Abstract
Current treatment of HER2-positive (HER2+) early stage I breast cancer consists of surgery and adjuvant chemotherapy (CHT) based on taxane and trastuzumab (T). In stages II and III, in the vast majority of cases, neoadjuvant CHT based on anthracycline and taxane or a combination of taxane and carboplatin (CBDCA) is indicated concomitantly with dual anti-HER2 blockade based on trastuzumab and pertuzumab (P).
After surgery, patients who achieve pathological complete remission (pCR) continue treatment with trastuzumab or a combination of T-P, and patients who remain after initial treatment with residual disease are indicated for treatment with trastuzumab emtansine (T-DM1). Relapses affect about 25% of women, the most common localities being the liver, lungs and central nervous system (CNS).
Neither first- -line palliative treatment based on the taxane-P-T combination nor second-line treatment based on T-DM1 reflects the pre-treatment of patients with pertuzumab and/or T-DM1. Therefore, new drugs are being developed from the range of tyrosine kinase inhibitors (TKIs) and monoclonal anti-HER2 antibody drug conjugates (ADC) with new mechanisms of action.
Phosphatidylinositol-3 kinase (PI3K) inhibitors are other molecules that could help overcome resistance to first-generation anti-HER2 therapy as well as resistance to hormonal therapy indicated in the hormone-positive subset of HER2+ tumors. Advances in the treatment of early breast cancer will require the identification of several markers of prognostic and/or predictive significance, hot candidates being tumor infiltrating lymphocytes (TIL) and molecular subtypes of HER2+ tumors that could contribute to personalized or escalating treatment and improve patients' quality of life.