BACKGROUND:Oncoplastic breast-conserving surgery (OP-BCS) is becoming increasingly popular to avoid mastectomy or optimize cosmetic outcomes of breast-conserving surgery (BCS). Few studies have compared clinical outcomes and patient-reported outcomes (PROs) of OP-BCS to conventional BCS (C-BCS). This study aims to compare clinical outcomes and short- and long-term PROs after OP-BCS and C-BCS in a large prospective breast cancer cohort. METHODS:Women in the prospective, multicenter UMBRELLA (Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion) breast cancer cohort who underwent OP-BCS or C-BCS were included. Clinical outcomes and PROs (measured by EORTC QLQ-C30/BR23) up to 24 months postoperatively were evaluated. Mixed-model analysis was performed to assess differences in PROs over time between groups. RESULTS:A total of 1628 (84.9%) patients received C-BCS and 290 (15.1%) received OP-BCS. After C-BCS and OP-BCS, free resection margins were obtained in 84.2% (n = 1370) and 86.2% (n = 250), respectively, reoperation for re-excision of margins within 3 months occurred in 5.3% (n = 86) and 4.8% (n = 14), and the median time interval from surgery until adjuvant systemic therapy was 66 and 63 days, and 36 and 41 days until radiotherapy. Shortly postoperative, OP-BCS was associated with statistically significant lower mean scores for physical functioning (83.6 vs 87.2) and body image (82.8 vs 89.4) and more pain (19.8 vs 26.5) and breast symptoms (22.7 vs 30.3) than C-BCS. Body image scores remained statistically significantly less favorable after OP-BSC than C-BCS up to 24 months postoperatively (87.8 vs 92.2). CONCLUSIONS:Oncoplastic surgery safely enables BCS but may lead to less favorable long-term body image compared to C-BCS. These findings are important for patient education and shared decision-making.

Background Immune checkpoint immunotherapy (CPI) targeting PD1/PD-L1 has been shown to be an effective treatment for gestational trophoblastic neoplasia (GTN). This includes those with multidrug resistance, ultra-high risk disease and ETT/PSTT subtypes that are inherently chemotherapy resistant, but there is also emerging evidence in low-risk disease. Objectives We set out to generate an overview of the current data supporting the use of CPI for GTN in both high risk and low risk disease and to consider future research goals and directions in order to implement CPI in current treatment guidelines. Methods We identified and reviewed the published data on the use of CPI agents in GTN. Outcome 133 patients were identified who had been treated with CPI for GTN with pembrolizumab (23), avelumab (22), camrelizumab (57), toripalimab (15) or other anti-PD-1 agents (16), of whom 118 had high risk disease, relapse or multi drug resistant disease, and 15 low risk disease. Overall 85 patients achieved complete remission, 77 (of 118) with high risk disease and 8 (of 15) with low risk disease. 1 patient with complete remission in the high risk group developed a relapse 22 months after anti-PD-1 treatment had been stopped. Treatment was generally well tolerated across studies. Conclusions and Outlook The majority of high risk patients (77/118) treated with CPI are cured and this is particularly relevant amongst those with chemotherapy resistant disease who otherwise have very limited treatment options. Priorities for future research include determining whether these agents have a role earlier in the disease course, the utility of combination with chemotherapy, and effects on future fertility. Treatment availability remains a concern due to the high price of these agents.

Background: Immediate oncoplastic breast conserving surgery (OP-BCS) is becoming increasingly popular to optimize cosmetic outcomes after BCS. Observational studies suggest promising oncological and aesthetic outcomes after OP-BCS. However, only few prospective studies evaluated patient-reported outcomes (PROs) after OP-BCS versus standard BCS (S-BSC) longitudinally. Therefore, the aim of this study was to compare short- and long-term quality of life (QoL), physical and psychosocial well-being, cosmetic and clinical outcomes in breast cancer survivors treated with OP-BCS versus S-BCS.

