In 2015, academic-led clinical trials provided evidence for reducing the intensity of adjuvant therapy for early breast cancer, answering questions about the optimization of adjuvant regional radiotherapy and first-line chemotherapy for advanced breast cancer. More importantly, the development of novel treatments and potential tools for individualized therapy will offer new hope for breast cancer patients.Nat Rev Clin Oncol published a review article online on January 20, 2016, reviewing the progress of breast cancer research in 2015.Medical Pulse recently published advances in adjuvant chemotherapy for HER2-positive breast cancer and lymph node-negative breast cancer patients.Today we continue to look at the research progress of carboplatin and palbocilib. Previously reported: 2015 Breast Cancer Research Advances – Research Illuminates the Clinic (above) The hurdle that all new drugs must pass before they can prove effective in metastatic breast cancer is usually set up in a phase II-III randomized clinical trial compared to a standard treatment approach. It is no surprise that the clinical research field is dominated by industrialized trials. In this regard, it is worth celebrating the head-to-head comparison trial of protein-bound paclitaxel plus isapirone with paclitaxel first-line chemotherapy regimens done by CALGB and NCCTG on 799 patients with metastatic breast cancer. The better efficacy in terms of progression-free survival (PFS) and time to treatment failure was seen with the relatively inexpensive paclitaxel. Carboplatin as first-line regimen improves progression-free survival in patients with BRCA-mutated, metastatic breast cancer Similarly, UK investigators should be proud of their clinical practice-changing trial comparing upfront carboplatin chemotherapy (AUC regimen x6 every 3 weeks) with docetaxel chemotherapy (100 mg/m2 every 3 weeks) in metastatic triple-negative breast cancer (TNBC) efficacy in female patients: response rates to alkylating agents were better than paclitaxel-based in 43 patients with BRCA mutations, which accounted for approximately 8% of the total number of cases in the trial. Patients treated with carboplatin had a median PFS of 6.8 months in patients with BRCA mutations, compared with 3.1 months in patients with BRCA wild type. The timing of the full publication of this important trial has not yet been determined. Related story: [SABCS2015] Neoadjuvant Plus Carboplatin Improves Disease-Free Survival in TNBC, BRCA Wild-Type Patients Palbocilib-Related Studies Because of the extensive research done by scientists over the past two decades to unravel the molecular mechanisms of endocrine resistance in breast cancer, we can celebrate the successful registration of new targeted agents that enable delayed onset of treatment resistance in patients with metastatic breast cancer The combination of the CDK4/6 inhibitor palbociclib and letrozole as first-line endocrine base therapy for patients with metastatic breast cancer received conditional accelerated approval from the FDA based on a phase II randomized clinical trial showing that the drug prolonged PFS in patients. The side effects (neutropenia and fatigue) caused by palbociclib were easily managed and overall quality of life was maintained. Whether a better survival prognosis will be obtained with palbociclib than with everolimus is uncertain. Notably, no biomarkers other than estrogen receptors are indicated for these drugs, which is a serious concern given the proliferation of drug prescription costs. Immunotherapy There remains a huge unmet medical need for patients with metastatic triple-negative breast cancer, as this disease typically presents with rapid disease progression after third- to fifth-line chemotherapy. To date, no targeted agents have been registered specifically for this disease, except for bevacizumab, whose clinical value has been questioned because it has not been shown to have an overall survival benefit. The immune checkpoint inhibitors pembrolizumab and atezolizumab have achieved encouraging results in heavily treated patients with advanced TNBC, thus generating widespread interest. The overall remission rates for these agents are still relatively low (~18%), but the median duration of remission had not been reached at the time of publication, implying that the drugs produced rare sustained remissions in heavily treated patients with advanced TNBC. Immunotherapy combined with selected cytotoxic agents or signal transduction inhibitors will undoubtedly be the focus of clinical studies in the coming years. Related story: [SABCS2015] PEMBRO monoclonal antibody is also effective in treating PD-L1-positive breast cancer The relationship between dense mesenchymal tumor-infiltrating lymphocytes (TILs) and improved prognosis in specific types of breast cancer has long been recognized by pathologists. the NeoALTTO clinical trial demonstrated pathologic complete remission of TILs in HER2-positive breast cancer patients ( PCR) and event-free survival (treatment-independent) with strong prognostic value. If this result is confirmed in the large ALTTO adjuvant trial, TILs could become an “actionable biomarker” for reducing treatment intensity. In conclusion, 2015 will be remembered for the very strong demonstration in 2015 that molecular imaging can decipher a great deal of tumor heterogeneity in advanced HER-2-positive breast cancer. In the academic-led ZEPHIR trial, 56 HER2-positive patients underwent HER2 PET-CT prior to T-DM1 treatment and showed that almost half of the patients had substantial HER2 expression differences between metastases. In addition, 29% of patients showed negative HER2 PET-CT presentation; importantly, patients who showed negative HER2 PET-CT showed marginal benefit from T-DM1 treatment. These findings may have very significant implications for improving our ability to identify patients who can benefit from anti-HER2 antibodies.