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Andersson, Yvette
Publications (8 of 8) Show all publications
Andersson, Y., Bergkvist, L., Frisell, J. & de Boniface, J. (2019). Do clinical trials truly mirror their target population?: An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer. Breast Cancer Research and Treatment, 177(2), 469-475
Open this publication in new window or tab >>Do clinical trials truly mirror their target population?: An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer
2019 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 177, no 2, p. 469-475Article in journal (Refereed) Published
Abstract [en]

Purpose: Increasing evidence suggests that completion axillary lymph node dissection (ALND) may be omitted in breast cancer patients with limited axillary nodal metastases. However, the representativeness of trial participants for the original clinical practice population, and thus, the generalizability of published trials have been questioned. We propose the use of background data from national registers as a means to assess whether trial participants mirror their target population and to strengthen the generalizability and implementation of trial outcomes.

Methods: The Swedish prospective SENOMIC trial, omitting a completion ALND in breast cancer patients with sentinel lymph node micrometastases, reached full target accrual in 2017. To assess the generalizability of trial results for the target population, a comparative analysis of trial participants versus cases reported to the Swedish National Breast Cancer Register (NKBC) was performed.

Results: Comparing 548 trial participants and 1070 NKBC cases, there were no significant differences in age, tumor characteristics, breast surgery, or adjuvant treatment. Only the mean number of sentinel lymph nodes with micrometastasis per individual was lower in trial participants than in register cases (1.06 vs. 1.09, p=0.037).

Conclusions: Patients included in the SENOMIC trial are acceptably representative of the Swedish breast cancer target population. There were some minor divergences between trial participants and the NKBC population, but taking these into consideration, upcoming trial outcomes should be generalizable to breast cancer patients with micrometastases in their sentinel lymph node biopsy.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Breast cancer, Sentinel node biopsy, Micrometastases, Axillary lymph node dissection, Cohort study, Register
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-392124 (URN)10.1007/s10549-019-05328-3 (DOI)000477675700020 ()31236811 (PubMedID)
Available from: 2019-09-03 Created: 2019-09-03 Last updated: 2019-09-03Bibliographically approved
de Boniface, J., Frisell, J., Bergkvist, L. & Andersson, Y. (2018). Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation. British Journal of Surgery, 105(12), 1607-1614
Open this publication in new window or tab >>Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation
2018 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 12, p. 1607-1614Article in journal (Refereed) Published
Abstract [en]

Background: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking.

Methods: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy.

Results: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79.5 versus 64.3 per cent respectively at 13 years; P < 0.001) and breast cancer-specific survival (90.5 versus 84.0 per cent at 13 years; P < 0.001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98.3 versus 96.2 per cent; P < 0.001).

Conclusion: The present data support the superiority or BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model.

Place, publisher, year, edition, pages
WILEY, 2018
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-369050 (URN)10.1002/bjs.10889 (DOI)000447124200008 ()29926900 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF)The Breast Cancer FoundationSwedish Cancer Society
Available from: 2018-12-14 Created: 2018-12-14 Last updated: 2018-12-14Bibliographically approved
Andersson, Y., Bergkvist, L., Frisell, J. & de Boniface, J. (2018). Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. Breast Cancer Research and Treatment, 171(2), 359-369
Open this publication in new window or tab >>Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes
2018 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 171, no 2, p. 359-369Article in journal (Refereed) Published
Abstract [en]

Purpose: The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort.

Methods: Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied.

Results: Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%).

Conclusions: Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.

Keywords
Breast cancer, Sentinel node biopsy, Lymph node status, Micrometastases, Isolated tumor cells, Prognosis
National Category
Cancer and Oncology Surgery
Identifiers
urn:nbn:se:uu:diva-363095 (URN)10.1007/s10549-018-4820-0 (DOI)000440766500011 ()29846847 (PubMedID)
Funder
The Breast Cancer FoundationSwedish Cancer SocietySwedish Society for Medical Research (SSMF)
Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2018-10-16Bibliographically approved
de Boniface, J., Frisell, J., Andersson, Y., Bergkvist, L., Ahlgren, J., Ryden, L., . . . Lundstedt, D. (2017). Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial. BMC Cancer, 17, Article ID 379.
Open this publication in new window or tab >>Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial
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2017 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 379Article in journal (Refereed) Published
Abstract [en]

Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.

Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1: 1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.

Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Breast cancer, Sentinel lymph node biopsy, Axillary lymph node dissection, Survival, Macrometastasis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-326229 (URN)10.1186/s12885-017-3361-y (DOI)000402334900006 ()28549453 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Society of MedicineSwedish Society for Medical Research (SSMF)
Available from: 2017-08-10 Created: 2017-08-10 Last updated: 2017-11-29Bibliographically approved
de Boniface, J., Frisell, J., Bergkvist, L. & Andersson, Y. (2017). Ten-year report on axillary recurrence after negative sentinel node biopsy for breast cancer from the Swedish Multicentre Cohort Study. British Journal of Surgery, 104(3), 238-247
Open this publication in new window or tab >>Ten-year report on axillary recurrence after negative sentinel node biopsy for breast cancer from the Swedish Multicentre Cohort Study
2017 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 3, p. 238-247Article in journal (Refereed) Published
Abstract [en]

Background: The omission of axillary lymph node dissection (ALND) in patients with breast cancer with a negative finding on sentinel node biopsy (SNB) has reduced armmorbidity substantially. Early follow-up reports have shown the rate of axillary recurrence to be significantly lower than expected, with a median false-negative rate of 7 per cent for SNB. Long-term follow-up is needed as recurrences may develop late.

