Loco-regional Recurrence
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1 Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer AGO AGO e. e. V. V. Loco-regional Recurrence
2 Loco-regional Recurrence Version 2002: Brunnert / Simon Versions : Audretsch / Bauerfeind / Costa / Dall / Fersis / Friedrich / Gerber / Göhring / Hanf / Lisboa / Mundhenke / Rezai / Souchon / Thomssen Version 2013: Fehm / Solomayer
3 Loco-regional Recurrence Incidence and Prognosis Localization Frequency 5-y. Overall (%) Survival (%) Ipsilateral recurrence 1 10 (2 20) 65 (45 79) (post BCT + irradiation) Chest wall 1 4 (2 20) 50 (24 78) (post mastectomy) As above plus supraclavicular fossa 2 34% 49% (3-y. OS) Axilla: After ALND 1 1 (0.1 8) 55 (31 77) After SNB % Multiple localizations 2 16 (8 19) 21 (18 23) 1 Haffty et al. Int J Radiat Oncol Biol Phys 21(2): , 1991; 2 Reddy JP. Int J Radiat Oncol Biol Phys 80(5):1453-7, 201; 3 Karabali-Dalamaga S et al. Br Med J 2(6139): ,1978; 4 Andersson Y, et al. Br J Surg 99(2):226-31,2012
4 Loco-regional Recurrence Staging Examinations before treatment: Oxford AGO LoE / GR Tissue Biopsy 5 D ++ Reassessment of ER, PR, HER2 5 D ++ Complete re-staging 5 D ++
5 Loco-Regional Recurrence Risk Factors at Primary Diagnosis Increased risk for loco-regional recurrence Oxford LoE Young age 1a Positive microscopic margins 1a Number of involved lymph nodes 1a Omitting adjuvant radiotherapy (if indicated) 1a Extensive intraductal component 1b Vessel invasion 1b Triple negative and HER2 / HR- vs. HR+ 2a Grading (G3 vs. G1) 1b* Elevated proliferation markers: partic. Ki67 2b pt (> 2 vs. 2cm) 1b* * node negative 1a pn (N1 vs. N0) 1a Medial tumor localisation (vs. central/lateral) 4
6 Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after Breast Cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat 133(3):831-41, 2012 Metaanalysis: 7174 BCT and 5418 ME After BCT: HR-positive tumors show a lower risk for LRR than... triple negative tumors (RR 0.38) and... HER2-expressing tumors (RR 0.34) After ME: HR-positive tumors show a lower risk for LRR than... HER2- expressing tumors (RR 0.69) and... triple negative tumors (RR 0.61) Result: HR-positive tumors exhibit the lowest rate of local recurrence.
7 Loco-regional Recurrence Prognostic / Predictive factors Parameters in local recurrence to define risk for re-recurrence Tumor size Multifocality Localisation Parameters in local recurrence to define risk for distant metastasis/survival Early (<2-3 yrs.) vs. late recurrence LVSI/Grade/ERneg/close margin (if > 2 factors pos.) Predictive factors for treatment considerations Oxford AGO LoE / GR 2a B 2a B 2b B 2b B 3b B HER2 2b B ++ ER and PgR 2b B ++
8 Panet-Raymond V et al., Clinicopathological factors of the recurrent tumor to predict outcome in patients with ipsilateral breast tumor recurrence. Cancer 117:2035, 2011 n=6020 pat., retrospective cohort-study pt1/2, N0 tumors, Breast conserving treatment 269 ipsilateral breast tumor recurrences (IBTR) Multivariate analysis: TTR <48 months LVSI (of the LRR) ER negative LR-tumor high grade close margins of recurrent tumor => if > 2 factors positive => worse OS
9 Ipsilateral Recurrence after BCT Surgery Oxford LoE/GR Mastectomy (aim: R0) 3b B ++ Re-BCS with tumor-free margins 3b C +/- flap reconstruction Disadvantage for overall survival cannot be excluded Impaired cosmetic result cannot be ruled out Impaired local tumor control cannot be fully excluded Axillary intervention after prior AxDiss if cn0 4 C - SNE after prior SNE if cn0* 4 D +/- Palliative surgery in M1-situation 5 D + (e.g. pain, ulceration, psychosocial) AGO * If no sentinel lymph node could be identified, axillary dissection is not recommended
10 Chest-Wall Recurrence after Mastectomy / Axillary Recurrence Surgery Oxford AGO LoE / GR Curative situation: R0-resection 2b A ++ Palliative situation: Resection of deep parts of the chest wall 5 D +/- Palliative surgery in M1-situation (e.g. pain, ulceration, psychosocial) 5 D +
11 Loco-regional Recurrence after R0-Resection Systemic Treatment According to pathohistological re-evaluation Oxford AGO of the recurrent tumor (ER, PgR, HER2) LoE / GR Endocrine therapy in endocrine responsive tumors 2b B ++ Chemotherapy (consider neoadjuvant) 2b B + In case of HER2 positive disease Chemotherapy + HER2 targeted therapy 5 D +
12 Cytotoxic treatment in pts with local recurrent breast cancer Aebi et al. SABCS 2012
13 Locoregional Recurrence in Case R0 Resection not Likely - Systemic Treatment According to pathohistological re-evaluation of the recurrent tumor (ER, PgR, HER2) Oxford AGO LoE / GR Endocrine therapy in endocrine responsive tumors 2b B ++ Chemotherapy (pre- or postoperatively) 2b B ++ HER2-targeted therapy in HER2-overexpressing 1b A ++ tumors(+ chemotherapy)
14 Ipsilateral Recurrence after BCT Radiotherapy Oxford LoE/GR AGO After Re-BCS Whole breast irradiation 3b C ++ (in case adjuvant radiotherapy was not performed) Re-breast irradiation (Partial breast radiation, brachytherapy, external beam RT) 3b C +/- After mastectomy Radiation of chest wall +/- regional lymph nodes 2b B +/- (14% involved supraclavicular metastases)
15 Chest-Wall Recurrence after Mastectomy / Axillary Recurrence Radiotherapy Oxford AGO LoE / GR Chest-Wall Recurrence after Mastectomy If no prior postmastectomy radiotherapy Curative situation: irradiation of the chest wall +/- regional lymph nodes 2b B + Re-irradiation (chest wall + hyperthermia) 1b B +/- Axillary recurrence Irradiation of axilla after R0-surgery No prior adjuvant irradiation of the axilla 3b C + Adjuvant irradiation of the axilla 5 D -/+
16 Loco-Regional Recurrence Treatment Options in Non Curative Cases Oxford AGO LoE/GR Topical chemotherapy (miltefosine) 3b C + Concomitant radio-chemotherapy 3b C + Hyperthermia (in centers listed on DKG website) In combination with radiotherapy 1b B + In combination with chemotherapy 4 C +/- Intra-arterial chemotherapy 4 C +/- Photodynamic therapy 4 C +/- Electrochemotherapy 3b C +/-
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