HER2 evaluation process for neoadjuvant targeted therapies in breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3034-3034
Author(s):  
Yoshio Mizuno ◽  
Naoko Takeda ◽  
Junichi Yamada ◽  
Hiroaki Abe ◽  
Yuko Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Targeted Therapies ◽  
False Negative ◽  
Fish Analysis ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Surgical Specimen ◽  
Amplification Ratio ◽  
Her2 Testing

3034 Background: Treatment with a combination of HER2-targeted therapies has emerged as an addition of trastuzumab to neoadjuvant chemotherapy regimens in breast cancer patients and it goes on increasing. For clinical HER2 determination, immunohistochemical (IHC) analysis is an attractive method and all IHC 2+ cases are categorized as equivocal and should be reflexed to fluorescence in situ hybridization (FISH) testing. However, research in recent years with respect to false-negative cases for HER2 testing have been reported, and it comes to the question of what considering the indication for trastuzumab in the neoadjuvant chemotherapy. To clarify these controversial points in applying the results of HER2 testing in the clinical setting, we performed a retrospective analysis of core needle biopsy (CNB) and surgical specimen results. Methods: 422 patients underwent primary operations for early breast cancer at Tokyo-West Tokushukai Hospital (Tokyo, Japan) from October 2008 to December 2012. Among these patients, 262 patients who received CNB prior to operation were enrolled. Those patients who received preoperative chemotherapy or had DCIS were excluded. With regard to diagnostic criteria, HER2 positivity was defined as either 3+ by IHC or FISH analysis amplification ratio of ≥2.2. In addition, if in any cases which CNB samples or surgical specimens showed HER2-positive had defined true HER2-positive cases, we assessed the false-negative results of the HER2 test via IHC using CNB samples and surgical specimens. Results: In a matched cohort of 262 patients, 59 cases showed HER2-positive (five cases were CNBs negative to surgical specimens positive, 14 cases were CNBs positive to surgical specimens negative, and 40 cases were both positive). If we decide for selection of trastuzumab target cases by CNBs only, we make mistakes in indications of trastuzumab for five (8.5%) of 59 HER2-positive cases who were CNBs negative to surgical specimens positive. Conclusions: There are quite a few cases show false negatives for HER2 testing in CNB samples. In cases of considering the indication for trastuzumab in the neoadjuvant chemotherapy, even if the CNB samples resulted in negative, we consider that retesting with FISH analysis should be carried out.

scholarly journals Adapted Physical Activity for Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Trastuzumab Against HER2 (APACAN2): A Protocol for a Feasibility Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Angeline Ginzac ◽  
Maureen Bernadach ◽  
Ioana Molnar ◽  
Martine Duclos ◽  
Emilie Thivat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Neoadjuvant Chemotherapy ◽  
Physical Activity Program ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Activity Program ◽  
Home Based ◽  
Positive Breast Cancer

BackgroundThe standard care for HER2-positive breast cancer is chemotherapy plus a HER2-directed therapy. This can lead to treatment-induced cardiotoxicity. On the other hand, the practice of physical activity is known to improve cardiac function; thus HER2-positive breast cancer patients could draw particular benefit from physical activity during treatment. However, at the time of diagnosis for breast cancer, the majority of patients are insufficiently active according to physical activity recommendations of World Health Organisation, and it is difficult to remain or become active during the treatment. There is a lack of data in the literature on the optimal program to propose to patients to encourage them to be active during treatment. The aim of our study is to assess the feasibility of a home-based physical activity program during neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer.MethodsThe APACAN2 study is a single-centre, non-randomized interventional trial. Patients with HER2-positive breast cancer treated with anthracycline-based neoadjuvant chemotherapy and trastuzumab are eligible for enrolment. The supervised home-based physical activity program takes place during neoadjuvant chemotherapy (NACT). It combines aerobic and strengthening exercises. The primary endpoint is the proportion of patients reaching the international physical activity recommendations, i.e. 150 minutes of moderate-intensity activity per week at the end of NACT. The study started in April 2018 and seventy patients are expected to be recruited.DiscussionIn the literature, the majority of studies on practice of physical activity in breast cancer focus on adjuvant chemotherapy or on the period after the end of treatment. To the best of our knowledge, the APACAN2 study is the first to evaluate a home-based physical activity program during neoadjuvant chemotherapy for HER2-positive breast cancer.Trial Registration NumberClinicaltrials.gov: NCT02963363, registered on July 11, 2016. Identifier with the French National Agency for the Safety of Medicines and Health Products N°ID RCB 2016-A01344-47, registered in August 2016. Protocol: version 8, 24 February 2021.

scholarly journals Minimally Invasive Complete Response Assessment of the Breast After Neoadjuvant Systemic Therapy for Early Breast Cancer (MICRA trial): Interim Analysis of a Multicenter Observational Cohort Study

