| 1. |
- Alkner, Sara, et al.
(författare)
-
Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.
- 2023
-
Ingår i: BMJ open. - 2044-6055. ; 13:9
-
Tidskriftsartikel (refereegranskat)abstract
- Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.NCT05634889.
|
|
| 2. |
- Alkner, Sara, et al.
(författare)
-
Quality assessment of radiotherapy in the prospective randomized SENOMAC trial
- 2024
-
Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 197
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.
|
|
| 3. |
- Andersson, Yvette, et al.
(författare)
-
Breast Cancer Survival in Relation to the Metastatic Tumor Burden in Axillary Lymph Nodes
- 2010
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 28:17, s. 2868-2873
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer. Patients and Methods Between September 2000 and January 2004, 3,369 patients with breast cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival. Results Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ. Conclusion This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.
|
|
| 4. |
- Andersson, Yvette, 1972-
(författare)
-
Sentinel Node in Clinical Practice : Implications for Breast Cancer Treatment and Prognosis
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The introduction of sentinel lymph node biopsy (SLNB) has conveyed several new issues, such as the risk of false negativity, long-term consequences, the prognostic significance of micrometastases and whether ALND can be omitted in sentinel lymph node- (SLN) positive patients.Archived SLN specimens from 50 false negative patients and 107 true negative controls were serially sectioned and stained with immunohistochemistry. The detection rate of previously unknown metastases did not differ between the false and the true negative patients. The risk of false negativity was higher in patients with multifocal or hormone receptor-negative tumours, or if only one SLN was found.In a Swedish multicentre cohort, 2216 SLN-negative patients in whom ALND was omitted were followed up for a median of 65 months. The isolated axillary recurrence rate was only 1.0%, and the overall survival was high (93%).The survival of 3369 breast cancer patients (2383 node-negative (pN0), 107 isolated tumour cells (pN0(i+), 123 micrometastases (pN1mi) and 756 macrometastases (pN1)) was analysed. The 5-year cause-specific and event-free survival was worse for pN1mi and pN1 patients than for pN0 patients. There was no difference in survival between pN0(i+) and pN0 patients.Tumour and SLN characteristics in 869 SLN-positive patients were compared between those with and without non-SLN metastases, and the Tenon score was calculated. The risk of non-SLN metastases was higher in case of SLN macrometastases (compared with micrometastases), a high positive/total SLN ratio and Elston grade 3 tumours, and increased with increasing tumour size. The area under the curve (AUC) for the Tenon score was 0.65, and the test thus performed inadequately in this population.In conclusion, despite the risk of false negativity, SLNB with omission of ALND in SLN-negative patients appears to be safe even in the long term. The presence of micrometastases is of prognostic importance and should entail adjuvant treatment. The need for ALND in patients with SLN micro- and even macrometastases has been questioned, but the occurrence of non-SLN metastases is hard to predict, and strong evidence for the safe omission of ALND is lacking.
|
|
| 5. |
|
|
| 6. |
- Banys-Paluchowski, Maggie, et al.
(författare)
-
Localization Techniques for Non-Palpable Breast Lesions : Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411)
- 2023
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:4
-
Forskningsöversikt (refereegranskat)abstract
- Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics.Methods: We performed a systematic review on localization techniques for non-palpable breast cancer.Results: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons’ and radiologists’ attitudes towards these techniques.Conclusions: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.Simple summaryMost breast cancers are small and can be treated using breast-conserving surgery. Since these tumors are non-palpable, they require a localization step that helps the surgeon to decide which tissue needs to be removed. The oldest localization technique is a guidewire placed into the tumor before surgery, usually using ultrasound or mammography. Afterwards, the surgeon removes the tissue around the wire tip. However, this technique has several disadvantages: It can cause the patient discomfort, requires a radiologist or another professional specialized in breast diagnostics to perform the procedure shortly before surgery, and 15–20% of patients need a second surgery to completely remove the tumor. Therefore, new techniques have been developed but most of them have not yet been examined in large, prospective, multicenter studies. In this review, we discuss all available techniques and present the MELODY study that will investigate their safety, with a focus on patient, surgeon, and radiologist preference.
|
|
| 7. |
- Bergkvist, Leif, et al.
