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Topic: 2019 AACR conference | LOBULAR related Abstracts

Forum: ILC (Invasive Lobular Carcinoma) — Just diagnosed, in treatment, or finished treatment for ILC.

Posted on: Mar 31, 2019 03:48PM

JohnSmith wrote:

The annual AACR (American Association for Cancer Research) conference started this weekend in Atlanta, Georgia, USA. The multi-day event provides a venue for physicians and scientists to present research results to a global audience of oncology professionals.

A quick search using the term "Lobular" generated the following Abstracts related to ILC. There may be more ILC related news, but these were the only three search engine results:

- Incidence of high Tumor Mutation Burden (TMB) and PD-L1 positivity in breast cancers and potential response to Immune Checkpoint Inhibitors (ICPIs)
https://www.abstractsonline.com/pp8/?sf100423114=1#!/6812/presentation/4963

Presenter/Authors
Ethan Sokol1, Lee Albacker1, Aixa Soyano2, Ricardo Parrondo2, Brenda Ernst2, Emmanuel Gabriel2, Garrett Frampton1, Jeffrey Ross1, Siraj Ali1, Jon Chung1, Saranya Chumsri2. 1Foundation Medicine, Cambridge, MA; 2Mayo Clinic, Jacksonville, FL
Disclosures
E. Sokol: ; Foundation Medicine. L. Albacker: ; Foundation Medicine. A. Soyano: ; Mayo Clinic. R. Parrondo: ; Mayo Clinic. B. Ernst: ; Mayo Clinic. E. Gabriel: ; Mayo Clinic. G. Frampton: ; Foundation Medicine. J. Ross: ; Foundation Medicine. S. Ali: ; Foundation Medicine. J. Chung: ; Foundation Medicine. S. Chumsri: ; Mayo Clinic.

Abstract
Background: Immune checkpoint inhibitors (ICPIs) have led to dramatic improvement in outcome of several cancers. Program death ligand1 (PD-L1) staining and tumor mutational burden (TMB) have emerged as independent predictive biomarkers of ICPIs in lung cancer. Here we examine the landscape of TMB and PD-L1 expression in breast cancer and present a case of patient with high TMB and PD-L1 negative breast cancer with exceptional response to ICPIs.
Methods: Hybrid-capture based comprehensive genomic profiling of 395 cancer related genes using the FoundationOne assay was performed on 14,867 breast carcinomas sequenced in the course of routine clinical care. Ventana (SP-263) PD-L1 status (n=1425) and hormone receptor status was available for a subset of patients. Subgroup analyses were performed based on histological type [invasive lobular carcinoma (ILC, n=740)], molecular subtypes [ER-positive (ER+; n= 1371), HER2-amplified (HER2+; n=1522), and TNBC (n=917)], patient age (≤45, 46-60, ≥61), and local vs. metastatic disease (n=5241 and 6710).
Results: Consistent with previous reports, the rates of positive PD-L1 staining are highest in TNBC (14%) and lowest in HER2+, ILC, and ER+ disease (6.0%, 5.1%, 2.3%). Interestingly, the rate of PD-L1 positivity, defined as ≥1% tumor staining, was significantly lower in metastatic disease vs. local disease (6.3% vs. 11.1%; p = 0.005). The frequency of high TMB, defined as >10 mutations/mb, was greatest in ILC and HER2+ disease (13.6% and 9.9%) and lowest in TNBC and ER+ disease (7.0% and 6.9%). Rates of high TMB were associated with increased patient age (3.7%, 9.3%, and 12.8% frequency in patients ≤45, 46-60, and ≥61) and were significantly higher in metastatic vs. local disease (11.1% vs 5.3%; p<2E-23). PD-L1 positive and TMB high populations were not significantly co-occurrent (OR = 1.02, p = 0.87). Similar percentages of PD-L1 positivity were observed in both TMB low (9.3%) and TMB high (9.5%). However, among patients with very high TMB (>20 mut/mb), there was a significant association between TMB and PD-L1 positivity (OR = 2.6, p = 0.023). Nevertheless, even with high cutoff, 79% of the TMB high samples were PD-L1 negative.
We also report on a stage IIIb (T4, N2, M0) ER+ HER2- breast cancer patient with high TMB (40muts/mb) and negative PD-L1 IHC who previously progressed on aromatase inhibitor with CDK4/6 inhibitor and chemotherapy but achieved durable complete response of > 1 year with nivolumab in combination with capecitabine.
CONCLUSION: Predictive biomarkers for ICPIs are critical to identify a subset of breast cancer patients who may respond to immunotherapy. TMB high and PD-L1 positivity do not significantly co-occur and the majority of TMB high cases were PD-L1 negative. Nevertheless, this group of patients may still benefit with ICPIs. Further studies are needed to evaluate this subset of patients.


