Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.

Human epithelial growth factor receptor 2 (HER2) overexpression and/or amplification is of predictive and prognostic value in infiltrating breast carcinoma (IBC). We evaluated the proportion of HER2-positive cases (score 3 overexpression/score 2 plus fluorescence in situ hybridization (FISH) amplification) in a consecutive series of 2163 patients. According to immunohistochemical analysis of HER2 expression, using Herceptest and FDA criteria, 839 cases had score 0, 476 score 1+, 699 score 2+, and 149 score 3+. Of the 699 scoring 2+ cases, 160 (22.88 %) showed Her2 gene amplification by FISH analysis, making a total of 309 (14.28 %) HER2-positive cases. Grade 1 ductal and special type IBC were never HER2 positive, while only three infiltrating lobular carcinomas but a relevant percentage of small IBC were HER2 positive. Of HER2-positive cases, 52.1 % was pT1 and of these, 38.5 % was pT1b or smaller. Logistic regression analysis revealed that estrogen receptor (ER), progesterone receptor (PgR), grade, and pT were significantly associated with HER2 positivity and that HER2 3+ cases were more frequently of higher grade and pT than HER2 2+/Her2 amplified cases. In addition, HER2 3+ cases were more frequently in ER and PgR negative than HER2 2+/Her2 amplified cases. We conclude that the proportion of HER2 positive cases is lower than that reported in older literature and that pathological characteristics differ between HER2 3+ and HER2 2+/Her2 amplified cases.

Goal of this study was to asses the performance of Aperio computer-assisted analysis for HER2 immunohistochemical measurement in 292 equivocally (score2+) HercepTest immunoreactive breast cancer cases, evaluated by an experienced pathologist and analyzed with fluorescent in situ hybridization (FISH). The automatic Aperio categorization and the percentage of immunoreactive cells as evaluated by the computer and by the pathologist were recorded. Computer-assisted analysis classified 7 (2.4%) cases as negative (0), 136 (46.6%) as faintly positive (1+), 134 (40.5%) as moderately positive (2+), and 15 (5.1%) as strongly positive (3+). Correlative component analysis (CCA) classification is associated with Her2 amplification (P<0.0001). Compared with the human evaluation, automated CCA classification would save 157 (58%) FISH analyses, while not identifying 15 amplified cases (6% false-negative rate). The mean computer percentage value (CPV) is 18.44% standard deviation ±19.00 (range, 0.01 to 76.10). CPV and the pathologist percentage value are significantly associated and correlated (P<0.001) and have similar sensitivity and specificity in identifying Her2 FISH-amplified cases. CPV has a very low interobserver variation. The difference in CPV in amplified and nonamplified subgroups is statistically significant (P<0.001). Receiver operating characteristic analysis indicates that CPV is good at separating FISH nonamplified from amplified cases (P<0.001). The optimal cut-off value maximizing both sensitivity and specificity is 17.6% (sensitivity=73.3%, specificity=71.6%). Using a different cut-off value (2% of positive cells) we would have missed only 3 amplified cases (1% false-negative rate) while not submitting to FISH 52 cases (18% of the whole series). This false-negative rate is well below the expected false-negative rate usually observed in score 1 cases, supporting the use of CCA with a modified cut-off value in routine diagnostics for equivocally stained HER2 cases.

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BACKGROUND: IBC is a heterogeneous disease with several subtypes molecularly identified by gene expression profile. Since subtypes defined by immuhistochemistry (IHC) panel are similar although not identical to molecular subtypes, IHC may represent an easier alternative to identify them. PURPUSE: To assess the clinical outcomes of pts who received NC for IBC and the differences by IHC-related subtypes. METHODS: We retrospectively reviewed the clinical records of the pts treated with NC for stage II-III IBC from 2000 to 2013. For each pt we recorded baseline tumor size, type of NC [which consisted of anthracyclines (A) + taxanes (T) in HER2- and T + trastuzumab (H) ± A in HER2+ pts), type of surgery, pathological response (pCR defined as the absence of invasive cells in the breast and the lymph nodes regardless of DCIS). IHC subtypes were defined according to ER and PgR expression, Ki-67 level, and HER2 status: Luminal A (LA): ER and PR+, neg HER2 and Ki67&lt; 14% (= 3%) Luminal B (LB): ER and/or PR+, neg HER2 and Ki67≥14% (=30%) Luminal HER2 (LHER2): ER and/or PR+, positive HER2 and any Ki67 (=27%) HER2 positive (HER2+): neg ER and PR, positive HER2 and any Ki67 (=12%) Triple negative (TN): neg ER and PR, neg HER2 and any Ki67 (13%) Unknown subtype in 33 cases (15%) The loco-regional and distant RFS and OS were evaluated according to pCR. pCR and survival outcomes were also assessed on the basis of both pre- and post- NC Ki67 levels. RESULTS: In the consecutive series of 213 pts who received NC median age was 50 yrs (r. 25-75). The NC consisted of an A+T based regimen in HER2 negative (145 pts) and of a T+ H with A (31 pts) or without A (34 pts) in HER2+ disease. Only 14 did not receive surgery: 10 for distant metastases development and 4 because still on NC. Quadrantectomy was performed in 120 pts (60%). Among all pts, pCR was achieved in 44 pts(22%) with further 4 pts showing a RT ≤1 mm. Relationship between pCR and subtypes, ki67 and recurrence rate LA (%)LB (%)LHER2 (%)HER2+TN (%)Median Ki67 (%)Recurrence Rate (%)pCR012.542.527.517.5484.5No pCR10042.329.28.814.63731.5p Value    &lt;0.001 =0.001 All but 19 HER2+ pts (84) received H obtaining pCR in 38% of cases regardless chemotherapy type (A-based 35% vs Not A- 38%) The median follow-up was 45 months (range 1-166 ms). The 4y-RFS and OS were better in which achieved pCR than those did no (RFS 92 vs to 74%; p=0.0014 and OS 95 vs 78%; p=0.0074). Median Ki67 in pretreated core biopsy was 40 compared to 27% in post-NC RT. Patients with high (&gt;30%) post-NC Ki67 levels showed significantly higher risk for disease relapse (4 y-RFS 60%; p=0.0019) and death (4y OS 71%; p=0.018) compared with patients with &lt;15% (4y-RFS 93 and OS 88%) or &gt;15-30 Ki67 levels (4y-RFS 83 and OS 82%). CONCLUSIONS: According to literature data, pts achieving pCR after NC showed better RFS and OS compared to no pCR pts. The pCR rate was significantly higher in aggressive subtypes (HER2 and TN). In HER2 disease, pCR was achieved by using chemo + H, irrespective of A-addition. Interestingly high pre-NC KI67 levels seem to predict the possibility obtaing pCR, while post-NC Ki67 levels seem to be of prognostic value in pts who do not receive pCR. Citation Format: Antonella Ferro, Alessia Caldara, Mariachiara Dipasquale, Chiara Trentin, Renza Triolo, Mattia Barbareschi, Daniela Bernardi, Marco Pellegrini, Daniela Cazzolli, Gabriella Berlanda, Fabio Gasperetti, Francesca Maines, Paolina Tuttobene, Orazio Caffo, Enzo Galligioni. Clinical outcomes according to pathological complete response (pCR) and proliferation index of residual tumor (RT) after neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-06.