Regional Recurrence Risk Following a Negative Sentinel Node Procedure Does Not Approximate the False-Negative Rate of the Sentinel Node Procedure in Breast Cancer Patients Not Receiving Radiotherapy or Systemic Treatment

Background: Although the false-negative rate of the sentinel lymph node biopsy (SLNB) in breast cancer patients is 5–7%, reported regional recurrence (RR) rates after negative SLNB are much lower. Adjuvant treatment modalities probably contribute to this discrepancy. This study assessed the 5-year RR risk after a negative SLNB in the subset of patients who underwent breast amputation without radiotherapy or any adjuvant treatment.Methods: All patients operated for primary unilateral invasive breast cancer between 2005 and 2008 were identified in the Netherlands Cancer Registry. Patients with a negative SLNB who underwent breast amputation and who were not treated with axillary lymph node dissection, radiotherapy, or any adjuvant systemic treatment were selected. The cumulative 5-year RR rate was estimated by Kaplan–Meier analysis.Results: A total of 13,452 patients were surgically treated for primary breast cancer and had a negative SLNB, and 2012 patients fulfilled the selection criteria. Thirty-eight RRs occurred during follow-up. Multifocal disease was associated with a higher risk of developing RR (P = 0.04). The median time to RR was 27 months and was significantly shorter in patients with estrogen receptor-negative (ER−) breast cancer (9.5 months; P = 0.003). The 5-year RR rate was 2.4% in the study population compared with 1.1% in the remainder of 11,440 SLNB-negative patients (P = 0.0002).Conclusions: Excluding the effect of radiotherapy and systemic treatment resulted in a twofold 5-year RR risk in breast cancer patients with a tumor-free SLNB. This 5-year RR rate was still much lower than the reported false-negative rate of the SLNB procedure.</p

Adherence to the Dutch Breast Cancer Guidelines for Surveillance in Breast Cancer Survivors:Real-World Data from a Pooled Multicenter Analysis

BACKGROUND: Regular follow-up after treatment for breast cancer is crucial to detect potential recurrences and second contralateral breast cancer in an early stage. However, information about follow-up patterns in the Netherlands is scarce. PATIENTS AND METHODS: Details concerning diagnostic procedures and policlinic visits in the first 5 years following a breast cancer diagnosis were gathered between 2009 and 2019 for 9916 patients from 4 large Dutch hospitals. This information was used to analyze the adherence of breast cancer surveillance to guidelines in the Netherlands. Multivariable logistic regression was used to relate the average number of a patient’s imaging procedures to their demographics, tumor–treatment characteristics, and individual locoregional recurrence risk (LRR), estimated by a risk-prediction tool, called INFLUENCE. RESULTS: The average number of policlinic contacts per patient decreased from 4.4 in the first to 2.0 in the fifth follow-up year. In each of the 5 follow-up years, the share of patients without imaging procedures was relatively high, ranging between 31.4% and 33.6%. Observed guidelines deviations were highly significant (P < .001). A higher age, lower UICC stage, and having undergone radio- or chemotherapy were significantly associated with a higher chance of receiving an imaging procedure. The estimated average LRR-risk was 3.5% in patients without any follow-up imaging compared with 2.3% in patients with the recommended number of 5 imagings. CONCLUSION: Compared to guidelines, more policlinic visits were made, although at inadequate intervals, and fewer imaging procedures were performed. The frequency of imaging procedures did not correlate with the patients’ individual risk profiles for LRR

Association between initiation of adjuvant chemotherapy beyond 30 days after surgery and overall survival among patients with triple-negative breast cancer

Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted in patients with triple-negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30 days is associated with reduced 10-year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast-conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity-score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10-year overall survival was favorable for patients with TTC within 30 days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22–2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10 years overall survival between those with TTC within or beyond 30 days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95% CI 0.84–1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30 days is associated with decreased 10 years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted

Monitoring evolving breast cancer care:reconstructive surgery, radiotherapy and gene profiling

Breast cancer is the most common cause of cancer among women worldwide and is responsible for over one million of the approximately 10 million cancers diagnosed yearly. The last fifteen years are characterized by many refinements of diagnostic test and treatment modalities. In this thesis, variation in the use of three novel test or treatment modalities and the adherence to changed recommendations in the guideline were assessed in daily practice. This thesis addressed the use of an immediate breast reconstruction, radiotherapy and gene-expression profiles. Immediate breast reconstruction Variation in the use of an immediate breast reconstruction was observed between hospitals in the Netherlands. After annihilating the intended variation by case-mix correction for these factors, the remaining unintended variation could be attributed to hospital factors such as hospital type and number of plastic surgeons available in the hospital. Furthermore, it was demonstrated that the decision to offer an immediate breast reconstruction was affected by multiple factors weighed differently by surgical oncologists and plastic surgeons involved. Radiotherapy An increase in utilization rate of radiotherapy was observed in the Netherlands and was specifically associated by the finding that more patients underwent radiotherapy after mastectomy. Variation in a radiation boost was observed between institutions. Different patient- and tumour- related factors affected the use of a boost and logistic regression analysis revealed that substantial institutional variation remained that could not be explained by differences in patient, tumour or predefined institutional characteristics. Following the implementation of a national guideline for boost use in patients with invasive cancers, the use and variation of administered boost decreased for invasive breast cancer, but remained unchanged for Ductal Carcinoma in Situ. Gene-expression profile Variation in relation to a prevailing guideline was observed for the use of a gene-expression profiling in Dutch hospitals. In 2014 nearly half of all patients for whom gene-expression profiles are considered worthwhile received a gene-expression profile. Gene-expression profiles were applied both inside and outside the guideline directed area and gene-expression profile test result yields to lower use of chemotherapy. Insight in the variation in breast cancer care between Dutch hospitals and the identification of unintended variation is important. Transparency regarding existing variance may help to reduce the bandwidth of the variation and ultimately improve breast cancer care

