Real-world data on malignant and borderline phyllodes tumors of the breast: A population-based study of all 921 cases in the Netherlands (1989 -2020).

AIM: The aim of our study is to analyze patterns in treatment and outcome in a population-based series of patients with borderline and malignant phyllodes tumors (PT). MATERIAL AND METHODS: Data on all patients with a borderline or malignant PT (1989-2020) were extracted from the Netherlands Cancer Registry and the Dutch nationwide pathology databank (Palga) and retrospectively analyzed. RESULTS: We included 921 patients (borderline PT n = 452 and malignant PT n = 469). Borderline PT patients more often had breast-conserving surgery (BCS) as final surgery (81 vs. 46%). BCS rates for borderline PT increased over time (OR 1.08 per year, 95%CI 1.04 - 1.13, P < 0.001). In malignant PT adjuvant radiotherapy was given in 14.7%; this rate increased over time (OR 1.07 per year, 95%CI 1.02 - 1.13, P = 0.012). Local recurrence rate (5-year estimate of cumulative incidence) was 8.7% (95%CI 6.0-11.4) for borderline PT and 11.7% (95%CI 8.6-14.8) for malignant PT (P = 0.187) and was related to tumor size ≥ 20 mm (HR 10.6 (95%CI 1.5-76.8) and positive margin (HR 3.0 (95%CI 1.6-5.6), p < 0.001), but not to negative margin width (HR 1.3 ( 95%CI 0.7-2.3), p = 0.350)). Distant metastasis occurred only in malignant PT with a 5-year cumulative incidence of 4.7% (95%CI 3.3 - 6.1). CONCLUSION: This population-based series showed an increase in BCS in borderline PT and an increase in adjuvant radiotherapy in malignant PT over time. We identified malignant PT, BCS, larger tumor size and positive final margins as possible risk factors for local recurrence. Small but negative margins can be accepted.

Oncological status is not a determinant of refraining from breast reconstruction among 490 candidates for mastectomy and post-mastectomy radiotherapy.

BACKGROUND: Although breast reconstruction in the setting of post-mastectomy radiotherapy (PMRT) is controversial, we offer nipple-sparing mastectomy and immediate implant-based breast reconstruction ([N]SSM/IIBR) to women needing primary mastectomy regardless of PMRT. Nevertheless, some of these women have no reconstruction. PURPOSE: To assess the uptake of breast reconstruction in women who undergo PMRT and the patient characteristics associated with such uptake. Additionally, we assessed the determinants of forgoing breast reconstruction. METHODOLOGY: Demographic, physical and oncological characteristics of women who underwent mastectomy, PMRT and breast reconstruction were compared to the characteristics of those who did not undergo breast reconstruction from 2013 through 2018. As determinants of delaying or refraining from breast reconstruction, we distinguished between an oncological reason, patient's preference, patient's co-morbidity, combined tobacco abuse and obesity and the need for PMRT. RESULTS: 490 women received PMRT. Of these, 396 women (81%) underwent combined [N]SSM/IIBR and PMRT or mastectomy and PMRT with delayed breast reconstruction. Ninety-four additional women (19%) did not undergo breast reconstruction. The latter group differed significantly from those who did in demographic and physical characteristics but not in terms of oncological diagnosis and history. Patient's preference was the single most frequent determinant of not performing either immediate or delayed breast reconstruction among these 94 women. Oncological status was not a major determinant in refraining from reconstruction. CONCLUSION: The significant difference in non-oncological characteristics between the reconstructed and non-reconstructed women confirms the importance of these characteristics in the preference for either reconstruction or non-reconstruction.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. METHODS: A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). RESULTS: For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p = .050, Choi p = .015) and necrosis (RECIST p < .001), and a higher median percentage of fibrosis (RECIST p = .005, Choi p = .008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p = .038). CONCLUSION: RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes.

Validation of the 70-gene signature test (MammaPrint) to identify patients with breast cancer aged ≥ 70 years with ultralow risk of distant recurrence: A population-based cohort study.

