Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer

Abstract

Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast-conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

Zusammenfassung

Fragestellung: Das Rezidivrisiko beim Mammakarzinom wird durch therapeutische Faktoren, aber auch durch den intrinsischen Subtyp beeinflusst. Diese Arbeit analysiert Risikofaktoren für lokales und lokoregionäres Rezidiv sowie systemische Rezidive, die Evaluation eventuell vorhandener Unterschiede sowie die Analyse des Rezidivrisikos in verschiedenen molekularen Subtypen. Material/Methoden: Analysiert wurden 3054 Patientinnen mit Mammakarzinom, die an den HSK-Wiesbaden und Kliniken Essen-Mitte zwischen 1998–2011 operiert und adjuvant behandelt wurden. Anhand immunhistochemischer Parameter erfolgte die Subgruppierung in Luminal A, Luminal B/HER2−, Luminal B/HER2+, HER2+ und TNBC. Ergebnisse: 67 % der Tumoren wurden als Luminal A, 13 % Luminal B/HER2−, 6 % Luminal B/HER2 +, 3 % HER2+ und 11 % TNBC kategorisiert. Nach einer medianen Nachbeobachtung von 6,6 Jahren traten 100 lokale (3,3 %), 32 lokoregionäre (1 %) Rezidive und 248 Fernmetastasen (8 %) auf. Das metastasenfreie 5-Jahres-Überleben für das Gesamtkollektiv betrug 92 %. In den multivariaten Analysen waren ein positiver Nodalstatus, der TNBC-Subtyp und die nicht durchgeführte Radiotherapie unabhängige Risikofaktoren für alle Rezidivformen. Für das Lokalrezidiv waren zudem Alter < 50 Jahre, Tumorgröße, Luminal B/HER2− und die brusterhaltende Therapie unabhängige Risikofaktoren. Das Risiko für systemische Rezidive war verglichen mit dem Luminal-A-Subtyp in allen weiteren Subtypen erhöht, neben dem Nachweis einer Lymphgefäßinvasion, nicht erfolgter Systemtherapie und Mastektomie. Schlussfolgerung: Insgesamt zeigt sich ein niedriges Risiko für lokale und lokoregionäre Rezidive. Neben dem Nodalstatus ist vor allem die Subgruppenklassifikation ausschlaggebend.

