Association of Oncotype-DX HER2 Single Gene Score With HER2 Expression Assessed by Immunohistochemistry in HER2-low Breast Cancer.

Background/Aim: "HER2-low" is an emerging subtype of breast cancer, with a documented role in predicting response to treatment with novel antibody-drug conjugates. It is defined based on immunohistochemistry, but increasing evidence is challenging this approach as appropriate for identifying the HER2-low subgroup, due to both interobserver variability and limitations of the method itself. Patients and Methods: We retrospectively analyzed data from 430 patients from our departmental databases who had been subjected to an Oncotype-DX score and assessed the correlation of the Oncotype-DX HER2 single-gene score with the HER2 expression on immunohistochemistry. The Oncotype-DX Recurrence Score was also evaluated in the HER2-0 versus HER2-low subgroups. Results: The HER2 single-gene score was found to accurately correlate with the HER2 result on immunohistochemistry, with a statistically significant difference both between HER2-0 and HER2 +1 tumors (p<0.0001), as well as between HER2 +1 and +2 tumors (p<0.0001). There was no statistically significant difference in the recurrence score between the HER2-0 and the HER2-low subgroups. Conclusion: Oncotype-DX single-gene scores for HER2 are a potential surrogate marker for assessing the precise HER2 status, with better reproducibility and less interobserver variance compared to immunohistochemistry. The use of rt-PCR emerges as an alternative method of assessment of the HER2-low subgroup.

Prognostic Significance of Low HER2 Expression in Patients With Metastatic Hormone Receptor-positive Breast Cancer Treated With First Line CDK4/6 Inhibitors: A Greek Multicenter Real-world Data Analysis.

BACKGROUND/AIM: Low expression of HER2 has defined a new "HER2-low" subgroup of breast cancer with distinct clinicopathological characteristics and both prognostic and predictive implications. The impact of low HER2 expression in metastatic hormone receptor-positive HER2-negative breast cancer treated with first-line CDK4/6 inhibitors has not been studied. Using real-world patient data, we aimed to identify prognostic differences in this patient population according to HER2 expression with immunohistochemistry. PATIENTS AND METHODS: We retrospectively analyzed 191 patients from 5 Oncology Department databases in Thessaloniki, Greece, with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors in the first line, for whom detailed immunohistochemical HER2 data could be retrieved. RESULTS: Median progression-free survival was numerically different among the different HER2 subgroups (3.35 years for HER2 0 tumors, 2.18 years for HER2 +1 tumors, 1.74 years for HER2 +2/ISH-negative tumors), but this difference was not statistically significant (p=0.477). Median PFS was statistically significantly longer in patients without visceral metastases (5.45 years) compared to patients with visceral metastases (1.61 years) (p=0.017). Median PFS was also statistically significantly longer in patients taking an aromatase inhibitor (2.99 years) compared to patients taking fulvestrant (1.33 years) (p<0.0001). There were no statistically significant differences in the other subgroups examined. CONCLUSION: CDK4/6 inhibitors are equally effective as first-line treatment agents, regardless of the exact level of HER2 expression. Numerical differences, however, do exist among the different HER2 subgroups, and merit further evaluation in future studies to better study this phenomenon.

Prognostic Significance of Low HER2 Expression in Patients With Early Hormone Receptor Positive Breast Cancer.

BACKGROUND/AIM: A possible role of antibody-drug conjugates against tumors with low HER2-expression, leads to the emergence of a new "low-HER2" classification in breast cancer, encompassing tumors from the hormonal-receptor-positive and the triple-negative subgroups. There is a need for data (clinical trial data and real-world evidence) that will accurately describe this population, the risk of recurrence and the possible benefit of HER2 targeted therapies. PATIENTS AND METHODS: We retrospectively analyzed 949 patients from our Department databases, with hormonal receptor-positive and HER2-negative early breast cancer, for whom detailed data for immunohistochemical HER2-staining could be retrieved. RESULTS: HER2-low expression was detected in 66.6% of patients (472 IHC +1 and 160 IHC +2 and ISH-negative). Lobular, or mixed lobular and ductal cancers had a statistically significantly lower chance of being HER2-low when compared to pure infiltrative ductal carcinomas (53.1% vs. 69.3% respectively). HER2-low status was not prognostic for recurrence-free survival or response to neoadjuvant chemotherapy. There was a non-significant trend for increased risk of recurrence for HER2-low, compared to HER2-0, in patients with lobular or mixed lobular and ductal carcinomas (HR=2.192, 95% CI=0.819-5.912). CONCLUSION: Low expression of HER2 in hormonal receptor-positive early breast cancer does not affect prognosis but may lead to a shorter progression-free-survival in lobular and mixed ductal and lobular cancers. Despite optimal management, a large proportion of hormonal receptor-positive patients will relapse. Targeting HER2 in HER2-low cancers may offer a potential additional treatment strategy to improve survival of this group.

