The availability of HER2-targeted therapy has dramatically improved patient outcome in HER2-positive (HER2+) early breast cancer (EBC) as recently demonstrated by the EBCTCTG metaanalysis on ...trastuzumab in HER2+ EBC: Adding trastuzumab to chemotherapy has reduced recurrence rates and breast-cancer related mortality by a third 1.
Today, neoadjuvant therapy has become standard of care for women with stage II or III tumors as pathological complete response (pCR) status after surgery can be used to individualize adjuvant systemic therapy. pCR is correlated with favorable patient outcome, particularly in hormone receptor (HR) negative HER2+ EBC, as demonstrated by the FDA meta-analysis. Moreover, for patients with non-pCR, 14 cycles of adjuvant T-DM1 have become a new adjuvant therapy standard based on the results of the KATHERINE trial. Primary surgery can be offered to patients with low tumor burden (cN0 cT1). For this low-risk subgroup, 12 weeks of adjuvant paclitaxel + trastuzumab for one year are correlated with excellent outcome based on the APT trial results. A multidisciplinary team is essential right from the beginning for optimal locoregional and systemic therapy in such a complex neoadjuvant – adjuvant continuum of care.
Clinical trials in HER2+ EBC are currently evaluating further therapy de-escalation in low-risk disease or patients with pCR whereas for patients with non-pCR, escalation trials are also ongoing. Newly approved drugs for HER2+ MBC like tucatinib or trastuzumab-deruxtecan or even immunotherapy combinations are being evaluated to improve upon efficacy of T-DM1 alone in the non-pCR setting. Regarding de-escalation, the WSG ADAPT trial demonstrated feasibility of avoiding overtreatment and individualizing neoadjuvant therapy without compromising outcome. Further de-escalation trials (e.g. DECRESCENDO, COMPASS-HER2) are currently ongoing.
Among women with previously untreated hormone-receptor–positive advanced breast cancer, the addition of the cyclin-dependent kinase inhibitor palbociclib to letrozole therapy resulted in longer ...progression-free survival than that with letrozole alone.
Hormone-receptor–positive breast cancer represents the largest therapeutic subtype of the disease, accounting for 60 to 65% of all malignant neoplasms of the breast. For more than 50 years, the treatment of hormone-receptor–positive disease has been focused on targeting the estrogen-receptor signaling pathway.
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However, both new and acquired resistance to hormonal blockade occurs in a large subset of these cancers, and new approaches are needed.
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The cyclin-dependent kinases (CDKs) are a large family of serine–threonine kinases that play an important role in regulating cell-cycle progression. The interaction of cyclin D with CDK4 and CDK6 facilitates the hyperphosphorylation of the retinoblastoma (Rb) . . .
In women with hormone-receptor–positive metastatic breast cancer that had progressed after endocrine therapy, palbociclib plus fulvestrant was associated with progression-free survival of more than 9 ...months, as compared with less than 4 months with fulvestrant alone.
Approximately 80% of breast cancers express estrogen receptors, progesterone receptors, or both. Endocrine therapies are the mainstay of treatment for these hormone-receptor–positive cancers, substantially reducing the relapse rate after presentation with early-stage cancer.
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Despite advances in endocrine therapy, many women have a relapse during or after completing adjuvant therapy. The care of these women remains a considerable clinical challenge. Single-agent treatment with an aromatase inhibitor or tamoxifen has shown limited clinical benefit.
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The selective estrogen-receptor degrader fulvestrant has modest activity in this population of patients,
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and the development of effective therapies that can reverse resistance to endocrine therapy . . .
The addition of pembrolizumab to platinum-based neoadjuvant chemotherapy significantly increased the percentage of patients with a pathological complete response among patients with locally advanced ...triple-negative breast cancer. Side effects of the immunotherapy were added to the usual toxic effects of chemotherapy, but most patients completed planned treatment.
