The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study.

BACKGROUND: Breast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival. METHODS: In this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20). RESULTS: Ex vivo cytokine production capacity of TNF, IL-6 and IL-1ß was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1ß after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1ß and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively). CONCLUSIONS: This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.

Long-term trends in incidence, characteristics and prognosis of screen-detected and interval cancers in women participating in the Dutch breast cancer screening programme.

BACKGROUND: No studies are available in which changes over time in characteristics and prognosis of patients with interval breast cancers (ICs) and screen-detected breast cancers (SDCs) have been compared. The aim was to study these trends between 1995 and 2018. METHODS: All women with invasive SDCs (N = 4290) and ICs (N = 1352), diagnosed in a southern mammography screening region in the Netherlands, were included and followed until date of death or 31 December 2022. RESULTS: The 5-year overall survival rate of women with SDCs increased from 91.4% for those diagnosed in 1995-1999 to 95.0% for those diagnosed in 2013-2018 (P < 0.001), and from 74.8 to 91.6% (P < 0.001) in the same periods for those with ICs. A similar trend was observed for the 10-year survival rates. After adjustment for changes in tumour characteristics, the hazard ratio (HR) for overall survival was 0.47 (95% confidence interval (CI): 0.38-0.59) for women with SDCs diagnosed in the period 2013-2018, compared to the women diagnosed in the period 1995-1999. For the women with ICs this HR was 0.27 (95% CI: 0.19-0.40). CONCLUSION: The prognosis of women with ICs has improved rapidly since 1995 and is now almost similar to that of women with SDCs.

De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy: nationwide registry study (BOOG 2013-07).

BACKGROUND: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. METHODS: Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. RESULTS: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. CONCLUSION: In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.

Routine and interval detection of locoregional breast cancer recurrences and risk of subsequent distant metastasis.

PURPOSE: Follow-up for breast cancer survivors consists of after care and surveillance. The benefits of routine surveillance visits remain debatable. In this study we compared the severity of locoregional recurrences (LRRs) and the subsequent risk of a distant metastasis (DM) between LRRs detected at routine and interval visits. METHODS: Women diagnosed with early breast cancer between 2003 and 2008 in one of the 15 participating hospitals, and who developed a LRR as first event after primary treatment, were selected from the Netherlands Cancer Registry (Cohort A). Chi-squared tests were used to compare the severity of routine- and interval-detected local recurrences (LRs) and regional recurrences (RRs), using tumor size, tumor grade, and number of positive lymph nodes. Data on the development of a subsequent DM after a LRR were available for a subset of patients (Cohort B). Cohort B was used to estimate the association between way of LRR-detection and risk of a DM. RESULTS: Cohort A consisted of 109 routine- and 113 interval-LRR patients. The severity of routine-detected LRs or RRs and interval-detected LRs or RRs did not significantly differ. Cohort B consisted of 66 routine- and 61 interval-LRR patients. Sixteen routine- (24%) and 17 (28%) interval-LRR patients developed a DM. After adjustment, way of LRR-detection was not significantly associated with the risk of a DM (hazard ratio: 1.22; 95% confidence interval: 0.49-3.06). CONCLUSION: The current study showed that routine visits did not lead to less severe LRRs and did not decrease the risk of a subsequent DM.

Changes in breast cancer treatment during the COVID-19 pandemic: a Dutch population-based study.

PURPOSE: We aimed to compare (1) treatments and time intervals between treatments of breast cancer patients diagnosed during and before the COVID-19 pandemic, and (2) the number of treatments started during and before the pandemic. METHODS: Women were selected from the Netherlands Cancer Registry. For aim one, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the treatment of women diagnosed within four periods of 2020: pre-COVID (weeks 1-8), transition (weeks 9-12), lockdown (weeks 13-17), and care restart (weeks 18-26), with data from 2018/2019 as reference. Wilcoxon rank-sums test was used to compare treatment intervals, using a two-sided p-value < 0.05. For aim two, number of treatments started per week in 2020 was compared with 2018/2019. RESULTS: We selected 34,097 women for aim one. Compared to 2018/2019, neo-adjuvant chemotherapy was less likely for stage I (OR 0.24, 95%CI 0.11-0.53), stage II (OR 0.63, 95%CI 0.47-0.86), and hormone receptor+/HER2- tumors (OR 0.55, 95%CI 0.41-0.75) diagnosed during transition. Time between diagnosis and first treatment decreased for patients diagnosed during lockdown with a stage I (p < 0.01), II (p < 0.01) or III tumor (p = 0.01). We selected 30,002 women for aim two. The number of neo-adjuvant endocrine therapies and surgeries starting in week 14, 2020, increased by 339% and 18%, respectively. The number of adjuvant chemotherapies decreased by 42% in week 15 and increased by 44% in week 22. CONCLUSION: The pandemic and subsequently altered treatment recommendations affected multiple aspects of the breast cancer treatment strategy and the number of treatments started per week.