- Staging with [18F]FDG PET/CT
https://www.abstractsonline.com/pp8/?sf100423114=1#!/6812/presentation/1501

Presenter/Authors
Ramsha Iqbal1, Tuba Aras1, Lemonitsa Mammatas2, Wouter V. Vogel2, Daniela E. Oprea-Lager1, Hendrik M. W. Verheul1, Ronald Boellaard1, Catharina W. Menke-van der Houven van Oordt1. 1Amsterdam University Medical Centers - location VU University Medical Center, Amsterdam, Netherlands; 2Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
Disclosures
R. Iqbal: None. T. Aras: None. L. Mammatas: None. W.V. Vogel: None. D.E. Oprea-Lager: None. H.M.W. Verheul: None. R. Boellaard: None. C.W. Menke-van der Houven van Oordt: None.

Abstract
Background: Accurate staging of patients with primary breast cancer is essential for an optimal treatment plan. The current imaging standard for staging, positron emission tomography/computed tomography with [18F]Fluorodeoxyglucose ([18F]FDG PET/CT), might be insufficient for detection of distant metastases, specifically in low grade, estrogen receptor positive (ER+) breast cancer, due to lower metabolic activity. The aim of this study was to investigate the efficacy of [18F]FDG PET/CT in staging patients with low-intermediate grade, ER+ breast cancer.
Methods: 79 patients diagnosed with grade 1-2, ER+ clinical stage IIB/III or locoregional recurrent breast cancer were retrospectively included. Visual analysis was performed, comparing the lesions detected on conventional imaging modalities (mammography, ultrasound, magnetic resonance imaging, computed tomography, bone scintigraphy) with lesions detected on [18F]FDG PET/CT. Conventional imaging and/or pathology outcomes were considered as the gold standard for this comparison. Tracer uptake in each PET-positive lesion was (semi)quantified: volumes of interest were defined on the PET scan to determine standardized uptake values (SUVmax, SUVmean, SUVpeak), total lesion glycolysis (TLG) and metabolic tumor volume (MTV). These quantitative parameters were correlated with pathological features of tumors (i.e. histological subtype, grade, ER/PR/HER2 expression and mitotic activity index) to assess whether tracer uptake is influenced by these features.
Results: Scans were analyzed visually and (semi)quantitatively. 370 lesions could be identified with all imaging modalities (primary lesions: 80, locoregional lymph nodes: 161, distant lesions: 129). Based on the gold standard, 226/370 (61.1%) lesions were interpreted as "true positive" on [18F]FDG PET, 134/370 (36.2%) as "false positive" and 10/370 (2.7%) as "false negative" on [18F]FDG PET (p = 0.016). "False positive" lesions were mainly located in the axilla region (e.g. reactive lesions), gynecological and gastro-intestinal tract (e.g. adenomas) whereas "false negative" lesions were predominantly located in osseous tissue. The average SUVmax for "true positive" and "false positive" lesions was 4.24 ± 2.97 and 3.96 ± 2.03, respectively. For "true positive" lesions SUVmax, SUVpeak, SUVmean and MTV correlated with histological subtype, showing higher uptake in ductal carcinoma compared to lobular carcinoma (p <0.023). SUVmax and SUVmean also correlated with PR expression (p <0.034). No other correlations could be found between quantitative parameters and pathology outcomes.
CONCLUSION: These preliminary data indicate that [18F]DGG PET/CT might not correctly identify a substantial amount of lesions and therefore could lead to incorrect staging of patients with low grade, ER+ breast cancer. This suggests that there is a need to improve current staging procedures.