In HER2-positive early breast cancer, neoadjuvant treatment with a combination of sequential chemotherapy and HER2-targeted therapy is currently the standard of care. This is followed by breast ...surgery, radiotherapy (if indicated), completion of 12 months of HER2-directed therapy, and - depending on the tumor biology - endocrine adjuvant therapy, and ultimately follow up. 10-year survival rates in the HER2-positive subgroup of breast cancer do reach now more than 75% with the introduction of first adjvuant and later neoadjuvant HER2-targeted therapies over the last 15 years. The neoadjvuant setting helps to downstage locally advanced tumors, to provide early information of tumor response, to assess the efficacy of new therapies in vivo, to reduce treatment duration, and to introduce new targeted therapies into the clinical routine. It also allows enrolling fewer patients into clinical trials in order to reach adequate effects in clinical outcome. The neoadjuvant approach and our interest in this setting are based on pCR (pathological complete response) and its translation into better long-term outcome. In recent trials, we have reached more than 60% pCR with a subsequent improvement of DFS and hopefully OS. Therefore, chemotherapy schedules and new HER2-targeted agents such as lapatinib, pertuzumab, and T-DM1 have been introduced into the neoadjuvant setting. To balance over- and undertreatment, current trials include personalized concepts and assess new biomarkers and tumorbiological factors. We have learned for example to differentiate between HR (hormone receptor)-positive and -negative tumors in the HER2-positive population. Depending on pCR or non-pCR after neoadjuvant treatment, the adjuvant therapy may be adjusted. This concept of post-neo-adjuvant trials is now entering the field of strategies in the neoadjuvant setting for HER2-positive non-metastatic primary breast cancer. The 2017 standard of care in the neoadjuvant setting according to national and international guidelines combines a taxane-containing chemotherapy with a dual blockade of trastuzumab and pertuzumab. This review will point out current trials and their strategies to continue improving outcome and reduce morbidity as well as mortality in HER2-positive early breast cancer.
The addition of ribociclib to hormone therapy showed a greater benefit with regard to overall survival than hormone therapy alone in women with hormone-receptor–positive, human epidermal growth ...factor receptor 2–negative advanced breast cancer.
The addition of palbociclib to fulvestrant prolonged overall survival among women with hormone receptor–positive, HER2-negative advanced breast cancer who had sensitivity to previous hormonal ...therapy. In the entire trial group, survival differences were not significant.
Health state transitions are reflected in characteristic changes in the molecular composition of biofluids. Detecting these changes in parallel, across a broad spectrum of molecular species, could ...contribute to the detection of abnormal physiologies. Fingerprinting of biofluids by infrared vibrational spectroscopy offers that capacity. Whether its potential for health monitoring can indeed be exploited critically depends on how stable infrared molecular fingerprints (IMFs) of individuals prove to be over time. Here we report a proof-of-concept study that addresses this question. Using Fourier-transform infrared spectroscopy, we have fingerprinted blood serum and plasma samples from 31 healthy, non-symptomatic individuals, who were sampled up to 13 times over a period of 7 weeks and again after 6 months. The measurements were performed directly on liquid serum and plasma samples, yielding a time- and cost-effective workflow and a high degree of reproducibility. The resulting IMFs were found to be highly stable over clinically relevant time scales. Single measurements yielded a multiplicity of person-specific spectral markers, allowing individual molecular phenotypes to be detected and followed over time. This previously unknown temporal stability of individual biochemical fingerprints forms the basis for future applications of blood-based infrared spectral fingerprinting as a multiomics-based mode of health monitoring.
For the second time, the St. Gallen Consensus Conference on early breast cancer treatment standards took place in Vienna, Austria, where it will remain for the foreseeable future (next date: March ...20-23, 2019). With the probably most prominent line-up of global breast cancer experts and more than 3,000 participants from over 100 countries, the 2017 St. Gallen/Vienna conference again was a huge success. A generation change took place with respect to the Conference Co-Chairpersons. Traditionally, the experts from all continents reviewed publications from the past 2 years, and discussed whether new diagnostic or therapeutic means were ready for routine everyday practice. This year, the conference's main theme was 'Escalating and Deescalating Treatment', and the traditional panel votings clarified a number of issues in this respect. Several subjects of all breast cancer modalities were further de-escalated (surgery: 'no ink on tumor' clearly confirmed as standard; resection within new limits after neoadjuvant systemic therapy; axillary dissection may also be avoided after mastectomy under certain circumstances; radiotherapy: hypofractionation is standard of care in breast conserving therapy; chemotherapy: can be avoided in low-risk patients). However, others were escalated: surgery: after neoadjuvant treatment and after mastectomy a positive sentinel node leads to axillary dissection; radiotherapy: regional nodes have to be irradiated in 4+ nodes situations; adjuvant therapy: bisphosphonates as standard for postmenopausal women. There was no clear panel opinion on the optimal use of multigenomic assays. As always, the panel recommendations are strictly opinion-based, and try to depict the 'usual' treatment for the 'average' patients. This rapid report by the editors-in-chief of Breast Care summarizes the results of the 2017 international panel votings with respect to loco-regional systemic treatment, and does not intend to replace the official St. Gallen Consensus publication.
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