Background: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare aggressive ovarian malignancy mainly affecting children, adolescents, and young adults. Since the discovery of mutations in the SMARCA4 gene in 2014, SCCOHT has become the subject of extensive investigation. However, international uniform treatment guidelines for SCCOHT are lacking and the outcome remains poor. The aim of this systematic review is to generate an overview of all reported patients with SCCOHT from 1990 onwards, describing the clinical presentation, genetic characteristics, treatment, and outcome. Methods: A systematic search was performed in the databases Embase, Medline, Web of Science, and Cochrane for studies that focus on SCCOHT. Patient characteristics and treatment data were extracted from the included studies. Survival was estimated using Kaplan–Meier’s methodology. To assess the difference between survival, the log-rank test was used. To quantify the effect of the FIGO stage, the Cox proportional hazard regression model was estimated. The chi-squared test was used to study the association between the FIGO stage and the surgical procedures. Results: Sixty-seven studies describing a total of 306 patients were included. The median patient age was 25 years (range 1–60 years). The patients mostly presented with non-specific symptoms such as abdominal pain and sometimes showed hypercalcemia and elevated CA-125. A great diversity in the diagnostic work-up and therapeutic approaches was reported. The chemotherapy regimens were very diverse, all containing a platinum-based (cisplatin or carboplatin) backbone. Survival was strongly associated with the FIGO stage at diagnosis. Conclusions: SCCOHT is a rare and aggressive ovarian cancer, with a poor prognosis, and information on adequate treatment for this cancer is lacking. The testing of mutations in SMARCA4 is crucial for an accurate diagnosis and may lead to new treatment options. Harmonization and international collaboration to obtain high-quality data on diagnostic investigations, treatment, and outcome are warranted to be able to develop international treatment guidelines to improve the survival chances of young women with SCCOHT.

BACKGROUND:Immune checkpoint immunotherapy (CPI) targeting programmed cell death 1 (PD-1)/ligand (PD-L1) has been shown to be an effective treatment for gestational trophoblastic neoplasia (GTN). This includes those with multidrug resistance, ultra-high-risk disease, and epithelioid trophoblastic tumour/placental site trophoblastic tumour subtypes that are inherently chemotherapy resistant, but there is also emerging evidence in low-risk disease.OBJECTIVES:We set out to generate an overview of the current data supporting the use of CPI for GTN in both high-risk and low-risk disease and to consider future research goals and directions in order to implement CPI in current treatment guidelines.METHODS:We identified and reviewed the published data on the use of CPI agents in GTN.OUTCOME:133 patients were identified who had been treated with CPI for GTN with pembrolizumab (23), avelumab (22), camrelizumab (57), toripalimab (15), or other anti-PD-1 agents (16), of whom 118 had high-risk diseases, relapse or multi-drug resistant disease, and 15 low-risk diseases. Overall 85 patients achieved complete remission, 77 (of 118) with high-risk disease, and 8 (of 15) with low-risk disease. 1 patient with complete remission in the high-risk group developed a relapse 22 months after anti-PD-1 treatment had been stopped. Treatment was generally well tolerated across studies.CONCLUSIONS AND OUTLOOK:The majority of high-risk patients (77/118) treated with CPI are cured and this is particularly relevant amongst those with chemotherapy resistant disease who otherwise have very limited treatment options. Priorities for future research include determining whether these agents have a role earlier in the disease course, the utility of combination with chemotherapy, and effects on future fertility. Treatment availability remains a concern due to the high price of these agents.

