Prognosefaktoren für das Rezidiv beim Mammakarzinom am Kollektiv der HSK Wiesbaden 1998 – 2003

Zusammenfassung

Fragestellung: Anhand einer Nachbeobachtung unseres Patientenkollektivs wurden Prädiktoren und Prognosefaktoren für das Auftreten eines ­Rezidivs des Mammakarzinoms und des Gesamtüberlebens untersucht. Ziel der Untersuchung war es, Prädiktoren und Prognosefaktoren für das Auftreten von Lokalrezidiven oder Fern­metastasen zu identifizieren. Außerdem wurde geprüft, welchen Einfluss das Auftreten eines ­lokoregionären Rezidivs auf das Gesamtüber­leben hat. Material und Methodik: Von 1/1998 – 12/2003 wurden 1313 Patientinnen mit unilateralem primär nicht metastasierten Mammakarzinom an unserer Klinik diagnostiziert und operiert. Die Nachbeobachtung betrug median 45 Monate. Mittels univariater und multivariater Analyse wurden relevante Prognosefaktoren isoliert. Ergebnisse: 66 Patientinnen (5 %) entwickelten ein lokoregionäres Rezidiv, bei 91 Patientinnen (6,9 %) trat eine Fernmetastasierung auf. Signifikante Prognosefaktoren für das Auftreten eines lokoregionären Rezidivs waren in der multivariaten Analyse Tumorgröße (T3/4-Tumoren, OR 4,4 [2,0 – 9,5] 95 %-KI; p = 0,000), positiver Nodal­status (OR 1,3 [1,05 – 3,3] 95 %-KI; p = 0,006) und negativer Rezeptorstatus (OR 3,9 [1,4 – 10,8] 95 %-KI; p = 0,000). Hinsichtlich des Auftretens von Fernmetastasen war zusätzlich die multi­zentrische/multifokale Tumorlokalisation (OR 1,7 [1,1 – 2,7] 95 %-KI; p = 0,029) von Bedeutung. Mit einem schlechteren Gesamtüberleben waren ­neben Alter > 70 Jahren und fortgeschrittener Tumor­größe auch eine Lymphangiosis carcinomatosa des Primärtumors (OR 7,2 [1,1 – 46,5] 95 %-KI; p = 0,038) und das Auftreten eines lokoregionären Rezidivs (OR 7,4 [3,3 – 16,8] 95 %-KI; p = 0,000) assoziiert. Schlussfolgerung: Bekannte Prognosefaktoren konnten bestätigt werden, so auch insbesondere der Einfluss des negativen Rezeptorstatus auf die Lokalrezidiv­rate. Die Bedeutung des lokoregionären Rezidivs als Prognose­faktor für ein schlechteres Gesamtüberleben konnte gezeigt ­werden.

Abstract

Purpose: In a retrospective analysis we examined the risk factors for locoregional failure, distant metastasis and poorer overall survival. In addition we tried to elucidate whether locoregional failure has an impact on overall survival (OS). Patients and methods: Our population consisted of 1313 patients with primary non-metastatic breast cancer or DCIS treated at the certified Breast Centre of the HSK Wiesbaden, Germany from 1998 – 2003. The median follow-up was 45 months. Using mono- and multivariate analysis we studied the impact of patient and tumour characteristics on locoregional failure, distant failure and overall survival. Results: 66 (5 %) patients developed locoregional failure and 91 patients (6.9 %) had distant failure as their first relapse. Factors which showed an ­independent impact on the locoregional recurrence rate in multivariate analysis were tumour size (T3/4 tumours OR 4.4 (2.0 – 9.5) 95 % CI; p = 0.000), positive nodal status (OR 1.3 [0.5 – 3.3] 95 % CI; p = 0.006) and hormone receptor negative tumours (OR 3.9 [1.4 – 10.8] 95 % CI; p = 0.000). An additional impact on distant failure was found for multicentric tumour localization (OR 7.2 [1.1 – 46.5] 95 % CI; p = 0.038). In addition to age > 70 and tumour size, poorer OS was associated with lymphangiosis carcinomatosa (OR 7.2 [1.1 – 46.5] 95 % CI; p = 0.038) and locoregional failure (OR 7.4 [3.3 – 16.8] 95 % CI; p = 0.000). Conclusion: We could prove the impact of established prognostic factors and particularly of a ­negative hormone receptor status on locoregional failure. In addition we found a strong influence of locoregional relapse on a poorer OS.

