Targeting HER2 in Breast Cancer: Latest Developments on Treatment Sequencing and the Introduction of Biosimilars
AbstractApproximately 20% of all breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). Targeting breast cancer through this vital oncogenic protein has been a major step towards improved patient outcomes. Today, several anti-HER2 agents are in clinical use including: the monoclonal antibodies trastuzumab and pertuzumab; the small molecule inhibitors lapatinib, neratinib, and tucatinib; and the antibody –drug conjugates ado-trastuzumab emtansine and trastuzumab deruxtecan, in some jurisdictions. In addition, several trastuzumab biosimilars have recently been granted regulatory approval in North America and the EU, and are enhancing patient access to HER2-directed therapy. The various agents diffe r greatly in their side-effect profiles and approved indications, from neoadjuvant and adjuvant use in early disease, to first- and later-line use in metastatic disease. This review discusses the current treatment recommendations for the use of anti-HER2 agents alone and in combination, examines the latest advances in HER2-targeted drugs and how they may be best applied in clinical practice, and provides guidance on optimal sequencing of the growing array of therapeutic options for HER2-positive breast cancer.
AbstractIntroductionPrediction models are useful to guide decision making. Our goal was to compare three published nomograms predicting axillary response to neoadjuvant chemotherapy (NAC), clinically node-positive breast cancer.MethodsPatients with cT1 –T4, cN1–N3 breast cancer treated with NAC and surgery from 2008 to 2019 were reviewed. The predicted probability of pathologic node-negative (ypN0) status was estimated for each nomogram. Area under the curve (AUC) was compared across models, overall and by biologic subtype.ResultsOf 581 patients, 253 (43.5%) were ypN0. ypN0 status varied by subtype: 23.9% for e...
We reported nodal and breast downstaging rates with NET, and compared axillary response rates following NET and neoadjuvant chemotherapy (NAC).MethodsConsecutive stage I –III breast cancer patients treated with NET and surgery from January 2009 to December 2019 were identified from a prospectively maintained database. Nodal pCR rates were compared between biopsy-proven node-positive patients treated with NET, and HR+/HER2- patients treated with NAC from November 2 013 to July 2019.Results127 cancers treated with NET and 338 with NAC were included. NET recipients were older, more likely to have lobular and lower-grade...
CONCLUSION: The probability of nodal positivity after neoadjuvant chemotherapy was less than 3 per cent in patients with TNBC or HER2-positive disease who achieved a breast rCR on MRI. These patients could be included in trials investigating the omission of sentinel node biopsy after neoadjuvant chemotherapy. PMID: 33031572 [PubMed - as supplied by publisher]
Conditions: HER2-positive Breast Cancer; Stage I Breast Cancer Intervention: Biological: Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination Sponsors: Fundacio Clinic Barcelona; SOLTI Breast Cancer Research Group; Roche Pharma AG Recruiting
Conditions: HER2-negative Breast Cancer; Neoadjuvant Chemotherapy Interventions: Drug: Epirubicin; Drug: Cyclophosphamid; Drug: Docetaxel; Drug: Paclitaxel Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University Recruiting
ConclusionsThis retrospective study demonstrated that age at diagnosis was independently associated with IBTR-free survival. Special caution is needed when clinical trials analyzing omission of breast surgery after NAC are enrolling younger patients (UMIN-CTR No. UMIN000037067).
Background: Breast cancer molecular subtypes (Luminal A and B, Triple negative, Her2-enriched) together with histology-based parameters (i.e. grading) are pivotal in understanding how tumor response is related to relapse risk and would help clinicians make decisions about additional treatment options after neoadjuvant chemotherapy (NCT). Different methods can be used to assess ER/PR status (Allred score, H score, semiquantitative score). Mitotic index (MI) can be performed on conventional histology or by using immunohistochemistry for phosphohistone H3 (PHH3).
Background: PIK3CA mutations are known to be associated with a reduced pathological complete response (pCR) rate in HER2+ breast cancer, but the relationship between PIK3CA mutations and the therapeutic effects of neoadjuvant chemotherapy in hormone receptor (HR) -positive or HR −/HER2− breast cancer is not clear. We herein analyzed PIK3CA mutations in primary breast cancers of patients who had undergone neoadjuvant chemotherapy. We also investigated the associations of these mutations with the therapeutic effects of neoadjuvant chemotherapy.
Background: HER2 is amplified approximately 20% of breast cancers and HER2 receptor targeting therapy is associated with a significant improvements in disease-free and overall survival. In NeoSphere and TRYPHAENA clinical trials, the pathologic complete remission (pCR) rate was significantly increased when combined with pertuzumab and trastuzumab treatment. Although the efficacy and safety of anti-HER2 dual blockade therapy has been reported, the markers that predict the response are still unclear.