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Joint Hospital Surgical Grand Round. Chiu Hiu Fung Jennifer Kwong Wah Hospital 25-1-2014. Is Breast Conserving Treatment (BCT) feasible for Ipsilateral Breast Tumour Recurrence (IBTR)?. Breast conserving surgery. BCT = wide local excision + radiotherapy
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Joint Hospital Surgical Grand Round • Chiu Hiu Fung Jennifer • Kwong Wah Hospital • 25-1-2014
Is Breast Conserving Treatment (BCT) feasible for Ipsilateral Breast Tumour Recurrence (IBTR)?
Breast conserving surgery • BCT = wide local excision + radiotherapy • Well-established treatment modality for early breast cancer • Equal local control and disease-free survival compared to mastectomy • Superior psychosocial outcomes - improved body image and lifestyle score National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial
Definition of local recurrence • IBTR - recurrent tumour within the ipsilateral breast after lumpectomy + radiotherapy • Recurrence within 6 months of primary surgery - primary treatment failure • Local recurrence - recurrence after mastectomy ie skin / chest wall • True recurrence (TR) vs New primary (NP)
Ipsilateral breast tumour recurrence (IBTR) rate after BCS + RT is 1-2% per year • In 1990s, IBTR rate after BCS (without RT) at 10 years: 19% • In 2000s, IBTR rate after BCS + RT at 10 years: 9% NSABP B-17 and B-24 trials
Risk factors for first recurrence: • Omission of radiotherapy • Young age • Involved margin • Multifocality • Extensive in-situ component • Lymphovascular invasion
No standard classification of True Recurrence (TR) vs New Primary (NP) • Different classifications include: • tumour location • histological subtype • ER status • DNA flow cytometry • Gene expression profiling data
True Recurrences: 44 - 78% • TR - shorter metastasis-free survival • mean time to disease recurrence - • 37 months for TRs vs 55 months for NPs Classification of ipsilateral breast tumor recurrence after breast-conserving therapy: New primary cancer allows a good prognosis. Nishimura S. Cancer 2005;12:112–117.
True recurrence is a poor prognostic factor - agressive biology intrinsic to the tumour itself • Lower overall survival and disease-free survival compared to NP group • Hypothesis that TR and NP tumours are distinct entities with different survival prognoses requires further confirmation with pathology review and molecular analyses Analysis of Ipsilateral Breast Tumor Recurrences after Breast-conserving Treatment Based on the Classification of True Recurrences and New Primary Tumors. Komoike Y. Breast Cancer. 2005;12(2):104-111.
Treatment options for IBTR • Salvage mastectomy - gold standard of local treatment for IBTR • Second local recurrence rate: 10% (3-32%) • 5 year disease free survival: 41-59% • 5 year overall survival: 70% (58-84%)
Is there any role for repeating BCS for IBTR? Is it safe?
Four different salvage options were analyzed: • (a) Salvage mastectomy alone • (b) Salvage mastectomy + re-irradiation • (c) 2nd BCS alone • (d) 2nd BCS + re-irradiation
Methods of Re-irradiation • Conventional external beam re-irradiation • Interstitial brachytherapy • low dose rate, high dose rate, or pulsed dose rate • Intra-operative radiotherapy
Salvage mastectomy alone for IBTR • Second local recurrence rate 10-15% (3 - 32%) • 10 year disease free survival: 40-45% (61 - 84%)
Second bcs without post-operative re-irradiation • Second local recurrence rate: 20% (7 - 32%) • 10 year disease free survival: 60% (61 - 64%) Second BCS without re-irradiation is associated with more second local recurrence and less 10 year overall survival when compared to salvage mastectomy
Second bcs with post-operative re-irradiation for IBTR • Second local recurrence rate: 2 - 26% • 5 year overall survival: 75% (61 - 97%) Grade 3-4 toxicity: 3 - 11%
Salvage mastectomy vs second BCS + Re-irradiation • Second local recurrence rate is similar (about 10%) • 5 year overall survival is similar, mainly influenced by distant metastatic progression • Difficult to conduct a randomized controlled trial • Large number of patients will be needed as IBTR is a rare event • Patient may not accept randomization between salvage mastectomy and second BCT
Retrospective analysis • 3155 patients with DCIS or IDC underwent breast conserving surgery from 1986 - 2010 • 132 developed IBTR (~3%) • 46 underwent salvage mastectomy, remaining 86 received second BCS • 8 patients that did not receive re-irradiation were excluded • Total of 78 patient with IBTR and were treated with second BCS + re-irradiation • 17 of 78 patients experienced second IBTR
Time >2 years ER +ve negative margins age at diagnosis >40 years ER +ve
Low risk: DFI > 2 years, ER positive or unknown, negative margins, and age at initial diagnosis >=40
Which type of patients are suitable for second BCS + re-irradiation?
Controversial... • Time to recurrence >2 years • Positive ER status • ? new primary tumors • Sizeable breasts
Conclusion • Both salvage mastectomy and second BCS + re-irradiation are treatment options of IBTR • Still need further large scale studies to compare local recurrence rate and overall survival • To identify the group of patients who can benefit from second BCT • Develop newer radiation techniques to reduce re-irradiation toxicity
References • Local treatment options for ipsilateral breast tumour recurrence. Hannoun-Levi JM. Cancer Treat Rev. 2013 Nov;39(7):737-41. • Analysis of Ipsilateral Breast Tumor Recurrences after Breast-conserving Treatment Based on the Classification of True Recurrences and New Primary Tumors. Komoike Y. Breast Cancer. 2005;12(2):104-111. • Repeat Lumpectomy for Ipsilateral Breast Tumor Recurrence after Breast-Conserving Treatment. Ishitobi M. Oncology. 2011;81:381-386 • True Recurrence Versus New Primary: An Analysis of Ipsilateral Breast Tumor Recurrences After Breast-Conserving Therapy. V Panet-Raymond. International Journal of Radiation Oncology. 2011;81(2):409-41 • Repeating Conservative Surgery after Ipsilateral Breast Tumor Reappearance: Criteria for Selecting the Best Candidates. Gentilini O. Ann Surg Oncol. 2012;19:3771-3776
interstitial brachytherapy • Brachy: short-distance • Can be used alone or in combination with surgery, external beam RT and chemotherapy
IORT group: 1 dose 21 Gy during surgery • External RT group: 50 Gy in 25 fractions of 2 Gy + boost of 10 Gy in 5 fractions • 5-year rate for IBTR 4.4% for IORT group; 0.4% for external RT • Same overall survival • Significantly fewer skin side-effects in IORT group (p=0.0002)
Toxicity of irradiation • radiation dermatitis, fibrosis, telangiectasia • pericarditis, pericardial effusion, pneumonitis • From double surgery: asymmetry