PurposeDuring the first SARS-CoV-2-infection wave, a deterioration in emotional well-being and increased need for mental health care were observed among patients treated or being treated for breast cancer. In this follow-up study, we assessed patient-reported quality of life (QoL), physical functioning, and psychosocial well-being during the second SARS-CoV-2-infection wave in a large, representative cohort.MethodsThis longitudinal cohort study was conducted within the prospective, multicenter UMBRELLA breast cancer cohort. To assess patient-reported QoL, physical functioning and psychosocial well-being, COVID-19-specific surveys were completed by patients during the first and second SARS-CoV-2-infection waves (April and November 2020, respectively). An identical survey was completed by a comparable reference population during the second SARS-CoV-2-infection waves. All surveys included the validated EORTC-QLQ-C30/BR23, HADS and "De Jong-Gierveld Loneliness" questionnaires. Pre-COVID-19 EORTC-QLQ-C30/BR23 and HADS outcomes were available from UMBRELLA. Response rates were 69.3% (n = 1106/1595) during the first SARS-CoV-2-infection wave and 50.9% (n = 822/1614) during the second wave. A total of 696 patients responded during both SARS-CoV-2-infection waves and were included in the analysis comparing patient-reported outcomes (PROs) during the second SARS-CoV-2-infection wave to PROs during the first wave. Moreover, PROs reported by all patients during the second SARS-CoV-2-infection wave (n = 822) were compared to PROs of a similar non-cancer reference population (n = 241) and to their pre-COVID-19 PROs.ResultsPatient-reported QoL, physical functioning, and psychosocial well-being of patients treated or being treated for breast cancer remained stable or improved from the first to the second SARS-CoV-2-infection wave. The proportion of emotional loneliness reduced from 37.6 to 29.9% of patients. Compared to a similar non-cancer reference population, physical, emotional, and cognitive functioning, future perspectives and symptoms of dyspnea and insomnia were worse in patients treated or being treated for breast cancer during the second SARS-CoV-2-infection wave. PROs in the second wave were similar to pre-COVID-19 PROs.ConclusionAlthough patients scored overall worse than individuals without breast cancer, QoL, physical functioning, and psychosocial well-being did not deteriorate between the first and second wave. During the second wave, PROs were similar to pre-COVID-19 values. Overall, current findings are cautiously reassuring for future mental health of patients treated or being treated for breast cancer.

Long axial field-of-view (LAFOV) PET/CT scanners have been introduced recently [1, 2], which offer numerous advantages [3].One important advantage of using LAFOV PET/CT for imaging 89 Zr-labelled monoclonal antibodies (mAbs), i.e., immunoPET, is the substantial increase in sensitivity compared with standard axial field-of-view (SAFOV) PET/CT systems, which may lead to a remarkable image quality improvement.This first study showcases such improvement for immunoPET with Biograph Vision Quadra™ (VQ) LAFOV PET/CT (Siemens Healthineers, Knoxville, TN, USA).Two patients suffering from metastatic HER2-positive breast cancer were administered with 37 MBq [ 89 Zr] trastuzumab in order to assist clinical decision-making [4,5].Patients were scanned 4 days postinjection with a Biograph™ mCT PET/CT (patient A) or a Biograph Vision™ PET/CT (patient B) (Siemens Healthineers, Knoxville, TN, USA), according to local standard operating procedures with overall scan durations of 45 min and 32 min, for, respectively, mCT and Vision.

Information may increase chemotherapy-related cognitive symptoms (CRCS). This randomized study tested the effects of informing 160 first-time breast cancer patients about CRCS with and without self-affirmation on the perceived frequency and severity of cognitive symptoms at 2.5-months and 6.5-months post-chemotherapy. Pre-treatment information added to experienced side-effects at 6.5-months post-chemotherapy. Self-affirmation attenuated these effects for the perceived severity of symptoms.Background: Informing patients about chemotherapy-related cognitive symptoms (CRCS) may increase perceived cognitive symptoms. This longitudinal randomized study evaluated this Adverse Information Effect (AIE) in breast cancer patients and examined whether self-affirmation (SA) can reduce AIEs (ClinicalTrials.gov identifier: NCT04813965). Patients and Methods: Before (neo) adjuvant chemotherapy, 160 newly diagnosed breast cancer patients were randomly allocated to receive: standard information on side-effects (control), standard information with additional information about CRCS (information), or standard and additional information with a subsequent self-affirmative text (information + SA). Online-questionnaires assessed the perceived frequency (MOS-cog) and severity (MDASI-cog) of cognitive symptoms before chemotherapy (baseline, T0), and 2.5-months (T1) and 6.5-months (T2) post-chemotherapy. Higher scores indicate less frequent, and more severe symptoms, respectively. Baseline-to-follow-up analyses using a mixed-effects modeling approach compared groups over time. Results: At T0-T2, 148, 140 and 133 patients responded, respectively (attrition rates: 8%, 5%, 5%). Frequency (ES =-0.36, P = .003) and severity (ES = 0.54, P < .001) of symptoms worsened from baseline to T1, without differences between groups. At T2, symptom frequency remained stable for informed (ES =-0.3, P = .021) and self-affirmed (ES =-0.3, P = .019) patients, but returned to baseline levels for controls. At T2, symptom severity remained increased for informed patients (ES = 0.3, P = .006), but normalized for self-affirmed patients (ES = 0.2, P = .178) and controls. Conclusion: No AIEs occurred until T2. The initial overall increase in perceived cognitive symptoms recovered at T2 for controls, but not for patients who received additional infor-mation about CRCS. Self-affirmation attenuated these longer-term AIEs for the perceived severity but not the frequency of symptoms.

