Prognostische Auswirkung des Resektionsrand-Status auf das Gesamtüberleben von Patientinnen mit Brustkrebs im Frühstadium: Eine retrospektive Analyse aus der Abteilung für Frauenheilkunde an der Charité – Universitätsmedizin Berlin

Zusammenfassung

Einleitung

Die Auswirkung des Resektionsrand-Status auf die Prognose von Brustkrebs im Frühstadium ist immer noch unklar, insbesondere in Anbetracht moderner medikamentöser Therapieoptionen. Ziel der Studie war es, zu untersuchen, wie sich positive Schnittränder nach einer Operation zur Behandlung des Mammakarzinoms im Frühstadium auf das Gesamtüberleben auswirken.

Methoden

Es wurde eine retrospektive Analyse von 3767 Patientinnen durchgeführt, die wegen primären Brustkrebses oder Carcinoma in situ zwischen 2006 und 2022 in der Charité – Universitätsmedizin Berlin operiert worden waren. Dazu wurden eine Überlebensanalyse hinsichtlich des Schnittrand-Status sowie eine multivariate Cox-Regressionsanalyse durchgeführt.

Ergebnisse

Die mediane Verlaufskontrolle betrug 72,2 Monate. Bei 81,4% der Patientinnen (n = 3068) waren die Schnittränder nach der primären Operation negativ, wohingegen 16,2% (n = 610) der Patientinnen eine Nach-Exzision benötigten. Nur 2,4% der Patientinnen (n = 89) hatten definitiv befallene Schnittränder. Befallene Schnittränder traten häufiger in Verbindung mit hormonrezeptorpositiver Erkrankung, lobulärem Subtyp, Carcinoma in situ oder lokal fortgeschrittenen Tumoren auf, und weniger häufig bei Patientinnen nach vorheriger neoadjuvanter Chemotherapie oder triple-negativem Mammakarzinom. Die Kaplan-Meier-Überlebenskurven zeigten ein schlechteres Outcome für Patientinnen mit definitiver R1-Resektion. Dagegen ermittelte die multivariate Cox-Regressionsanalyse keinen statistisch signifikanten Unterschied beim Gesamtüberleben basierend auf dem Schnittrand-Status. Eine brusterhaltende Therapie (HR 0,66; 95%-KI 0,54–0,81) sowie HER2-Überexpression (HR 0,65; 95%-KI 0,48–0,89) waren mit einem besseren Überleben assoziiert.

Schlussfolgerung

Patientinnen, die sich in unserer Studie einer brusterhaltenden Operation unterzogen hatten, wiesen bessere Outcomes auf als Patientinnen nach einer Mastektomie. Auch wenn der Schnittrand-Status keine signifikante Auswirkung auf das Gesamtüberleben hatte, werden große multizentrische Studien benötigt, um die prognostischen Auswirkungen freier oder befallener Schnittränder nach abgeschlossener operativer Therapie hinsichtlich verschiedener Tumorstadien, Tumor-Subtypen und lokalen bzw. systemischen Behandlungen zu evaluieren.

Abstract

Introduction

The impact of surgical margins on the prognosis of early breast cancer remains uncertain, particularly in the context of modern treatment approaches. This study aimed to investigate whether margins involved after surgery for early breast cancer affect overall survival.

Methods

We conducted a retrospective analysis of 3767 patients who underwent surgery for primary breast cancer or carcinoma in situ between 2006 and 2022 at Charité – University Hospital Berlin. Survival analysis based on margin status and a subsequent multivariate Cox regression analysis were conducted.

Results

With a median follow-up of 72.2 months, clear margins were achieved in 81.4% of patients (n = 3068) after primary surgery, while 16.2% (n = 610) required re-excision. Only 2.4% of patients (n = 89) had definitively involved margins. Margin involvement was more common in hormone receptor-positive disease, lobular subtype, carcinoma in situ, or locally advanced tumors, but less frequent in patients with previous neoadjuvant chemotherapy or triple-negative breast cancer. The Kaplan-Meier survival curves showed a significant separation with worse outcomes for patients with definitive R1 resections. However, the multivariate Cox regression analysis detected no statistically significant difference in overall survival based on margin status. Breast conserving surgery (HR 0.66; 95% CI 0.54–0.81) and HER2 overexpression (HR 0.65; 95% CI 0.48–0.89) were associated with improved survival.

Conclusion

Patients who underwent breast-conserving surgery in our study demonstrated favorable outcomes compared to patients after mastectomy. Although margin status did not significantly affect overall survival, larger multicenter studies are needed to evaluate the prognostic implications of margin involvement in breast cancer treatment in different tumor stages, tumor subtypes and local and systemic treatments.

