Anthracycline-free versus anthracycline-based neoadjuvant therapy in HER2-positive breast cancer: A Propensity...

Anthracycline-free TCHP and anthracycline-based AC-THP are both used as neoadjuvant dual anti-HER2 regimens for HER2-positive breast cancer, but direct comparisons accounting for HER2 immunohistochemistry (IHC) intensity are lacking. Because IHC 3+ tumors respond substantially better to dual blockade, any between-group imbalance in IHC intensity can bias observational comparisons.

In this single-center retrospective observational study, we identified HER2-positive patients treated with TCHP (n = 161) or AC-THP (n = 317) and performed 1:1 propensity score matching on seven covariates, including HER2 IHC status (3+ vs 2+/FISH-amplified), yielding 125 matched pairs. The primary endpoint was pCR (ypT0/is ypN0).

Before matching, HER2 IHC 3+ was more prevalent with AC-THP (92.4% vs 80.1%; P = .0002); after matching, all covariates were balanced (SMD ≤  0.093). pCR was comparable between TCHP and AC-THP (50.4% vs 45.6%; McNemar exact P = .519; conditional odds ratio [cOR], 1.22; 95% CI, 0.71-2.03). HER2 IHC 3+ was the strongest independent predictor of pCR (OR, 5.22; 95% CI, 2.32-11.75; P < .001); treatment assignment was not (P = .350). Inverse-probability-of-treatment weighting produced concordant results (OR, 1.14; 95% CI, 0.64-2.02).

Among propensity-matched patients treated in routine practice, pCR was comparable between regimens, and tumor biology, rather than chemotherapy backbone, was the principal determinant of pathologic response. The study was not powered to establish equivalence; a clinically meaningful difference cannot be excluded. Regimen selection may reasonably be informed by cardiac risk, tolerability, and cost rather than assumed differences in efficacy; cardiac comparisons in this cohort were exploratory.

In this propensity score-matched, real-world cohort of 250 HER2-positive breast cancer patients, pathologic complete response did not differ significantly between anthracycline-free (TCHP) and anthracycline-based (AC-THP) neoadjuvant regimens (50.4% vs 45.6%; P = .519). HER2 immunohistochemistry intensity, not chemotherapy backbone, was the strongest independent predictor of response, suggesting that regimen selection may reasonably be guided by toxicity, cardiac risk, and cost rather than an expected difference in efficacy.