Purpose To evaluate perceived access to health care and preferences for health care provision among patients (being) treated for breast cancer during the COVID-19 pandemic. Methods Longitudinal study within the prospective, multicenter UMBRELLA cohort of patients (being) treated for breast cancer. All cohort participants enrolled in UMBRELLA between October 2013 and November 2020 were sent a COVID-19-specific survey during the first and second wave of the COVID-19 pandemic, i.e., April 2020 and November 2020, respectively. Results In total, 1106 (69.3%) and 822 (50.9%) cohort participants completed the survey in the first and second wave, respectively. The proportion of patients experiencing that their treatment or follow-up care was affected due to COVID-19 decreased from 28.4% (n = 198) in April 2020 to 14.8% (n = 103) in November 2020. Throughout the pandemic, one or more hospital consultations were postponed in 10.0% (n = 82) of all patients and changed into a teleconsultation in 23.1% (n = 190). The proportion of patients who experienced a higher threshold to contact their general practitioner due to COVID-19 decreased from 29.9% (n = 204) in the first wave to 20.8% (n = 145) in the second wave. In-person consultations remained most preferred in 35.2% (n = 289) of all patients. Nearly half of all patients (48.3%, n = 396) indicated that telehealth would be a useful alternative for in-person consultations in future. Conclusion Perceived access to health care has improved substantially throughout the pandemic. Digital care is well received by patients (being) treated for breast cancer.

Purpose To evaluate symptoms of late radiation toxicity, side effects, and quality of life in breast cancer patients treated with hyperbaric oxygen therapy (HBOT). Methods For this cohort study breast cancer patients treated with HBOT in 5 Dutch facilities were eligible for inclusion. Breast cancer patients with late radiation toxicity treated with ≥ 20 HBOT sessions from 2015 to 2019 were included. Breast and arm symptoms, pain, and quality of life were assessed by means of the EORTC QLQ-C30 and -BR23 before, immediately after, and 3 months after HBOT on a scale of 0–100. Determinants associated with persistent breast pain after HBOT were assessed. Results 1005/1280 patients were included for analysis. Pain scores decreased significantly from 43.4 before HBOT to 29.7 after 3 months ( p < 0.001). Breast symptoms decreased significantly from 44.6 at baseline to 28.9 at 3 months follow-up ( p < 0.001) and arm symptoms decreased significantly from 38.2 at baseline to 27.4 at 3 months follow-up ( p < 0.001). All quality of life domains improved at the end of HBOT and after 3 months follow-up in comparison to baseline scores. Most prevalent side effects of HBOT were myopia (any grade, n = 576, 57.3%) and mild barotrauma ( n = 179, 17.8%). Moderate/severe side effects were reported in 3.2% ( n = 32) of the patients. Active smoking during HBOT and shorter time (i.e., median 17.5 vs. 22.0 months) since radiotherapy were associated with persistent breast pain after HBOT. Conclusion Breast cancer patients with late radiation toxicity reported reduced pain, breast and arm symptoms, and improved quality of life following treatment with HBOT.

