UK Interdisciplinary Breast Cancer Symposium Should lobular phenotype be considered when deciding treatment? Michael J Kerin Professor of Surgery National University of Ireland, Galway and Galway University Hospitals January 2018
Breast Cancer: Evolution of Care 1900 1970/80s 1986 Forrest Report This fits the model for ductal cancer Does the same 1990s/2000s apply to lobular? 2010+ Neoadjuvant Chemo Genetic Screening Immunological Influence
Nottingham Prognostic Index The era before systemic chemo and tumour subtyping Tumour Grade Tumour Size Lymphovascular Invasion 2007 1982
Treatment Paradigm for breast cancer Luminal A Luminal B Her 2 Basal Oncotype DX Chemotherapy Herceptin Radiotherapy Surgery Hormonal Agent Chemotherapy Herceptin Radiotherapy Surgery? Neoadjuvant Surgery Hormonal therapy Chemotherapy Radiotherapy Surgery Hormonal therapy Radiotherapy
Effectiveness of therapy Group A Group B Group C Absolute improvement in outcome differs greatly between groups. Relative improvement (20%) is the same for all Biomarker would be very helpful Clinical utility and cost of the therapy varies with the group Interpretation of result varies (all derive benefit or only those between curves benefit)
Chemotherapy Benefit
Invasive Lobular Carcinoma Current clinical considerations Prognosis Surgical considerations Molecular Subtypes Response to neoadjuvant chemotherapy Necessity for chemo in Luminal A Trastuzumab Role Optimal endocrine therapy Slides courtesy of Dr Caroline Brodie
Lobular Cancer Histology Rakha et al. 2008 Classic ILC Tubule formation - Low = 3 Nuclear Plemorphism Moderate = 2 Mitotic Index Low = 1 Guiu et al. 2014
ILC Vs. IDC Outcomes Survival based on ER status ILC (n=211) vs IDC (n=422) Overall Survival: No sig difference between ILC and IDC ER+ IDC significantly better survival than ER+ ILC (Fig.1) ER- ILC significantly better survival than ER- IDC (Fig.2) All pts on this study treated in tamoxifen era. Later studies will have Her2 data
ILC mostly Luminal A ILC Molecular Subtypes Role for Progesterone Receptor Luminal A Luminal B HER2 Overexp. Triple Negative 83% 10% PR- 4.8% Her2+ 1.5% 0
ILC Molecular Subtypes Guiu et al, Crit Rev Haematol Oncol 2014; 235-257
Intrinsic Molecular Subtypes/Oncotype Oncotype Dx not optimal tool for ILC ILC only 1.5% high risk score Vs. 20% IDC high risk (IDC 20% high risk),
Surgical Considerations in ILC Tend to be bigger- increased mastectomy rates Same considerations for breast conservation as IDC Achieve negative margins (no tumour on ink) Multiple studies have shown similar LRR rates as IDC Sentinel node appropriate and ACOSOGZ011 and AMAROS show axillary clearance can be omitted in patients with 1-2 positive nodes MRI can increase unnecessary mastectomy rates Discipline of Surgery
Neoadjuvant Chemo and pcr Pooled analysis 12 RCTs 11955 patients ypt0ypn0 significantly improved DFS compared to ypt0 alone. TN and Her2 + better correlation between PCR and EFS-OS pcr not a valid surrogate endpoint fo improved DFS and OS. Luminal A 11.8% Luminal B 30.9% pcr Triple Neg 33.6% Her2 50.3% Rates of pcr post NACT by breast cancer subtype
Pathological Complete response Pooled analysis of 6377 cases from 7 trials of primary breast cancer receiving neoadjuvant anthracycline-taxane based chemotherapy n=6377 844 (13.6%) ILC ILC pcr: 51 (6%) IDC pcr: 800 (16.1%) pcr is only predictive of DFS and OS in Grade 2, 3 /ER- tumours Von Minctwitz et al. 2012 JCO
Adjuvant Therapy HERA Trial (JCO 2013): 3,401participants- 4.5% Lobular (ILC is not synonymous with HER2- ) DFS Benefit of trastuzumab is similar for HER2+ ILC and IDC OS 1yr of adjuvant trastuzumab should be offered to HER2+ early stage ILC patients
BIG 1-98 Metzger-Filho et al. JCO 2015 ILC benefits more from letrozole vs tamoxifen ILC n=324 v IDC n=2599 LA-like (73% of ILC) ER and/or PgR positive HER2 negative Ki-67 LI less than 14%, LB-like (27% ILC) ER and/or PgR positive HER2 negative Ki-67 LI 14%
ILC Vs. IDC AI therapy IDC n=5021, ILC n=688 Clinical trial MA.27 Anastrozole v Exemestane Postmenopausal, HR+ early breast cancer ILC patients: Marginally Better OS when treated with anastrozole vs. exemestane (Fig b) IDC patients: No difference between treatment group (Fig a)
Invasive Lobular Breast Carcinoma Therapeutic implications ILC is as common as multiple myeloma and requires consideration for specific prospective trials Often larger than IDC, less screen detectable, more often Grade 2 Demonstrates a subtype related response to NACT More late relapses True Luminal A chemo insensitive (v low rates pcr), endocrine responsive disease, more common in ILC than IDC Implications for systemic therapy, neoadjuvant chemotherapy and choice of endocrine agent