Introduction
What is new in the phenotypic and molecular characteristics of lobular carcinoma in situ?
Lee et al. [29] | Harrison et al. [27] | Shamir et al. [33] | Ciriello et al. [32] | Michaut et al. [34] | Desmedt et al. [35] | Rosa-Rosa et al. [36] | Zhu et al. [37] | Richard et al. [38] | Pareja et al. [39] | Sokol et al. [40] | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CLCIS (n = 43) | PLCIS (17) FLCIS (2) (n = 19) | PLCIS (10) FLCIS (6) (n = 16) | ILC (n = 127) | ILC (n = 144) | ILC (n = 413) | PILC (n = 27) | PILC (n = 17) | Primary ILC (n = 32) | Metastatic ILC (n = 32) | Primary ILC (n = 127) | Metastatic ILC (n = 132) | Metastatic ILC (n = 180)* | ||
Mutations | CDH1 | 81.0% | 94.7% | 94.0% | 63.0% | 42.7% | 65.4% | 89.0% | 59.8% | 53% | 62.5% | 82% | 76% | 77% |
PIK3CA | 32.0% | 31.6% | 56.2% | 48.0% | 33.8% | 43.3% | 33.0% | 52.9% | 44% | 44% | 57% | 52% | 52.9% | |
ERBB2 | 7.0% | 68.4% | 37.5% | 4.0% | 4.3% | 5.1% | 26.0% | 17.6% | 12.5% | 15.6% | 2% | 12% | 8.3% | |
ERBB3 | NR | 21.1% | 18.8% | NR | 2.9% | 3.6% | NR | 23.5% | 3% | 0% | NR | NR | < 5% | |
RUNX1 | 2.3% | 21.1% | NR | 10.0% | NR | 3.4% | NR | 11.8% | 3% | 6% | 9% | 5% | ~ 7% | |
CBFB | 19.0% | 15.8% | 12.5% | 2.0% | NR | NR | NR | 17.6% | NR | NR | NR | NR | NR | |
FOXA1 | 4.7% | 10.5% | 31.3% | 7.0% | NR | 9.0% | NR | 5.9% | 15.6% | 15.6% | 8% | 11% | NR | |
GATA3 | 4.7% | 10.5% | 12.5% | 5.0% | 5.1% | 7.3% | 7.0% | 5.9% | 15.6% | 15.6% | 3% | 7% | 2.2% | |
ARID1A | 2.3% | 10.5% | 6.3% | 17.0% | 7.0% | 6.3% | 15.0% | 5.9% | 12.5% | 12.5% | 8% | 11% | ~ 12% | |
TP53 | 0% | 5.3% | 18.8% | 8.0% | 3.6% | 7.3% | 19.0% | 11.8% | 18.7% | 9% | 9% | 20% | 23.9% | |
TBX3 | 9.3% | NR | NR | 9.0% | 8.0% | 13.3% | 7.0% | 23.5% | 21.8% | 18.7% | 10% | 16% | 12.8% | |
KMT2C | 2.3% | NR | NR | 7.0% | 10.0% | 8.0% | 19.0% | 35.3% | NR | NR | NR | NR | < 5% | |
MAP3K1 | 4.7% | NR | NR | 6.0% | 5.1% | 5.0% | 19.0% | 35.3% | 18.7% | 15.6% | 10% | 10% | < 5% | |
ESR1 | NR | NR | NR | NR | 1.4% | NR | NR | 5.9% | 12.5% | 15.6% | 2% | 15% | 17% | |
AKT1 | 4.7% | NR | NR | 2.4% | 5.1% | 4.1% | 7.0% | 5.9% | 6.2% | 9.4% | NR | NR | ~ 5% | |
PTEN | 0% | NR | 6.2% | 7.0% | 1.4% | 3.9% | NR | 0% | 3.1% | 0% | 9% | 9% | ~ 10% | |
NF1 | NR | NR | 0% | NR | 4.3% | 1.0% | 7.0% | 24% | 3.1% | 6.2% | 2% | 8% | 12.2 | |
Amp | CCND1 | NR | 26.3% | 18.8% | 17.0% | 15.0% | 38.0% | 11.0% | 12.0% | 33.3% | 38.0% | 17% | 17% | 22% |
ERBB2 | 4.7% | 31.5% | 12.5% | 7.0% | 4.0% | 0.0% | 4.0% | 6.0% | 33.3% | 15.6% | 2% | 5% | NR | |
FGFR1 | 0% | 0% | NR | NR | NR | 25.3% | 7.0% | 23.5% | 6.2% | 6.2% | 7% | 11% | 7.8% |
Study | ERBB2 alteration frequency | ERBB3 alteration frequency | Notes | |||||
---|---|---|---|---|---|---|---|---|
Total % | Mut | Amp | Total % | Mut | Amp | |||
In situ | Harrison et al. [27] | 94.7% | 13/19 | 6/19 | 21% | 4/19 | 0/19 | 17 PLCIS; 2 FLCIS |
Shamir et al. [33] | 50% | 6/16 | 2/16 | 18.7% | 3/16 | 0/16 | 10 PLCIS; 6 FLCIS; ERBB2 and/or ERBB3 alterations in 60% PLCIS and 50% FLCIS | |
Primary ILC | Zhu et al. [37] | 17.6% | 3/17 | – | 23.5% | 4/17 | – | PILC |
