Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013
European Institute of Oncology1, Harvard University2, University of Sydney3, Institut Jules Bordet4, Kantonsspital St. Gallen5, University of St. Gallen6, Loyola University Chicago7, Institut Gustave Roussy8, Karolinska Institutet9, University of Bordeaux10, University of Geneva11, University of Pittsburgh12, University of Copenhagen13, University of Newcastle14, Medical University of Vienna15, University of Toronto16, University of Michigan17, Memorial Sloan Kettering Cancer Center18, Mayo Clinic19, Gdańsk Medical University20, University of Gothenburg21, Baylor College of Medicine22, University of North Carolina at Chapel Hill23, Université libre de Bruxelles24, Netherlands Cancer Institute25, Fudan University26, Kyoto University27, King's College London28, University of Göttingen29, Emory University30
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.
About: This article is published in Annals of Oncology.The article was published on 2013-09-01 and is currently open access. It has received 2831 citations till now. The article focuses on the topics: Breast cancer & Adjuvant therapy.
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TL;DR: This work presents the results of a meta-analysis conducted at the 2016 European Oncology and Radiotherapy Guidelines Working Group (ESMO) workshop on breast cancer diagnosis and prognosis of women with atypical central giant cell granuloma (CGM) who have previously had surgery.
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TL;DR: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given.
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TL;DR: Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC, and an association between higher levels ofTILs and increased trastuzumab benefit in HER2+ disease is reported for the first time.
1,021 citations
Cites background from "Personalizing the treatment of wome..."
...While our finding may not change current chemotherapy options for TNBC patients, this is still a clinically relevant finding as TILs could be useful as stratification or adjustment factor in future clinical studies, as well as providing the rationale for evaluating immunotherapeutic approaches [25]....
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TL;DR: This paper aims to provide new ideas for TNBC treatment by summarizing existing treatment regimens, therapeutic drugs, and their efficacy for different TNBC subtypes and reviewing some new preclinical studies and targeted treatment regimen for T NBC.
Abstract: Triple-negative breast cancer (TNBC), a specific subtype of breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2), has clinical features that include high invasiveness, high metastatic potential, proneness to relapse, and poor prognosis. Because TNBC tumors lack ER, PR, and HER2 expression, they are not sensitive to endocrine therapy or HER2 treatment, and standardized TNBC treatment regimens are still lacking. Therefore, development of new TNBC treatment strategies has become an urgent clinical need. By summarizing existing treatment regimens, therapeutic drugs, and their efficacy for different TNBC subtypes and reviewing some new preclinical studies and targeted treatment regimens for TNBC, this paper aims to provide new ideas for TNBC treatment.
731 citations
Cites background from "Personalizing the treatment of wome..."
...Gallen International Breast Cancer Conference issued a new definition of breast cancer molecular subtypes: luminal A (ER/PR, HER2, Ki67 < 20%, with the percentage indicating the immunohistochemical staining results for patient samples), luminal B (ER/PR < 20%, HER2, Ki67 ≥ 20%); HER2 B2 (ER/PR, HER2 overexpression), HER2 overexpression (ER, PR, HER2 overexpression), basal-like TNBC (ER, PR, HER2), and other special subtypes [2]....
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TL;DR: Data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications within triple-negative breast cancer (TNBC) and within hormone receptor-positive and HER2-negative early breast cancer.
676 citations
References
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Daniel C. Koboldt1, Robert S. Fulton1, Michael D. McLellan1, Heather Schmidt1 +352 more•Institutions (35)
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.
9,355 citations
5,867 citations
TL;DR: D diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer.
Abstract: Purpose To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression–based “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like. Methods A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. Results The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for t...
3,913 citations
"Personalizing the treatment of wome..." refers background or methods in this paper
...Intrinsic subtypes Identification of intrinsic subtypes is most precise using molecular technologies [22]....
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...neoadjuvant chemotherapy among patients with low ROR [22]....
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...A risk of recurrence (ROR) score based on PAM50 showed that there were no or very few pathological complete responses to neoadjuvant chemotherapy among patients with low ROR [22]....
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TL;DR: Broad treatment recommendations are presented, recognizing that detailed treatment decisions need to consider disease extent, host factors, patient preferences, and social and economic constraints.
3,160 citations
TL;DR: Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival, and overall survival was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating thatSLND alone is noninherited.
Abstract: (95% confidence interval [CI], 89.1%-94.5%) with ALND and 92.5% (95% CI, 90.0%95.1%) with SLND alone; 5-year disease-free survival was 82.2% (95% CI, 78.3%86.3%) with ALND and 83.9% (95% CI, 80.2%-87.9%) with SLND alone. The hazard ratio for treatment-related overall survival was 0.79 (90% CI, 0.56-1.11) without adjustment and 0.87 (90% CI, 0.62-1.23) after adjusting for age and adjuvant therapy. Conclusion Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival.
2,608 citations