Cardiac safety of neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel/pertuzumab/trastuzumab for HER2-positive breast cancer patients.

PURPOSE: Early-stage, HER2-positive breast cancer is increasingly treated with neoadjuvant chemotherapy (NAC). After the positive results of the Neosphere trial, the standard of care has been the combination of chemotherapy with two anti-HER2 agents, trastuzumab and pertuzumab. Many oncologists use the sequence of four cycles of anthracycline-containing regimen followed by four cycles of taxane with the two monoclonals. We report here the cardiac safety of four cycles of epirubicin with cyclophosphamide followed by four cycles of docetaxel with trastuzumab and pertuzumab, given at the neoadjuvant setting in early, HER2-positive breast cancer. METHODS: We retrospectively collected data from the medical records of patients treated at our clinic between 2014 and 2020. RESULTS: It total, 55 patients treated with the same regimen were identified. There were 20 estrogen receptor (ER)-negative and 35 ER-positive patients. Complete pathologic response was observed in 64.8% of the patients. After a median cardiac follow-up of 2.61 years, and a total of 283 echocardiograms, there was only one recorded asymptomatic Left Ventricular Ejection Fraction (LVEF) fall > 25% and no symptomatic left ventricular systolic dysfunction. LVEF consistently dropped during treatment, but the drop was not significant enough to necessitate treatment interruption, and improved during follow-up. CONCLUSION: Our data confirm the effectiveness and cardiac safety of the aforementioned neoadjuvant regimen.

Breast cancer in women younger than 35 years old.

PURPOSE: Women ≤ 35 years old with breast cancer constitute a special group. Considering the impact of the disease and its prognosis, these patients face some specific problems that are not present in older women. What are the prognostic features of the survival rate in very young women with breast cancer? METHODS: Retrospective analysis of very young women with breast cancer from the Surgical-Oncologic Breast Cancer Department at "Theagenio" Anticancer Hospital, 2003-2016. Patient and tumor characteristics, treatment options and follow-up information were collected. Univariate-multivariate analyses were conducted and survival rates were calculated. RESULTS: The median age was 34 years old. 53 patients (41%) had T1, 36 (28%) had T2, 7 (5.4%) had T3 and 33 (25.6%) had T4 stage tumors. Most women, 114 (88.4%), had ductal carcinoma in their histology. Furthermore, positive axillary lymph nodes were present in 62 women (48%). In the immunochemistry report, 91 patients (70.5%) were hormone receptor positive, HER2 was overexpressed in 32 patients (24.8%) and 27 patients presented with triple-negative subtype. Out of 65 patients tested for Ki-67, 51 (78.5%), had a high expression (cut-off value of 20%). After adjusting for all possible factors, the risk of recurrence and death was six times higher in the positive lymph node group, (p < 0.001). The median disease-free and overall survival was 133 and > 173 months, respectively. CONCLUSION: Breast cancer in very young women appears with large size and high-grade tumors, high incidence of infiltrated axillary lymph nodes, high Ki-67 expression and intrinsic subtypes with poor prognosis. As a result, these women need to be treated by a multidisciplinary team.

Immune checkpoint inhibitor-induced musculoskeletal manifestations. A multicentre prospective study.

BACKGROUND: Immune checkpoint inhibitors (ICI) are anti-cancer drugs that act by enhancing anti-tumour immunity. Due to their mechanism of action, they have been associated with immune related adverse events (Ir-AE), including musculoskeletal manifestations. AIM: To assess a) the prevalence, clinical and imaging (MRI) characteristics of ICI-induced musculoskeletal immune related adverse events (ir-AE) in a prospective manner, b) the potential association of musculoskeletal ir-AE with oncologic response and changes in the immune system at the level of soluble molecules (cytokines) as well as T/B cell subpopulations. METHODS: This a multicentre prospective study. We plan to recruit all patients who are going to start treatment with ICI from October 2019 until October 2020 in all collaborating Oncology Departments. This study is consisted of a clinical and a laboratory arm. RESULTS: The study is currently recruiting patients. CONCLUSIONS: We anticipate that this study will provide useful data regarding the clinical characteristics of ICI-induced musculoskeletal manifestations as well as potential predictive biomarkers.