Breast Cancer 2013 – Interpretation of New and Known Data

Abstract

The treatment options and characteristics for therapeutic decisions for patients with primary and advanced breast cancer are becoming more and more numerous. New targeted therapies in combination with established chemotherapy regimens are expending the spectrum but potentially promising combinations do not also give a better result. The latest data from pharmacogenomics point to prognosis and predictive factors that take not only the properties of the tumour but also the hereditary genetic features of the patient into account. Current therapy decisions are thus based on a combination of classical clinical and modern molecular biomarkers. Health-economic aspects are also being taken into account more often, so that health-political considerations may also play a part. The present review article summarises parts of the results presented at the 2012 San Antonio Breast Cancer Symposia (SABCS), ESMO 2012 and St. Gallen 2013 together with new and important publications on the prevention of and therapy for breast cancer.

Zusammenfassung

Die Behandlungsoptionen und die Charakteristika zur Therapieentscheidung der Patientin mit einem primären und fortgeschrittenen Mammakarzinom werden immer vielfältiger. Neue zielgerichtete Therapien in Kombination mit etablierten Chemotherapien erweitern das Spektrum, doch potenziell vielversprechende Kombinationen bringen nicht immer ein besseres Ergebnis. Neueste Daten aus der Pharmakogenomik weisen auf Prognose- und Prädiktivfaktoren hin, die nicht nur die Eigenschaften des Tumors, sondern auch die vererbbaren genetischen Eigenschaften der Patientin berücksichtigen. Die aktuelle Therapieentscheidung ist somit mittlerweile eine Kombination aus klassischerweise klinischen und modernen molekularen Biomarkern. Immer häufiger werden auch gesundheitsökonomische Aspekte berücksichtigt, sodass auch gesundheitspolitische Überlegungen eine Rolle spielen können. Diese Übersichtsarbeit fasst einen Teil der auf dem 2012 San Antonio Breast Cancer Symposion (SABCS), ESMO 2012 und St. Gallen 2013 behandelten Ergebnisse und aktuelle hochrangige Publikationen zur Prävention und Therapie der Patientin mit einem Mammakarzinom zusammen.