- NCI Molecular Analysis for Therapy Choice (NCI-MATCH EAY131) arm B: Phase II study of afatinib in patients with HER2 (ERBB2) activating mutations
https://www.abstractsonline.com/pp8/?sf100423114=1#!/6812/presentation/9940

Presenter/Authors
Philippe L. Bedard1, Shuli Li2, Kari B. Wisinski3, Eddy S. Yang4, Sewanti A. Limaye5, Edith P. Mitchell6, James A. Zwiebel7, Jeffrey Moscow8, Robert J. Gray9, Lisa M. McShane10, Larry V. Rubenstein10, David R. Patton11, P. Mickey Williams12, Stanley R. Hamilton13, Barbara A. Conley14, Carlos L. Arteaga15, Lyndsay N. Harris14, Peter J. O'Dwyer16, Alice P. Chen17, Keith T. Flaherty18. 1Princess Margaret Cancer Centre, Toronto, ON, Canada; 2E-A Biostatistical Center, Boston, MA; 3University of Wisconsin, Madison, WI; 4University of Alabama-Birmingham, Birmingham, AL; 5Columbia University, New York, NY; 6Thomas Jefferson University Hospital, Philadelphia, PA; 7Investigational Drug Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; 8Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; 9Dana Farber Cancer Institute – ECOG-ACRIN Biostatistics Center, Boston, MA; 10Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; 11Center for Biomedical Informatics & Information Technology, National Cancer Institute, Bethesda, MD; 12Frederick National Laboratory for Cancer Research, Frederick, MD; 13MD Anderson Cancer Center, Houston, TX; 14Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; 15UT Southwestern Medical Center, Dallas, TX; 16University of Pennsylvania, Philadelphia, PA; 17Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; 18Massachusetts General Hospital, Boston, MA
Disclosures
P.L. Bedard: ; BristolMyersSquibb. ; Sanofi. ; Roche/Genentech. ; Merck. ; AstraZeneca. ; Nektar. ; Novartis. ; GlaxoSmithKline. ; Pfizer. ; Mersana. S. Li: None. K.B. Wisinski: None. E.S. Yang: ; Strata Oncology. ; AstraZeneca. ; Eli Lilly. ; Novartis. ; Tesaro. S.A. Limaye: ; AstraZeneca. ; BristolMyersSquibb. ; Roche. ; Boerhinger Ingelheim. ; Merck. ; Novartis. ; MSD. E.P. Mitchell: ; Exelixis. ; Novartis. ; Pfizer. ; Celgene. ; Lilly. ; Genentech. J.A. Zwiebel: ; Boston Pharmaceuticals. ; Scandion Oncology. J. Moscow: None. R.J. Gray: None. L.M. McShane: None. L.V. Rubenstein: None. D.R. Patton: None. P.M. Williams: None. S.R. Hamilton: ; Halio DX. ; Illumina. ; Merck. ; ThermoFisher Scientific. ; Cell Medica. ; LOXO-Oncology. ; UT MD Anderson Cancer Center. B.A. Conley: None. C.L. Arteaga: ; Novartis; Merck; Sanofi; Symphogen. ; TAIHO Oncology; H3 Biomedicine; OrigiMed; Daiichi Sankyo. ; Lilly; Puma; Radius. ; Pfizer. ; Takeda. ; Bayer. ; Provista. ; Y-TRAP. ; Scientific Advisory Board; Komen Foundation. L.N. Harris: None. P.J. O'Dwyer: ; Pfizer. ; Genentech. ; BristolMyersSquibb. ; GlaxoSmithKline. ; Five Prime. ; FortySeven. ; BBI. ; Novartis. ; Celgene. ; Boehringer Ingelheim. A.P. Chen: None. K.T. Flaherty: ; Loxo Oncology; Clovis Oncology; Strata Oncology. ; Vivid Biosciences; X4 Pharmaceuticals; PIC Therapeutics. ; Fount; Shattuck Labs; Apricity. ; Oncoceutics; Fog Pharma; Tvardi. ; Sanofi; Amgen; Asana. ; Adaptimmune; Aeglea; Array Biopharma. ; Arch Oncology; Tolero; Neon. ; Novartis; Genentech; BMS. ; Merck; Takeda; Verastem; Checkmate. ; Boston Biomedical; Pierre Fabre; Cell Medica; Debiopharm.

