Tove Filtenborg Tvedskov

Stage migration after introduction of sentinel lymph node dissection in breast cancer treatment in Denmark: A nationwide study

PURPOSE To estimate the size and therapeutic consequences of stage migration after introduction of sentinel lymph node dissection (SLND) in breast cancer treatment in Denmark. PATIENTS AND METHODS We compared the distribution of lymph node metastases in breast cancer patients operated in 1993-1996 and 2005-2008; before and after introducing SLND. The study was based on data from the national Danish Breast Cancer Cooperative Group (DBCG) database. RESULTS We included 24,051 patients in the study; 10,231 patients from the first period and 13,820 from the second period. The proportion of patients having macrometastases was not significantly different in the two periods, whereas the proportion of patients with micrometastases increased from 5.1% to 9.0% (P<0.0001). However, this only resulted in an estimated change, from 7.8% to 8.8%, in the proportion of patients offered adjuvant systemic treatment due to positive nodal status as the only high-risk criterion, when using todays criteria for risk-allocation. In addition, we found that negative hormone receptor status was associated to negative nodal status when adjusted for confounders (odds ratios (OR) 0.83, P<0.0001). CONCLUSION Introduction of SLND in breast cancer treatment in Denmark has resulted in a stage migration on 4% due to identification of more micrometastases. However, this stage migration has only minor impact on patients offered adjuvant systemic treatment because nodal status today is less important in risk-allocation.

High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node

Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non‐sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002–2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases.

Cross-validation of three predictive tools for non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node

BACKGROUND We cross-validated three existing models for the prediction of non-sentinel node metastases in patients with micrometastases or isolated tumor cells (ITC) in the sentinel node, developed in Danish and Finnish cohorts of breast cancer patients, to find the best model to identify patients who might benefit from further axillary treatment. MATERIAL AND METHOD Based on 484 Finnish breast cancer patients with micrometastases or ITC in sentinel node a model has been developed for the prediction of non-sentinel node metastases. Likewise, two separate models have been developed in 1577 Danish patients with micrometastases and 304 Danish patients with ITC, respectively. The models were cross-validated in the opposite cohort. RESULTS The Danish model for micrometatases was accurate when tested in the Finnish cohort, with a slight change in AUC from 0.64 to 0.63. The AUC of the Finnish model decreased from 0.68 to 0.58 when tested in the Danish cohort, and the AUC of the Danish model for ITC decreased from 0.73 to 0.52, when tested in the Finnish cohort. The Danish micrometastatic model identified 14-22% of the patients as high-risk patients with over 30% risk of non-sentinel node metastases while less than 1% was identified by the Finish model. In contrast, the Finish model predicted a much larger proportion of patients being in the low-risk group with less than 10% risk of non-sentinel node metastases. CONCLUSION The Danish model for micrometastases worked well in predicting high risk of non-sentinel node metastases and was accurate under external validation.

Evaluating TIMP-1, Ki67, and HER2 as markers for non-sentinel node metastases in breast cancer patients with micrometastases to the sentinel node

Tvedskov TF, Bartels A, Jensen M‐B, Paaschburg B, Kroman N, Balslev E, Brünner N. Evaluating TIMP‐1, Ki67 and HER2 as markers for non‐sentinel node metastases in breast cancer patients with micrometastases to the sentinel node. APMIS 2011; 119: 844–52.

Robust and validated models to predict high risk of non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node.

Abstract Background. Benefit from axillary lymph node dissection in sentinel node positive breast cancer patients is under debate. Based on data from 1820 Danish breast cancer patients operated in 2002–2008, we have developed two models to predict high risk of non-sentinel node metastases when micrometastases or isolated tumor cells are found in sentinel node. The aim of this study was to validate these models in an independent Danish dataset. Material and methods. We included 720 breast cancer patients with micrometastases and 180 with isolated tumor cells in sentinel node operated in 2009–2010 from the Danish Breast Cancer Cooperative Group database. Accuracy of the models was tested in this cohort by calculating area under the receiver operating characteristic curve (AUC) as well as sensitivity and specificity. Results. AUC for the model for patients with micrometastases was comparable to AUC in the original cohort: 0.63 and 0.64, respectively. The sensitivity and specificity for predicting risk of non-sentinel node metastases over 30% was 0.36 and 0.81, respectively, in the validation cohort. AUC for the model for patients with isolated tumor cells decreased from 0.73 in the original cohort to 0.60 in the validation cohort. When dividing patients with isolated tumor cells into high and low risk of non-sentinel node metastases according to number of risk factors present, 37% in the high-risk group had non-sentinel node metastases. Specificity and sensitivity was 0.48 and 0.88, respectively, in the validation cohort when using this cut-point. Conclusion. In this independent dataset, the model for patients with micrometastases was robust with accuracy similar to the original cohort, while the model for patients with isolated tumor cells was less accurate. The models may be used to identify patients where axillary lymph node dissection should still be considered.

