356P - Prognostic value of the residual cancer burden after neoadjuvant chemotherapy for invasive lobular breast cancer: An international pooled cohort study

Background

Residual Cancer Burden (RCB) after neoadjuvant chemotherapy (NAC) has been validated to predict event-free survival (EFS) across breast cancer subtypes but its prognostic ability has not been specifically studied for invasive lobular carcinoma (ILC).

Methods

We studied patient-level data (histologic subtype, RCB, and EFS) from a previously published pooled cohort from 12 institutions in the US and Europe. ILC was defined by local institutional protocols. Characteristics in pure ILC vs. non-ILC were compared using t-test or chi-squared test. Associations between continuous RCB index and EFS were assessed in both groups with mixed effect Cox models and multivariable analyses. Recursive partitioning was used in an exploratory model to stratify prognosis by individual clinicopathologic variables and the components of RCB.

Results

Of 5161 patients, the diagnosis was ILC in 216 (4.2%) and non-ILC in 4945. ILC cases were older, had lower grade, higher tumor (T) category, and more hormone receptor (HR) positive HER2 -negative subtype (73.6% vs 36.4%) (all p-values <0.05). Pathologic complete response (pCR/RCB 0) was achieved in 10.6% of ILCs and 33.4% of non-ILC (2.5% and 11.8% respectively among HR+HER2- cases, p<0.0005). Increased RCB index was significantly associated with worse EFS in both ILC and non-ILC (p<0.05) and remained prognostic when adjusted for age, grade, T category, baseline nodal status, and receptor subtype. While continuous RCB index had a linear relationship with probability of EFS event (log scale) in non-ILC, this relationship was non-linear in ILC cases; for ILC, prognosis was similar for RCB index ≤1.9, with increasing risk for RCB index >1.9. Recursive partitioning demonstrated residual tumor cellularity as most prognostic in ILC, followed by number of positive nodes and tumor dimensions.

Conclusions

While pCR rate after NAC is low in ILC, RCB retains prognostic value, with residual cellularity providing the most information. RCB index values ≤1.9 had similar prognosis to pCR. These results underscore the utility of RCB for evaluating NAC response in those with ILC for clinical management and as an endpoint for clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Institutes of Health (United States), National Cancer Institute, Award #: K08CA256047.

Disclosure

H.M. Earl: Financial Interests, Institutional, Research Funding, Grants from Roche and Sanofi-Aventis: Roche and Sanofi-Aventis; Financial Interests, Speaker, Consultant, Advisor, Consultant for Daiichi Sankyo, AstraZeneca, Intas Pharmaceuticals, and prIME Oncology: Daiichi Sankyo, AstraZeneca, Intas Pharmaceuticals, prIME Oncology; Financial Interests, Other, Travel support from Daiichi Sankyo, AstraZeneca, Intas Pharmaceuticals, Pfizer, and Amgen: Daiichi Sankyo, AstraZeneca, Intas Pharmaceuticals, Pfizer, Amgen. C. Yau: Financial Interests, Full or part-time Employment, Salary from Quantum Leap Healthcare Collaborative: Quantum Leap Healthcare Collaborative. D.A. Cameron: Financial Interests, Institutional, Advisory Board: Roche, Pfizer, AstraZeneca, Daiichi Sankyo, SeaGen, Synthon, Zymeworks; Financial Interests, Institutional, Other, Have done advisory boards, spoken at a webinar and involved in a manuscript with Lilly - all recompense to my institution: Lilly; Financial Interests, Institutional, Other, Have done advisory boards and been involved in a health economic analysis and publication. All recompense to my institution: Novartis; Financial Interests, Institutional, Coordinating PI, funding and drug for UK participation in a French led Novartis funded study. Institutional funding received for consultancy work: Novartis; Non-Financial Interests, Principal Investigator, one of three PIs for the Ameera-6 trial - which has now closed early as the company have stopped all development of the drug: Sanofi; Other, Chair of the board of this small Scottish charity for secondary breast cancer: Make Seconds Count; Other, Chair of the Board of B.I.G. - a group of international breast cancer research groups: Breast International Group; Other, Chair of the European Breast Cancer Council which organises the bi-annual EBCC meetings: EBCC. J. Abraham: Financial Interests, Research Grant: AstraZeneca; Financial Interests, Other, Lecture fees: Pfizer, Eisai. L. Hayward: Financial Interests, Research Grant, Grants from Roche and Sanofi-Aventis: Roche and Sanofi-Aventis; Financial Interests, Other, Travel expenses from Roche, AstraZeneca, Pfizer and Sanofi-Aventis, all outside the submitted work.: Roche, AstraZeneca, Pfizer , Sanofi-Aventis. G.S. Sonke: Financial Interests, Institutional, Research Funding, Institutional research funding from AstraZeneca, Merck, Novartis, Roche.: AstraZeneca, Merck, Novartis, Roche. J. Boughey: Financial Interests, Institutional, Research Funding, Research funding to institution from Eli Lilly: Eli Lilly. M.P. Goetz: Financial Interests, Institutional, Advisory Board: ARC Therapeutics, Biotheranostics, Blueprint Medicines, Rna Diagnostics, Sanofi Genzyme; Financial Interests, Institutional, Other, Consulting: AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Other, General Consulting: Lilly; Financial Interests, Personal, Invited Speaker, CME Activity: Research to Practice, Clinical Education Alliance, Medscape, MJH Life Sciences; Financial Interests, Personal, Invited Speaker, CME Panel Discussant: Total Health Conferencing; Financial Interests, Personal, Other, Moderator for CME Activity: Curio Science; Financial Interests, Institutional, Local PI: Lilly, Pfizer, LOXO, ATOSSA Therapeutics, AstraZeneca, Sermonix. L. Pusztai: Financial Interests, Personal, Advisory Board, Advisory Board, Trial Steering Committee membership: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Roche Genentech, Novartis, Exact Sciences, Natera; Financial Interests, Personal, Advisory Board, advisory board, trial steering committee: Merck; Financial Interests, Personal, Advisory Board, advisory board: Biotheranostics; Financial Interests, Personal, Advisory Board, investigator meeting: Biovica; Financial Interests, Institutional, Trial Chair, clinical trial support to institution: Pfizer, Merck; Financial Interests, Institutional, Local PI, clinical trial support to institution: Seagen, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant: Bristol Myers Squibb; Non-Financial Interests, Advisory Role, member of the scientific advisory board: Breast Cancer Research Foundation; Non-Financial Interests, Member of Board of Directors: SWOG Hope Foundation; Non-Financial Interests, Institutional, Product Samples, material transfer agreement: Pfizer. P. Sharma: Financial Interests, Institutional, Research Funding: Novartis, Merck, BMS; Financial Interests, Advisory Board, Consulting/advisory board from Merck, Novartis, Seattle genetics, Gilliad/Immunomedics, AstraZaneca, ExactSciences.: Merck, Novartis, Seattle genetics, Gilliad/Immunomedics, AstraZaneca, ExactSciences. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: Geicam; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Advisory Board: Asra Zeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, GSK, Roche, Pierre Fabre, Seagen, Menarini_Stemline, Gebro Pharma; Non-Financial Interests, Member of Board of Directors: Geicam, Seom. F. Symmans: Financial Interests, Ownership Interest, Shares intellectual property: Delphi Diagnostics. All other authors have declared no conflicts of interest.