Abstract 3505
Background
Seth et al. (ASCO 19) identified four biologic classes based on longitudinal molecular profiling of TNBC tumors pre- and post- neoadjuvant adriamycin/cyclophosphamide (AC). The four groups were defined based on the enriched and depleted hallmark pathways that were observed. The low-overall change (LOC) group was defined as having no significant change in the pathways in pre- and post-AC biopsies. Of note, this group of patients had lower pathological complete response (pCR) rates. The aim of this study is to describe the clinical features of early-stage (I-III) TNBC patients with tumors exhibiting LOC in their biopsies with neoadjuvant therapy.
Methods
We analyzed the clinical characteristics of 48 patients with early stage (I-III) TNBC enrolled in the ARTEMIS trial (NCT02276443). All patients received neoadjuvant AC; 48% of patients were subsequently treated on a clinical trial and 52% received standard taxane-based chemotherapy. We compared the clinical characteristics of 17 patients in the LOC group with 31 patients in the other three biologic classes. Two-group comparison was performed using Chi-squared test.
Results
Age at diagnosis, histology, Vanderbilt subtype, Ki-67, sTIL levels and vimentin expression were similar between the groups. Median age at diagnosis in the LOC group was 58 (range, 27-74). All patients in this group were stage II-III, with no stage I identified. 59% of patients in the LOC group had stage III disease compared with 26% in the other groups (p = 0.02), Also, 47% of patients in this group had AR ≥ 10% compared to 19% in the other biological groups (p = 0.04).Table:
252P
Variable | Group | Low-Overall Change Group (n = 17) | % | Other Biologic Classes (n = 31) | % | p |
---|---|---|---|---|---|---|
Age at diagnosis | ≤60 | 10 | 59 | 25 | 81 | 0.10 |
>60 | 7 | 41 | 6 | 19 | ||
Stage | I | 0 | 0 | 6 | 19 | N/A |
II | 7 | 41 | 17 | 55 | 0.36 | |
III | 10 | 59 | 8 | 26 | 0.02 | |
Histology | Invasive ductal | 15 | 88 | 26 | 84 | 0.23 |
Metaplastic | 0 | 0 | 4 | 13 | ||
Apocrine | 1 | 6 | 0 | 0 | ||
Other | 1 | 6 | 1 | 3 | ||
Vanderbilt subtype | BL | 3 | 18 | 8 | 26 | 0.24 |
LAR | 4 | 24 | 2 | 6 | ||
M/MSL | 3 | 18 | 11 | 35 | ||
IM | 2 | 12 | 4 | 12 | ||
Ki-67 (%) | ≥ 50 | 8 | 47 | 21 | 68 | 0.16 |
< 50 | 9 | 53 | 10 | 32 | ||
Androgen Receptor Expression (%) | ≥ 10 | 8 | 47 | 6 | 19 | 0.04 |
< 10 | 9 | 53 | 25 | 81 | ||
Vimentin Expression (%) | ≥50 | 2 | 12 | 4 | 13 | 0.91 |
<50 | 15 | 88 | 27 | 87 | ||
sTIL | Low (<5) | 7 | 41 | 15 | 48 | 0.37 |
Moderate (≥5-30) | 9 | 52 | 11 | 35 | ||
High (>30) | 0 | 0 | 1 | 3 |
Conclusions
Patients with low-overall change in their tumors had later-stage disease and higher AR expression. Previous analysis by Seth et al. has demonstrated a lower pCR rate in this group with standard neoadjuvant chemotherapy. This analysis highlights the potential role of androgen deprivation in this class of tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The University of Texas MD Anderson Cancer Center Moonshots Program and a CPRIT Multi-Investigator Research Award (MIRA).
Disclosure
S. Moulder: Research grant / Funding (self): Pfizer; Research grant / Funding (self): Genentech; Research grant / Funding (self): Novartis; Research grant / Funding (self): Seattle Genetics; Research grant / Funding (self): EMD Serono; Research grant / Funding (self): Bayer; Research grant / Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
4250 - Phase II study of avelumab in combination with cetuximab as a rechallenge strategy in pre-treated RAS wild type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) Colon.
Presenter: Erika Martinelli
Session: Poster Display session 2
Resources:
Abstract
5234 - The ORCHESTRA trial; A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Presenter: Lotte Bakkerus
Session: Poster Display session 2
Resources:
Abstract
5294 - EMERGE: Epigenetic Modulation of the Immune Response in Gastrointestinal cancers
Presenter: Elizabeth Cartwright
Session: Poster Display session 2
Resources:
Abstract
913 - Phase III, international, multicenter, randomized, open-label trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for surgically resected pancreatic adenocarcinoma (APACT): subgroup analyses
Presenter: Margaret Tempero
Session: Poster Display session 2
Resources:
Abstract
1668 - FOLFIRINOX in locally advanced (LA) and borderline resectable (BR) pancreatic adenocarcinoma : update of the AGEO cohort.
Presenter: Edouard Auclin
Session: Poster Display session 2
Resources:
Abstract
2559 - Impact of adjuvant treatment with nab-paclitaxel and gemcitabine (nab-P+GEM) vs gemcitabine alone (GEM) on health-related quality of life (QoL) in patients (pts) with surgically resected pancreatic adenocarcinoma (PA) in the Adjuvant Pancreatic Adenocarcinoma Clinical Trial (APACT)
Presenter: Hanno Riess
Session: Poster Display session 2
Resources:
Abstract
4897 - Early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumor DNA
Presenter: Xiao-ding Liu
Session: Poster Display session 2
Resources:
Abstract
1755 - Evaluation of minimal important difference (MID) for the European Organisation for Research and Treatment of Cancer (EORTC) Pancreatic Cancer Module (PAN26) in patients with surgically resected pancreatic adenocarcinoma
Presenter: Michele Reni
Session: Poster Display session 2
Resources:
Abstract
2876 - Multispectral analysis of lymphocyte complexity in periampullary adenocarcinoma
Presenter: Sebastian Lundgren
Session: Poster Display session 2
Resources:
Abstract
1902 - Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)
Presenter: Jae Ho Jeong
Session: Poster Display session 2
Resources:
Abstract