Mammakarzinom - Prognosefaktor - lokoregionäres Rezidiv - Fernmetastasen - Gesamtüberleben

breast cancer - prognostic factor - locoregional failure - distant failure - overall survival

Literatur

• 1 Parkin D M, Muir C, Whelan S L. et al .Cancer incidence in five continents. Vol. VI. Lyon, France; International Agency for Research on Cancer Scientific Publications 1992
• 2 http://www.rki.de/cln_049/nn_203956/DE/Content/GBE/DackdokKrebs
• 3 Krebs in Deutschland 2003 – 2004. Häufigkeiten und Trends. 6. über­arbeitete Auflage. Robert-Koch-Institut und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V., Hrsg. Berlin; 2008
• 4 Halsted W S. A clinical and historical study of certain adenocarcinoma of the breast and a brief consideration of the supraclavicular operation and of the results of operation for cancer of the breast from 1889 to 1898 at the Johns Hopkins Hospital.  Ann Surg. 1898;  28 557-576
• 5 Fisher B, Anderson S, Bryant J, Margoles R G, Deutsch M, Fisher E R, Jeong J-H, Wolmark N. Twenty-five-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
• 6 Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. 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
• 7 Kreienberg R, Kopp I, Lorenz W, Dubach W, Duns J, Lück H-J, v. Minckwitz G, Possinger K, Sauerbrei W, Sauerland S, Souchon R, Thomssen C, Untch M, Volm T, Weiss J, Schmitt-Reißer B, Koller M, Heilmann V. Diagnostik, Therapie und Nachsorge des Mammakarzinoms der Frau, eine nationale S3-Leitlinie. Deutsche Krebsgesellschaft e. V. 2004
• 8 Du Bois A. Therapiestandard in der Klinik für Gynäkologie & gynäko­logische Onkologie, HSK Wiesbaden. 9. erweiterte und aktualisierte ­Auf­lage. Wiesbaden; 2008 http://www.hsk-wiesbaden.de/Home/Kliniken/Gynaekologie_und_gynaekologische Onkologie/Leitlinien_Standards
• 9 Singletary S E, Allred C, Ashley P, Basset L W, Berry D, Bland K I, Borgen P I, Clark G, Edge S B, Hayes D F, Hughes L L, Hutter R VP, Morrow M, Page D L, Recht A, Theirault R L, Thor A, Weaver D L, Wienand H S, Greene F L. Revision of the American Joint Committee on Cancer Staging for breast cancer.  J Clin Oncol. 2002;  20 3628-3636
• 10 Elston C W, Ellis I O. Pathological prognostic factors in breast cancer: experience from a large study with long-term follow-up.  Histopathol. 1991;  19 403-410
• 11 Kaplan E L, Meier P. Nonparametric estimation from incomplete observations.  J Am Stat Ass. 1958;  53 457-481
• 12 Cox D R. Regression models and life tables.  J R Stat Soc Series B. 1972;  34 187-220
• 13 Fisher B, Bauer M, Margolese R, Poisson R, Pilch Y, Redmond C, Fisher E, Wolmark N, Deutsch M, Montague E. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer.  N Enl L Med. 1985;  312 665-673
• 14 Veronesi U, Saccozzi R, Del Vecchio M, Banfi A, Clemente C, De Lena M, Gallus G, Luini A, Marubini E, Muscolino G, Rilke F, Salvadori B, Zecchini A, Zucali R. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast.  N Engl J Med. 1981;  305 6-11
• 15 Voogd A C, Nielsen M, Peterse J L, Blichert-Toft M, Bartelink H, Overgaard M, van Tienhoven G, Anderden K W, Sylvester R J, van Dongen J A. Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials.  J Clin Oncol. 2001;  19 1688-1697
• 16 van Dongen J A, Voogd A C, Fentiman I S, Legrand A, Sylvester R J, Tong D, van der Schueren E, Helle P A, van Zijl K, Bartelink H. Long-term results of a randomized trial comparing breast-conservation therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 Trial.  J Natl Cancer Inst. 2000;  92 1143-1150
• 17 Fisher B, Anderson S. Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP trials. National Surgical Adjuvant Breast and Bowel Project.  World J Surg. 1994;  18 63-69
• 18 Katz A, Strom E A, Buchholz T A, Theriault R, Singletary E, McNeeese M A. The influence of pathologic tumor characteristics on locoregional recurrence rates following mastectomy.  Int J Rad Oncol Biol Phys. 2001;  50 735-742
• 19 Borger J, Kempermann H, Hart A, Peterse H, van Dongen J, Bartelink H. Risk factors in breast-conservation therapy.  J Clin Oncol. 1994;  12 653-660
• 20 Fisher B, Anderson S. Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP trials. National Surgical Adjuvant Breast and Bowel Project.  World J Surg. 1994;  18 63-69