INTRODUCTION: When risk estimation in older patients with hormone receptor positive breast cancer (HR + BC) is based on the same factors as in younger patients, age-related factors regarding recurrence risk and other-cause mortality are not considered. Genomic risk assessment could help identify patients with ultralow risk BC who can forgo adjuvant treatment. However, assessment tools should be validated specifically for older patients. This study aims to determine whether the 70-gene signature test (MammaPrint) can identify patients with HR + BC aged ≥70 years with ultralow risk for distant recurrence. MATERIALS AND METHODS: Inclusion criteria: ≥70 years; invasive HR + BC; T1-2N0-3M0. EXCLUSION CRITERIA: HER2 + BC; neoadjuvant therapy. MammaPrint assays were performed following standardized protocols. Clinical risk was determined with St. Gallen risk classification. Primary endpoint was 10-year cumulative incidence rate of distant recurrence in relation to genomic risk. Subdistribution hazard ratios (sHR) were estimated from Fine and Gray analyses. Multivariate analyses were adjusted for adjuvant endocrine therapy and clinical risk. RESULTS: This study included 418 patients, median age 78 years (interquartile range [IQR] 73-83). Sixty percent of patients were treated with endocrine therapy. MammaPrint classified 50 patients as MammaPrint-ultralow, 224 patients as MammaPrint-low, and 144 patients as MammaPrint-high risk. Regarding clinical risk, 50 patients were classified low, 237 intermediate, and 131 high. Discordance was observed between clinical and genomic risk in 14 MammaPrint-ultralow risk patients who were high clinical risk, and 84 patients who were MammaPrint-high risk, but low or intermediate clinical risk. Median follow-up was 9.2 years (IQR 7.9-10.5). The 10-year distant recurrence rate was 17% (95% confidence interval [CI] 11-23) in MammaPrint-high risk patients, 8% (4-12) in MammaPrint-low (HR 0.46; 95%CI 0.25-0.84), and 2% (0-6) in MammaPrint-ultralow risk patients (HR 0.11; 95%CI 0.02-0.81). After adjustment for clinical risk and endocrine therapy, MammaPrint-high risk patients still had significantly higher 10-year distant recurrence rate than MammaPrint-low (sHR 0.49; 95%CI 0.26-0.90) and MammaPrint-ultralow patients (sHR 0.12; 95%CI 0.02-0.85). Of the 14 MammaPrint-ultralow, high clinical risk patients none developed a distant recurrence. DISCUSSION: These data add to the evidence validating MammaPrint's ultralow risk threshold. Even in high clinical risk patients, MammaPrint-ultralow risk patients remained recurrence-free ten years after diagnosis. These findings justify future studies into using MammaPrint to individualize adjuvant treatment in older patients.

Short-Term Surgical Complications of Skin-Sparing Mastectomy and Direct-to-Implant Immediate Breast Reconstruction in Women Concurrently Treated with Adjuvant Radiotherapy for Breast Cancer.

Background Postmastectomy radiotherapy (PMRT) is allegedly associated with a higher risk of complications of combined nipple-sparing or skin-sparing mastectomy and subpectoral direct-to-implant immediate breast reconstruction ([N]SSM/SDTI-IBR). For this reason, this combination is usually advised against or, even, refused in women who need to undergo PMRT. Because this advice has never been justified, we assessed the short-term complications that may potentially be associated with PMRT after [N]SSM/SDTI-IBR. Methods We compared the complications requiring reintervention and implant loss occurring after 273 [N]SSM/SDTI-IBR that were exposed to PMRT within the first 16 postoperative weeks (interventional group) to those occurring in 739 similarly operated breasts that were not (control group). Additionally, we compared the fraction of complications requiring reintervention occurring after the onset of radiotherapy in the interventional group to that occurring after a comparable postoperative period in the control group. Results The fraction of breasts requiring unscheduled surgical reinterventions for complications and the loss of implants did not differ significantly between both groups but significantly more reinterventions were needed among the controls ( p = 0.00). The fraction of events after the onset of radiotherapy in the interventional group was higher than the fraction of events after 6.2 weeks in the control group, but not significantly so. Conclusion We found no prove for the alleged increase of short-term complications of adjuvant radiotherapy. Therefore, we advise that these should not be considered valid arguments to advice against [N]SSM/SDTI-IBR.

[Treatment of older breast cancer patients: de-escalation in oncology]. / De behandeling van oudere vrouwen met borstkanker.

The prognosis of breast cancer patients has greatly improved in recent decades. Innovations in imaging techniques, pathological assessment, optimized surgical and radiotherapy techniques have contributed to this. Much of the improvement is due to the increase of the range of effective systemic treatment and the continual expansion of the indication for this purpose. However, broadening the guidelines for adjuvant systemic treatments, results in a smaller absolute gain. The balance between effectiveness and side-effects could therefore be compromised, which is an incentive to search for possibilities for de-escalation to prevent potential damage, without unnecessarily increasing the risk of recurrence. Currently, in The Netherlands this is being investigated in older breast cancer patients.