Methods: The Swedish Multicentre Cohort Study included 3518 women with breast cancer and a clinically negative axilla, in whom SNB was planned. ALND was performed only in patients with sentinel node metastasis. Twenty-six centres contributed to enrolment between September 2000 and January 2004. The primary endpoint was the axillary recurrence rate and the secondary endpoint was breast cancer-specific survival, calculated using Kaplan-Meier survival estimates.

Results: Some 2216 sentinel node-negative patients with 2237 breast cancers were analysed. The median follow-up time was 126 (range 0-174) months. Isolated axillary recurrence was found in 35 patients (1.6 per cent). High histological grade and multifocal tumours were risk factors for axillary recurrence, whereas the removal of more than two sentinel nodes decreased the risk. Fourteen (40 per cent) of 35 patients died as a consequence of axillary recurrence.

Conclusion: The risk of axillary recurrence remains lower than expected after a negative finding on SNB at 10-year follow-up. Axillary recurrences may occur long after primary surgery, and lead to a significant risk of breast cancer death.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-317593 (URN)10.1002/bjs.10411 (DOI)000393597100010 ()28052310 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF)Swedish Cancer Society
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2017-11-29Bibliographically approved
Andersson, Y., de Boniface, J., Jönsson, P.-E., Ingvar, C., Liljegren, G., Bergkvist, L. & Frisell, J. (2012). Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer. British Journal of Surgery, 99(2), 226-231
Open this publication in new window or tab >>Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer
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2012 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 2, p. 226-231Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the standard axillary staging procedure in breast cancer. Follow-up studies in SLN-negative women treated without ALND report low rates of axillary recurrence, but most studies have short follow-up, and few are multicentre studies.

METHODS: Between September 2000 and January 2004, patients who were SLN-negative and did not have ALND were included in a prospective cohort. Kaplan-Meier estimates were used to analyse the rates of axillary recurrence and survival. The risk of axillary recurrence was also compared in centres with high and low experience with the SLN biopsy (SLNB) technique.

RESULTS: A total of 2195 patients with 2216 breast tumours were followed for a median of 65 months. Isolated axillary recurrence was diagnosed in 1·0 per cent of patients. The event-free 5-year survival rate was 88·8 per cent and the overall 5-year survival rate 93·1 per cent. There was no difference in recurrence rates between centres contributing fewer than 150 SLNB procedures to the cohort and centres contributing 150 or more procedures.

CONCLUSION: This study confirmed the low risk of axillary recurrence 5 years after SLNB for breast cancer without ALND.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-171035 (URN)10.1002/bjs.7820 (DOI)000303148200012 ()22180063 (PubMedID)
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2017-12-07Bibliographically approved
Andersson, Y., Frisell, J., de Boniface, J. & Bergkvist, L. (2012). Prediction of non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastases: evaluation of the tenon score. Breast Cancer : Basic and Clinical Research, 6, 31-38
Open this publication in new window or tab >>Prediction of non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastases: evaluation of the tenon score
2012 (English)In: Breast Cancer : Basic and Clinical Research, ISSN 1178-2234, E-ISSN 1178-2234, Vol. 6, p. 31-38Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION:

Current guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SLN) metastasis larger than 0.2 mm. However, in 50%-65% of these patients, the non-SLNs contain no further metastases and cALND provides no benefit. Several nomograms and scoring systems have been suggested to predict the risk of metastases in non-SLNs. We have evaluated the Tenon score.

PATIENTS AND METHODS:

In a retrospective review of the Swedish Sentinel Node Multicentre Cohort Study, risk factors for additional metastases were analysed in 869 SLN-positive patients who underwent cALND, using uni- and multivariate logistic regression models. A receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity of the Tenon score, and the area under the curve (AUC) was calculated.

RESULTS:

Non-SLN metastases were identified in 270/869 (31.1%) patients. Tumour size and grade, SLN status and ratio between number of positive SLNs and total number of SLNs were significantly associated with non-SLN status in multivariate analyses. The area under the curve for the Tenon score was 0.65 (95% CI 0.61-0.69). In 102 patients with a primary tumour <2 cm, Elston grade 1-2 and SLN metastases ≤2 mm, the risk of non SLN metastasis was less than 10%.

CONCLUSION:

The Tenon score performed inadequately in our material and we could, based on tumour and SLN characteristics, only define a very small group of patients in which negative non-sentinel nodes could be predicted.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-171037 (URN)10.4137/BCBCR.S8642 (DOI)22346360 (PubMedID)
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2017-12-07Bibliographically approved
Andersson, Y. (2012). Sentinel Node in Clinical Practice: Implications for Breast Cancer Treatment and Prognosis. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Sentinel Node in Clinical Practice: Implications for Breast Cancer Treatment and Prognosis
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. p. 55
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 754
Keywords
breast cancer, sentinel node, micrometastases, survival, non-sentinel node metastases
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-171078 (URN)978-91-554-8316-6 (ISBN)
Public defence
2012-05-12, Aulan, Ingång 21, Västmanlands Sjukhus, Västerås, 09:15 (English)
Opponent
Supervisors
Available from: 2012-04-20 Created: 2012-03-15 Last updated: 2012-08-01Bibliographically approved
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