2020 ◽  
Author(s):  
Ariane A. van Loevezijn ◽  
Marieke E.M. van der Noordaa ◽  
Erik D. van Werkhoven ◽  
Claudette E. Loo ◽  
Gonneke A. O. Winter-Warnars ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Therapy ◽  
Triple Negative ◽  
False Negative ◽  
False Negative Rate ◽  
Complete Response ◽  
Ultrasound Guided ◽  
Her2 Positive ◽  
Surgical Specimen ◽  
Neoadjuvant Systemic Therapy

Abstract Background The added value of surgery in breast cancer patients with pathological complete response (pCR) after neoadjuvant systemic therapy (NST) is uncertain. The accuracy of imaging identifying pCR for omission of surgery, however, is insufficient. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI. Methods We performed a multicenter, prospective single-arm study in three Dutch hospitals. Patients with T1–4(N0 or N +) breast cancer with MRI rPR and enhancement ≤ 2.0 cm or MRI rCR after NST were enrolled. Eight ultrasound-guided 14-G core biopsies were obtained in the operating room before surgery close to the marker placed centrally in the tumor area at diagnosis (no attempt was made to remove the marker), and compared with the surgical specimen of the breast. Primary outcome was the false-negative rate (FNR). Results Between April 2016 and June 2019, 202 patients fulfilled eligibility criteria. Pre-surgical biopsies were obtained in 167 patients, of whom 136 had rCR and 31 had rPR on MRI. Forty-three (26%) tumors were hormone receptor (HR)-positive/HER2-negative, 64 (38%) were HER2-positive, and 60 (36%) were triple-negative. Eighty-nine patients had pCR (53%; 95% CI 45–61) and 78 had residual disease. Biopsies were false-negative in 29 (37%; 95% CI 27–49) of 78 patients. The multivariable associated with false-negative biopsies was rCR (FNR 47%; OR 9.81, 95% CI 1.72–55.89; p = 0.01); a trend was observed for HR-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95–21.73; p = 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87–1.00; p = 0.051). Conclusion The MICRA trial showed that ultrasound-guided core biopsies are not accurate enough to identify breast pCR in patients with good response on MRI after NST. Therefore, breast surgery cannot safely be omitted relying on the results of core biopsies in these patients.

Prognostic factors in breast cancer patients evaluated by PET/CT prior to neoadjuvant chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12113-e12113
Author(s):  
Mark K Farrugia ◽  
Geraldine M. Jacobson ◽  
Mohamad Adham Salkeni
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Triple Negative ◽  
Primary Breast Tumor ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Pet Ct ◽  
Pre Treatment

e12113 Background: Neoadjuvant chemotherapy (NAC) is an important modality in breast cancer treatment. We sought to identify pre-treatment prognostic factors in patients who had positron emission tomography paired with diagnostic quality contrast-enhanced CT (PET/CT) prior to neoadjuvant chemotherapy with respect to pathologic complete response (pCR) , survival and relapse-free survival (RFS). Methods: We retrospectively analyzed 118 breast cancer patients who had pre-treatment PET/CT imaging and received NAC from 2008-2014. We collected data on molecular markers, PET/CT, pCR, survival, and disease status. Results: The median follow up was 44 months(range 7.3-101.5),median age was 51 years; 47% were stage II, 53% stage III. 52% of patients had hormone receptor (HR) positive/HER2 negative disease, 31% of tumors were HER2 positive, and 17% of tumors were triple-negative. 92.5% with HER2 positive tumors received NAC containing at least one HER2 targeted agent. Pre-treatment standard uptake value (SUV) max of the primary breast tumor showed no statistically significant relationship to survival, RFS, or pCR. PET avid (>2 SUV) extra-axillary nodes such as internal mammary and supraclavicular was associated with a non-statistically significant trend towards reduced RFS (p=0.06, HR=0.13-1.06). pCR overall was 37.5% for HER2 positive tumors, 15% in triple-negative tumors, and 8% in HR positive/HER2 negative tumors. Log-rank analysis with post-hoc pairwise comparisons showed a significant difference between the RFS of triple-negative tumors and HER2 positive tumors (p=0.001), while comparison between HR positive/HER2 negative and HER2 positive was not statistically significant (p=0.11). Multivariate cox regression analysis, which included grade and stage of tumors, showed HER2 positivity to be associated with a favorable outcome (p=0.04, HR=0.22 (0.05-0.94)). Conclusions: Within this cohort, pre-treatment SUV max of the primary tumor showed no prognostic value with regard pCR or RFS. PET avid extra-axillary metastasis trended towards reduced RFS. Patients with HER2 positive tumors had the highest pCR and RFS comparable to classically favorable subgroups such as HR positive/HER 2 negative.

Rate of use of NCCN “preferred” chemotherapy regimens for the treatment of HER2 positive breast cancer.