A moderate dose of preoperative radiotherapy may improve resectability in myxoid liposarcoma.

BACKGROUND: Histotype specific neoadjuvant therapy response data is scarce in soft tissue sarcomas. This study aimed to assess the impact of a moderate radiotherapy (RT) dose on resectability and to correlate MRI parameters to pathological treatment response in Myxoid Liposarcoma (MLS). METHODS: This prospective, multicenter, single-arm, phase 2 trial assessed the radiological effects of 36 Gy of preoperative radiotherapy in primary non-metastatic MLS (n=34). Distance of the tumor to the neurovascular bundle, tumor dimensions, fat fraction, enhancing fraction were determined on MRI scans at baseline, after 8 and 16 fractions, and preoperatively. Pathological response was established by central pathology review. RESULTS: Preoperative radiotherapy resulted in a median increase of 2 mm (IQR 0 to 6) of the distance of the tumor to the neurovascular bundle. As compared to baseline, the median change of the tumor volume, craniocaudal diameter and axial diameter at preoperative MRI were -60% (IQR -74 to -41), -19% (IQR -23 to -7) and -20% (IQR -29 to -12), respectively. The median fat fraction of 0.1 (IQR 0.0-0.1) and enhancing fraction of 0.8 (IQR 0.6 to 0.9) at baseline, changed to 0.2 (IQR 0.1 to 0.5) and to 0.5(IQR 0.4 to 0.9) preoperatively, respectively. Radiological signs of response in terms of volume, enhancing fraction and fat fraction were correlated with specific pathological signs of response like hyalinization, necrosis and fatty maturation. CONCLUSIONS: A moderate dose of preoperative radiotherapy may improve resectability in MLS and could facilitate achievement of clear margins and function preservation. MRI features which were predictive for expressions of pathological response, can play a role in further personalization of neoadjuvant treatment strategies in order to improve outcome in MLS.

Local control and postponement of systemic therapy after modest dose radiotherapy in oligometastatic myxoid liposarcomas.

INTRODUCTION: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that satisfactory local control and postponement of systemic therapy could be achieved with a modest radiotherapy(RT) dose in oMLS. METHODS: The DOREMY trial is a multicenter, phase 2 trial evaluating efficacy and toxicity of a modest RT dose in both localized and oMLS; this report presents the data of the oMLS cohort treated with 36 Gy in 12-18 fractions with optional subsequent metastasectomy. The primary endpoint was local progression free survival(LPFS). Secondary endpoints included postponement of systemic therapy, symptom reduction, radiological objective response, and toxicity. RESULTS: Nine patients with a total of 25 lesions were included, with a median follow-up of 23 months. The median number of lesions per patient was three and the trunk wall and bone were the most frequently affected sites. In lesions treated with definitive RT(n = 21), LPFS rates at 1, 2, and 3 years were respectively 73%, 61%, and 40%. Radiological objective response and clinical symptom reduction were achieved in 8/15(53%) and 9/10(90%) of the evaluable lesions, respectively. No local recurrences occurred in lesions treated with RT and metastasectomy(n = 4). For the entire study population, the median postponement of systemic therapy was 10 months. Grade ≥ 2 toxicity was observed in 2/9(22%) of patients. CONCLUSIONS: This trial suggests that 36 Gy could possibly be effective to achieve local control, postpone systemic therapy and reduce symptoms in oMLS. Given the minimal toxicity this treatment could be reasonably considered in oMLS.

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial.

IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCE: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.

Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients.

PURPOSE: Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT. METHODS AND MATERIALS: Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction. RESULTS: A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted. CONCLUSIONS: ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink.

Radiation Therapy as Sole Management for Solitary Fibrous Tumors (SFT): A Retrospective Study From the Global SFT Initiative in Collaboration With the Sarcoma Patients EuroNet.

