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Introduction: In up to 72 % of HER2+ invasive breast cancer (IBC), a ductal carcinoma in situ (DCIS) component is present. The presence of DCIS is associated with increased positive surgical margins after breast-conserving surgery (BCS). The aim of this study was to assess surgical margins, recurrence and survival in a nationwide cohort of HER2+ IBC with versus without a DCIS component, treated with neoadjuvant systemic therapy (NST) and BCS., Materials and Methods: Women diagnosed with HER2+ IBC treated with NST and BCS, between 2010 and 2019, were selected from the Netherlands Cancer Registry and linked to the Dutch Nationwide Pathology Databank. Kaplan-Meier and Cox regression analyses were performed to determine locoregional recurrence rate (LRR) and overall survival (OS) and associated clinicopathological variables. Surgical outcomes and prognosis were compared between IBC only and IBC+DCIS., Results: A total of 3056 patients were included: 1832 with IBC and 1224 with IBC+DCIS. Patients with IBC+DCIS had significantly more often positive surgical margins compared to IBC (12.8 % versus 4.9 %, p < 0.001). Five-year LRR was significantly higher in patients with IBC+DCIS compared to IBC (6.8 % versus 3.6 %, p < 0.001), but the presence of DCIS itself was not significantly associated with LRR after adjusting for confounders in multivariable analysis. Five-year OS did not differ between IBC+DCIS and IBC (94.9 % versus 95.7 %, p = 0.293)., Conclusion: The presence of DCIS is associated with higher rates of positive surgical margins, but not with LRR and lower OS when adjusted for confounders. Further research is necessary to adequately select IBC+DCIS patients for BCS after NST., Competing Interests: Declaration of competing interest Prof. Dr. Smidt reports grants from Nutricia and Servier Pharmaceuticals for microbiome research in colorectal cancer, and use of material from Illumina, not related to this study. Dr. T. van Nijnatten received institutional grant support from Bayer, and speaker honoraria from GE Healthcare and Bayer, not related to this study. L. Kooreman reports consulting fees from Novartis and educational fees from SCEM, not related to this study. All author authors report no declarations of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is an ongoing clinical dilemma of how best to treat patients who present themselves with visceral crisis. The time needed to undo the state of visceral crisis is the most relevant outcome for this patient group. We describe four patients treated with CDK4/6 inhibitor plus endocrine therapy for HR+/HER2- metastatic breast cancer who presented themselves with a visceral crisis. Two of them are male and three of them had synchronous metastatic breast cancer. Two patients had lymphangitis carcinomatosis of the lungs, one extensive disease of the eye and one of the liver. Time to first clinical response was observed within a few weeks in three patients. For one patient a switch to chemotherapy was needed. These cases show that treatment with CDK4/6 inhibitors can achieve a rapid response in patients experiencing visceral crisis. We conclude that chemotherapy is not the sole possibility in visceral crisis, and that CDK4/6 inhibitors can be considered as well.

Background: This study aims to explore whether first-line pertuzumab use modifies the effect of prior use of (neo-) adjuvant trastuzumab on the PFS of first-line HER2-targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC)., Methods: Patients diagnosed with HER2-positive ABC in 2008 to 2018 in 9 Dutch hospitals were derived from the SONABRE Registry (NCT03577197). Patients diagnosed with de novo metastatic breast cancer were excluded. Patients receiving first-line trastuzumab-based therapy for ABC were selected and divided into trastuzumab naïve (n = 113) and trastuzumab pretreated (n = 112). Progression-free survival (PFS) was compared using multivariable Cox proportional hazard models. The interaction effect of first-line pertuzumab was tested using the likelihood-ratio test., Results: The median follow-up time was 47 months (95% confidence interval [CI]: 42-52). When comparing trastuzumab pretreated with trastuzumab naïve patients, the hazard ratio for first-line progression was 2.07 (CI:1.47-2.92). For trastuzumab pretreated patients who received first-line trastuzumab without pertuzumab, the hazard ratio for progression was 2.60 (95% CI:1.72-3.93), whereas for those who received first-line trastuzumab with pertuzumab the hazard ratio was 1.43 (95% CI: 0.81-2.52) (P interaction = .10)., Conclusions: Prior use of trastuzumab as (neo-)adjuvant treatment had a negative impact on PFS of first-line HER2-targeted therapy outcomes. Adding pertuzumab to first-line trastuzumab-based therapy decreased the negative impact of prior (neo-)adjuvant trastuzumab use on first-line PFS. Further studies are needed to assess the effect of prior (neo-)adjuvant pertuzumab use on the outcomes of first-line pertuzumab-based therapy., Competing Interests: Disclosure Khava I.E. Ibragimova: Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); Novartis BV; Roche; Pfizer; Eli Lilly; Sandra M.E. Geurts: Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); Novartis BV; Roche; Pfizer; Eli Lilly; AstraZeneca, Gilead, Daiichi-Sankyo; Marissa Meegdes: Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); Novartis BV; Roche; Pfizer Eli Lilly; AstraZeneca, Gilead; Aude de Fallois: Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); Novartis BV; Roche; Pfizer Eli Lilly; AstraZeneca, Gilead; Vivianne C.G. Tjan-Heijnen: Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); Accord Healthcare; Novartis BV; Roche; Pfizer Eli Lilly; AstraZeneca; Gilead; Daiichi-Sankyo. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Ductal carcinoma in situ (DCIS) is present in more than half of HER2-positive invasive breast cancer (IBC). Recent studies show that DCIS accompanying HER2-positive IBC can be completely eradicated by neoadjuvant systemic therapy (NST). Our aim was to determine the percentage of pathologic complete response of the DCIS component in a nationwide cohort and to assess associated clinicopathologic variables. Furthermore, the impact on surgical treatment after NST was investigated., Methods: Women diagnosed with HER2-positive IBC, treated with NST and surgery, between 2010 and 2020, were selected from the Netherlands Cancer Registry. Pre-NST biopsy and postoperative pathology reports were obtained from the Dutch Nationwide Pathology Databank and assessed for the presence of DCIS. Clinicopathologic factors associated with DCIS response were assessed using logistic regression analyses., Results: A DCIS component was present in the pre-NST biopsy in 1403 (25.1%) of 5598 included patients. Pathologic complete response of the DCIS component was achieved in 730 patients (52.0%). Complete response of DCIS occurred more frequently in case of complete response of IBC (63.4% versus 33.8%, p < 0.001). ER-negative IBC (OR 1.79; 95%CI 1.33-2.42) and more recent years of diagnosis (2014-2016 OR 1.60; 95%CI 1.17-2.19, 2017-2019 OR 1.76; 95%CI 1.34-2.34) were associated with DCIS response. Mastectomy rates were higher in IBC+DCIS compared to IBC (53.6% versus 41.0%, p < 0.001)., Conclusion: Pathologic complete response of DCIS occurred in 52.0% of HER2-positive IBC patients and was associated with ER-negative IBC and more recent years of diagnosis. Future studies should investigate imaging evaluation of DCIS response to improve surgical decision making., (© 2023. The Author(s).)

Background: This study aims to evaluate whether changes in therapeutic strategies have improved survival of patients diagnosed with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer (ABC) in real-world., Methods: All 1950 patients systemically treated for HR+/HER2- ABC and diagnosed between 2008 and 2019 in eight hospitals were retrieved from the SONABRE Registry (NCT-03577197). Patients were categorized per three-year cohorts based on year of ABC diagnosis. Tests for trend were used to examine differences in baseline characteristics, Kaplan-Meier methods and Cox proportional hazards for survival analyses, and competing-risk methods for 3-year use of systemic therapy., Findings: Over time, patients were older (≥70 years, 37%, n = 169/456 in 2008-2010, 47%, n = 233/493 in 2017-2019, p = 0.004) and more often had multiple metastatic sites at ABC diagnosis (48%, n = 220/456 in 2008-2010, 56%, n = 275/493 in 2017-2019, p = 0.002). Among patients with metachronous metastases the prior exposure to (neo-) adjuvant therapies increased over time (chemotherapy, 38%, n = 138/362 in 2008-2010, 48%, n = 181/376 in 2017-2019, p = <0.001; endocrine therapy, 64%, n = 231/362 in 2008-2010, 72%, n = 271/376 in 2017-2019, p = <0.001). Overall survival significantly improved from median 31.1 months (95% CI:28.2-34.3) for patients diagnosed in 2008-2010 to 38.4 months (95% CI:34.0-41.1) in 2017-2019 (adjusted hazard ratio = 0.76, 95% CI:0.64-0.90; p = 0.001). Three-year use of CDK4/6 inhibitors increased from 0% for patients diagnosed in 2008-2010 to 54% for diagnosis in 2017-2019. Conversely, three-year use of chemotherapy was 50% versus 36%, respectively., Interpretation: Over time, patients diagnosed with HR+/HER2- ABC presented with less favourable patient characteristics. Nevertheless, we observed that overall survival of ABC increased between 2008 and 2019, with increased use of endocrine/targeted therapies., Funding: The SONABRE Registry is supported by the Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); Novartis BV; Roche; Pfizer; and Eli Lilly & Co. Funding sources had no role in the writing of the manuscript., Competing Interests: MM report grants institutional grants from Gilead. SG reports institutional grants from Novartis BV, Roche, Pfizer, Eli Lilly, Daiichi Sankyo and Gilead, and personal fees from Astra-Zeneca. VTH reports institutional grants and personal fees from Roche, Novartis, Pfizer, and Eli Lilly, personal fees from Accord Healthcare, institutional grants from AstraZeneca, Eisai, Daiichi Sankyo and Gilead. All remaining authors have declared no conflicts of interest., (© 2022 The Authors.)