Schlüsselwörter

Mammakarzinom - Schnittrand - R1-Resektion - Überleben

Keywords

breast cancer - margin - R1 resection - survival

• Literatur

• 1 Bray F, Laversanne M, Sung H. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74: 229-263
• 2 Hubner J, Katalinic A, Waldmann A. et al. Long-term Incidence and Mortality Trends for Breast Cancer in Germany. Geburtshilfe Frauenheilkd 2020; 80: 611-618
• 3 Curigliano G, Burstein HJ, Gnant M. et al. Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023. Ann Oncol 2023; 34: 970-986
• 4 Gerber B, Marx M, Untch M. et al. Brustrekonstruktion nach Mammakarzinom. Dtsch Arztebl Int 2015; 112: 593-600
• 5 Banys-Paluchowski M, Thill M, Kuhn T. et al. AGO Recommendations for the Surgical Therapy of Breast Cancer: Update 2022. Geburtshilfe Frauenheilkd 2022; 82: 1031-1043
• 6 Houssami N, Macaskill P, Marinovich ML. et al. The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis. Ann Surg Oncol 2014; 21: 717-730
• 7 Bundred JR, Michael S, Stuart B. et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. BMJ 2022; 378: e070346
• 8 Krekel NM, Haloua MH, Lopes Cardozo AM. et al. Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial. Lancet Oncol 2013; 14: 48-54
• 9 De La Cruz L, Blankenship SA, Chatterjee A. et al. Outcomes After Oncoplastic Breast-Conserving Surgery in Breast Cancer Patients: A Systematic Literature Review. Ann Surg Oncol 2016; 23 (10) 3247-3258
• 10 Wj H, As E, Js R. et al. Rates of margin positive resection with breast conservation for invasive breast cancer using the NCDB. Breast 2021; 60: 86-89
• 11 Dieterich M, Dieterich H, Moch H. et al. Re-excision Rates and Local Recurrence in Breast Cancer Patients Undergoing Breast Conserving Therapy. Geburtshilfe Frauenheilkd 2012; 72: 1018-1023
• 12 Tamburelli F, Maggiorotto F, Marchio C. et al. Reoperation rate after breast conserving surgery as quality indicator in breast cancer treatment: A reappraisal. Breast 2020; 53: 181-188
• 13 Lanner M, Nikolova T, Gutic B. et al. Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists. Int J Gynecol Cancer 2021; 31: 575-584
• 14 Pan H, Wu N, Ding H. et al. Intraoperative ultrasound guidance is associated with clear lumpectomy margins for breast cancer: a systematic review and meta-analysis. PLoS One 2013; 8: e74028
• 15 St John ER, Al-Khudairi R, Ashrafian H. et al. Diagnostic Accuracy of Intraoperative Techniques for Margin Assessment in Breast Cancer Surgery: A Meta-analysis. Ann Surg 2017; 265: 300-310
• 16 Hisada T, Sawaki M, Ishiguro J. et al. Impact of intraoperative specimen mammography on margins in breast-conserving surgery. Mol Clin Oncol 2016; 5: 269-272
• 17 Kolberg HC, Hartkopf AD, Fehm TN. et al. Update Breast Cancer 2023 Part 3 – Expert Opinions of Early Stage Breast Cancer Therapies. Geburtshilfe Frauenheilkd 2023; 83: 1117-1126
• 18 Maishman T, Cutress RI, Hernandez A. et al. Local Recurrence and Breast Oncological Surgery in Young Women With Breast Cancer: The POSH Observational Cohort Study. Ann Surg 2017; 266: 165-172
• 19 Livi L, Paiar F, Saieva C. et al. Survival and breast relapse in 3834 patients with T1-T2 breast cancer after conserving surgery and adjuvant treatment. Radiother Oncol 2007; 82: 287-293
• 20 Peterson ME, Schultz DJ, Reynolds C. et al. Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience. Int J Radiat Oncol Biol Phys 1999; 43: 1029-1035
• 21 Deurzen CH. Predictors of Surgical Margin Following Breast-Conserving Surgery: A Large Population-Based Cohort Study. Ann Surg Oncol 2016; 23 (Suppl. 05) 627-633
• 22 Lai HW, Huang RH, Wu YT. et al. Clinicopathologic factors related to surgical margin involvement, reoperation, and residual cancer in primary operable breast cancer – An analysis of 2050 patients. Eur J Surg Oncol 2018; 44: 1725-1735
• 23 Kurniawan ED, Wong MH, Windle I. et al. Predictors of surgical margin status in breast-conserving surgery within a breast screening program. Ann Surg Oncol 2008; 15: 2542-2549
• 24 Harbeck N. Neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer. Breast 2022; 62 (Suppl. 1) S12-S16
• 25 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
• 26 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
• 27 Boniface J, Szulkin R, Johansson ALV. Survival After Breast Conservation vs Mastectomy Adjusted for Comorbidity and Socioeconomic Status: A Swedish National 6-Year Follow-up of 48 986 Women. JAMA Surg 2021; 156: 628-637
• 28 Maaren MC, de Munck L, de Bock GH. et al. 10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study. Lancet Oncol 2016; 17: 1158-1170
• 29 Fisher S, Yasui Y, Dabbs K. et al. Re-excision and survival following breast conserving surgery in early stage breast cancer patients: a population-based study. BMC Health Serv Res 2018; 18: 94
• 30 Hennigs A, Fuchs V, Sinn HP. et al. Do Patients After Reexcision Due to Involved or Close Margins Have the Same Risk of Local Recurrence as Those After One-Step Breast-Conserving Surgery?. Ann Surg Oncol 2016; 23: 1831-1837
• 31 Bundred J, Michael S, Bowers S. et al. Do surgical margins matter after mastectomy? A systematic review. Eur J Surg Oncol 2020; 46: 2185-2194
• 32 Schmitz R, van den Belt-Dusebout AW, Clements K. et al. Association of DCIS size and margin status with risk of developing breast cancer posttreatment: multinational, pooled cohort study. BMJ 2023; 383: e076022
• 33 Lupe K, Truong PT, Alexander C. et al. Subsets of women with close or positive margins after breast-conserving surgery with high local recurrence risk despite breast plus boost radiotherapy. Int J Radiat Oncol Biol Phys 2011; 81: e561-e568