De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study.

BACKGROUND: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline. METHODS: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. FINDINGS: 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group. INTERPRETATION: In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. FUNDING: Dutch Cancer Society. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

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.

Failure of stereotactic core needle biopsy in women recalled for suspicious calcifications at screening mammography: frequency, causes, and final outcome in a multi-institutional, observational follow-up study.

OBJECTIVES: We determined the failure rate of stereotactic core needle biopsy (SCNB) and its causes and final outcome in women recalled for calcifications at screening mammography. METHODS: We included a consecutive series of 624,039 screens obtained in a Dutch screening region between January 2009 and July 2019. Radiology reports and pathology results were obtained of all recalled women during 2-year follow-up. RESULTS: A total of 3495 women (19.6% of 17,809 recalls) were recalled for suspicious calcifications. SCNB was indicated in 2818 women, of whom 12 had incomplete follow-up and another 12 women refused biopsy. DCIS or invasive cancer was diagnosed in 880 of the remaining 2794 women (31.5%). SCNB failed in 62 women (2.2%, 36/2794). These failures were mainly due to a too posterior (n = 30) or too superficial location (n = 17) of the calcifications or calcifications too faint for biopsy (n = 13). Of these 62 women, 10 underwent surgical biopsy, yielding one DCIS (intermediate grade) and two invasive cancers (one intermediate grade and one high grade) and another two women were diagnosed with DCIS (both high grade) at follow-up. Thus, the malignancy rate after SCNB failure was 8.1% (5/62). Calcifications were depicted neither at SCNB specimen radiography nor at pathology in 16 women after (repeated) SCNB (0.6%, 31/2732). None of them proved to have breast cancer at 2-year follow-up. CONCLUSIONS: The failure rate of SCNB for suspicious calcifications is low but close surveillance is warranted, as breast cancer may be present in up to 8% of these women. KEY POINTS: • The failure rate of stereotactic core needle biopsy (SCNB) for calcifications recalled at screening mammography was 2.2%. • Failures were mainly due to calcifications that could not be reached by SCNB or calcifications too faint for biopsy. • The management after failed SCNB was various. At least, close surveillance with a low threshold for surgical biopsy is recommended as breast cancer may be present in up to 8% of women with SCNB failure.

Quilting following mastectomy reduces seroma, associated complications and health care consumption without impairing patient comfort.

BACKGROUND: An important complication following mastectomy is seroma formation. Quilting, in which skin flaps are sutured to the underlying muscle, is reported to reduce seroma incidence, but might induce pain and impair shoulder function. Main objective is to compare quilting with conventional wound closure, regarding seroma incidence, health care consumption, and patient discomfort. METHODS: In a combined prospective and retrospective study, 254 patients undergoing mastectomy and/or axillary lymph node dissection (ALND) were included. Patients received quilting sutures or conventional closure. Primary outcome was clinical significant seroma (CSS). In prospectively included patients shoulder function and analgesic use was observed. RESULTS: CSS incidence was 12.9% in the quilted versus 62.3% in the nonquilted cohort (p < 0.001). Surgical site infections were reported significantly less in the quilted cohort. Duration of hospital stay was shorter and outpatient clinic visits were less in the quilted cohort. Surgical procedure required 10 additional minutes for quilting. No significant differences were observed in postoperative shoulder function and analgesic use. CONCLUSION: Quilting following mastectomy reduces CSS incidence. Quilting requires 10 additional minutes during surgery. It facilitates day treatment and results in less additional outpatient clinic visits culminating in reduced health care consumption. Shoulder function and pain are not affected by quilting.

Using guideline-based clinical decision support in oncological multidisciplinary team meetings: A prospective, multicenter concordance study.

