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.

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.

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.

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.

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).

Breast conserving therapy and mastectomy revisited: Breast cancer-specific survival and the influence of prognostic factors in 129,692 patients.

This large population-based study compared breast-conserving surgery with radiation therapy (BCT) with mastectomy on (long-term) breast cancer-specific (BCSS) and overall survival (OS), and investigated the influence of several prognostic factors. Patients with primary T1-2N0-2M0 breast cancer, diagnosed between 1999 and 2012, were selected from the Netherlands Cancer Registry. We investigated the 1999-2005 (long-term outcome) and the 2006-2012 cohort (contemporary adjuvant systemic therapy). Cause of death was derived from the Statistics Netherlands (CBS). Multivariable analyses, per time cohort, were performed in T1-2N0-2, and separately in T1-2N0-1 and T1-2N2 stages. The T1-2N0-1 stages were further stratified for age, hormonal receptor and HER2 status, adjuvant systemic therapy and comorbidity. In total, 129,692 patients were included. In the 1999-2005 cohort, better BCSS and OS for BCT than mastectomy was seen in all subgroups, except in patients < 40 years with T1-2N0-1 stage. In the 2006-2012 cohort, superior BCSS and OS were found for T1-2N0-1, but not for T1-2N2. Subgroup analyses for T1-2N0-1 showed superior BCSS and OS for BCT in patients >50 years, not treated with chemotherapy and with comorbidity. Both treatments led to similar BCSS in patients <50 years, without comorbidity and those treated with chemotherapy. Although confounding by severity and residual confounding cannot be excluded, this study showed better long-term BCSS for BCT than mastectomy. Even with more contemporary diagnostics and therapies we identified several subgroups that may benefit from BCT. Our results support the hypothesis that BCT might be preferred in most breast cancer patients when both treatments are suitable.

Assessment of HER2 status in breast cancer biopsies is not affected by accelerated tissue processing.

AIMS: To establish whether core needle biopsy (CNB) specimens processed with an accelerated processing method with short fixation time can be used to determine accurately the human epidermal growth factor receptor 2 (HER2) status of breast cancer. METHODS AND RESULTS: A consecutive case-series from two high-volume breast clinics was created. We compared routine HER2 immunohistochemistry (IHC) assessment between accelerated processing CNB specimens and routinely processed postoperative excision specimens. Additional amplification-based testing was performed in cases with equivocal results. The formalin fixation time was less than 2 h and between 6 and 72 h, respectively. Fluorescence in-situ hybridisation and multiplex ligation-dependent probe amplification were used for amplification testing. One hundred and forty-four cases were included, 15 of which were HER2-positive on the routinely processed excision specimens. On the CNB specimens, 44 were equivocal on IHC and required an amplification-based test. Correlation between the CNB specimens and the corresponding excision specimens was high for final HER2 status, with an accuracy of 97% and a kappa of 0.85. CONCLUSIONS: HER2 status can be determined reliably on CNB specimens with accelerated processing time using standard clinical testing methods. Using this accelerated technology the minimum 6 h of formalin fixation, which current guidelines consider necessary, can be decreased safely. This allows for a complete and expedited histology-based diagnosis of breast lesions in the setting of a one-stop-shop, same-day breast clinic.

Postoperative Complications After Breast Cancer Surgery are Not Related to Age.

INTRODUCTION: Consensus about surgical treatment options for breast cancer in elderly patients remains elusive due to exclusion from clinical trials. Fear of complications due to increased age often is an important factor in the choice of treatment and might result in different treatment of the older patient. METHODS: A total of 1258 female patients who underwent breast cancer surgery for primary diagnosed breast cancer in 2010-2014 were included. Incidence of postoperative complications (POCs) was compared between the younger (18-70 years, N = 1008) and older (≥71 years, N = 250) patients. Multivariate logistic regression was performed to identify the correlation between age and POCs. RESULTS: POCs developed in 25.9% of the younger and 31.6% of the older patients (p = 0.042). In multivariable logistic regression analysis of the overall study population, age was no risk factor for POC (odds ratio 0.950, 95% confidence interval 0.640-1.410, p = 0.798). More extensive surgery (mastectomy and/or axillary lymph node dissection compared with single lumpectomy) and increased body mass index increased the odds of developing a POC. Analyses of the ≥71-year group separately revealed only type of surgery to be of influence. CONCLUSIONS: Fear of increased risk of complications in the older patient is unjustified. Neither increased age nor high American Society of Anesthesiologists classification are predictors for developing POC. Type of surgery is the most important determinant. Choosing mastectomy while breast-conserving surgery is suitable should be discouraged, particularly in the older patient.

Interval breast cancer characteristics before, during and after the transition from screen-film to full-field digital screening mammography.