Purpose To identify factors associated with (perceived) access to health care among (ex-)breast cancer patients during the COVID-19 pandemic. Methods Cross-sectional study within a large prospective, multicenter cohort of (ex-)breast cancer patients, i.e., UMBRELLA. All participants enrolled in the UMBRELLA cohort between October 2013 and April 2020 were sent a COVID-19-specific survey, including the Hospital Anxiety and Depression Scale (HADS) questionnaire. Results In total, 1051 (66.0%) participants completed the survey. During COVID-19, 284 (27.0%) participants reported clinically relevant increased levels of anxiety and/or depression, i.e., total HADS score ≥ 12. Participants with anxiety and/or depression reported statistically significant higher barriers to contact their general practitioner (47.5% vs. 25.0%, resp.) and breast cancer physicians (26.8% vs. 11.2%, resp.) compared to participants without these symptoms. In addition, a higher proportion of participants with anxiety and/or depression reported that their current treatment or (after)care was affected by COVID-19 compared to those without these symptoms (32.7% vs. 20.5%, resp.). Factors independently associated with symptoms of anxiety and/or depression during COVID-19 were pre-existent anxiety (OR 6.1, 95% CI 4.1–9.2) or depression (OR 6.0, 95% CI 3.5–10.2). Conclusion During the COVID-19 pandemic, (ex-)breast cancer patients with symptoms of anxiety and/or depression experience higher barriers to contact health care providers. Also, they more often report that their health care was affected by COVID-19. Risk factors for anxiety and/or depression during COVID-19 are pre-existent symptoms of anxiety or depression. Extra attention—including mental health support—is needed for this group.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic (officially declared on the March 11, 2020), and the resulting measures, are impacting daily life and medical management of breast cancer patients and survivors. We evaluated to what extent these changes have affected quality of life, physical, and psychosocial well-being of patients previously or currently being treated for breast cancer. Methods This study was conducted within a prospective, multicenter cohort of breast cancer patients and survivors (Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion). Shortly after the implementation of COVID-19 measures, an extra survey was sent to 1595 participants, including the validated European Organization for Research and Treatment of Cancer (EORTC) core (C30) and breast cancer- specific (BR23) Quality of Life Questionnaire (EORTC QLQ-C30/BR23) and Hospital Anxiety and Depression Scale (HADS) questionnaire. Patient-reported outcomes (PROs) were compared with the most recent PROs collected within UMBRELLA pre–COVID-19. The impact of COVID-19 on PROs was assessed using mixed model analysis, adjusting for potential confounders. Results 1051 patients and survivors (65.9%) completed the survey; 31.1% (n = 327) reported a higher threshold to contact their general practitioner amid the COVID-19 pandemic. A statistically significant deterioration in emotional functioning was observed (mean = 82.6 [SD = 18.7] to 77.9 [SD = 17.3]; P < .001), and 505 (48.0%, 95% confidence interval [CI] = 45.0% to 51.1%) patients and survivors reported moderate to severe loneliness. Small improvements were observed in quality of life and physical, social, and role functioning. In the subgroup of 51 patients under active treatment, social functioning strongly deteriorated (77.3 [95% CI = 69.4 to 85.2] to 61.3 [95% CI = 52.6 to 70.1]; P = .002). Conclusion During the COVID-19 pandemic, breast cancer patients and survivors were less likely to contact physicians and experienced a deterioration in their emotional functioning. Patients undergoing active treatment reported a substantial drop in social functioning. One in 2 reported loneliness that was moderate or severe. Online interventions supporting mental health and social interaction are needed during times of social distancing and lockdowns.