Rosa-Rosa et al. [36] | 26% | 7/27 | 1/27 | – | – | – | PILC; association with nuclear grade 3 | |
Christgen et al. [41] | 5% | 5/106 | – | – | – | – | Grade 3 but no association with solid or pleomorphic | |
Cao et al. [42] | 19% | – | 13/70 | – | – | – | Amplification; no mutation assessment | |
Deniziaut et al. [43] | 15% | 6/55 | – | 0% | 0/55 | – | Grade 3; positive association with solid presentation | |
Ping et al. [44] | 6% | 6/100 | – | – | – | – | CDH1 altered with ERBB2 mutation correlates with poor prognosis | |
Lien et al. [31] | 52.2% | 5/24 | 8/24 | – | – | – | PILC; 2% in classic ILC | |
mILC | Ma et al. [45] | 7.8% | 4/51 | – | – | – | – | Metastatic ILC; confirmed neratinib efficacy in ERBB2 mutants in phase II trial; detection in ctDNA |
Ross et al. [46] | 22.7% | 4/22 | 1/22 | Relapsed ILC; ERBB2 mutation enriched in CDH1 mutant tumours; I gene fusion not tabulated (ERBB2–GRB7) |
What is new in invasive lobular carcinoma?
Refining the histopathology of ILC
The immune microenvironment of ILC
The genomic landscape of ILC and its morphological variants
Mutational drivers of therapy resistance in ILC progression
Molecular prognostication
Test | Ref. | Cohort | Results | Study conclusion | |
---|---|---|---|---|---|
GGI/MapQuantDx™ | [89] | 166 ILC | Test outperformed grade | Prognostic value in ILC | |
MammaPrint | [90] | 217 ILC | Independent value of MammaPrint, specifically in lymph node-negative ILC | ||
[91] | 487 ILC (255 CILC) | 10.2% CILC and 22.8% of ILC variants were high risk | Prognostic value in ILC | ||
OncotypeDx | [55] | 353 ILC | 20% low-, 72% intermediate-, and 8% high-risk score | ILC more likely low/int score but 5-year DMFS equivalent to non-ILC | |
[92] | 30 ILC | All ILC low or int risk | Questions utility in ILC; more data required | ||
[93] | 97 ILC | 1% of ILC (non-pleomorphic) record high-risk RS | Questions utility in ILC; more data required | ||
[94] | 102 ILC | Different RS distribution in ILC v IBC-NST | More data required | ||
[95] | 59 ILC | 50% ILC in low risk | More data required | ||
[96] | 9037 ILC | SEER data | 38.1% ILC intermediate risk; 2.4% high risk | More data required | |
[97] | 7316 ILC | SEER data | 72% ILC in intermediate-risk group; 8% high risk | Adjuvant Ctx did not confer survival benefit to int or high risk; note LN+ cases included | |
[98] | 49,819 ILC | Genomic Health clinical lab 2004–2017 | 63.9% ILC in low risk, 33.6 in intermediate, 2.5% in high risk | Classic ILCs have lower average RS (16.3) compared to IDC (18.4) and ILC variants (18.2), and lower rate of tumours with high scores (2.5% vs. 10.7% vs. 8.4%, respectively) | |
Prosigna | [99] | 341 ILC | Danish Breast Cancer Group | ILC had poorer 10-year DR rates than ROR matched IDC | Prognostic value in ILC |
EndoPredict/EPClin | [100] | 470 ILC | TransATAC and ABCSG-6/8 | 63.4% were low EPClin risk group (a 10-year DR risk of 4.8%) compared to 172 (36.6%) women in the high-risk group (110-year DR risk of 26.6%) | Significant prognostic value; Ctx in low-risk group not indicated |