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Geburtshilfe Frauenheilkd 2010; 70(11): 875-886
DOI: 10.1055/s-0030-1250437
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Aktuelle Therapie der Patientin mit einem Mammakarzinom

Breast Cancer Therapy – A State of the Art ReviewP. A. Fasching1 , 2 , T. Fehm3 , W. Janni4 , S. Kümmel5 , D. Lüftner6 , M. P. Lux2 , N. Maass7
  • 1University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, Los Angeles, CA, USA
  • 2Frauenklinik des Universitätsklinikums Erlangen, Erlangen
  • 3Frauenklinik des Universitätsklinikums Tübingen, Tübingen
  • 4Frauenklinik des Universitätsklinikums Düsseldorf, Düsseldorf
  • 5Klinik für Senologie, Kliniken Essen-Mitte, Essen
  • 6Medizinische Klinik und Poliklinik II, Campus Charité Mitte, Berlin
  • 7Frauenklinik des Universitätsklinikums Aachen, Aachen
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Publication History

eingereicht 26.9.2010

akzeptiert 27.9.2010

Publication Date:
15 November 2010 (online)

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Zusammenfassung

Die Behandlungsoptionen und auch 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 berušcksichtigen. Die aktuelle Therapieentscheidung ist somit mittlerweile eine Kombination aus klassischerweise klinischen und modernen molekularen Biomarkern. Immer häufiger werden auch gesundheitsökonomische Aspekte berušcksichtigt, sodass auch gesundheitspolitische Überlegungen eine Rolle spielen können. Auf der Jahrestagung der American Society of Clinical Oncology (ASCO) 2010 in Chicago wurden zu allen Aspekten des Therapiealgorithmus beim Mammakarzinom aktuelle Daten vorgestellt und zum Teil kontrovers diskutiert.

Abstract

The treatment options for primary and metastatic breast cancer patients as well as the characteristics considered for therapy decision continue to become more diverse. New target therapies in combination with established chemotherapy regimens extend the range, however, potentially promising combinations do not always result in a benefit for the patient. Latest pharmacogenomics results hint towards prognosis and predictive factors, which do not only focus on the individual properties of the tumor, they also consider the hereditary genetics of the patient. As a result, state of the art therapy decision includes classical clinical as well as modern molecular biomarkers, however, pharmacoeconomic aspects continue to increase in importance in physicians' treatment algorithms. The Annual Meeting of the American Society of Clinical Oncology (ASCO) 2010 in Chicago revealed latest data for all aspects of the breast cancer therapy algorithm and allowed for partially controversial discussions.

