Early HER2-Positive Breast Cancer: Current Treatment and Novel Approaches

Abstract

<b><i>Background:</i></b> Trastuzumab significantly improves outcomes in early HER2-positive breast cancer, irrespectively of any prognostic or predictive factors. Unfortunately, about a quarter of patients receiving neoadjuvant trastuzumab experience disease recurrence, revealing the unquestionable need for further improvement of treatment outcomes. <b><i>Summary:</i></b> Adding HER2 blockade to adjuvant trastuzumab with pertuzumab and neratinib improves invasive disease-free survival (IDFS), particularly for those at highest risk of recurrence. A shift toward a neoadjuvant strategy for patients with a higher risk of recurrence could result in further treatment optimization. For patients without a pathological complete response (pCR) after the neoadjuvant part of the therapy, a switch to adjuvant trastuzumab emtansine significantly improves IDFS and distant recurrence-free survival and shows a trend towards improved overall survival (OS). On the other hand, for low-risk patients, chemotherapy deescalation should be strongly considered with the use of trastuzumab monotherapy as an anti-HER2 backbone. <b><i>Key Messages:</i></b> Neoadjuvant therapy should be offered for a significant proportion of HER2-positive early breast cancer patients with a higher risk of recurrence. Postneoadjuvant treatment should be tailored according to the initial stage of disease and the response to neoadjuvant treatment.

Safety and Clinical Evaluation of Dual Inhibition with Pertuzumab and Trastuzumab Biosimilar SB3 in HER2-Positive Breast Cancer Patients

“…The latter was a conditional approval which had to be confirmed in the positive adjuvant Aphinity trial [16]. All these trials led to wide implementation of the combination in HER2-positive patients [17]. Thus, it can be expected that trastuzumab biosimilars will be widely implemented in this combination to lower the total costs of the treatment.…”

“…In the phase III CLEOPATRA trial, the combination of pertuzumab with trastuzumab and docetaxel improved progression-free survival and overall survival when compared to trastuzumab and docetaxel alone [12,13]. The efficacy and safety of both HER2-directed agents in combination with chemotherapy was also confirmed in the neoadjuvant setting, demonstrating low rates of CD when pertuzumab and trastuzumab were given in combination with anthracycline-free chemotherapy, but also with anthracycline-containing regimens [14][15][16][17]. Cardiac safety was confirmed in a 5-year follow-up [18].…”

The benefits of trastuzumab in the treatment of HER2+ breast cancer as a function of exposure time

“…Trastuzumab is a turning point in treating breast cancer patients with HER2 overexpression/amplification [ 8 ]. Its implementation leads to improved DMFS [ 20 ], DFS [ 8 , 20 ], OS [ 8 ] and even locoregional relapse-free survival [ 20 ].…”

“…Trastuzumab is a turning point in treating breast cancer patients with HER2 overexpression/amplification [ 8 ]. Its implementation leads to improved DMFS [ 20 ], DFS [ 8 , 20 ], OS [ 8 ] and even locoregional relapse-free survival [ 20 ]. This retrospective study demonstrated that trastuzumab is the leading systemic therapy associated with improved outcomes, even compared to an adequate multimodal systemic treatment.…”

“…Historically, HER2 overexpression/amplification is related to the worst outcome in breast cancer patients [ 7 ]. However, the development of targeted trastuzumab therapy has caused a revolution in the prognosis of these patients [ 8 ]. Trastuzumab is a neutralising monoclonal antibody that mainly leads to HER2 blockade, by impeding its signalling pathway activation, which is associated with cell proliferation and survival [ 9 ].…”