Abstract Background: To date, histologic grade is widely used to guide therapeutic management of invasive breast cancer (IBC), as it remains one of the most well established prognostic biomarkers. In the Netherlands, with similar guidelines to the rest of Europe, grade even indicates the need for adjuvant chemotherapy in approximately one third of breast cancer patients. However, we previously showed that inter- and intra-laboratory variation in grading is substantial in daily pathology practice. To facilitate quality improvement of histologic grading, feedback reports were sent to all individual pathology laboratories. Reports included the case-mix adjusted laboratory proportions per grade, benchmarked against other laboratories and the nationwide average. Hence, pathologists were enabled to discuss and reflect upon their grading practices. We assessed the effect of these feedback reports on grading variation in daily pathology practice on a nationwide level. Methods: Synoptic pathology reports of all IBC resection specimens, obtained between March 1 2017 and March 1 2019 were retrieved from the Dutch nationwide pathology registry (PALGA). Feedback reports were sent on March 1 2018. Absolute differences in laboratory-proportions of grades I-III were compared to the overall nationwide proportion before (March 1, 2017 to March 1, 2018) and after the laboratories received their feedback reports (March 2, 2018 to March 1, 2019) from PALGA. To compare the absolute deviation for all grades at once, a SUM-score, representing the sum of deviations from the grade-specific nationwide proportions, was calculated. Case-mix correction was performed by multivariable logistic regression, providing laboratory-specific odds ratios (ORs) for high (grade II-III) versus low-grade (grade I) IBC. The multivariate ORs before and after the feedback reports were compared by Wilcoxon signed rank test. Results: We included 17,102 synoptic IBC reports from 33 laboratories of which 8,676 were reported before and 8,335 were reported after the feedback reports were sent. Nationwide proportions before and after the feedback reports were 30.5% and 32.0% for grade I, 49.5% and 49.2% for grade III, and 20.0% and 18.8% for grade III, respectively. After feedback, the total range between laboraratories decreased for all grades; from 17.5-45.5% to 17.3%-41.5% for grade I (range -3.8%), from 34.3-64.5% to 35.0-58.8% for grade II (range -6.4) and from 10.9%-37.1% to 9.9-29.5% for grade III (range -6.6%). The maximum SUM-score of 34.1% before the feedback reports decreased to 29.4% after feedback. However, SUM-scores per laboratory before and after the feedback reports did not significantly differ (Wilcoxon signed rank test, p=0.955). Furthermore, comparison of the multivariate ORs confirmed that changes were not significant (Wilcoxon signed rank test, p=0.640). Conclusion: After implementation of feedback reports, an encouraging decrease in nationwide grading variation was observed, reflected by the decrease of the absolute range between laboratories after the feedback reports for all grades (I-III) and the decrease of the maximum overall deviation (SUM-score). As feedback reports were sent by PALGA for the first time, this was not (yet) a closed quality loop. Hence, we do not know if and how laboratories implemented the feedback reports. Therefore, although feedback reports seem to decrease grading variation, the full potential of these reports is still unclear. However, overall grading variation remains substantial, which emphasizes that continuous monitoring and benchmarking is essential as it creates insight and awareness. Closing the quality loop and further training of pathologists, for example by e-learning, may help to further decrease grading variation and improve clinical decision making. Citation Format: Carmen van Dooijeweert, Paul J van Diest, Inge O Baas, Elsken van der Wall, Ivette AG Deckers. The effect of laboratory-specific feedback reports on grading variation of invasive breast cancer; results of a nationwide study in the Netherlands [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-12.

Background Histologic grade of ductal carcinoma in situ of the breast (DCIS) may become the single biomarker that decides whether patients will be treated. Yet, evidence shows that grading variation in daily practice is substantial. To facilitate quality improvement, feedback reports, in which laboratory-specific case-mix adjusted proportions per grade were benchmarked against other laboratories, were sent to the individual laboratories by March 1, 2018. One year later, the effect of these feedback reports on inter-laboratory variation was studied. Methods Synoptic pathology reports of all pure DCIS resection specimens between March 1, 2017 and March 1, 2019 were retrieved from PALGA (the nationwide Dutch pathology registry). Laboratory-specific proportions per grade were compared to the overall proportion in the year before and after feedback. The absolute deviation for all three grades at once, represented by the overall deviation score (ODS), was calculated as the sum of deviations from the grade-specific overall proportions. Case-mix adjusted, laboratory-specific odds ratios (ORs) for high- (grade III) versus low-grade (grade I-II) DCIS were obtained by multivariable logistic regression. Results Overall, 2954 DCIS reports from 31 laboratories were included. After feedback, the range between laboratories decreased by 22 and 6.5% for grades II and III, while an increase of 6.2% was observed for grade I. Both the mean ODS (27.2 to 24.1%) and maximum ODS (87.7 to 59.6%) decreased considerably. However, the range of case-mix adjusted ORs remained fairly stable and substantial (0.39 (95% CI: 0.18–0.86) to 3.69 (95% CI: 1.30–10.51)). Conclusion A promising decrease in grading variation was observed after laboratory-specific feedback for DCIS grades II-III, while this was not observed for DCIS grade I. Overall, grading variation remained substantial which needs to be addressed considering its clinical implications. Nationwide consensus on a classification, and training of (expert breast) pathologists, for example by e-learning, may help to further improve grading standardization.