Key words

breast cancer - treatment - local recurrence - metastases - trials

Schlüsselwörter

Mammakarzinom - Behandlung - Lokalrezidiv - Metastasen - Studien

• References

• 1 Fasching PA, Ekici AB, Adamietz BR et al. Breast cancer risk – genes, environment and clinics. Geburtsh Frauenheilk 2011; 71: 1056-1066
• 2 Rauh C, Hack CC, Haberle L et al. Percent mammographic density and dense area as risk factors for breast cancer. Geburtsh Frauenheilk 2012; 72: 727-733
• 3 Vachon CM, Scott CG, Fasching PA et al. Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk. Cancer Epidemiol Biomarkers Prev 2012; 21: 1156-1166
• 4 Heusinger K, Loehberg CR, Haeberle L et al. Mammographic density as a risk factor for breast cancer in a German case-control study. Eur J Cancer Prev 2011; 20: 1-8
• 5 Garcia-Closas M, Couch FJ, Lindstrom S et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 2013; 45: 392-398
• 6 Bojesen SE, Pooley KA, Johnatty SE et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 2013; 45: 371-384
• 7 Michailidou K, Hall P, Gonzalez-Neira A et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 2013; 45: 353-361
• 8 Nickels S, Truong T, Hein R et al. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors. PLoS Genetics 2013; 9: e1003284
• 9 Gaudet MM, Kuchenbaecker KB, Vijai J et al. Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk. PLoS Genetics 2013; 9: e1003173
• 10 French JD, Ghoussaini M, Edwards SL et al. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. Am J Hum Genet 2013;
• 11 Antoniou AC, Wang X, Fredericksen ZS et al. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet 2010; 42: 885-892
• 12 Antoni S, Sasco AJ, Dos Santos Silva I et al. Is mammographic density differentially associated with breast cancer according to receptor status? A meta-analysis. Breast Cancer Res Treat 2013; 137: 337-347
• 13 Heusinger K, Jud SM, Haberle L et al. Association of mammographic density with the proliferation marker Ki-67 in a cohort of patients with invasive breast cancer. Breast Cancer Res Treat 2012; 135: 885-892
• 14 Heusinger K, Jud SM, Haberle L et al. Association of mammographic density with hormone receptors in invasive breast cancers – results from a case-only study. Int J Cancer 2012;
• 15 Fasching PA, Pharoah PD, Cox A et al. The role of genetic breast cancer susceptibility variants as prognostic factors. Hum Mol Genet 2012; 21: 3926-3939
• 16 Fisher B, Anderson S, Bryant J et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347: 1233-1241
• 17 Veronesi U, Cascinelli N, Mariani L et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002; 347: 1227-1232
• 18 Giuliano AE. Lymphatic mapping and sentinel node biopsy in breast cancer. JAMA 1997; 277: 791-792
• 19 Bani HA, Fasching PA, Lux MM et al. Lymphedema in breast cancer survivors: assessment and information provision in a specialized breast unit. Patient Educ Couns 2007; 66: 311-318
• 20 Haviland JS, Agrawal R, Aird E et al. The UK START (Standardisation of Breast Radiotherapy) Trials: 10-year follow-up results. Cancer Res 2012; 72 (Suppl. 24) 100s
• 21 Flyger H, Massarut S, Alvarado M et al. Targeted intraoperative radiotherapy for early breast cancer: TARGIT-A trial- updated analysis of local recurrence and first analysis of survival. Cancer Res 2012; 72 (Suppl. 24) 100s
• 22 Boughey JC, Suman VJ, Mittendorf EA et al. The role of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy – results from the ACOSOG Z1071 trial. Cancer Res 2012; 72 (Suppl. 24) 94s
• 23 Kuehn T, Bauerfeind IGP, Fehm T et al. Sentinel lymph node biopsy before or after neoadjuvant chemotherapy – final results from the prospective German, multiinstitutional SENTINA-trial. Cancer Res 2012; 72 (Suppl. 24) 95s
• 24 von Minckwitz G, Untch M, Blohmer JU et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012;
• 25 Denkert C, Huober J, Loibl S et al. HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer. Breast Cancer Res 2013; 15: R11
• 26 Witzel I, Loibl S, von Minckwitz G et al. Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab – a translational project in the neoadjuvant GeparQuinto trial. Br J Cancer 2012; 107: 956-960
• 27 Fasching PA, Heusinger K, Haeberle L et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 2011; 11: 486