(författare)
-
Axillary recurrence rate after negative sentinel node biopsy in breast cancer : three-year follow-up of the Swedish Multicenter Cohort Study
- 2008
-
Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 247:1, s. 150-156
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sentinel lymph node biopsy is an established staging method in early breast cancer. After a negative biopsy, most institutions will not perform a completion axillary dissection. The present study reports the current axillary recurrence (AR) rate, overall and disease-free survival in the Swedish Multicenter Cohort Study.Methods: From 3534 patients with primary breast cancer ≤3 cm prospectively enrolled in the Swedish multicenter cohort study, 2246 with a negative sentinel node biopsy and no further axillary surgery were selected. Follow-up consisted of annual clinical examination and mammography. Twenty-six hospitals and 131 surgeons contributed to patient accrual.Results: After a median follow-up time of 37 months (0-75), the axilla was the sole initial site of recurrence in 13 patients (13 of 2246, 0.6%). In another 7 patients, axillary relapse occurred after or concurrently with a local recurrence in the breast, and in a further 7 cases, it coincided with distant or extra-axillary lymphatic metastases. Thus, a total of 27 ARs were identified (27 of 2246, 1.2%). The overall 5-year survival was 91.6% and disease-free survival 92.1%.Conclusions: This is the first report from a national multicenter study that covers, not only highly specialized institutions but also small community hospitals with just a few procedures per year. Despite this heterogeneous background, the results lie well within the range of AR rates published internationally (0%-3.6%). The sentinel node biopsy procedure seems to be safe in a multicenter setting. Nevertheless, long-term follow-up data should be awaited before firm conclusions are drawn.
|
|
| 8. |
- de Boniface, Jana, et al.
(författare)
-
Completion axillary lymph node dissection for the identification of pN2–3 status as an indication for adjuvant CDK4/6 inhibitor treatment : a post-hoc analysis of the randomised, phase 3 SENOMAC trial
- 2024
-
Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 25:9, s. 1222-1230
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1–2, grade 1–2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2–3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial.Methods: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1–T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1–2, histological grade 1–2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing.Findings: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52–71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6–59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery.Interpretation: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. Funding: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.
|
|
| 9. |
- de Boniface, Jana, 1971-
(författare)
-
Sentinel Node Biopsy in Breast Cancer : Clinical and Immunological Aspects
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The most important prognostic factor in breast cancer is the axillary lymph node status. The sentinel node biopsy (SNB) is reported to stage the axilla with an accuracy > 95 % in early breast cancer. Tumour-related perturbation of T-cell function has been observed in patients with malignancies, including breast cancer. The down-regulation of the important T-cell activation molecules CD3-ζ and CD28 may cause T-cell dysfunction, anergy, tolerance and deletion.The expression of CD3-ζ and CD28 was evaluated in 25 sentinel node biopsies. The most pronounced down-regulation was seen in the paracortical area, where the best agreement between both parameters was observed. CD28 expression was significantly more suppressed in CD4+ than in CD8+ T-cells.From the Swedish sentinel node database, 109 patients with breast cancer > 3 cm planned for both SNB and a subsequent axillary dissection were identified. The false negative rate (FNR) was 12.5%. Thirteen cases of tumour multifocality were detected on postoperative pathology. The FNR in this subgroup was higher (30.8%) than in patients with unifocal disease (7.8%; P = 0.012).From the Swedish SNB multicentre cohort trial, 2246 sentinel node-negative patients who had not undergone further axillary surgery were selected for analysis. After a median follow-up time of 37 months (range 0-75), 13 isolated axillary recurrences (13/2246; 0.6%) were found. In another 14 cases, local or distant failure preceded or coincided with axillary relapse (27/2246; 1.2%). In conclusion, the immunological analysis of the sentinel node might provide valuable prognostic information and aid selection of patients for immunotherapy. SNB is encouraged in breast cancer larger than 3 cm, if no multifocal growth pattern is present. The axillary recurrence rate after a negative SNB in Sweden is in accordance with international figures. However, a longer follow-up is mandatory before the true failure rate of the SNB can be determined.
|
|
| 10. |
- Fitzal, Florian, et al.
(författare)
-
Retrospective, Multicenter Analysis Comparing Conventional with Oncoplastic Breast Conserving Surgery : Oncological and Surgical Outcomes in Women with High-Risk Breast Cancer from the OPBC-01/iTOP2 Study
- 2022
-
Ingår i: Annals of Surgical Oncology. - : Springer Nature. - 1068-9265 .- 1534-4681. ; 29:2, s. 1061-1070
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Recent data suggest that margins >= 2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tubingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tubingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tubingen 3-4). Methods Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. Results A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 ("ink on tumor") in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. Conclusions Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.
|
|
