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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
HER2-positive breast cancer caught early is usually cured. Chemotherapy with the antibodies trastuzumab and pertuzumab comes before surgery; if the tumour has gone by then, antibodies alone finish the year, and if cancer remains, trastuzumab emtansine or trastuzumab deruxtecan take over. Small tumours get a gentler regimen, and trials now ask how much treatment can be left out.
A year of trastuzumab is the foundation. HERA, NSABP B-31 and NCCTG N9831, reported together in 2005, showed that adding trastuzumab to adjuvant chemotherapy cut deaths by about a third, with ten-year overall survival of 84 percent against 75.2 percent in the joint American analysis. PERSEPHONE found six months almost as good as twelve (four-year disease-free survival 89.4 against 89.8 percent) with half the cardiac toxicity, but twelve months remains the standard. For tumours of 3 cm or less without node involvement, the single-arm APT study of twelve weeks of paclitaxel with a year of trastuzumab gave 93 percent seven-year disease-free survival and became the standard for stage I disease without a randomised trial.
For stage II and III disease treatment moved before surgery, where pathological complete response predicts cure and guides what follows. NeoSphere showed that pertuzumab added to trastuzumab and docetaxel raises the complete response rate, and TRAIN-2 (438 patients) showed that carboplatin and paclitaxel with both antibodies matched an anthracycline regimen (complete response 67 against 68 percent) with less cardiac damage, so anthracycline-free regimens became usual. KRISTINE (444 patients) tested replacing chemotherapy with trastuzumab emtansine plus pertuzumab and found fewer complete responses (44.4 against 55.7 percent) and more progression before surgery, a warning against de-escalating on antibody-drug conjugates alone. KATHERINE (1,486 women with residual invasive disease) showed that fourteen cycles of trastuzumab emtansine instead of trastuzumab halved recurrence (three-year invasive disease-free survival 88.3 against 77.0 percent) and improved seven-year overall survival (89.1 against 84.4 percent), and APHINITY (4,805 women) showed adjuvant pertuzumab adds a few points of invasive disease-free survival in node-positive disease and nothing in node-negative disease.
| Setting | Approach | Guideline |
|---|---|---|
| Stage I, small node-negative tumours | Surgery first, then twelve weeks of paclitaxel with a year of trastuzumab (APT). | not mapped |
| Stage II to III, before surgery | Carboplatin, a taxane, trastuzumab and pertuzumab for six cycles without an anthracycline (TRAIN-2), or trastuzumab deruxtecan followed by taxane, trastuzumab and pertuzumab (DESTINY-Breast11). | not mapped |
| Pathological complete response at surgery | Trastuzumab, with pertuzumab in node-positive disease, to complete one year (APHINITY, HERA); endocrine therapy if hormone receptor-positive. | not mapped |
| Residual invasive disease at surgery | Trastuzumab deruxtecan (DESTINY-Breast05) or trastuzumab emtansine for fourteen cycles (KATHERINE). | not mapped |
| Local therapy and the heart | Breast conservation or mastectomy with sentinel node biopsy, radiotherapy by stage, and echocardiography every three months during trastuzumab. | not mapped |