Use and Impact of the 21-Gene Recurrence Score in Relation to the Clinical Risk of Developing Metastases in Early Breast Cancer Patients in the Netherlands

Background: The nationwide use of the 21-gene recurrence score (21-RS) and implications regarding chemotherapy administration in relation to clinical risk in early breast cancer patients are investigated. Methods: Breast cancer patients surgically treated between 2014 and 2016 were selected from the Netherlands Cancer Registry and categorized as having a clinical low, intermediate, or high risk of developing metastases. Deployment of the 21-RS is advocated in patients with an intermediate risk of developing metastases. The use and impact of the 21-RS test result on chemotherapy administration were assessed in relation to the clinical risk as well as patient and tumor characteristics; χ2 tests were used for analysis. Results: Of all patients, 20,488 were considered as clinical low-, 4,309 as intermediate-, and 15,266 as high-risk patients. The 21-RS was deployed in 0.1% (n = 23), 3.2% (n = 137), and 0.6% (n = 90) of these categories, respectively. In the clinical intermediate-risk group, the 21-RS assigned 73.7, 13.1, and 13.1% of patients to the genomic low-, intermediate-, and high-risk category, respectively. Adherence to the 21-RS was 95.6% in these patients. Conclusion: In the Netherlands, the 21-RS test is applied both inside and outside the guideline-directed area. In case of discordance between the genomic and clinical risk, patients were treated in line with the result of the 21-RS

Factors Associated with the Use of Gene Expression Profiles in Estrogen Receptor-Positive Early-Stage Breast Cancer Patients: A Nationwide Study

Background: Breast cancer guidelines suggest the use of gene expression profiles (GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom controversy exists regarding adjuvant chemotherapy benefit based on traditional prognostic factors alone. We evaluated the current use of GEPs in these patients in the Netherlands. Patients and Methods: Primary breast cancer patients treated between January 1, 2011 and December 31, 2014 and eligible for GEP use according to the Dutch national breast cancer guideline were identified in the Netherlands Cancer Registry: ER+ patients 2 cm or grade 2 tumors 1-2 cm without overt lymph node metastases (pN0-Nmi). Mixed-effect logistic regression analysis was performed to associate characteristics of patients, tumors and hospitals with GEP use. Results: GEPs were increasingly deployed: 12% of eligible patients received a GEP in 2011 versus 46% in 2014. Lobular versus ductal morphology (OR 0.58, 95% CI 0.47-0.72), pN1mi status (versus pN0, OR 0.52, 95% CI 0.40-0.68), and tumor size (>3 cm vs. >2 cm, OR 0.33, 95% CI 0.14-0.88) were inversely associated with GEP use. High socioeconomic status (SES) (OR 1.32, 95% CI 1.06-1.64) and younger age (OR 0.96/year increasing age, 95% CI 0.95-0.96) were positively associated with GEP use. GEP use per hospital did vary, but no predefined institutional factors remained independently associated with GEP use. Conclusion: GEP use increased over time and was influenced by patient- and tumor-associated factors as well as by SES

Development and Validation of an Algorithm to Identify Patients with Advanced Cutaneous Squamous Cell Carcinoma from Pathology Reports

To facilitate nationwide epidemiological research on advanced cutaneous squamous cell carcinoma (cSCC), that is, locally advanced, recurrent, or metastatic cSCC, we sought to develop and validate a rule-based algorithm that identifies advanced cSCC from pathology reports. The algorithm was based on both hierarchical histopathological codes and free text from pathology reports recorded in the National Pathology Registry. Medical files from the Erasmus Medical Center of 186 patients with stage III/IV/recurrent cSCC and 184 patients with stage I/II cSCC were selected and served as the gold standard to assess the performance of the algorithm. The rule-based algorithm showed a sensitivity of 91.9% (95% confidence interval = 88.0‒95.9), a specificity of 96.7% (95% confidence interval = 94‒2-99.3), and a positive predictive value of 78.5% (95% confidence interval = 74.2‒82.8) for all advanced cSCC combined. The sensitivity was lower per subgroup: locally advanced (52.3‒86.2%), recurrent cSCC (23.3%), and metastatic cSCC (70.0%). The specificity per subgroup was above 97%, and the positive predictive value was above 78%, with the exception of metastatic cSCC, which had a positive predictive value of 62%. This algorithm can be used to identify advanced patients with cSCC from pathology reports and will facilitate large-scale epidemiological studies of advanced cSCC in the Netherlands and internationally after external validation

An actualised population‐based study on the use of radiotherapy in breast cancer patients in the Netherlands

The utilization rate of RT increased from 64.4% in 2011 to 70.3% in 2015. After BCS and mastectomy, 97.3% and 26.1% of the patients received RT, respectively. For patients undergoing BCS and mastectomy, lower age and ER + tumours were associated with higher RT utilisation rates. After mastectomy, also larger tumour sizes, lymph node involvement, grade‐2 and 3 tumours and diagnosis in more recent years were associated with higher RT use