Schlüsselwörter

BRCA1 - TOP2A - Aromatasehemmer - zirkulierende Tumorzellen (ZTZ) - QALY

Key words

BRCA1 - TOP2A - aromatase inhibitor - circulating tumor cells (CTC) - QALY

Literatur

  • 1 Byrski T, Gronwald J, Huzarski T et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy.  J Clin Oncol. 2010;  28 375-379
    CrossrefPubMedGoogle Scholar
  • 2 Ingle J, Schaid D, Goss P Mayo Clinic, Rochester, MN; Harvard University, Boston, MA; RIKEN Center for Genomic Medicine, Tokyo, Japan; NCIC Clinical Trials Group, Kingston ON, Canada; Washington University, St. Louis, MO; Indiana University, Indianapolis, I et al. A genome-wide association study in patients experiencing musculoskeletal adverse events on aromatase inhibitors as adjuvant therapy in early breast cancer entered on NCIC CTG trial MA.27. A Pharmacogenetics Research Network-RIKEN Collaboration. San Antonio Breast Cancer Symposium 2009; Abstr. 15. 
    Google Scholar
  • 3 Kroetz L, Baldwin R M, Owzar K Cancer and Leukemia Group B et al. Inherited genetic variation in EPHA5, FGD4, and NRDG1 and paclitaxel (P)-induced peripheral neuropathy (PN): Results from a genome-wide association study (GWAS) in CALGB 40101.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 3021)
    PubMedGoogle Scholar
  • 4 Goetz M P, Reinicke K E, Reid J M Mayo Clinic, Rochester, MN; Mayo Clinic, Jacksonville, FL et al. Tamoxifen, HER2, and endoxifen: The role of CYP2D6 as a predictor of tamoxifen resistance in ER+/HER2+ breast cancer. SABCS2009; Abstr. 2006. 
    Google Scholar
  • 5 Schroth W, Hamann U, Fasching P A et al. CYP2D6 polymorphisms as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification.  Clin Cancer Res. 2010;  16 4468
    CrossrefPubMedGoogle Scholar
  • 6 Press M, Sauter G, Buyse M et al. Alteration of topoisomerase II-alpha gene in human breast cancer: Association with responsiveness to anthracycline-based chemotherapy.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 518)
    PubMedGoogle Scholar
  • 7 Di Leo A, Desmedt C, Bartlett J et al. Final results of a meta-analysis testing HER2 and topoisomerase IIα genes as predictors of incremental benefit from anthracyclines in breast cancer.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 519)
    PubMedGoogle Scholar
  • 8 Weidhaas J B. A KRAS-variant as a biomarker of ovarian cancer risk.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 5016)
    PubMedGoogle Scholar
  • 9 Kaufmann M, Eiermann W, Schuette M et al. Long-term results from the neoadjuvant GeparDuo trial: A randomized, multicenter, open phase III study comparing a dose-intensified 8-week schedule of doxorubicin hydrochloride and docetaxel (ADoc) with a sequential 24-week schedule of doxorubicin hydrochloride/cyclophosphamide followed by docetaxel (AC-Doc) regimen as preoperative therapy (NACT) in patients (pts) with operable breast cancer (BC).  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 537)
    PubMedGoogle Scholar
  • 10 Von Minckwitz G, Untch M, Nueesch E et al. Impact of treatment characteristics on response of different breast cancer subtypes: Pooled multilayer analysis of the German neoadjuvant chemotherapy trials.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 501)
    PubMedGoogle Scholar
  • 11 Steger G G, Greil R, Jakesz R et al. Pathologic complete response (pCR) in patient subgroups: An analysis of ABCSG-24, a phase III, randomized study of anthracycline- and taxane-based neoadjuvant therapy with or without capecitabine in early breast cancer (EBC).  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 530)
    PubMedGoogle Scholar
  • 12 Krag D N, Anderson S J, Julian T B et al. Primary outcome results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patient.  J Clin Oncol. 2010;  28 18s (Suppl.; Abstr. LBA505)
    PubMedGoogle Scholar
  • 13 Giuliano A E, McCall L M, Beitsch P D et al. ACOSOG Z0011: A randomized trial of axillary node dissection in women with clinical T1–2 N0 M0 breast cancer who have a positive sentinel node.  J Clin Oncol. 2010;  28 18s (Suppl.; Abstr. CRA506)
    PubMedGoogle Scholar
  • 14 Geffrelot J, Toudic Emily F, Levy C et al. Determination of clear margin in breast-conserving surgery: Is 1 mm needed?.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 515)
    PubMedGoogle Scholar
  • 15 Hughes K S, Schnaper L A, Cirrincione C et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 or older with early breast cancer.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 507)
    PubMedGoogle Scholar
  • 16 Joensuu H, Kellokumpu-Lehtinen P L, Huovinen R et al. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial.  Lancet Oncol. 2009;  10 1145-1151
    CrossrefPubMedGoogle Scholar
  • 17 Joensuu H, Kellokumpu-Lehtinen P L, Huovinen R et al. Integration of capecitabine (X) into adjuvant therapy comprising docetaxel (T) followed by 5-FU, epirubicin, and cyclophosphamide (CEF): Efficacy in patients with triple-negative breast cancer (BC).  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 531)
    PubMedGoogle Scholar
