Search

Introduction: The administration of chemotherapy before (neoadjuvant), rather than after surgery (adjuvant) in early breast cancer has been considered an optional strategy for patients with operable breast cancer. We reviewed this concept considering recent results in the field., Areas Covered: Herein, the authors cover neoadjuvant chemotherapy with or without biologics in triple-negative and HER2-positive operable breast cancer with a focus on rates of complete pathological remission (pCR) in the breast and axilla. The impact of the CREATE X and KATERINE randomized clinical trials of post-surgical treatments in patients with residual disease after neoadjuvant chemotherapy is also discussed., Expert Opinion: The CREATE X and KATERINE clinical trials show for the first time and with methodological strengths that, in TNBC and HER2-positive breast cancer patients, post-surgical capecitabine and T-DM1, respectively, can improve prognosis when the disease persists after neoadjuvant chemotherapy. Therefore, the role of pCR as a treatment endpoint and a guide for further treatment decisions is now demonstrated. On account of these results, neoadjuvant chemotherapy becomes not an option, but rather the preferred treatment strategy for more and more TNBC and HER2-positive breast cancer patients in clinical practice.

Introduction: Endocrine therapy is the mainstay of treatment for a substantial proportion of hormone receptor positive (HR+) breast cancer (BC). Indeed, patients with metastatic disease not immediately life threatening may experience long disease control across several lines of endocrine therapy. The major limitation of this therapeutic approach is primary or acquired resistance. A better understanding of endocrine resistance has resulted in newer targeted agents to be added to endocrine therapy. Areas covered: This review highlights new findings in the treatment of HR+/HER2- BC, with a particular focus on new drugs from phase 3 development onwards. Expert opinion: Combining endocrine therapy with agents targeting putative mechanisms of endocrine resistance is a newer treatment paradigm in HR+ BC. Adding a biologically targeted agent to endocrine therapy results in improved response rate, and clinical benefit rate, and prolonged progression-free survival. A clear advantage in overall survival has not yet been reported. Combination therapy allows to delay chemotherapy but increases toxicities and costs, which are critical factors in decision making in the clinical practice. Moreover, identification and validation of biomarkers of response are needed. Ongoing and future trials should elucidate the role of these compounds in the treatment of HR+/HER2- BC.

The San Antonio Breast Cancer Symposium is considered by researchers and physicians involved in breast cancer management as one of the most important international events on the subject. A dense program of plenary presentations of novel findings, main lectures, poster discussions and displays, it encompasses all the aspects of the rapidly evolving field of breast cancer research and treatment. This article briefly summarises some of the presentations that are expected to have an impact on the medical treatment of breast cancer.

Introduction: Endocrine therapy is a fundamental component of the therapeutic repertoire for treatment of metastatic, hormone receptor-positive breast cancer. Inevitably, however, tumors develop resistance to these compounds, and overcoming this phenomenon is a key motivator of research in this field., Areas Covered: This review summarizes the current status of endocrine therapy for the treatment of metastatic disease, with a main focus on postmenopausal patients. Furthermore, strategies that could potentially sustain endocrine resistance and future perspectives in this direction are also to be described. Relevant references were identified by PubMed searches and from the abstract books of the annual meetings of The European Society of Clinical Oncology (ESMO), The American Society of Clinical Oncology (ASCO) and from the San Antonio Breast Cancer Symposia., Expert Opinion: Combinations of endocrine therapy with HER2 targeting agents, as well as with compounds that can interfere with PI3K/Akt/mTOR signaling, are two promising strategies for delaying or overcoming endocrine resistance, mediated by these relevant biological pathways. Due to increased costs and the burden of toxicity associated with these combination therapies, compared to endocrine therapy alone, it is imperative to concentrate efforts on establishing biomarkers that can predict efficacy.

Introduction: Pharmacological targeting of the tyrosine kinase receptor HER2 with the monoclonal antibody trastuzumab has dramatically changed the outlook of HER2-positive breast cancer patients. However, HER2 is part of a more complex biological network that, when deregulated, plays a central role in sustaining the cancer phenotype. These interactions account for primary or acquired resistance to drugs that hit a single biological target, like trastuzumab. Several preclinical models suggest that simultaneous targeting of crucial metabolic pathways has the potential to circumvent or delay the onset of resistance phenomena in HER2-positive breast cancer cells., Areas Covered: This review describes the rationale and results of clinical trials using biologically targeted agents in HER2-positive breast cancer patients. Single drugs that hit multiple targets and cocktails of biologically targeted agents are considered, whereas combinations with chemotherapy are not addressed., Expert Opinion: Most of the studies using biological agents to hit multiple targets in HER2-positive breast cancer patients confirm that resistance to single-agent HER2-targeting can be overcome. Further developments will include combination of multi-targeting strategies with chemotherapy in patients with earlier-stage disease. In addition, it is possible that newer molecular predictive factors may allow a more rationale choice of the most appropriate targeting for each individual patient.

The 29th edition of the San Antonio Breast Cancer Symposium was attended by a total of > 8000 basic scientists, translational researchers, clinical investigators and physicians gathering from approximately 80 countries worldwide. This is the largest meeting focusing on breast cancer, encompassing a wide array of topics from prevention, aetiology and diagnosis to molecular biology and treatment. From the main presentations at the meeting, it seems clear that combined efforts at prevention and treatment of this disease have translated into small, but significant, achievements. Much of the research in the area is focused on improving the therapeutic ratio of available treatments by better selection of patients.

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Trastuzumab, a humanised monoclonal antibody directed against the extracellular domain of HER-2, has been shown to be active against HER-2-overexpressing metastatic breast cancer, either as single agent or when used in combination with chemotherapy. In preclinical models, trastuzumab has shown additive and even synergistic anti-tumour activity with the most active chemotherapeutic agents used in the treatment of breast cancer. In a large, randomised, Phase III trial, the combination of trastuzumab plus chemotherapy was shown to improve response rate and survival. The high incidence of cardiotoxicity seen with the combination of trastuzumab plus anthracycline drugs prompted carrying out of several clinical studies combining trastuzumab with other chemotherapeutic agents, including docetaxel, vinorelbine, platinum salts, gemcitabine and capecitabine. This article summarises the available data on trastuzumab-based combinations for breast cancer.