Features of response to modern neoadjuvant chemotherapy with dual anti-HER2 blockade (trastuzumab and pertuzumab) in the patients with HER2-positive breast cancer stage II–III

Background. Neoadjuvant chemotherapy (NACT) with dual anti-HER2 blockade has become a priority in the treatment of patients with HER2+ breast cancer (BC) stages II–III. However, the question of the accordance of various systems for assessing tumor response to NACT, as well as identifying predictor factors for achieving a complete pathomorphological response (pCR) in HER2+ BC remains open.

Aim. To assess the accordance of various systems for assessing tumor response to neoadjuvant chemotherapy (NACT) in patients with HER2+ BC and to identify predictor factors for achieving pCR and residual cancer burden.

Materials and methods. The study included 49 women with HER2+ BC stage II–III, who underwent NACT with anti-HER2 blockade, followed by surgical treatment and morphological analysis of the results. The median age of the patients was 47 years; 91.8% had tumor size ≥T2, N+ status – 71.4%; tumor grade G3 – 73.5%, luminal and non-luminal HER2+ subtype – 44.9 and 55.1% of patients, respectively. Ki67≥30% was observed in 93.9% of cases, the level of TILs in the tumor was <10%, 10–20% and >20% – in 38.1, 9.5 and 52.4% of cases, respectively. The patients received combinations of anthracyclines and taxanes or the anthracycline-free regimen of docetaxel + carboplatin; 87.8% of patients received a dual blockade of trastuzumab + pertuzumab, and 12.2% – trastuzumab. After the end of NACT, all patients underwent a radical surgery (mastectomy or breast-conserving) with an assessment of the pathomorphological response, the pathomorphological stage of ypTN, and the residual cancer burden according to the RCB system.

Results. The rate of complete pathomorphological response (tpCR/RCB-0/ypT0N0) in HER2+ BC was 61.2%; significant predictors of achieving tpCR were only 3 factors: primary operable BC stages (T1–3N0–1) – the rate of tpCR was 71.4%, the level of TILs>20% – the proportion of tpCR reached 95.5%, and the dual anti-HER2 therapy (trastuzumab + pertuzumab) – tpCR was 65.1%. Residual tumor was presented by classes RCB-I, RCB-II, RCB-III in 10.2, 24.5, 4.1%. The RCB-I class included of patients with a residual tumor less than 1.0 cm in the absence of regional lymph node involvement (80% of cases); class RCB-II was represented by the presence of a residual tumor less than 2.0 cm in combination with the absence or presence of residual metastases in 1–3 lymph nodes (83.4%), and class RCB-III was presented the residual tumors ≥2.0 cm and N1–2 status in 100% of cases (p<0.0001).

Conclusion. Modern NACT with dual anti-HER2 blockade (trastuzumab + pertuzumab) are highly effective – the rate of tpCR is 61.2%, and in the presence of high TILs>20% reaches 95.5%. Residual tumor in most cases was presented by class RCB-I or RCB-II, only 4% of patients had massive residual tumor load (class RCB-III).