Quantifying the number of lymph nodes identified in one-stage versus two-stage axillary dissection in breast cancer.

PURPOSE To establish whether a different number of lymph nodes is identified in a delayed versus an immediate axillary lymph node dissection (ALND) in breast cancer patients. METHODS Using data from the Danish National Patient Register and the Danish Breast Cancer Cooperative Group Database we identified 864 breast cancer patients with sentinel lymph node dissection (SLND) and delayed ALND and 7393 breast cancer patients with SLND and immediate ALND operated between 2002 and 2010. We compared the number of lymph nodes identified in the two groups by a students t-test. RESULTS The mean number of lymph nodes identified in patients with immediate and delayed ALND was 16.55 and 15.59, respectively. This difference was statistically significant (P < 0.0001). CONCLUSION The number of lymph nodes identified in breast cancer patients is slightly reduced if delayed ALND is performed. However, the difference is small and considered to be without clinical significance.

5014 ORAL High Risk of Non-sentinel Node Metastases in a Group of Breast Cancer Patients With Micrometastases in the Sentinel Node

Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002–2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases.

The accuracy of preoperative staging of the axilla in primary breast cancer: a national register based study on behalf of Danish Breast Cancer Group (DBCG)

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Oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy: a population-based study

Abstract Background: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison to lumpectomy and mastectomy. Material and methods: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded. Results: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively), the time from surgery to onset of adjuvant chemotherapy, nor total time from biopsy to the onset of adjuvant chemotherapy (mean time 52.7, 51.9 and 53.2 days, respectively). Conclusions: Our study shows that oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy in comparison with mastectomy and lumpectomy. Accordingly, patients should not be excluded from treatment with oncoplastic breast surgery due to concerns of delay in adjuvant chemotherapy.

Risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected breast cancers

Abstract Background: Symptomatic breast cancers may be more aggressive as compared to screen-detected breast cancers. This could favor axillary lymph node dissection (ALND) in patients with symptomatic breast cancer and positive sentinel nodes. Method: We identified 955 patients registered in the Danish Breast Cancer Cooperative Group (DBCG) Database in 2008 – 2010 with micrometastases (773) or isolated tumor cells (ITC) (182) in the sentinel node. Patients were cross-checked in the Danish Quality Database of Mammography Screening and 481 patients were identified as screen-detected cancers. The remaining 474 patients were considered as having symptomatic cancers. Multivariate analyses of the risk of non-sentinel node metastases were performed including known risk factors for non-sentinel node metastases as well as method of detection. Results: 18% of the patients had metastases in non-sentinel nodes. This was evenly distributed between patients with symptomatic and screen-detected cancers; 18.5% vs 17.5% (OR 1.07; 95% CI 0.77–1.49; p = 0.69). In patients with micrometastases 21% had non-sentinel node metastases in the group with symptomatic cancers compared to 19% of patients with screen-detected cancers. This difference was not significant (OR 1.16; 95% CI 0.81–1.65, p = 0.43). Neither the multivariate analysis showed an increased risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected cancers (OR 1.12, CI 0.77–1.62, p = 0.55). In patients with ITCs 8% of patients with symptomatic cancers had non-sentinel node metastases compared to 13% of patients with screen-detected cancers. This difference was not significant (OR 0.58; 95% CI 0.22–1.54, p = 0.27). In the multivariate analysis, the risk of non-sentinel node metastases was still not significantly increased in patients with symptomatic cancers compared to screen-detected cancers (OR 0.45; 95% CI 0.16–1.27, p = 0.13). Conclusion: We did not find any clinically relevant difference in the risk of non-sentinel node metastases between patients with symptomatic and screen-detected cancers with micrometastases or ITC in the sentinel node.