2017 ◽  
Vol 35 (8_suppl) ◽  
pp. 163-163
Author(s):  
Eric J. Gratias ◽  
Margaret Rausa ◽  
Lee N. Newcomer ◽  
Kurt Andrews ◽  
Nick Andrews ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Treatment Options ◽  
Management Program ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Nccn Guidelines ◽  
Her2 Breast Cancer

163 Background: The National Comprehensive Cancer Network (NCCN) Guidelines represent a well-established standard of care for the treatment of HER2+ breast cancer patients. eviCore healthcare is a licensee of NCCN that uses the NCCN guidelines to support its proprietary chemotherapy management program. All regimens assigned NCCN Category of Evidence 1, 2A, or 2B are adherent treatments in the eviCore program. NCCN recommends many systemic treatment options for HER2+ breast cancer, and a limited group is designated by NCCN as “preferred” based on superior efficacy and/or safety. This study evaluated the frequency of NCCN-preferred regimen use by practicing oncologists in HER2+ breast cancer patients. Methods: Chemotherapy authorizations for all HER2+ breast cancer patients with ≥ 1 injectable drug from 4/1/2015-9/30/2016 for multiple payers were included; > 90% of authorizations occurred in United HealthCare members. Cases with incomplete data were excluded. 3685 fully evaluable cases were stratified by stage, ER/PR status, and NCCN-preferred vs. NCCN-recommended status. The frequency of NCCN-preferred regimen selection was calculated for each subgroup. Results: There were 2883 HER2+/ER+ and/or PR+ cases and 802 HER2+/ER-/PR- cases. The highest frequency of NCCN-preferred regimen use occurred in neoadjuvant chemotherapy for patients with Stage III HER2+/ER+ and/or PR+ disease, where 88% of 289 patients used an NCCN-preferred regimen. Metastatic HER2+ patients had a markedly lower rate of NCCN-preferred regimen use at 62% of 557 cases. Only 48% of 1096 patients with Stage I/II HER2+/ER+ and/or PR+ disease received NCCN-preferred regimens. Conclusions: Patients receiving neoadjuvant chemotherapy for HER2+ breast cancer receive NCCN-preferred regimens at significantly higher rates than patients receiving adjuvant chemotherapy or metastatic treatment. Less than half of patients receiving adjuvant chemotherapy are receiving NCCN-preferred regimens. Further study is needed to determine the reasons for low preferred regimen use and ways to optimize preferred regimen use in HER2+ breast cancer.

Genomic profiling of residual tumor after neoadjuvant chemotherapy for breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12106-e12106
Author(s):  
Masaya Hattori ◽  
Padma Sheila Rajagopal ◽  
Lise Sveen ◽  
Galina Khramtsova ◽  
Toshio Yoshimatsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Tissue Bank ◽  
Residual Tumor ◽  
Cancer Tissue ◽  
Genomic Profiling ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Metastatic Recurrence

e12106 Background: Patients who have residual disease after neoadjuvant chemotherapy (NAC) have a higher risk of metastatic recurrence. Residual disease likely includes therapy-resistant subclones of breast cancer cells, which untreated lead to metastases. The aim of this study was to identify additional adjuvant therapies based on genomic profiling of residual disease post NAC therapy. Methods: Next-generation sequencing of tumor samples from patients (pts) with residual invasive breast cancer after NAC was performed using a Tempus xT, 595 gene panel on matched tumor-normal samples. All samples were obtained from the University of Chicago Breast Cancer tissue bank. Clinical information was obtained from electronic health records and the cancer registry. Results: Of 23 evaluable patients enriched for African Americans, 65% were HER2-positive, 22% TNBC and 13% ER+/HER2-. At a median follow up of 2.9 years, 8 pts (35%) have recurred and 8 were dead. We identified 119 clinically actionable variants in 22 tumors, and the most commonly altered genes were TP53 (18 alterations, 74% of cases), ERBB2 (8, 26%), PIK3CA (7, 30%), CDK4 (4, 17%), MCL1 (4, 17%), and MDM2 (4, 17%). Of significance, 67% of HER2-positive pts had no detectable ERBB2 copy number gain in the residual tumor. 78% of pts had at least one potential druggable target according to CIViC and/or OncoKB: 19 variants in HER2-positive, 8 in HER2-negative. The mean estimated tumor mutation burden (TMB) was 4.34 m/MB (range: 0-26.7), and 13% were considered TMB-high ( > 9 m/MB). No patients had high-microsatellite instability type residual tumors. Conclusions: Many potentially targetable alterations reside in residual disease of both HER2-positive and -negative breast cancer after NAC. Post-NAC treatment targeting these harbored alterations and post-NAC immunotherapy could have impact on the prognosis of breast cancer patients who have residual disease after NAC. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document