Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival.

PURPOSE: Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. METHODS AND MATERIALS: Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). RESULTS: Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P = .02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P = .02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). CONCLUSIONS: The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

In a cohort of breast cancer screened patients the proportion of HER2 positive cases is lower than that earlier reported and pathological characteristics differ between HER2 3+ and HER2 2+/Her2 amplified cases.

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.

Diagnostic value of automated Her2 evaluation in breast cancer: a study on 272 equivocal (score 2+) Her2 immunoreactive cases using an FDA approved system.

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.