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Background: Guidelines recommend systemic therapy for stage I HER2+ breast cancer (BC). Neoadjuvant systemic treatment (NAST) allows response-guided adjuvant treatment. However, prior to NAST only clinical nodal staging is available, risking undertreatment if ypN+ is observed. Here, we aim to evaluate the impact of FDG-PET/CT and NAST on nodal disease status in patients with small, node-negative HER2+ BC. Methods: This retrospective study included patients with small (≤3 cm), clinically node-negative HER2+ BC diagnosed between 2011 and 2023. Primary outcome was the proportion of patients with nodal disease on final pathology after upfront surgery or NAST followed by surgery with or without FDG-PET/CT. Patients received either paclitaxel + trastuzumab (PT) or a more extensive regimen. Results: Of the 370 included patients, 183 underwent FDG-PET/CT, detecting regional or distant metastases in 14 patients (7.7 %).Among 356 patients with cN0 disease, 44.1 % (n = 157/356) had upfront surgery, with only 3 % (5/157) having an FDG-PET/CT. The remaining 55.9 % (199/356) started with NAST, with 82 % (n = 164/199) having an FDG-PET/CT. Among patients treated with NAST, 36 % received PT.Nodal involvement on pathology was seen in 19.1 % (n = 29/152) after upfront surgery without FDG-PET/CT and 6.1 % (10/164) after NAST combined with FDG-PET/CT.After NAST, 58 % had a pCR (PT: 49 %, other: 63 %). Nodal involvement on final pathology was seen in 6.9 % after PT and in 5.5 % after more extensive regimen. Conclusions: The proportion of patients with ypN + after NAST combined with FDG-PET/CT was only 6.1 %. Neoadjuvant treatment can be a safe treatment strategy for patients with stage I HER2+ BC.

Objective: This study aims to evaluate the response to and surgical benefits of neoadjuvant endocrine therapy (NET) in ER+/HER2-breast cancer patients who are clinically high risk, but genomic low risk according to the 70-gene signature (MammaPrint). Methods: Patients with ER+/HER2-invasive breast cancer with a clinical high risk according to MINDACT, who had a genomic low risk according to the 70-gene signature and were treated with NET between 2015 and 2023 in our center, were retrospectively analyzed. RECIST 1.1 criteria were used to assess radiological response using MRI or ultrasound. Surgical specimens were evaluated to assess pathological response. Two breast cancer surgeons independently scored the eligibility of breast conserving therapy (BCS) pre- and post- NET. Results: Of 72 included patients, 23 were premenopausal (100% started with tamoxifen of which 4 also received OFS) and 49 were postmenopausal (98% started with an aromatase inhibitor). Overall, 8 (11%) showed radiological complete response. Only 1 (1.4%) patient had a pathological complete response (RCB-0) and 68 (94.4%) had a pathological partial response (RCB-1 or RCB-2). Among the 26 patients initially considered for mastectomy, 14 (53.8%) underwent successful BCS. In all 20 clinical node-positive patients, a marked axillary lymph node was removed to assess response. Four out of 20 (20%) patients had a pathological complete response of the axilla. Conclusion: The study showed that a subgroup of patients with a clinical high risk and a genomic low risk ER+/HER2-breast cancer benefits from NET resulting in BCS instead of a mastectomy. Additionally, NET may enable de-escalation in axillary treatment.

Purpose: Tailored recommendation for adjuvant chemotherapy in breast cancer patients is of great importance. This survey assessed agreement among oncologists on risk assessment and chemotherapy recommendation, the impact of adding the 70-gene signature to clinical-pathological characteristics, and changes over time. Methods: A survey consisting of 37 discordant patient cases from the MINDACT trial (T1-3N0-1M0) was sent to European breast cancer specialists for assessment of risk (high or low) and chemotherapy administration (yes or no). In 2015 the survey was sent twice (survey 1 and 2), several weeks apart, and in 2021 a third time (survey 3). Only the second and third surveys included the 70-gene signature result. Results: 41 breast cancer specialists participated in all three surveys. Overall agreement between respondents decreased slightly between survey 1 and 2, but increased again in survey 3. Over time there was an increase in agreement with the 70-gene signature result on risk assessment, 23% in survey 2 versus 1 and 11% in survey 3 versus 2. With information available indicating a low risk 70-gene signature (n = 25 cases), 20% of risk assessments changed from high to low and 19% of recommendations changed from yes to no chemotherapy in survey 2 versus 1, further increasing with 18% and 21%, respectively, in survey 3 versus 2. Conclusion: There is a variability in risk assessment of early breast cancer patients among breast cancer specialists. The 70-gene signature provided valuable information, resulting in fewer patients being assessed as high risk and fewer recommendations for chemotherapy, increasing over time.

Abstract Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.

IntroductionPediatric thyroid carcinoma is a rare malignancy and data on long-term oncological outcomes are sparse. The aim of this study was to describe the long-term oncological outcomes of pediatric papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) in a national cohort, and to identify risk factors for recurrence.MethodsWe conducted a nationwide, retrospective cohort study, in which we combined two national databases. Patients aged