminal lesion in the proximal trachea, which was reported as small cell carcinoma on biopsy. There was no evidence of loco-regional recurrence of the previously treated breast cancer. Whole-body positron emission tomography did not show any distant metastases. As it was a small cell carcinoma, she was treated with concurrent chemo-radiotherapy and remains loco-regionally controlled. Decision-making in such instances should take into account prior treatment and needs to be individualized. There is a need for increased awareness amongst primary care physicians regarding second malignant neoplasms in the long-term follow-up of breast cancer patients treated with radiation and chemotherapeutic agents that have carcinogenic potential.

Incidence of cardiovascular events in breast cancer patients receiving chemotherapy in clinical practice

To assess the incidence of cardiovascular events among breast cancer patients after chemotherapy. Women > or =18 years with a breast tumour who received chemotherapy in 1992-2003 were selected from the PHARMO RLS. Chemotherapy with anthracyclines, a combination of anthracyclines and taxanes or second line treatment with trastuzumab was classified as cardiotoxic. Cardiovascular events were determined based on drug use and hospital admissions. Incidence rates of cardiovascular events and hazard ratios (HR) for the cardiotoxic versus non-cardiotoxic chemotherapy group were assessed during the first year and total follow-up. Of 648 patients with breast cancer included in the study cohort, 353 (54%) received cardiotoxic chemotherapy. At baseline, patients who received cardiotoxic chemotherapy compared with patients receiving non-cardiotoxic chemotherapy, received less anticoagulants/haemostatics (5 vs. 11%; p = 0.012) and had been less often hospitalised for cardiovascular disease (1 vs. 5%; p = 0.007) 2 years before the cohort entry date. After 1-year follow-up, the incidence rate of cardiovascular events was 69/1000 person years (py) for patients with cardiotoxic chemotherapy and 98/1000 py for patients with non-cardiotoxic chemotherapy, which did not differ significantly (HR 0.74 95% confidence interval (CI): 0.39, 1.41). After total follow-up, this was 81/1000 py for patients with cardiotoxic and 92/1000 py for patients with non-cardiotoxic chemotherapy (HR 0.81, 95%CI: 0.54, 1.20). This study showed similar cardiovascular incidence rates during follow-up for breast cancer patients treated with cardiotoxic and non-cardiotoxic chemotherapy. Specialists seemed to take pre-existing cardiovascular diseases into account when treating the breast cancer patient.

Lymphödem bei Mammakarzinom - Konsensus zur Sektoren übergreifenden Diagnostik und Therapie des postoperativen Lymphödems bei Patientinnen mit primärem Mammakarzinom

Secondary lymphedema is one of the most frequent long-term side effects affecting up to 30% of all breast cancer patients after local surgical and radiation treatment. Destruction of the lymphatic system causes a progressive and chronic condition with functional impairments and disabilities limiting patients in their daily activities and involving nearly all aspects of their quality of life. Also, problems in the occupational area may be caused by lymphedema. The need for improving oncological management for early diagnosis and referral for effective treatment of lymphedema is a major goal of breast cancer heath care while survival improves. A systematic consensus process was performed involving all relevant partners and providers of lymphedema health care to develop a practical documentation concept and make recommendations according to the evidence of clinical studies and currently available guidelines. A practical concept of documentation with defined assessment points was developed for evaluation and monitoring of lymphedema, which included the assessment of quality of life parameters with recognised instruments by the patient themselves. Consensus recommendations for the postoperative management, prevention, treatment and follow-up of breast cancer patients along a clinical algorithm for in- and outpatient care were finalized. With improved survival, long-term side effects with major impact on quality of life become a most important end point criteria of oncological treatment. The clearly defined documentation concept and the comprehensive recommendations for lymphedema management may assist clinicians and patients to make timely decisions about in- and outpatient health care practice to optimize the interface between acute medicine and rehabilitation. Patients' compliance with treatment and prevention routines will be as important as ensuring the continuity of care. A longitudinal prospective study evaluating the effectiveness and efficacy of the consensus recommendation is currently being implemented.