BACKGROUND: Multidisciplinary team meetings formulate guideline-based individual treatment plans based on patient and disease characteristics and motivate reasons for deviation. Clinical decision trees could support multidisciplinary teams to adhere more accurately to guidelines. Every clinical decision tree is tailored to a specific decision moment in a care pathway and is composed of patient and disease characteristics leading to a guideline recommendation. OBJECTIVE: This study investigated (1) the concordance between multidisciplinary team and clinical decision tree recommendations and (2) the completeness of patient and disease characteristics available during multidisciplinary team meetings to apply clinical decision trees such that it results in a guideline recommendation. METHODS: This prospective, multicenter, observational concordance study evaluated 17 selected clinical decision trees, based on the prevailing Dutch guidelines for breast, colorectal and prostate cancers. In cases with sufficient data, concordance between multidisciplinary team and clinical decision tree recommendations was classified as concordant, conditional concordant (multidisciplinary team specified a prerequisite for the recommendation) and non-concordant. RESULTS: Fifty-nine multidisciplinary team meetings were attended in 8 different hospitals, and 355 cases were included. For 296 cases (83.4%), all patient data were available for providing an unconditional clinical decision tree recommendation. In 59 cases (16.6%), insufficient data were available resulting in provisional clinical decision tree recommendations. From the 296 successfully generated clinical decision tree recommendations, the multidisciplinary team recommendations were concordant in 249 (84.1%) cases, conditional concordant in 24 (8.1%) cases and non-concordant in 23 (7.8%) cases of which in 7 (2.4%) cases the reason for deviation from the clinical decision tree generated guideline recommendation was not motivated. CONCLUSION: The observed concordance of recommendations between multidisciplinary teams and clinical decision trees and data completeness during multidisciplinary team meetings in this study indicate a potential role for implementation of clinical decision trees to support multidisciplinary team decision-making.

Comprehensive trends in incidence, treatment, survival and mortality of first primary invasive breast cancer stratified by age, stage and receptor subtype in the Netherlands between 1989 and 2017.

Our study aimed to provide a comprehensive overview of trends in incidence, survival, mortality and treatment of first primary invasive breast cancer (BC), according to age, stage and receptor subtype in the Netherlands between 1989 and 2017. Data from all women diagnosed with first primary stage I to IV BC (N = 320 249) were obtained from the Netherlands Cancer Registry. BC mortality and general population data were retrieved from Statistics Netherlands. Age-standardised incidence and mortality rates were calculated with annual percentage change (APC) and average annual percentage change (AAPC) statistics. The relative survival (RS) was used as estimator for disease-specific survival. The BC incidence for all BC patients combined significantly increased until 2013 from 126 to 158 per 100 000 person-years, after which a declining trend was observed. Surgery became less extensive, but (neo-)adjuvant systemic treatments and their combinations were given more frequently. The RS improved for all age groups and for most stages and receptor subtypes, but remained stable for all subtypes since 2012 to 2013 and since 2000 to 2009 for Stage IV BC at 15 years of follow-up. Overall, the 5- and 10-year RS increased from 76.8% (95% confidence interval [CI]: 76.1, 77.4) and 55.9% (95% CI: 54.7, 57.1) in 1989 to 1999 to 91.0% (95% CI: 90.5, 91.5) and 82.9% (95% CI: 82.2, 83.5), respectively, in 2010 to 2016. BC mortality improved regardless of age and overall decreased from 57 to 35 per 100 000 person-years between 1989 and 2017. In conclusion, the BC incidence in the Netherlands has steadily increased since 1989, but the latest trends show promising declines. Survival improved markedly for most patients and the mortality decreased regardless of age.

Improved risk estimation of locoregional recurrence, secondary contralateral tumors and distant metastases in early breast cancer: the INFLUENCE 2.0 model.

