Treatment of HER2-positive early (minimal) breast cancer

For women with stage II or III breast cancer (BC), preoperative or neoadjuvant systemic therapy has a clinically significant effect in reducing tumor size, which may influence the extent of breast and axillary surgery. In addition, the use of preoperative treatment suggests individualization of therapy depending on the degree of therapeutic pathomorphism, which serves as a prognostic marker and may identify women with residual tumor who will require additional adjuvant systemic therapy. In 2021, St. Gallen approved preoperative systemic therapy as an effective option for women with stage II or III HER2-positive or triple-negative breast cancer (TNBC). Neoadjuvant therapy is preferred in stage II or III and in advanced ER-positive breast cancer. Ten years ago, it was proposed to use predictive measurement of pCR as an endpoint for accelerated approval of treatment regimens in the neoadjuvant setting. Despite dozens of randomized trials with different regimens, only one drug (pertuzumab) has received pCR approval to date. Gallen-2021 Audience and Panel of experts were asked: Is pCR an appropriate endpoint to define standard treatment regimens for early breast cancer? Panel of experts (60%) and audience (83%) believe that pCR is not an appropriate endpoint for defining standard neo/adjuvant regimens, preferring longer-term endpoints such as relapse-free or overall survival commonly used to validate new treatments treatment. But the prognosis after achieving a pathological complete response (pCR) for a particular tumor subtype is usually the same regardless of treatment used to reach that goal. In summary, two conclusions can be drawn: neoadjuvant trials aimed at evaluation of standards for treatment should include long-term follow-up with reliable relapse and survival data, and risk stratification based on pCR after neoadjuvant therapy serves as a strategy for optimizing post-neoadjuvant treatment. Neoadjuvant regimens (rastuzumab and pertuzumab in combination with taxane and/or anthracycline- or platinum-based chemotherapy) are preferred for the treatment of HER2-positive tumors. Post-neoadjuvant therapy is often selected according to the grade of residual tumor after preoperative treatment. Patients who achieve a pathological complete response (pCR) after standard neoadjuvant chemotherapy should be on standard adjuvant therapy (eg, anti-HER2 maintenance therapy). Gallen-2021 panel of experts approved the adjuvant use of trastuzumab-emtansine for patients with residual HER2-positive breast cancer following standard neoadjuvant regimens with a low threshold for treatment (including residual tumor <5 mm and ypN0). The Gallen-2020 experts do not consider that the use of capecitabine (for TNBC) or trastuzumab-emtansine (for HER2+ breast cancer) in the presence of residual invasive tumor is sufficient to avoid surgery with axillary dissection. Almost all patients with invasive breast cancer are recommended to receive adjuvant systemic therapy. The threshold for starting treatment is very low, even among malignancies without lymph node metastases. Adjuvant endocrine therapy is recommended in almost all patients with ER-positive microinvasive breast cancer or minimal tumor size (≥1 mm) to reduce the risk of distant and local recurrence, as well as secondary breast cancer. The threshold for prescribing adjuvant chemotherapy with targeted (anti-HER2 therapy) for HER2-positive breast cancer is ~5 mm. Almost half of the St. Gallen-2021 experts recommended chemotherapy and anti-HER2 therapy also for ER-negative, HER2-positive tumors <5 mm.

HER2-positive breast cancer, anti-HER2 neoadjuvant and adjuvant therapy