Abstract
BACKGROUND: NCI-MATCH is a multi-cohort, signal finding trial that assigns pts with advanced cancers to targeted therapies based on central tumor genomic testing. Arm B evaluated afatinib, an ErbB family blocker, in pts with ERBB2 activating mutations.
METHODS: Eligible pts had advanced refractory solid tumors, lymphoma, or multiple myeloma, tumor biopsies with selected ERBB2 single nucleotide variants or insertions/deletions, but no ERBB2 amplification detected by the NCI-MATCH next generation sequencing assay. Pts had performance status (PS) ≤1, left ventricular ejection fraction >50%, grade ≤1 diarrhea, and no prior HER2 therapy. Non-small cell lung cancers were excluded. Pts received afatinib 40 mg daily in 28 day cycles. Concomitant endocrine therapy was not allowed. Tumor assessments were every two cycles. The primary objective was overall response rate (ORR). Secondary objectives were: 6-month progression-free survival (PFS6), overall survival, toxicity and molecular correlates. Initial planned enrollment was 35 pts, but a subsequent amendment permitted accrual of up to 70 pts to provide additional information in rarer histologies.
RESULTS: 59 pts were assigned and 40 enrolled (37 evaluable) to Arm B. Median age was 62 (range 29-83), 78% female, 32% PS0, and 58% had received >3 prior therapies. Tumor histologies: breast (n=12; 5 lobular/7 ductal, all ER+), colorectal (n=5), urothelial (n=4), biliary (n=3), cervix (n=2), small bowel (n=2) and other (n=9). The qualifying ERBB2 variants were L755S (n=6), V777L (n=6), V842I (n=6), S310F (n=6), D769Y (n=5), S310Y (n=4), V777_G778insGSP (n=2), and other (n=7). The ORR was 2.7% (n=1/37; 90% CI 0.14%-12.2%) and PFS6 was 11% (90% CI 5.0%-23.5%). A confirmed partial response (PR) occurred in a patient with adenocarcinoma of extra-mammary Paget disease of skin who progressed after cycle 6. Two unconfirmed PRs were observed (low grade serous gynecological tract and ER+/HER2- IHC breast ductal carcinoma). Of 12 evaluable breast cancer pts, there was 1 additional pt with lobular carcinoma (ER+/HER2-FISH) who had 51% reduction in target lesions but progressed due to a new lesion at cycle 6. The most common (>20%) treatment-related AEs were: diarrhea (68%), mucositis (43%), fatigue (40%), acneiform rash (30%) dehydration (27%), vomiting (27%), nausea (27%), anemia (27%) and anorexia (22%). Most AEs were grade ≤2. Four pts (11%) discontinued due to AEs.
CONCLUSION: Although afatinib did not meet the pre-specified threshold for anti-tumor activity, the response in a rare tumor type is notable. The results in breast/gynecologic malignancies, along with the SUMMIT trial (Hyman Nature 2018), suggest differential activity of HER2 inhibitors in ERBB2 mutant cancers by tumor histology. The safety profile of afatinib was consistent with prior studies.

Wife was Age 45 at Dx 4/2014. BMX Surgery 6/2014 revealed: ILC, Stage 2 (Multifocal ILC, largest lesion 2.2 cm), Grade 2, ER+/PR+ (95%), HER2-, Ki-67 5-10%, Oncotype 11; Variant in the ATM gene Dx 4/8/2014, ILC, Left, 2cm, Stage IIA, Grade 2, 0/3 nodes, ER+/PR+, HER2- (IHC) Surgery 6/26/2014 Mastectomy; Reconstruction (left); Reconstruction (right)
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Apr 9, 2019 11:41AM Texas357 wrote:

Thank you!

DX 9/08, ILC, Stage 3A, ER+/PR+, HER2-, 7/13 pos nodes. Mastectomy & six months chemo & 32 rads.Prophy mx 8/09 and they found DCIS and LCIS. Implant only on proph side; LD flap on rad side. 13 surgeries since diagnosis.

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