PURPOSE: Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of large prospective studies on radiation therapy (RT) with definitive and/or palliative intent in SFT patients, this retrospective study aimed to better define the benefit of RT in this disease. METHODS AND MATERIALS: A retrospective observational study was performed across 7 sarcoma centers. Clinical information was retrieved from all patients receiving RT without surgery over the course of their locally advanced and/or metastatic disease. Differences in treatment characteristics between subgroups were tested using analysis-of-variance tests. Local control (LC) and overall survival (OS) rates were calculated as time from the start of RT until local progression and death from any cause, respectively. RESULTS: Since 1990, a total of 40 patients were identified. RT was applied with definitive intent in 16 patients and with palliative intent in 24. The median follow-up period was 62 months. In patients treated with definitive RT (receiving approximately 60 Gy), the objective response rate was 67%. At 5 years, the LC rate was 81.3%, and the OS rate was 87.5%. In the case of palliative RT (typically 39 Gy), the objective response rate was 38%. The LC and OS rates at 5 years were 62.5% and 54.2%, respectively. In both subgroups, RT-associated toxicities were mild with predominantly grade 1 acute and late side effects. CONCLUSIONS: This retrospective study suggests a clinically meaningful benefit for RT given with either definitive or palliative intent without surgery in SFT management. Prospective registries potentially in collaboration with patient advocacy groups are warranted to further assess the role of RT in patients with this rare malignancy.

The feasibility of manual parameter tuning for deformable breast MR image registration from a multi-objective optimization perspective.

Deformable image registration is typically formulated as an optimization problem involving a linearly weighted combination of terms that correspond to objectives of interest (e.g. similarity, deformation magnitude). The weights, along with multiple other parameters, need to be manually tuned for each application, a task currently addressed mainly via trial-and-error approaches. Such approaches can only be successful if there is a sensible interplay between parameters, objectives, and desired registration outcome. This, however, is not well established. To study this interplay, we use multi-objective optimization, where multiple solutions exist that represent the optimal trade-offs between the objectives, forming a so-called Pareto front. Here, we focus on weight tuning. To study the space a user has to navigate during manual weight tuning, we randomly sample multiple linear combinations. To understand how these combinations relate to desirability of registration outcome, we associate with each outcome a mean target registration error (TRE) based on expert-defined anatomical landmarks. Further, we employ a multi-objective evolutionary algorithm that optimizes the weight combinations, yielding a Pareto front of solutions, which can be directly navigated by the user. To study how the complexity of manual weight tuning changes depending on the registration problem, we consider an easy problem, prone-to-prone breast MR image registration, and a hard problem, prone-to-supine breast MR image registration. Lastly, we investigate how guidance information as an additional objective influences the prone-to-supine registration outcome. Results show that the interplay between weights, objectives, and registration outcome makes manual weight tuning feasible for the prone-to-prone problem, but very challenging for the harder prone-to-supine problem. Here, patient-specific, multi-objective weight optimization is needed, obtaining a mean TRE of 13.6 mm without guidance information reduced to 7.3 mm with guidance information, but also providing a Pareto front that exhibits an intuitively sensible interplay between weights, objectives, and registration outcome, allowing outcome selection.

[Radiotherapy and breast conserving therapy: past, present and future]. / Radiotherapie bij borstsparende behandeling: verleden, heden en toekomst.

Clinical trials in the 1970s and 80s showed the survival rate of women with early breast cancer (stage I-II, 0-5 cm) who underwent treatment by means of breast conserving therapy (BCT) to be equal to that of those who underwent radical mastectomy. Since the 1980s the risk of both local recurrence and late toxicity after BCT has been significantly reduced. Studies are identifying subgroups of patients with low-risk breast cancer in whom it is possible to abstain from giving further radiation treatment. Over recent years the number of effective systemic therapy options has increased, leading to a reduction in the risk of recurrence in breast cancer. Developments in genetic profiling are expected to lead to further individualized loco-regional treatment.

Feasibility of tailored follow-up for patients with early breast cancer.

As the number of breast cancer survivors increases, this study prospectively examined whether tailored follow-up with differentiated number of visits per risk group, based on a prognostic index for local recurrence, is feasible and acceptable for patients and professionals. Between March 2007 and March 2010, 180 breast cancer patients (pT1-2N0-2cM0) were included. Primary endpoint was feasibility of tailored follow-up, based on the number of follow-up visits, patient satisfaction, anxiety and attitude towards follow-up. Secondary endpoints were reasons for visits, incidence, time to detection of local recurrences and the use of alternative care. In the second and third year of follow-up, the results show a 22% reduction in visits per patient in the low-risk group compared to the intermediate-risk group; 2.8 versus 3.6 visits. The majority of interval visits in both groups was initiated by the professional. No significant differences were found in attitude towards follow-up, patient satisfaction, anxiety and depression, alternative health care use or local recurrences between the risk groups. In conclusion, implementation of a tailored follow-up programme with decreased number of visits for low-risk patients is feasible and acceptable to patients. Appointing one coordinating professional, possibly a nurse practitioner, could further reduce the number of follow-up visits.

