The longest DMFS was observed in the Luminal A (LUMA) subtype (mean 39 months) whereas the shortest was seen in the HER2-positive (HER2+) subtype (mean 21 months; p = 0.012).
This comparison showed that immunohistochemical bio-profiles select those cases not associated with high risk-of-recurrence of disease (luminal-A/B and luminal A/B Bcl2) and those that are instead at high risk and therefore worthy of chemotherapy (luminal-B ki67 and luminal-B Bcl2/Ki67), strongly suggesting to only submit PGR-positive/Bcl2-Ki67 altered cases to Oncotype Dx, thus reducing the number of cases to be tested.
In study group 2, the KRAS variant was significantly enriched in women with triple-negative breast cancer (19 [21%] of 90 cases) compared with 64 (13%) of 478 for luminal A, 13 (15%) of 87 for luminal B, and two (6%) of 35 for HER2-positive subgroups (p=0.044).
Basal and HER2 subtype patients had higher histologic grades (Grade 3 = 75% vs. 10% LA/LB; P < .001), larger tumors (13.0 mm basal vs. 10.7 mm LA/LB; P = .059), and were more likely to receive chemotherapy (68% vs. 15% LA/LB; P < .001).
By clinical subtype, the take rate was 51.3% (20/39) in triple negative (TN) breast cancer, 26.5% (9/34) in HER2+, 5.0% (2/40) in luminal B and 0% (0/3) in luminal A.
Determination of PgR expression combined with that of Ki-67 could thus improve the accuracy of IHC-based classification of luminal A and luminal B breast cancer, especially for postmenopausal women.
We classified breast cancer cases into four subtypes using information on tumor marker expression such as estrogen receptor (ER), progesterone receptor (PR), and Cerb2 receptor (HER2); luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2-overexpressing (ER-, PR-, and HER2+), and triple-negative (ER-, PR-, and HER2-).
When combining both cohorts, worse survival was found for patients with CCND1-amplified tumours in luminal A (HR = 1.68; 95% CI, 1.15-2.46), luminal B (1.37; 1.01-1.86) and ER+/LN-/HER2- (1.66; 1.14-2.41) subgroups.
Intrinsic subtypes were defined as follows: Luminal A, ER or PR >0%, HER2-negative, PR >10% and Ki67 < 14%; Luminal B, ER or PR >0%, (PR ≤10% or HER2-positive or Ki67 ≥ 14%); HER2E, ER 0%, PR 0%, HER2 positive; Core basal, ER 0%, PR 0%, HER2 negative and EGFR positive.
Among the 298 tumors, the immunohistochemical panel classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2 enriched, and 36 (12%) as TNBC.
We found that 1) the luminal group (luminal A and luminal B) are clustered together, as well as the basal group (basal-like and HER2+) and 2) luminal A and luminal B are more close to each other than basal-like and HER2+ to each other.
NBRST IHC/FISH HR+/HER2- breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type.
The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched.
Comprehensive transcriptional profiling studies have revealed at least 4 principal subtypes that, in practice, are often distinguished by immunohistochemical staining of the estrogen receptor (ER), progesterone receptor (PR), and HER2, along with a determination of histologic grade or Ki-67 staining: luminal A (ER+/HER2-/grade 1 or 2), luminal B (ER+/HER2-/grade 3), HER2 enriched (any HER2+ tumor), and basal like (ER-/PR-/HER2-).
With the advent of microarray-based gene expression profiling, unsupervised analysis methods have resulted in a classification of ER-positive disease into subtypes with different outcomes (ie, luminal A and luminal B); subsequent studies have demonstrated that these subtypes have different patterns of genetic aberrations and outcome.
The aims of the current study were (1) to analyze invasive breast carcinomas using standardized 4-IHC and quantitative image analysis and (2) to compare the results obtained in the classification of biological subtypes using current Ki67 and PR threshold values proposed by different authors to sub-classifying the luminal A-like and the luminal B-like (HER2-negative) subtypes.
Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal- like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia.
Investigation of antiapoptotic Bcl-2 family members in clinical breast cancer datasets revealed greater expression and more frequent gene amplification of <i>MCL1</i> as compared with <i>BCL2</i> or <i>BCL2L1</i> (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like.
In BC, the classification of tumors as either ERα+ (Luminal A and Luminal B), HER2+ (ERα+ or ERα-) or triple-negative (TNBC)(Basal-like, claudin-low) guides both prognostication and therapy.
From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes.
Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like breast cancer (ER-, PR-, HER2-, HER1, or CK 5/6+), and one SNP (rs3104746) was associated with both.
On the other hand, low RECQL1 mRNA was linked to intClust.8 [luminal Aestrogen receptor-positive (ER<sup>+</sup>) subgroup; P = 0.0455] and intClust.9 (luminal B ER<sup>+</sup> subgroup; P = 0.0346) molecular phenotypes.
Five tumor subtypes were defined according to hormonal receptors (HR) and Her2: Luminal A (HR + Her2- Grade 1-2), Her2 (Her2+ HR-), Triple-negative (HR- Her2-), Luminal B Her2- (HR + Her2- Grade 3), Luminal B Her2+ (HR + HER2+).