  • 18 Park Y, Kim S, Ok O et al. Risk stratification by hormonal receptor (ER, PgR) and HER2 status in small (≤ 1 cm) invasive breast cancer: Who might be a possible candidate for adjuvant treatment?.  J Clin Oncol. 2009;  27 15s (Suppl.; Abstr. 564)
    PubMedGoogle Scholar
  • 19 McArthur H L, Mahoney K, Morris P G et al. Use of adjuvant trastuzumab with chemotherapy in women with small, node-negative, HER2-positive breast cancers.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 615)
    PubMedGoogle Scholar
  • 20 Chew H K, Brunson A, Brown M. Cause-specific and all-cause mortality of HER2-positive, node-negative, T1a and T1b breast cancers.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. CRA583)
    PubMedGoogle Scholar
  • 21 Jackisch C, Harbeck N. AGO-Guidelines Breast 2010.1.0D. Adjuvante Chemotherapie + Trastuzumab: Optimale Substanzen/Dosierung/Trastuzumab. http://www.ago-online.de
    Google Scholar
  • 22 Harbeck N, Hadji P, Jackisch C et al. First results from the Patient's Anastrozole Compliance to Therapy (PACT) program evaluating the influence of a standardized information service on compliance in postmenopausal women with early breast cancer (EBC).  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 523)
    PubMedGoogle Scholar
  • 23 Del Mastro L, Boni L, Michelotti A et al. Role of luteinizing hormone-releasing hormone analog (LHRHa) triptorelin (T) in preserving ovarian function during chemotherapy for early breast cancer patients: Results of a multicenter phase III trial of Gruppo Italiano Mammella (GIM) group.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 528)
    PubMedGoogle Scholar
  • 24 Ribi K, Aldridge J, Phillips K et al. Changes in cognitive function in postmenopausal women 1 year after completing adjuvant letrozole or tamoxifen in the Breast International Group (BIG) 1–98 trial.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 527)
    PubMedGoogle Scholar
  • 25 World Cancer Research Fund and American Institute for Cancer Research, Food Nutrition, Physical activity and the prevention of cancer .A global perspective.. Washington, DC: AICR; 2007
    Google Scholar
  • 26 Chlebowski R T, Blackburn G L, Thomson C A et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the women's intervention nutrition study.  J Natl Cancer Inst. 2006;  98 1767-1776
    CrossrefPubMedGoogle Scholar
  • 27 Hepp P G, Rack B K, Annecke K et al. Obesity and disease-free survival in patients with nodal-positive early-stage breast cancer: The ADEBAR trial.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 541)
    PubMedGoogle Scholar
  • 28 Andergassen U, Rack B K, Annecke K et al. Obesity and tumor characteristics in nodal-positive early-stage breast cancer: Results of the German ADEBAR study.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 591)
    PubMedGoogle Scholar
  • 29 Gnant M, Mlineritsch B, Stoeger H et al. Mature results from ABCSG-12: Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combination with zoledronic acid, in premenopausal women with endocrine-responsive early breast cancer.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 533)
    PubMedGoogle Scholar
  • 30 Pfeiler G, Königsberg R, Singer C F et al. Impact of body mass index (BMI) on endocrine therapy in premenopausal breast cancer patients: Analysis of the ABCSG-12 trial.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 512)
    PubMedGoogle Scholar
  • 31 Crown J, Dieras V, Staroslawska E et al. Phase III evaluation of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC).  J Clin Oncol. 2010;  28 18s (Suppl.; Abstr. LBA1011)
    PubMedGoogle Scholar
  • 32 Bergh J, Greil R, Voytko N et al. Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC).  J Clin Oncol. 2010;  28 18s (Suppl.; Abstr. LBA1010)
    PubMedGoogle Scholar
  • 33 O'Shaughnessy J, Miles D, Gray R J et al. A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 1005)
    PubMedGoogle Scholar
  • 34 Twelves C, Loesch D, Blum J L et al. A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician's choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane.  J Clin Oncol. 2010;  28 18s (Suppl.; Abstr. CRA1004)
    PubMedGoogle Scholar
  • 35 Amir E, Clemons M, Freedman O C et al. Tissue confirmation of disease recurrence in patients with breast cancer: pooled analysis of two large prospective studies.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 1007)
    PubMedGoogle Scholar
  • 36 Rack B K, Schindlbeck C, Andergassen U et al. Use of circulating tumor cells (CTC) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy to predict risk for relapse: The SUCCESS trial.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 1003)
    PubMedGoogle Scholar
  • 37 Fehm T, Sauerbrei W. Information from CTC measurements for metastatic breast cancer prognosis – we should do more than selecting an “optimal cut point”.  Breast Cancer Res Treat. 2010;  122 219-220
    CrossrefPubMedGoogle Scholar
  • 38 Giordano A, Giuliano M, Hsu L et al. Prognostic value of circulating tumor cells (CTC) in metastatic breast cancer (MBC): correlation with immunohistochemically defined molecular subtypes and metastatic disease sites.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 1000)