BACKGROUND: To determine the proportion of "true" interval cancers and tumor characteristics of interval breast cancers prior to, during and after the transition from screen-film mammography screening (SFM) to full-field digital mammography screening (FFDM). METHODS: We included all women with interval cancers detected between January 2006 and January 2014. Breast imaging reports, biopsy results and breast surgery reports of all women recalled at screening mammography and of all women with interval breast cancers were collected. Two experienced screening radiologists reviewed the diagnostic mammograms, on which the interval cancers were diagnosed, as well as the prior screening mammograms and determined whether or not the interval cancer had been missed on the most recent screening mammogram. If not missed, the cancer was considered an occult ("true") interval cancer. RESULTS: A total of 442 interval cancers had been diagnosed, of which 144 at SFM with a prior SFM (SFM-SFM), 159 at FFDM with a prior SFM (FFDM-SFM) and 139 at FFDM with a prior FFDM (FFDM-FFDM). The transition from SFM to FFDM screening resulted in the diagnosis of more occult ("true") interval cancers at FFDM-SFM than at SFM-SFM (65.4% (104/159) versus 49.3% (71/144), P < 0.01), but this increase was no longer statistically significant in women who had been screened digitally for the second time (57.6% (80/139) at FFDM-FFDM versus 49.3% (71/144) at SFM-SFM). Tumor characteristics were comparable for the three interval cancer cohorts, except of a lower porportion (75.7 and 78.0% versus 67.2% af FFDM-FFDM, P < 0.05) of invasive ductal cancers at FFDM with prior FFDM. CONCLUSIONS: An increase in the proportion of occult interval cancers is observed during the transition from SFM to FFDM screening mammography. However, this increase seems temporary and is no longer detectable after the second round of digital screening. Tumor characteristics and type of surgery are comparable for interval cancers detected prior to, during and after the transition from SFM to FFDM screening mammography, except of a lower proportion of invasive ductal cancers after the transition.

10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study.

BACKGROUND: Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer. METHODS: In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1-2, N0-1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data. FINDINGS: Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 [95% CI 0·49-0·53]; p<0·0001; adjusted HR 0·81 [0·78-0·85]; p<0·0001), and this improvement remained significant for all subgroups of different T and N stages of breast cancer. After adjustment for confounding variables, breast-conserving surgery plus radiotherapy did not significantly improve 10 year distant metastasis-free survival in the 2003 cohort overall compared with mastectomy (adjusted HR 0·88 [0·77-1·01]; p=0·07), but did in the T1N0 subgroup (adjusted 0·74 [0·58-0·94]; p=0·014). Breast-conserving surgery plus radiotherapy did significantly improve 10 year relative survival in the 2003 cohort overall (adjusted 0·76 [0·64-0·91]; p=0·003) and in the T1N0 subgroup (adjusted 0·60 [0·42-0·85]; p=0·004) compared with mastectomy. INTERPRETATION: Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer. FUNDING: None.

Type and Extent of Surgery for Screen-Detected and Interval Cancers at Blinded Versus Nonblinded Double-Reading in a Population-Based Screening Mammography Program.

BACKGROUND: This study aimed to compare the type and extent of surgery in patients with screen-detected and interval cancers after blinded or nonblinded double-reading of screening mammograms. METHODS: The study investigated a consecutive series of screens double-read in either a blinded (n = 44,491) or nonblinded (n = 42,996) fashion between 2009 and 2011. During a 2 year follow-up period, the radiology reports, surgical correspondence, and pathology reports of all the screen-detected and interval cancers were collected. RESULTS: Screen-detected breast cancer was diagnosed for 325 women at blinded and 284 women at nonblinded double-reading. The majority of the women were treated by breast-conserving surgery (BCS) at both reading strategies (78.2 vs. 81.7 %; p = 0.51). Larger total resection volumes were observed at BCS for ductal carcinoma in situ (DCIS) treatment for patients after blinded double-reading (p = 0.005). The proportions of positive resection margins after BCS were comparable for patients with DCIS (p = 0.81) or invasive screen-detected cancers (p = 0.38) for the two reading strategies. A total of 158 interval cancers were diagnosed. The proportions of patients treated with BCS were comparable for the two reading strategies (p = 0.42). The total resection volume (p = 0.13) and the proportion of positive resection margins after BCS (p = 0.32) for invasive interval cancer were comparable for the two cohorts. The BCS rate was higher for women after nonblinded double-reading (p = 0.04). CONCLUSIONS: Blinded and nonblinded double-reading yielded comparable surgical treatments for women with screen-detected or interval breast cancer except for larger total resection volumes at BCS for screen-detected DCIS and a higher BCS rate for interval cancers at nonblinded double-reading.

Does Nipple Discharge Color Predict (pre-) Malignant Breast Pathology?

Unilateral single-duct nipple discharge is associated with an increased risk for underlying breast malignancy. There is no consensus whether color of nipple discharge independently indicates the risk of malignancy. We sought to assess the relationship between the color of discharge and the risk of malignancy. Patients with unilateral single-duct nipple discharge without abnormalities on clinical and radiologic examination were included. Prior to diagnostic microdochectomy nipple discharge characteristics were registered. Multiple logistic regressions were performed to assess the relationship between color of nipple discharge and malignancy, corrected for age. During a mean follow-up period of 7.1 years we determined complication rate and false-negative rate of microdochectomy. A total of 184 patients were included (median age 53 years, range 19-84). Histologic examination revealed (in situ or invasive) breast carcinoma in 10.9% (20) of patients and high-risk lesions in 11.4% (21). Malignancy or high-risk lesions were found in 25% (OR: 1.37; 95% CI: 0.62-3.00) of patients with bloody discharge. Risk of underlying malignancy increased in patients >60 years (OR: 2.35; 95% CI: 1.14-4.83). Complication rate of microdochectomy was 2.7%. Single-duct, unilateral nipple discharge is a sign of underlying malignancy in a substantial proportion of cases. The majority of patients with unilateral single-duct nipple discharge, diagnosed with breast cancer, present with bloody discharge. However, the association between bloody nipple discharge and malignancy is not strong enough to distinguish high-risk patients. Therefore, invasive diagnostic procedures like microdochectomy should be offered to all patients with unilateral uniductal nipple discharge to search for underlying malignancy.