Target volume delineation in external beam partial breast irradiation: less inter-observer variation with preoperative- compared to postoperative delineation.

The challenge of adequate target volume definition in external beam partial breast irradiation (PBI) could be overcome with preoperative irradiation, due to less inter-observer variation. We compared the target volume delineation for external beam PBI on preoperative versus postoperative CT scans of twenty-four breast cancer patients.

Breast-conserving surgery with or without radiotherapy in older breast patients with early stage breast cancer: a systematic review and meta-analysis.

BACKGROUND: In early stage breast cancer, radiotherapy is an integral part of locoregional treatment with breast-conserving surgery. However, few older patients are included in the clinical trials upon which these recommendations are based. Therefore, we performed a systematic review and meta-analysis to evaluate outcomes of radiotherapy after breast-conserving surgery in older patients. METHODS: A systematic search of PubMed and Embase was undertaken. Inclusion was restricted to randomized controlled trials in postmenopausal breast cancer patients. Pooled odds ratios were calculated for locoregional recurrence, distant recurrence, and overall survival. RESULTS: We included 5 randomized clinical trials comprising 3,190 patients. Overall, 39 % of the patients were ≥ 70 years old, and most had hormone receptor-positive T1 tumors without nodal involvement. All patients received adjuvant systemic therapy. Patients who received radiotherapy had a lower relative risk of locoregional recurrence (pooled odds ratio [OR] 0.36; 95 % confidence interval [CI] 0.25-0.50). The 5-year absolute risk was 2.2 % (95 % CI 1.6-3.1) among patients who received radiotherapy, versus 6.5 % (95 % CI 5.3-7.9) among patients who did not. The absolute risk difference was 4.3 % (95 % CI 2.9-5.7), corresponding with a number needed to treat of 24. No differences were observed for distant recurrence or overall survival. CONCLUSIONS: Although patients who received radiotherapy had a lower relative risk of locoregional recurrence, the absolute risk was low, and overall survival was not affected. We propose that the debate should not only focus on the relative risk but also on the absolute benefit of radiotherapy and the number needed to treat. Both treatment options may be reasonable in clinical practice.

Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

BACKGROUND AND PURPOSE: The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer. The present analyses explored the association between locoregional therapy and recurrence (LRR) in this population. MATERIAL AND METHODS: Between 2001 and 2006, 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS+RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST+RT). Patients with unknown data on surgery, radiotherapy, tumor or nodal stage (n=199), and patients treated by lumpectomy without radiotherapy (n=349) were excluded. RESULTS: After a median follow-up of 5.2 years, 270 LRRs occurred (2.9%) among 9231 patients. The 5-years actuarial incidence of LRR was 4.2% (95% CI 3.3-4.9%) for MST-only, 3.4% (95% CI 2.4-4.2%) for MST+RT and 1.9% (95% CI 1.5-2.3%) for BCS+RT. After adjustment for prognostic factors, the hazard ratio (HR, reference BCS+RT) for LRR remained significantly higher for MST-only (HR 1.53; 95% CI 1.10-2.11), not for MST+RT (HR 0.78; 95% CI 0.50-1.22). CONCLUSION: This explorative analysis showed a higher LRR risk after MST-only than after BCS+RT, even after adjustment for prognostic factors. As this effect was not seen for MST+RT versus BCS+RT, it might be explained by the beneficial effects of radiation treatment.

Costs of different follow-up strategies in early breast cancer: a review of the literature.

We reviewed the literature between January 1985 and June 2011 on the costs of different follow-up strategies for patients treated for early breast cancer. A total of 186 abstracts were retrieved of which eleven publications were considered relevant; 6 randomised clinical trials, 4 retrospective cohort studies and 1 'minisymposium'. The follow-up strategies, outcome measures and methods of analysis used in these studies vary widely, so no general conclusions can be drawn. However, from the results we infer that patient-led follow-up by a nurse practitioner, follow-up by a general practitioner, or telephone follow-up is feasible and cost-effective, without routine additional tests, except annual mammograms. In this era of increasing health care costs, cost-effectiveness, evaluated in a standardised way, should be taken into account in future clinical trials.