• 28 Untch M, Fasching PA, Konecny GE et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 2011; 29: 3351-3357
• 29 Untch M, Fasching PA, Konecny GE et al. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer – results at the time of surgery. Ann Oncol 2011; 22: 1988-1998
• 30 Untch M, Loibl S, Bischoff J et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 2012; 13: 135-144
• 31 Untch M, Rezai M, Loibl S et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 2010; 28: 2024-2031
• 32 Untch M, von Minckwitz G, Konecny GE et al. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer – outcome on prognosis. Ann Oncol 2011; 22: 1999-2006
• 33 von Minckwitz G, Eidtmann H, Loibl S et al. Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial. Ann Oncol 2011; 22: 301-306
• 34 von Minckwitz G, Eidtmann H, Rezai M et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 2012; 366: 299-309
• 35 von Minckwitz G, Jonat W, Fasching P et al. A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer. Breast Cancer Res Treat 2005; 89: 165-172
• 36 von Minckwitz G, Rezai M, Loibl S et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol 2010; 28: 2015-2023
• 37 von Minckwitz G, Untch M, Nuesch E et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 2011; 125: 145-156
• 38 Fasching PA, Jud SM, Hauschild M et al. Anticancer activity of letrozole plus zoledronic acid as neoadjuvant therapy for postmenopausal patients with breast cancer: FEMZONE trial results. Cancer Res 2012; 72 (Suppl. 24) 123s
• 39 Cortazar P, Zhang L, Untch M et al. Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC). Cancer Res 2012; 72 (Suppl. 24) 93s
• 40 Anders CK, Hsu DS, Broadwater G et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 2008; 26: 3324-3330
• 41 Loibl S, Jackisch C, Gade S et al. Neoadjuvant chemotherapy in the very young 35 years of age or younger. Cancer Res 2012; 72 (Suppl. 24) 96s
• 42 Cameron D, Brown J, Dent R et al. Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple negative breast cancer. Cancer Res 2012; 72 (Suppl. 24) 108s
• 43 Carmeliet P, Pallaud C, Deurloo RJ et al. Plasma (p) VEGF-A and VEGFR-2 biomarker (BM) results from the BEATRICE phase III trial of bevacizumab (BEV) in triple negative early breast cancer (BC). Cancer Res 2012; 72 (Suppl. 24) 321s
• 44 Lambrechts D, Claes B, Delmar P et al. VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol 2012; 13: 724-733
• 45 Lambrechts D, Lenz HJ, de Haas S et al. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 2013; 31: 1219-1230
• 46 Moebus V, Schneeweis A, du Bois A et al. Ten year follow-up analysis of intense dose-dense adjuvant ETC (epirubicin (E), paclitaxel (T) and cyclophosphamide (C)) confirms superior DFS and OS benefit in comparison to conventional dosed chemotherapy in high-risk breast cancer patients with ≥ 4 positive lymph nodes. Cancer Res 2012; 72 (Suppl. 24) 97s
• 47 Aebi S, Gelber S, Lang I et al. Chemotherapy prolongs survival for isolated local or regional recurrence of breast cancer: the CALOR trial (Chemotherapy as Adjuvant for Locally Recurrent breast cancer; IBCSG 27-02, NSABP B-37, BIG 1-02). Cancer Res 2012; 72 (Suppl. 24) 96s
• 48 Davies C, Pan H, Godwin J et al. ATLAS – 10 v 5 years of adjuvant tamoxifen (TAM) in ER+ disease: Effects on outcome in the first and in the second decade after diagnosis. Cancer Res 2012; 72 (Suppl. 24) 89s
• 49 Metzger O, Giobbie-Hurder A, Mallon E et al. Relative effectiveness of letrozole compared with tamoxifen for patients with lobular carcinoma in the BIG 1-98 trial. Cancer Res 2012; 72 (Suppl. 24) 89s
• 50 Luftner D, Lux MP, Maass N et al. Advances in breast cancer – looking back over the year. Geburtsh Frauenheilk 2012; 72: 1117-1129
• 51 Pivot X, Romieu G, Bonnefoi H et al. PHARE trial results of subset analysis comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. Cancer Res 2012; 72 (Suppl. 24) 104s
• 52 Earl HM, Cameron DA, Miles D et al. PERSEPHONE: duration of trastuzumab with chemotherapy in women with HER2 positive early breast cancer. Cancer Res 2012; 72 (Suppl. 24) 557s
• 53 Di Leo A, Jerusalem G, Petruzelka L et al. Final analysis of overall survival for the phase III CONFIRM trial: fulvestrant 500 mg versus 250 mg. Cancer Res 2012; 72 (Suppl. 24) 90s
