Cross-country Treatment Practices after pCR Following Neoadjuvant Trastuzumab (H) and Pertuzumab (P) in HER2+ Early Breast Cancer: Preliminary Results from the PEARL-HER2 Study

<p style="-webkit-font-smoothing: antialiased; max-width: 60rem; color: rgb(18, 24, 31); font-family: Synthese, sans-serif; font-size: 20px; line-height: var(--sabcs-lh-body-base); caret-color: rgb(18, 24, 31);"><span style="-webkit-font-smoothing: antialiased;">Background:&nbsp;</span>Pts with HER2+ early BC who achieve pCR following neoadjuvant chemotherapy (NACT) with HP routinely continue dual anti-HER2 therapy, although the added benefit of continuing HP versus H alone in this setting remains uncertain, with added cost and toxicity. PEARL-HER2 aims to clarify this question by evaluating whether adjuvant HP provides additional clinical benefit compared to H alone.<span style="-webkit-font-smoothing: antialiased;">&nbsp;</span>Here, we report a preliminary cross-country comparison of clinical practices.&nbsp;<span style="-webkit-font-smoothing: antialiased;">Method:&nbsp;</span>PEARL-HER2 is an international, retrospective cohort study including pts with HER2+ early BC who achieved pCR (ypT0/isN0) after NACT and HP. Eligible pts started NACT between Jan-2014 and Dec-2023. This descriptive analysis, data cut-off of 20-Jun-2025, summarizes diagnostic, and treatment data stratified by country.&nbsp;<span style="-webkit-font-smoothing: antialiased;">Results:&nbsp;</span>Of 1045 pts screened, 649 with pCR were eligible for this analysis. Country-level characteristics are shown in Table 1. Differences in baseline characteristics included a higher proportion of pre-/perimenopausal pts in Argentina (56%), higher ER positivity in Belgium (58%) and lower Ki-67 expression in Turkey (21%). Imaging practices also differed: breast MRI was routinely used in Spain, Portugal, and Belgium, but infrequent in Turkey (15%). Staging with FDG-PET was more commonly employed in Turkey (65%) and Belgium (44%), whereas CT and bone scan were predominant elsewhere. Anthracycline-free regimens were more frequent in Argentina (100%) and Belgium (34%), contrasting with near-universal anthracycline use in Portugal and Turkey. Adjuvant HP was continued in &gt;90% of pts in Belgium vs. &lt;9% in Iberian countries, highlighting disparities in access. Among ER+ patients, ET use was near-universal (97%), though OFS-based combinations were infrequent even in very young pts. With a median follow-up of 44 months (IQR 29-67), only 35 relapses (5.4%) were reported, 18 (51%) of which in the central nervous system (CNS).<span style="-webkit-font-smoothing: antialiased;">Conclusion:&nbsp;</span>This preliminary analysis reveals marked international variability in post-pCR management of HER2+ early BC. These findings should be interpreted with consideration of the unequal distribution of patients across countries, with Portugal contributing over two-thirds of the cohort. Differences in imaging and tumor burden likely reflect national screening and staging practices, while variation in adjuvant P use likely reflects national funding policies, with routine access in Belgium but limited or no reimbursement in Iberian countries. Notably, over half of reported relapses occurred in the CNS. PEARL-HER2 continues to accrue and follow patients to clarify the role of adjuvant P in this setting. <table id="{CF9C7995-894C-43C1-BA85-3967363FDD2E}" class="DisplayTable" border="1" cellpadding="1" style="-webkit-font-smoothing: antialiased; text-indent: 0px; caret-color: rgb(18, 24, 31); color: rgb(18, 24, 31); font-family: Synthese, sans-serif; font-size: 20px;"><caption style="-webkit-font-smoothing: antialiased;">Table 1. Country-level characteristics</caption><tbody style="-webkit-font-smoothing: antialiased;"><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">Characteristics</span></td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><div style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">Total (n=649)</span></div></td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><div style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">Argentina (n=18)</span></div></td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><div style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">Belgium (n=86)</span></div></td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><div style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">Portugal (n=437)</span></div></td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><div style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">Spain (n=80)</span></div></td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><div style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">Turkey (n=28)</span></div></td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;"><span style="-webkit-font-smoothing: antialiased;">p-value</span></td></tr><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">Age at diagnosis in years, median (IQR)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">51.9 (44.4-62.0)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">52.9 (40.9-63.2)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">52.7 (43.9-64.2)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">52.1 (45.0-61.4)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">53.8 (42.5-62.1)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">48.6 (45.2-57.9)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">0.729</td></tr><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">Pre-/peri-menopausal status, n (%)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">303 (46.7)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">10 (55.6)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">36 (41.9)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">208 (47.7)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">35 (43.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">14 (50.0)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">0.039</td></tr><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">NST subtype, n (%)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">595 (91.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">15 (88.2)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">81 (94.2)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">396 (90.6)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">75 (93.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">28 (100.0)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">0.788</td></tr><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">Lobular subtype, n (%)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">18 (2.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">1 (5.9)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">4 (4.7)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">11 (2.5)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">2 (2.5)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">0 (0.0)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">–</td></tr><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">Grade 3, n (%)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">322 (49.7)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">8 (47.1)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">54 (62.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">216 (49.4)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">31 (38.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">13 (46.4)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">0.318</td></tr><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">ER-negative, n (%)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">314 (48.4)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">14 (77.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">36 (41.9)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">207 (47.4)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">39 (48.8)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">18 (64.3)</td><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">&lt;0.001</td></tr><tr style="-webkit-font-smoothing: antialiased;"><td colspan="1" rowspan="1" style="-webkit-font-smoothing: antialiased;">Ki-67 &lt;20%, n (%)</td><td colspan="1" rowspan="1" style="-w