• 21 Rosenman J, Bernard S, Kober c, Leland W, Varia M, Newsome J. Local ­recurrences in patients with breast cancer at the North Carolina ­Memorial Hospital (1970 – 1982).  Cancer. 1986;  57 1421-1425
• 22 Locker A P, Ellis I O, Morgan D AL, Elston C W, Mitchell A, Blamey R W. Factors influencing local recurrence after excision and radiotherapy for primary breast cancer.  Br J Surg. 1989;  76 890-894
• 23 Pendlebury S C, Ivanov O, Renwick S, Stevens G N. Long-term review of a breast conservation series and pattern of care over 18 years.  ANZ J of Surg. 2003;  73 577-583
• 24 Westend P J, Meurs C JC, Damhuis R AM. Tumor size and vascular invasion predict distant metastasis in stage I breast cancer. Grade distinguishes early and late metastasis.  J Clin Pathol. 2005;  58 196-201
• 25 Veronesi U, Ettore M, Del Vecchio M, Manzari A, Anreola S, Greco M, ­Luini A, Merson M, Saccozzi R, Rilke F, Salvadori B. Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events.  J Natl Cancer Inst. 1995;  87 19-27
• 26 Blamey R W, Bishop H M, Blake J R, Doyle P J, Elston C W, Haybittle J L, ­Nicholson R I, Griffiths K. Relationship between primary tumor receptor status and patient survival.  Cancer. 1980;  46 2765-2769
• 27 Osborne C K, Yochmowitz M G, Knight W A, McGuire W L. The value of ­estrogen and progesterone receptors in the treatment of breast cancer.  Cancer. 1980;  46 2884-2888
• 28 Ferno M, Stal O, Baldetrop B, Hatschek T, Kallstrom A C, Malmstrom P, Nordenskjold B, Reyden S. Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels. South Sweden Breast Cancer Group, and South-East Sweden breast Cancer Group.  Breast Cancer Res Treat. 2000;  59 69-76
• 29 Bardou V J, Arpino G, Elledge R M, Osborne C K, Clark G M. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases.  J Clin Oncol. 2003;  21 1973-1979
• 30 Costa S D, Lange S, Klinga K, Merkle E, Kaufmann M. Factors influencing the prognostic role of oestrogen and progesterone receptor levels in breast cancer-results of the analysis of 670 patients with 11 years follow-up.  European Journal of Cancer. 2002;  38 1329-1334
• 31 Wallgren A, Bonetti M, Gelber R D, Goldhirsch A, Castiglione-Gertsch M, Holmberg S B, Lindtner J, Thurlimann B, Fey M, Werner I D, Forbes J K, Price K, Coates A S, Collins J. Risk factors for locoregional recurrence among breast cancer patients: results from an International Breast Cancer Study Trials I through IV.  J Clin Oncol. 2003;  21 1205-1213
• 32 Huang E H, Tucker S L, Strom E A, McNeese M D, Kuerer H M, Hortobagyi G N, Buzdar A U, Valero V, Perkins G H, Schechter N R, Hunt K K, Sahin A A, Buchholz T A. Predictors for locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy.  Int J Rad Oncol Biol Phys. 2005;  62 351-357
• 33 Gaspari G, Weidner N, Bevilacqua P, Maluta S, Dalla Palma P, Caffo O, Barbareschi M, Boracchi P, Marubini E, Pozza F. Tumor microvessel ­density, p 53 expression, tumor size and peritumoral lymphatic vessel ­invasion are relevant prognostic markers in node negative breast carcinoma.  J Clin Oncol. 1994;  12 454-466
• 34 Truong P T, Yong C M, Abnousi F, Lee J, Hyayshi A, Olivotto I A. Lymphovascular invasion is associated with reduced locoregional control and survival in women with node-negative breast cancer treated with mastectomy and systemic therapy.  J Am Coll Surg. 2005;  200 912-921
• 35 Kemperman H, Borger J, Hart A, Petersen H, Bartelink H, van Dongen J. Prognostic factors for survival after breast conserving therapy for Stage I and II breast cancer. The role of local recurrence.  Eur J Cancer. 1995;  31 A 690-698
• 36 Dunst J, Steil B, Furch S, Fach A, Lautenschlager C, Diestelhorst A, Lampe D, Kolbl H, Richter C. Prognostic significance of local recurrence in breast cancer after postmastectomy radiotherapy.  Strahlenther Onkol. 2001;  177 504-510
• 37 Schmoor C, Sauerbrei W, Bastert G, Schumacher M. Role of isolated loco­regional recurrence of breast cancer: results of four prospective studies.  J Clin Oncol. 2000;  18 1696-1708
• 38 Voogd A C, van Oost F J, Rutgers E JT, Elkhuizen P H, van Geel A N, Scheijmans L JEE, van der Sangen M JC, Botka G, Hoekstra C J, Jobsen J J, van der Velde C JH, Meyenfeldt M F, Tabak J M, Peterse J L, van de Vijver M J, Coebergh J WW, van Tienhoven G. Long-term prognosis of patients with ­local recurrence after conservative surgery and radiotherapy for early breast cancer.  Eur J Cancer. 2005;  41 2637-2644