PURPOSE: To extend the functionality of the existing INFLUENCE nomogram for locoregional recurrence (LRR) of breast cancer toward the prediction of secondary primary tumors (SP) and distant metastases (DM) using updated follow-up data and the best suitable statistical approaches. METHODS: Data on women diagnosed with non-metastatic invasive breast cancer were derived from the Netherlands Cancer Registry (n = 13,494). To provide flexible time-dependent individual risk predictions for LRR, SP, and DM, three statistical approaches were assessed; a Cox proportional hazard approach (COX), a parametric spline approach (PAR), and a random survival forest (RSF). These approaches were evaluated on their discrimination using the Area Under the Curve (AUC) statistic and on calibration using the Integrated Calibration Index (ICI). To correct for optimism, the performance measures were assessed by drawing 200 bootstrap samples. RESULTS: Age, tumor grade, pT, pN, multifocality, type of surgery, hormonal receptor status, HER2-status, and adjuvant therapy were included as predictors. While all three approaches showed adequate calibration, the RSF approach offers the best optimism-corrected 5-year AUC for LRR (0.75, 95%CI: 0.74-0.76) and SP (0.67, 95%CI: 0.65-0.68). For the prediction of DM, all three approaches showed equivalent discrimination (5-year AUC: 0.77-0.78), while COX seems to have an advantage concerning calibration (ICI < 0.01). Finally, an online calculator of INFLUENCE 2.0 was created. CONCLUSIONS: INFLUENCE 2.0 is a flexible model to predict time-dependent individual risks of LRR, SP and DM at a 5-year scale; it can support clinical decision-making regarding personalized follow-up strategies for curatively treated non-metastatic breast cancer patients.

The Impact of Preoperative Breast MRI on Surgical Margin Status in Breast Cancer Patients Recalled at Biennial Screening Mammography: An Observational Cohort Study.

BACKGROUND: This study aimed to examine the association between preoperative magnetic resonance imaging (MRI) and surgical margin involvement, as well as to determine the factors associated with positive resection margins in screen-detected breast cancer patients undergoing breast-conserving surgery (BCS). METHODS: Breast cancer patients eligible for BCS and diagnosed after biennial screening mammography in the south of The Netherlands (2008-2017) were retrospectively included. Missing values were imputed and multivariable regression analyses were performed to analyze whether preoperative MRI was related to margin involvement after BCS, as well as to examine what factors were associated with positive resection margins, defined as more than focally (>4 mm) involved. RESULTS: Overall, 2483 patients with invasive breast cancer were enrolled, of whom 123 (5.0%) had more than focally involved resection margins. In multivariable regression analyses, preoperative MRI was associated with a reduced risk of positive resection margins after BCS (adjusted odds ratio [OR] 0.56, 95% confidence interval [CI] 0.33-0.96). Lobular histology (adjusted OR 2.86, 95% CI 1.68-4.87), large tumor size (per millimeter increase, adjusted OR 1.05, 95% CI 1.03-1.07), high (>75%) mammographic density (adjusted OR 3.61, 95% CI 1.07-12.12), and the presence of microcalcifications (adjusted OR 4.45, 95% CI 2.69-7.37) and architectural distortions (adjusted OR 1.85, 95% CI 1.01-3.40) were independently associated with positive resection margins after BCS. CONCLUSIONS: Preoperative MRI was associated with lower risk of positive resection margins in patients with invasive breast cancer eligible for BCS using multivariable analysis. Furthermore, specific mammographic characteristics and tumor characteristics were independently associated with positive resection margins after BCS.

Follow-up after breast cancer: Variations, best practices, and opportunities for improvement according to health care professionals.

OBJECTIVE: Follow-up after breast cancer can be divided into surveillance and aftercare. It remains unclear how follow-up can ideally be organised from the perspective of health care professionals (HCPs). The aim of this study was to gain insight in the organisation of follow-up in seven Dutch teaching hospitals and to identify best practices and opportunities for improvement of breast cancer (all stages) follow-up as proposed by HCPs. METHODS: Semi-structured in-depth group interviews were performed, one in each of the participating hospitals, with in total 16 HCPs and 2 patient advocates. To describe the organisation of follow-up, transcripts were analysed using a deductive approach. Best practices and opportunities were derived using an inductive approach. RESULTS: Variation was found in the organisation of aftercare, especially in timing, frequency, and disciplines of involved HCPs. Less variation was observed for surveillance, which was guided by the national guideline. Best practices focused on case management and adequate collaboration between HCPs of different disciplines. Mentioned opportunities were improving the structured monitoring of patients' needs and a comprehensive guideline for organisation and content of aftercare. CONCLUSIONS: Variation in follow-up existed between hospitals. Shared decision-making (SDM) about surveillance is desirable to ensure that surveillance matches the patient needs, preferences, and personal risk for recurrences.

Ten-year recurrence rates for breast cancer subtypes in the Netherlands: A large population-based study.