    PubMedGoogle Scholar
  • 39 Braun S, Naume B. Circulating and disseminated tumor cells.  J Clin Oncol. 2005;  23 1623-1626
    CrossrefPubMedGoogle Scholar
  • 40 Cote R, Giuliano A E, Hawes D et al. ACOSOG Z0010: A multicenter prognostic study of sentinel node (SN) and bone marrow (BM) micrometastases in women with clinical T1/T2 N0 M0 breast cancer.  J Clin Oncol. 2010;  28 18s (Suppl.; Abstr. 504)
    PubMedGoogle Scholar
  • 41 Rack B K, Janni W, Schindlbeck C et al. Effect of zoledronate on persisting isolated tumor cells (ITC) in the bone marrow (BM) of patients without recurrence of early breast cancer.  J Clin Oncol. 2004;  ASCO Annual Meeting Proceedings (Post-Meeting Edition) Vol. 22: No 14S (July 15 Suppl.), 2004: 9515
    PubMedGoogle Scholar
  • 42 Solomayer E, Gebauer G, Hirnle P et al. Influence of zoledronic acid on disseminated tumor cells (DTC) in primary breast cancer patients. San Antonio Breast Cancer Symposium 2008; Abstr. 2048. 
    Google Scholar
  • 43 Greenberg S, Park J W, Melisko M E et al. Effect of adjuvant zoledronic acid (ZOL) on disseminated tumor cells (DTC) in the bone marrow (BM) of women with early-stage breast cancer (ESBC): Updated results.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 1002)
    PubMedGoogle Scholar
  • 44 Grann V R, Patel P R, Jacobson J S et al. Comparative effectiveness of screening, surgery, and chemoprevention among BRCA1/2 mutation carriers.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 6011)
    PubMedGoogle Scholar
  • 45 Dinh T, Green L, Alperin P et al. Cost-effectiveness of adding information about common risk alleles to current decision models for breast cancer chemoprevention.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 6042)
    PubMedGoogle Scholar
  • 46 Topaloglu O, Unalp A. Review of cost-effectiveness studies on aromatase inhibitors for the treatment of early-stage breast cancer.  J Clin Oncol. 2010;  28 (Suppl.; Abstr. e11030)
    PubMedGoogle Scholar
  • 47 Delea T E, Lipsitz M A, Zelt S C et al. Cost-effectiveness of letrozole (LET) versus anastrozole (ANA) in postmenopausal women (PMW) with hormone receptor-positive (HR+) early-stage breast cancer (EBC) based on indirect comparison of BIG 1–98 and ATAC.  J Clin Oncol. 2010;  28 (Suppl.; Abstr. e11013)
    PubMedGoogle Scholar
  • 48 Regan M M. Adjusting for selective crossover in analyses of letrozole (Let) versus tamoxifen (Tam) in the BIG 1 – 98 trial. San Antonio Breast Cancer Symposium 2009; Abstr. 16. 
    Google Scholar
  • 49 Karnon J, Kaura S. Updated survival-based analysis using inverse probability of censoring weighted analysis (IPCW) to estimate the cost-effectiveness of letrozole and anastrozole versus tamoxifen as adjuvant therapy in postmenopausal women with early breast cancer.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 656)
    PubMedGoogle Scholar
  • 50 Younis T, Rayson D, Skedgel C. Adjuvant endocrine monotherapy with tamoxifen or aromatase inhibitors for postmenopausal women with breast cancer: What is the economic impact of CYP 2D6 testing?.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 6010)
    PubMedGoogle Scholar
  • 51 De Boer M, Adang E M, Van Dycke K C et al. Cost-effectiveness of adjuvant systemic therapy in early-stage breast cancer patients with isolated tumor cells or micrometastases in regional lymph nodes.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 614)
    PubMedGoogle Scholar
  • 52 Lee J A, Press M F. HER2 testing: A health economics perspective on alternative test strategies.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 606)
    PubMedGoogle Scholar
  • 53 Sofrygin O, Delea T E, Tappenden P et al. Cost-effectiveness of lapatinib plus capecitabine (LAP+C) versus capecitabine alone (C-only) or trastuzumab plus capecitabine (TZ+C) in women with HER2-positive metastatic breast cancer (MBC) who have received prior therapy with trastuzumab (TZ) from the U.K. National Health Service (NHS) perspective.  J Clin Oncol. 2010;  28 7s (Suppl.; Abstr. 6037)
    PubMedGoogle Scholar
  • 54 Thurston S J, Zelt S C, Botteman M. Cost-effectiveness of zoledronic acid (ZOL) for the treatment of bone loss in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the United States (US).  J Clin Oncol. 2010;  28 (Suppl.; Abstr. e11007)
    PubMedGoogle Scholar
  • 55 Teuffel O, Amir E, Sung L et al. Treatment strategies for low-risk febrile neutropenia in adult cancer patients: A cost-utility analysis.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 6102)
    PubMedGoogle Scholar
  • 56 Mourits M J, Bijen C J, Vermeulen K M et al. Laparoscopic hysterectomy versus abdominal hysterectomy in early-stage endometrial cancer.  J Clin Oncol. 2010;  28 15s (Suppl.; Abstr. 5054)
    PubMedGoogle Scholar

PD Dr. med. Diana Lüftner

Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie
Charité Campus Mitte

Schumannstraße 20/21

10117 Berlin

Email: diana.lueftner@charite.de

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