Multigene signatures (MGS) are used to guide adjuvant chemotherapy (aCT) decisions in patients diagnosed with estrogen receptor (ER)-positive HER2-negative early breast cancer. We used results from three MGS (Oncotype DX® (ODX), MammaPrint® (MP) or Prosigna®) and assessed the concordance between high or low risk of recurrence and the predicted risk of recurrence based on statistical models. In addition, we looked at the impact of MGS results on final aCT administration during the multidisciplinary meeting (MDM).
View Article and Find Full Text PDFBackground: High levels of stromal tumor-infiltrating lymphocytes (sTIL) are associated with increased pathological complete response (pCR) rate and longer survival after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Here, we evaluated the value of sTIL in predicting pCR and explored prognosis in TNBC patients treated with neoadjuvant chemotherapy according to body mass index (BMI).
Methods: sTIL were scored centrally on pretreatment biopsies from 2 retrospective series of nonunderweight TNBC patients (n = 445).
A previously developed and centrally validated MammaPrint® (MP) and BluePrint® (BP) targeted RNA next-generation sequencing (NGS) kit was implemented and validated in two large academic European hospitals. Additionally, breast cancer molecular subtypes by MP and BP RNA sequencing were compared with immunohistochemistry (IHC). Patients with early breast cancer diagnosed at University Hospitals Leuven and Curie Institute Paris were prospectively included between September 2017 and January 2018.
View Article and Find Full Text PDFPurpose: To assess clinical pathological characteristics and outcome of triple-negative breast cancers (TNBC) by androgen receptor (AR) protein expression.
Methods: We retrospectively evaluated AR by immunohistochemistry on core-needle biopsy, (CNB) and residual disease (RD) in a consecutive institutional series of TNBC patients treated with neo-adjuvant chemotherapy (NACT) between 2000 and 2017. We investigated univariate associations between AR-expression on CNB (using different cut-offs), clinical pathological variables, and pathologic complete response (pCR).
Purpose: Tamoxifen is widely prescribed as adjuvant therapy in patients with early-stage breast cancer. It has been postulated that concentrations of endoxifen, the active metabolite of tamoxifen, are a better predictor of tamoxifen efficacy than CYP2D6 genotypes. Although in a retrospective study, an endoxifen threshold of 5.
View Article and Find Full Text PDFDr. Arteaga serves on an Advisory Board for Novartis and was a consultant for AstraZeneca from 2015 to 2016. All other authors declare that they have no competing interests.
View Article and Find Full Text PDFPurpose: The human epidermal growth factor receptor 2 (ERBB2) may harbour somatic mutations that drive breast tumorigenesis. Here, we study prevalence, tumour characteristics and disease outcome of ERBB2 mutations in a large unselected cohort of metastatic breast cancer (mBC) patients.
Methods: We retrospectively included all mBC patients with sufficient primary breast tumour, diagnosed between 2000 and 2015 (n = 775).
We present the case of a postmenopausal patient with a secondary metastatic ER-positive, HER2-negative breast cancer who was successfully treated with fulvestrant and alpelisib following six lines of therapy. The tumour showed two uncommon PIK3CA mutations, and with the combination of alpelisib and fulvestrant the patient went from ECOG grade 3, before the start of this therapy, to ECOG grade 1 during treatment until progressive disease after 6 months. This unexpected benefit emphasizes the importance of performing a Next Generation Sequencing (NGS)-based assay to screen for several cancer genes in the metastatic setting, even after more than four lines of therapy and a high ECOG grade.
View Article and Find Full Text PDFBackground: In estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER-2) negative breast cancers, the progesterone receptor (PR) is an independent prognostic marker. Little is known about the prognostic value of PR by tumor grade. We assessed this in two independent datasets.
View Article and Find Full Text PDFLevels of endoxifen, the most active metabolite of tamoxifen, vary by the highly polymorphic cytochrome P450 (CYP) 2D6 enzyme. We prospectively investigated tamoxifen efficacy by serum endoxifen levels and the tamoxifen activity score (TAS). A prospective observational multicenter study included postmenopausal women with an estrogen receptor-positive breast cancer receiving first-line tamoxifen, 20 mg daily in the neoadjuvant or metastatic setting, recruited between February 2009 and May 2014.
View Article and Find Full Text PDFInvestigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind.
View Article and Find Full Text PDFBackground: Limited data are available on the prognostic performance of Adjuvant! Online (AOL) and Nottingham Prognostic Index (NPI) in young breast cancer patients.
Methods: This multicentre hospital-based retrospective cohort study included young (⩽40 years) and older (55-60 years) breast cancer patients treated from January 2000 to December 2004 at four large Belgian and Italian institutions. Predicted 10-year overall survival (OS) and disease-free survival (DFS) using AOL and 10-year OS using NPI were calculated for every patient.
We report on a postmenopausal patient with a secondary metastatic apocrine breast cancer successfully treated with low-dose hydrocortisone only following several lines of chemotherapy. The tumor cells in the primary and metastatic lesion exhibited a 'triple-negative' status (estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative); the androgen receptor (AR) was strongly expressed. Twenty milligrams of hydrocortisone, a low substitution dose known to suppress adrenal steroid production, twice daily led to a clinical benefit lasting for one year, with symptom control, radiologically stable disease, and steady decrease in CA15.
View Article and Find Full Text PDFOpinion statement: Five years after adjuvant endocrine treatment for estrogen receptor (ER)-positive breast cancer, patients have a 2 to 20 % risk of metastatic relapse during the next 5 years. Extended adjuvant endocrine therapy seems to further lower this. In UZ Leuven, extended endocrine therapy is now discussed unless the tumor was a grade 1-2, pT1N0, ER-positive, progesterone receptor (PR)-positive, HER2-negative lesion.
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