Here we report for the first time the relation between breast cancer subtypes and 10-year recurrence rates and mortality in the Netherlands. All operated women diagnosed with invasive non-metastatic breast cancer in 2005 in the Netherlands were included. Patients were classified into breast cancer subtypes according to ER, PR, HER2 status and grade: luminal A, luminal B, HER2 positive and triple negative. Percentages and hazards of recurrence were compared among subtypes. Adjusted 10-year overall (OS) and recurrence-free survival (RFS) were calculated using multivariable Cox regression. Of 8,062 patients, 4,482 (56%) were luminal A, 2,090 (26%) luminal B, 504 (6%) HER2 positive and 986 (12%) triple negative. Local recurrences (7.5%) and distant metastases (25.6%) occurred most often in HER2 positive disease and the least often in luminal A (3.7% and 9.5%, respectively). Regional recurrences were most often diagnosed in triple negative disease (5.2%), and the least often in luminal A (1.7%). HER2 positive and triple negative subtypes had the highest recurrence rates in the second year, while luminal A and B showed a more continuous pattern over time, with lobular tumours recurring more often. After adjustment for differences in baseline characteristics, triple negative disease showed worse 10-year OS and triple negative and HER2 positive disease had the lowest 10-year RFS. In the Netherlands, breast cancer subtypes are important predictors for 10-year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes, in combination with other prognostic factors, can support patient-tailored treatment and individualised follow-up.

Trends in frequency and outcome of high-risk breast lesions at core needle biopsy in women recalled at biennial screening mammography, a multiinstitutional study.

Between January 1, 2011, and December 31, 2016, we studied the incidence, management and outcome of high-risk breast lesions in a consecutive series of 376,519 screens of women who received biennial screening mammography. During the 6-year period covered by the study, the proportion of women who underwent core needle biopsy (CNB) after recall remained fairly stable, ranging from 39.2% to 48.1% (mean: 44.2%, 5,212/11,783), whereas the proportion of high-risk lesions at CNB (i.e., flat epithelial atypia, atypical ductal hyperplasia, lobular carcinoma in situ and papillary lesions) gradually increased from 3.2% (25/775) in 2011 to 9.5% (86/901) in 2016 (p < 0.001). The mean proportion of high-risk lesions at CNB that were subsequently treated with diagnostic surgical excision was 51.4% (169/329) and varied between 41.0% and 64.3% through the years, but the excision rate for high-risk lesions per 1,000 screens and per 100 recalls increased from 0.25 (2011) to 0.70 (2016; p < 0.001) and from 0.81 (2011) to 2.50 (2016; p < 0.001), respectively. The proportion of all diagnostic surgical excisions showing in situ or invasive breast cancer was 29.0% (49/169) and varied from 22.2% (8/36) in 2014 to 38.5% (5/13) in 2011. In conclusion, the proportion of high-risk lesions at CNB tripled in a 6-year period, with a concomitant increased excision rate for these lesions. As the proportion of surgical excisions showing in situ or invasive breast cancer did not increase, a rising number of screened women underwent invasive surgical excision with benign outcome.

Validation of the online prediction model CancerMath in the Dutch breast cancer population.

PURPOSE: CancerMath predicts the expected benefit of adjuvant systemic therapy on overall (OS) and breast cancer-specific survival (BCSS). Here, CancerMath was validated in Dutch breast cancer patients. METHODS: All operated women diagnosed with stage I-III primary invasive breast cancer in 2005 were identified from the Netherlands Cancer Registry. Calibration was assessed by comparing 5- and 10-year predicted and observed OS/BCSS using χ2 tests. A difference > 3% was considered as clinically relevant. Discrimination was assessed by area under the receiver operating characteristic (AUC) curves. RESULTS: Altogether, 8032 women were included. CancerMath underestimated 5- and 10-year OS by 2.2% and 1.9%, respectively. AUCs of 5- and 10-year OS were both 0.77. Divergence between predicted and observed OS was most pronounced in grade II, patients without positive nodes, tumours 1.01-2.00 cm, hormonal receptor positive disease and patients 60-69 years. CancerMath underestimated 5- and 10-year BCSS by 0.5% and 0.6%, respectively. AUCs were 0.78 and 0.73, respectively. No significant difference was found in any subgroup. CONCLUSION: CancerMath predicts OS accurately for most patients with early breast cancer although outcomes should be interpreted with care in some subgroups. BCSS is predicted accurately in all subgroups. Therefore, CancerMath can reliably be used in (Dutch) clinical practice.