AimsHistological grade is widely used to guide the management of invasive breast cancer (IBC). Yet, substantial interlaboratory and intralaboratory grading variations exist in daily pathology practice. To create awareness and to facilitate quality improvement, feedback reports, containing case-mix-adjusted laboratory-specific grades benchmarked against other laboratories, were sent to the individual laboratories by 1 March 2018. We studied the effect of these feedback reports on interlaboratory grading variation up till 1 year later.MethodsOverall, 17 102 synoptic pathology reports of IBC resection specimens from 33 laboratories, obtained between 1 March 2017 and 1 March 2019 were retrieved from the Dutch Pathology Registry (PALGA). An overall deviation score (ODS), representing the sum of deviations from the grade-specific overall proportions, was calculated to compare the absolute deviation for all grades at once. Case-mix correction was performed by two multivariable logistic regression analyses, providing laboratory-specific ORs for high-grade versus low-grade IBC.ResultsAfter feedback, the overall range between laboratories decreased by 3.8%, 6.4% and 6.6% for grades I, II and III, respectively. Though the mean ODS remained similar (13.8% vs 13.7%), the maximum ODS decreased from 34.1% to 29.4%. The range of laboratory-specific ORs decreased by 21.9% for grade III versus grades I–II.ConclusionsAn encouraging decrease in grading variation of IBC was observed after laboratory-specific feedback. Nevertheless, the overall grading variation remains substantial. In view of the important role of grading in patient management, it is adamant that not only feedback should be provided on a regular basis but also other interventions, such as additional training, are required.

Patient management of invasive breast cancer (IBC) is to a large extent based on hormone- and HER2-receptor assessment. High-quality, reliable receptor assessment is of key importance as false results may lead to under- or overtreatment of patients. Surveillance of case-mix adjusted positivity rates has been suggested as a tool to identify laboratories with insufficient testing assays, as this covers the whole process of receptor assessment and enables laboratories to benchmark their positivity rates against other laboratories. We studied laboratory-specific variation in hormone- and HER2 positivity rates of 33,046 breast cancer patients using real-life nationwide data. All synoptic pathology reports of IBC resection-specimens, obtained between 2013 and 2016, were retrieved from the nationwide Dutch pathology registry (PALGA). Absolute and case-mix adjusted receptor positivity rates were compared to the mean national proportion and presented in funnel plots in separate analyses for estrogen (ER), progesterone (PR) and HER2. Case-mix adjustment was performed by multivariable logistic regression. 33,794 IBC lesions from 33,046 patients of 39 pathology laboratories were included. After case-mix adjustment, mean positivity rates were 87.2% for ER (range 80.4–94.3), 71.3% for PR (62.5–77.5%), and 9.9% for HER2 (5.5–12.7%). Overall, 14 (35.9%), 17 (43.6%) and 11 (28.2%) laboratories showed positivity rates outside the 95% confidence interval for ER, PR and HER2, respectively. This nationwide study shows that absolute variation in hormone- and HER2-receptor positivity rates between Dutch pathology laboratories is limited. Yet, the considerable number of outlying laboratories shows that there is still need for improvement. Continuous monitoring and benchmarking of positivity rates may help to realize this.