Publications by authors named "Rutgers E"

Small, hormone receptor-positive (HR+), HER2-negative (HER2-), lymph node-negative breast cancers are associated with relatively low rates of disease recurrence and have therefore been underrepresented in clinical trials assessing the effects of systemic therapy. Consequently, it remains uncertain if this patient population derives benefit from these treatments. For this exploratory analysis, we selected MINDACT (NCT00433589) patients with a HR+, HER2-, T1ab (≤1 cm) tumor and negative lymph nodes.

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The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS).

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Article Synopsis
  • The study explored the association between a 70-gene risk score and the likelihood of locoregional recurrence (LRR) in early-stage breast cancer patients who underwent breast-conserving surgery (BCS).
  • Out of 6,693 patients, 5,470 had BCS, with an 8-year LRR incidence of 3.2%, and a lower 2.7% for those with a low-risk 70-gene signature.
  • The findings suggest that while the 70-gene signature is not an independent predictor for LRR at this time, the overall low recurrence rate indicates potential for reducing the intensity of local therapy in future trials.
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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.

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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).

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Purpose: Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10-89% of patients will attain pathologic complete response (pCR). In patients with pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival.

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Article Synopsis
  • A polygenic risk score (PRS) made up of 313 genetic variants is linked to breast cancer and its recurrence, prompting this study to explore its relationship with tumor characteristics and survival rates in breast cancer patients.
  • The research involved nearly 100,000 women of European ancestry and around 13,000 of Asian ancestry, analyzing data through logistic and Cox regression to evaluate the association between PRS and factors like tumor grade and hormone receptor status.
  • While higher PRS was related to better tumor features and initially appeared to correlate with improved overall and breast cancer-specific survival, these associations diminished after accounting for other clinical factors, suggesting PRS isn't useful for clinical management upon diagnosis.
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Article Synopsis
  • Following a unilateral breast cancer diagnosis, more patients are opting for contralateral prophylactic mastectomy (CPM), which raises important considerations about patient guidance and care.
  • The manifesto outlines key strategies to enhance outcomes for women, emphasizing effective communication of risks, reserving CPM for specific cases, and encouraging treatment of the primary cancer first.
  • It also advocates for personalized risk assessments, psychological support, and uniform reimbursement practices across countries to ensure equitable access to care.
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Purpose: The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life.

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The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities.

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Introduction: Prognostic gene expression signatures can be used in combination with classical clinicopathological factors to guide adjuvant chemotherapy decisions in ER-positive, HER2-negative breast cancer. However, long-term outcome data after introduction of genomic testing in the treatment decision-making process are limited.

Methods: In the prospective RASTER study, the tumours of 427 patients with cTanyN0M0 breast cancer were tested to assess the 70-gene signature (MammaPrint).

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Aim: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario.

Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology.

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Purpose: Patients with 70-gene signature ultralow-risk breast cancers have shown excellent survival in historic cohorts, including randomized trials. The ultralow-risk subgroup was characterized to help avoid overtreatment. We evaluated outcomes of ultralow-risk patients in the largest cohort to date.

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Purpose: To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia.

Methods: In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.

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Purpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages, and mast cells, we identified the relevance of nonimmune cell types for breast cancer survival and therapy benefit, including fibroblasts, myoepithelial cells, muscle cells, endothelial cells, and seven distinct epithelial cell types.

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Background: Adjuvant systemic treatments (AST) reduce mortality, but have associated short- and long-term toxicities. Careful selection of patients likely to benefit from AST is needed. We evaluated outcome of low-risk breast cancer patients of the EORTC 10041/BIG 3-04 MINDACT trial who received no AST.

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Backgrounds: Sentinel lymph node biopsy (SLNB) is standard care as a staging procedure in patients with invasive breast cancer. The axillary recurrence rate, even after positive SLNB, is low. This raises serious doubts regarding the clinical value of SLNB in early breast cancer.

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Background: Mastectomy may be needed in the context of previous radiotherapy in cases of breast carcinoma following mantle field radiotherapy for Hodgkin lymphoma or in cases of local relapse or second primary tumours after breast conserving therapy including whole-breast irradiation (BCT). The outcome of combined skin-sparing mastectomy and immediate implant-based breast reconstruction (SSM-IIBR) has been reported to be unfavourable in these cases.

Purpose: To compare the outcome of SSM-IIBR after mantle field radiotherapy to that after BCT and to compare both to the outcome observed in non-irradiated breasts.

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Purpose: Studies have shown that screen detection by national screening programs is independently associated with better prognosis of breast cancer. The aim of this study is to evaluate the association between tumor biology according to the 70-gene signature (70-GS) and survival of patients with screen-detected and interval breast cancers.

Methods: All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041/BIG3-04) accrued 2007-2011, who participated in the national screening program (biennial screening, ages 50-75) were included (n = 1102).

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Background: Many cT3 breast cancer patients are treated with mastectomy, regardless of response to neoadjuvant systemic therapy (NST). We evaluated local control of cT3 patients undergoing breast-conserving therapy (BCT) based on magnetic resonance imaging (MRI) evaluation post-NST. In addition, we analyzed predictive characteristics for positive margins after breast-conserving surgery (BCS).

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Rationale: On October 15th, 2020, the first Surgical National Consensus Conference on neoadjuvant chemotherapy (NACT) was promoted by the Italian Association of Breast Surgeons (ANISC).

Method: The Consensus Conference was entirely held online due to anti-Covid-19 restrictions and after an introductory four lectures held by national and international experts in the field, a total of nine questions were presented and a digital "real-time" voting system was obtained. A consensus was reached if 75% or more of all panelists agreed on a given question.

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Article Synopsis
  • * Conducted across 112 hospitals in nine European countries, the trial enrolled patients aged 18-70 with specific breast cancer stages and used genomic and clinical assessments to determine the treatment strategy.
  • * The study aimed to explore long-term outcomes and included a random assignment for patients with conflicting risk results to evaluate the effectiveness of chemotherapy versus observation based on their risk profiles.
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The low incidence of special types of breast cancer hinders adequate clinical research efforts. As such, collecting sufficient data to develop well-established therapy strategies are difficult. The aim of our study was to obtain more data on these special types in order to better understand the different characteristics and optimize therapy strategies.

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