Recommendations...First line treatment...ET may be added to pertuzumab/trastuzumab maintenance after completion of ChT for HER2-positive, HR-positive tumours.

Eligible patients with inoperable HER2-positive LR/mBC...received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab...more favourable in patients with HR-positive than HR-negative LR/mBC...Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy.

...- Participants with HER2-positive and hormone receptor-positive advanced metastatic or locally advanced breast cancer...

...1.Local recurrent or metastatic HR+HER2+ breast cancer diagnosed by imaging and pathology; 2.Female, age >= 18 years old; 3.The local laboratory evaluates primary or metastatic tumors as HER2 positive, which is defined as the immunohistochemical of HER2 is 3 + or the fluorescence in situ hybridization (FISH) is +; 4.The local laboratory evaluates primary or metastatic tumors as hormone receptor positive, requiring ER >= 10% and PR >= 10%; 5.Not suitable for radical resection or radiotherapy; 6.No previous anticancer treatment for local recurrent or metastatic diseases, such as systemic endocrine therapy, chemotherapy, biological therapy or targeted therapy. ...

The pCR rate in the ET plus trastuzumab and pertuzumab arm was 23.7% (95% CI, 15.7%-33.4%) vs 56.4% (95% CI, 46.2%-66.3%) in the paclitaxel plus trastuzumab and pertuzumab arm (odds ratio, 0.24; 95% CI, 0.12-0.46; P < .001)….The WSG-TP-II randomized clinical trial is, to our knowledge, the first prospective trial comparing 2 neoadjuvant de-escalation treatments in HR-positive/ERBB2-positive EBC and demonstrated an excellent pCR rate after 12 weeks of paclitaxel plus trastuzumab and pertuzumab that was clearly superior to the pCR rate after ET plus trastuzumab and pertuzumab.

In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer...Median PFS was 20.6 versus 15.8 months in Arms A and B, respectively (stratified HR, 0.67; P = 0.006)….These data provide additional evidence of the role of first-line pertuzumab and trastuzumab in HER2-positive M/LABC.

Both T-DM1/P and THP arms ‘graduate’ in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Amongst all HER2+ patients in the TDM-1/P and TH arms, T-DM1/P had a higher estimated pCR rate (55%; 95% PI 41–69%) than TH (25%; 95% PI 11–38%), corresponding to a 99.9% probability that T-DM1/P was superior to TH...In summary, both T-DM1/P and THP significantly increased estimated pCR rates over TH in HER2+ patients, within both HR+ and HR– groups.

The addition of IFN-γ to neoadjuvant chemotherapy using paclitaxel, trastuzumab and pertuzumab was well tolerated with manageable toxicities. This study evaluated de-escalated treatments only 12 weeks duration and the anthracycline-free regimen which was highly effective with pCR of 44%. The pCR for HR+ HER2 + BC subtype was 47% (16/34) which compares favorably to the expected pCR of 25% with neoadjuvant chemotherapy alone in HR+HER2+ patients. Updated results will be presented at the meeting including correlative studies.

This non-randomized prospective study was performed in two medical oncology departments in Portugal. It included HER2+ breast cancer patients that had tumours larger than 2cm and/or axillary disease that have been being treated since 2018. These patients were put on the following treatment scheme: 4 cycles of doxorrubicin and cyclofosfamid, followed by 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles....pCR was achieved in 60,5% of the patients, 58,6 % in the hormonal receptor (HR) positive subgroup and 66,7% in HR-negative patients.

Patients with HER2 positive breast cancer, verified by ISH, T >20 mm and/or verified lymph node metastases were randomized to six three-weekly courses of either docetaxel, trastuzumab SC and pertuzumab (group A), or trastuzumab emtansine (T-DM1, group B)....pCR rates were lower in the group of patients with hormone receptor (HR)–positive compared with HR-negative tumors but similar in both treatment groups...

...PerELISA study, aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HER2+/HR+ patients (pts) selected on the basis of Ki67 response after a short course letrozole (L)...A pCR was observed in 9 cases (20.5%). pCR rate was significantly higher in HER2-E vs other subtypes (45.5% vs 13.8%, p = 0.042).