• 54 Baselga J, Campone M, Piccart M et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366: 520-529
• 55 Piccart M, Baselga J, Noguchi S et al. Final progression-free survival analysis of BOLERO-2: a phase III trial of everolimus for postmenopausal women with advanced breast cancer. Cancer Res 2012; 72 (Suppl. 24) 492s
• 56 Finn RS, Crown JP, Lang I et al. Results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole vs. letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (BC). Cancer Res 2012; 72 (Suppl. 24) 91s
• 57 Swain SM, Kim SB, Cortes J et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2013; 14: 461-471
• 58 Baselga J, Cortés J, Im SA et al. Biomarker analyses in CLEOPATRA: A phase III, placebo-controlled study of pertuzumab in HER2-positive, first-line metastatic breast cancer (MBC). Cancer Res 2012; 72 (Suppl. 24) 103s
• 59 Hartkopf AD, Banys M, Krawczyk N et al. Circulating tumor cells in early-stage breast cancer. Geburtsh Frauenheilk 2011; 71: 1067-1072
• 60 Jaeger BAS, Rack BK, Andergassen U et al. Circulating tumor cells (CTC) may express HER2/neu in patients with early HER2/neu negative breast cancer – results of the German SUCCESS C trial. Cancer Res 2012; 72 (Suppl. 24) 215s
• 61 Sgroi DC, Sestak I, Zhang Y et al. Evaluation of prognostic and predictive performance of breast cancer index and its components in hormonal receptor-positive breast cancer patients: a TransATAC study. Cancer Res 2012; 72 (Suppl. 24) 248s
• 62 Dubsky P, Brase JC, Fisch K et al. The EndoPredict score identifies late distant metastases in ER+/HER2- breast cancer patients. Cancer Res 2012; 72 (Suppl. 24) 101s
• 63 Cheang MC, Chia SK, Voduc D et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009; 101: 736-750
• 64 Schmidt M, Fasching PA, Beckmann MW et al. Biomarkers in breast cancer – an update. Geburtsh Frauenheilk 2012; 72: 819-832
• 65 Denkert C, Blohmer JU, Müller BM et al. Ki67 levels in pretherapeutic core biopsies as predictive and prognostic parameters in the neoadjuvant GeparTrio trial. Cancer Res 2012; 72 (Suppl. 24) 102s
• 66 Yamauchi H, Nakagawa C, Yamashige S et al. Societal economics of the 21-gene Recurrence Score® in estrogen receptor-positive early-stage breast cancer in Japan. Cancer Res 2012; 72 (Suppl. 24) 458s
• 67 Blohmer JU, Rezai M, Kummel S et al. Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting. J Med Econ 2013; 16: 30-40
• 68 Jacobs VR, Augustin D, Wischnik A et al. Analysis of test-therapy concordance for biomarkers uPA and PAI-1 in primary breast cancer in clinical hospital routine: results of a prospective multi-center study at certified breast cancers in Germany. Cancer Res 2012; 72 (Suppl. 24) 455s-456s
• 69 Conter HJ, Conter D, Wolff RA et al. The benefit of targeted therapeutics in medical oncology since the development of trastuzumab. Cancer Res 2012; 72 (Suppl. 24) 456s
• 70 Xie J, Diener M, De G et al. Budget impact analysis of everolimus for estrogen receptor positive, human epidermal growth factor receptor-2 negative metastatic breast cancer patients in the United States. Cancer Res 2012; 72 (Suppl. 24) 457s
• 71 Wolff AC, Hammond ME, Schwartz JN et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007; 25: 118-145
• 72 Sauter G, Lee J, Bartlett JM et al. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 2009; 27: 1323-1333
• 73 Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Kommission Mamma. Diagnostik und Therapie von Patientinnen mit primärem metastasiertem Brustkrebs. Version 2013.10. http://www.ago-online.de
• 74 Martin M, Loibl S, von Minckwitz G et al. on behalf of GEICAM (Spanish Breast Cancer Research Group); GBG (German Breast Group). Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer – first efficacy results from the LEA study. Cancer Res 2012; 72 (Suppl. 24) 91s-92s
• 75 Kaufman PA, Awada A, Twelves C et al. A Phase III, open-label, randomized, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Cancer Res 2012; 72 (Suppl. 24) 109s
• 76 Kreienberg R, Albert U-S, Follmann M et al. Interdisciplinary GoR level III guidelines for the diagnosis, therapy and follow-up care of breast cancer – Short version – AWMF Registry No.: 032-045OL. Geburtsh Frauenheilk 2013; 73: 556-583