Key words

hormone receptor - HER2/neu - breast cancer

Schlüsselwörter

Hormonrezeptor - Her2/neu - Mammakarzinom

• References

• 1 Krebs in Deutschland. Häufigkeiten und Trends 2013; Online: http://www.rki.de
• 2 Online: http://www.onkozert.de
• 3 Del Turco MR, Ponti A, Bick U et al. Quality indicators in breast cancer care. Eur J Cancer 2010; 46: 2344-2356
• 4 Rutgers EJ. Quality control in the locoregional treatment of breast cancer. Eur J Cancer 2001; 37: 447-453
• 5 Arriagada R, Lê MG, Rochard F et al. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol 1996; 14: 1558-1564
• 6 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
• 7 Poggi MM, Danforth DN, Sciuto LC et al. Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy: the National Cancer Institute Randomized Trial. Cancer 2003; 98: 697-702
• 8 van Dongen JA, Voogd AC, Fentiman IS et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000; 92: 1143-1150
• 9 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
• 10 Blanchard DK, Donohue JH, Reynolds C et al. Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer. Arch Surg 2003; 138: 482-487 discussion 487–488
• 11 Giuliano AE, Haigh PI, Brennan MB et al. Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol 2000; 18: 2553-2559
• 12 Veronesi U, Paganelli G, Viale G et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349: 546-553
• 13 Krag DN, Anderson SJ, Julian TB et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 2010; 11: 927-933
• 14 Perou CM, Sorlie T, Eisen MB et al. Molecular portraits of human breast tumours. Nature 2000; 406: 747-752
• 15 Sorlie T, Perou CM, Tibshirani R et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001; 98: 10869-10874
• 16 Livasy CA, Karaca G, Nanda R et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006; 19: 264-271
• 17 Jacquemier J, Ginestier C, Rougemont J et al. Protein expression profiling identifies subclasses of breast cancer and predicts prognosis. Cancer Res 2005; 65: 767-779
• 18 Dominici LS, Mittendorf EA, Wang X et al. Implications of constructed biologic subtype and its relationship to locoregional recurrence following mastectomy. Breast Cancer Res 2012; 14: R82
• 19 Tang P, Skinner KA, Hicks DG. Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready?. Diagn Mol Pathol 2009; 18: 125-132
• 20 Arvold ND, Taghian AG, Niemierko A et al. Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol 2011; 29: 3885-3891
• 21 Millar EK, Graham PH, OʼToole SA et al. Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. J Clin Oncol 2009; 27: 4701-4708
• 22 Nguyen PL, Taghian AG, Katz MS et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 2008; 26: 2373-2378
• 23 Voduc KD, Cheang MC, Tyldesley S et al. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 2010; 28: 1684-1691
• 24 Sinn P, Aulmann S, Wirtz R et al. Multigene assays for classification, prognosis, and prediction in breast cancer: a critical review on the background and clinical utility. Geburtsh Frauenheilk 2013; 73: 932-940
• 25 Lux MP, Hildebrandt T, Bani M et al. Health economic evaluation of different decision aids for the individualised treatment of patients with breast cancer. Geburtsh Frauenheilk 2013; 73: 599-610
• 26 Empfehlungen gynäkologische Onkologie Kommission Mamma. Online: http://www.ago-online.de
• 27 NCCN Guidelines Version 3.2014. Online: http://www.nccn.org
• 28 Leitlinienreport der S3 Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. 2012. Online: http://www.krebsgesellschaft.de
• 29 Goldhirsch A, Winer EP, Coates AS et al. 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. Ann Oncol 2013; 24: 2206-2223
• 30 Buchholz TA, Somerfield MR, Griggs JJ et al. Margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer: American Society of Clinical Oncology endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology consensus guideline. J Clin Oncol 2014; 32: 1502-1506
• 31 Moran MS, Schnitt SJ, Giuliano AE et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. J Clin Oncol 2014; 32: 1507-1515
• 32 Morrow M, Jagsi R, Alderman AK et al. Surgeon recommendations and receipt of mastectomy for treatment of breast cancer. JAMA 2009; 302: 1551-1556
• 33 McCahill LE, Single RM, Aiello Bowles EJ et al. Variability in reexcision following breast conservation surgery. JAMA 2012; 307: 467-475
• 34 Lynch SP, Lei X, Hsu L et al. Breast cancer multifocality and multicentricity and locoregional recurrence. Oncologist 2013; 18: 1167-1173
• 35 Lynch SP, Lei X, Chavez-Macgregor M et al. Multifocality and multicentricity in breast cancer and survival outcomes. Ann Oncol 2012;
• 36 Weissenbacher T, Zschage M, Janni W et al. Multicentric and multifocal versus unifocal breast cancer: is the tumor-node-metastasis classification justified?. Breast Cancer Res Treat 2010; 122: 27-34
• 37 Yerushalmi R, Kennecke H, Woods R et al. Does multicentric/multifocal breast cancer differ from unifocal breast cancer? An analysis of survival and contralateral breast cancer incidence. Breast Cancer Res Treat 2009; 117: 365-370
• 38 Nixon AJ, Neuberg D, Hayes DF et al. Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol 1994; 12: 888-894
• 39 Kroman N, Holtveg H, Wohlfahrt J et al. Effect of breast-conserving therapy versus radical mastectomy on prognosis for young women with breast carcinoma. Cancer 2004; 100: 688-693
• 40 Bollet MA, Sigal-Zafrani B, Mazeau V et al. Age remains the first prognostic factor for loco-regional breast cancer recurrence in young (< 40 years) women treated with breast conserving surgery first. Radiother Oncol 2007; 82: 272-280
• 41 Cabioglu N, Hunt KK, Buchholz TA et al. Improving local control with breast-conserving therapy: a 27-year single-institution experience. Cancer 2005; 104: 20-29
• 42 van Laar C, van der Sangen MJ, Poortmans PM et al. Local recurrence following breast-conserving treatment in women aged 40 years or younger: trends in risk and the impact on prognosis in a population-based cohort of 1143 patients. Eur J Cancer 2013; 49: 3093-3101
• 43 Zumsteg ZS, Morrow M, Arnold B et al. Breast-conserving therapy achieves locoregional outcomes comparable to mastectomy in women with T1-2N0 triple-negative breast cancer. Ann Surg Oncol 2013; 20: 3469-3476
• 44 Adkins FC, Gonzalez-Angulo AM, Lei X et al. Triple-negative breast cancer is not a contraindication for breast conservation. Ann Surg Oncol 2011; 18: 3164-3173
• 45 Partridge AH, Pagani O, Abulkhair O et al. First international consensus guidelines for breast cancer in young women (BCY1). Breast 2014; 23: 209-220
• 46 Fisher B, Bryant J, Dignam JJ et al. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol 2002; 20: 4141-4149
• 47 Davies C, Godwin J, Gray R et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771-784
• 48 Kiess AP, McArthur HL, Mahoney K et al. Adjuvant trastuzumab reduces locoregional recurrence in women who receive breast-conservation therapy for lymph node-negative, human epidermal growth factor receptor 2-positive breast cancer. Cancer 2012; 118: 1982-1988
• 49 Sanpaolo P, Barbieri V, Genovesi D. Prognostic value of breast cancer subtypes on breast cancer specific survival, distant metastases and local relapse rates in conservatively managed early stage breast cancer: a retrospective clinical study. Eur J Surg Oncol 2011; 37: 876-882
• 50 Harris EE, Hwang WT, Lee EA et al. The impact of HER-2 status on local recurrence in women with stage I–II breast cancer treated with breast-conserving therapy. Breast J 2006; 12: 431-436
• 51 Lowery AJ, Kell MR, Glynn RW et al. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat 2012; 133: 831-841
• 52 Pilewskie M, Ho A, Orell E et al. Effect of margin width on local recurrence in triple-negative breast cancer patients treated with breast-conserving therapy. Ann Surg Oncol 2014; 21: 1209-1214