Pathologic complete response and overall survival in breast cancer subtypes in stage III inflammatory breast cancer.

PURPOSE: To analyze the influence of hormone receptors (HR) and Human Epidermal growth factor Receptor-2 (HER2)-based molecular subtypes in stage III inflammatory breast cancer (IBC) on tumor characteristics, treatment, pathologic response to neoadjuvant chemotherapy (NACT), and overall survival (OS). METHODS: Patients with stage III IBC, diagnosed in the Netherlands between 2006 and 2015, were classified into four breast cancer subtypes: HR+/HER2- , HR+/HER2+ , HR-/HER2+ , and HR-/HER2- . Patient-, tumor- and treatment-related characteristics were compared. In case of NACT, pathologic complete response (pCR) was compared between subgroups. OS of the subtypes was compared using Kaplan-Meier curves and the log-rank test. RESULTS: 1061 patients with stage III IBC were grouped into subtypes: HR+/HER2- (N = 453, 42.7%), HR-/HER2- (N = 258, 24.3%), HR-/HER2+ (N = 180,17.0%), and HR+/HER2+ (N = 170,16.0%). In total, 679 patients (85.0%) received NACT. In HR-/HER2+ tumors, pCR rate was highest (43%, (p < 0.001). In case of pCR, an improved survival was observed for all subtypes, especially for HR+/HER2+ and HR-/HER2+ tumor subtypes. Trimodality therapy (NACT, surgery, radiotherapy) improved 5-year OS as opposed to patients not receiving this regimen: HR+/HER2- (74.9 vs. 46.1%), HR+/HER2+ (80.4 vs. 52.6%), HR-/HER2+ (76.4 vs. 29.7%), HR-/HER2- (47.6 vs. 27.8%). CONCLUSIONS: In stage III IBC, breast cancer subtypes based on the HR and HER2 receptor are important prognostic factors of response to NACT and OS. Patients with HR-/HER2- IBC were less likely to achieve pCR and had the worst OS, irrespective of receiving most optimal treatment regimen to date (trimodality therapy).

Correction to: Frequency and characteristics of contralateral breast abnormalities following recall at screening mammography.

The original version of this article, published on 17 April 2018, unfortunately contained a mistake.

Characteristics of screen-detected cancers following concordant or discordant recalls at blinded double reading in biennial digital screening mammography.

OBJECTIVES: To analyse which mammographic and tumour characteristics led to concordant versus discordant recalls at blinded double reading to further optimise our breast cancer screening programme. METHODS: We included a consecutive series of 99,013 screening mammograms obtained between July 2013 and January 2015. All mammograms were double read in a blinded fashion. Discordant readings were routinely recalled without consensus or arbitration. During the 2-year follow-up, relevant data of the recalled women were collected. We compared mammographic characteristics, screening outcome and tumour characteristics between concordant and discordant recalls. RESULTS: There were 2,543 concordant recalls (71.4%) and 997 discordant recalls (28.0%). The positive predictive value of a concordant recall was significantly higher (23.5% vs. 10.0%, p < 0.001). The proportion of BI-RADS 0 was significantly higher in the discordant recall group (75.7% vs. 56.3%, p < 0.001). Discordant recalls were more often an asymmetry or architectural distortion (21.8% vs. 13.2% and 9.3% vs. 6.5%, respectively, p < 0.001). There were no differences in the distribution of DCIS and invasive cancers and tumour characteristics were comparable for the two groups, except for a more favourable tumour grade in the discordant recall group (54.7% vs. 39.9% grade I tumours, p = 0.022). CONCLUSIONS: Screen-detected cancers detected by a discordant reading show a more favourable tumour grade than cancers diagnosed after a concordant recall. The higher proportion of asymmetries and architectural distortions in this group provide a possible target for improving screening programmes by additional training of screening radiologists and the implementation of digital breast tomosynthesis. KEY POINTS: • With blinded double reading of screening mammograms, screen-detected cancers detected by a discordant reading show a more favourable tumour grade than cancers diagnosed after a concordant recall. • The proportions of asymmetries and architectural distortions are higher in case of a discordant reading. • Possible improvement strategies could target additional training of screening radiologists and the implementation of digital breast tomosynthesis in breast cancer screening programmes.