Marcus Vetter

Bone targeted therapies in advanced breast cancer

Bone targeted therapies are of increasing importance, not only for bone health in the clinical course of breast cancer, but recently also in the adjuvant setting as preventative, anticancer and prognosis-improving agents. It is well established that women with advanced breast cancer receive bisphosphonates or denosumab to prevent therapy-related osteoporosis. As many as 70% of these patients suffer from bone metastases and receive bone targeted agents in order to prevent skeletal related events (SREs), which are debilitating or diminish the quality of life. A number of trials provided guidance, identifying zoledronic acid as the most efficient bisphosphonate, showing that intravenous bisphosphonate administration is superior to oral intake and illustrating the different safety profile of denosumab, which has been reported to be more beneficial than zoledronic acid in delaying the time to first and subsequent (multiple) SREs. New studies have suggested that bone targeted therapies improve rates of overall survival and contribute to preventing recurrence of breast cancer at all sites. Increased bone turnover is both a consequence and a driving factor for tumour growth, expansion, formation of bone lesions and potentially also activation of disseminated tumour cells, leading to bone relapses. We review the current knowledge of bone targeted therapies in advanced breast cancer, with a focus on new insights into their bone-preserving and antitumor activity. Current guidelines, pathology of bone metastasis, mode of action and common side effects have been summarised. We also elaborate on the use of bisphosphonates and denosumab in early breast cancer, during adjuvant therapy with aromatase inhibitors.

Hodgkin's Lymphoma and Paraneoplastic Phenomena in the Central Nervous System: A Case Report and Review of the Literature

A 25-year-old male patient presented to our Ear, Nose and Throat clinic with a history of nausea, vomiting, headache, vertigo and weight loss of 5 kg over the preceding 3 months. An enlarged cervical lymph node was detected at clinical examination. Lymph node biopsy showed nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL, nodular paragranuloma). Because of the neurological symptoms a cerebral MRI scan was performed and revealed an intense perivascular, bilateral, contrast-medium enhancing lesion of the temporal lobes suggestive of cerebral vasculitis. Cerebrospinal fluid analysis showed an increased number of mononuclear cells, but there was no indication for neurotropic viral or bacterial infections. EEG revealed a left temporal epileptic focus, and anti-epileptic therapy was initiated. NLPHL was treated with 2 cycles of ABVD chemotherapy and 20 Gy involved-field radiotherapy. Steroid therapy (prednisone 100 mg q.d.) for the presumed paraneoplastic neurological manifestation was started 1 week before chemotherapy and led to the rapid disappearance of complaints. Because of renewed onset of nausea and vertigo after 3 weeks of treatment with ABVD chemotherapy and 4 weeks of treatment with steroids, a follow-up brain MRI and EEG were performed and demonstrated complete disappearance of the ‘vasculitic’ changes without additional pathologic findings. Five months after therapy, the patient is without neurological symptoms and a PET-CT showed a complete remission. This case is a unique example of paraneoplastic central nervous system (CNS) involvement in a patient with newly diagnosed NLPHL. We present a review of the literature on paraneoplastic CNS symptoms in Hodgkin’s lymphoma.

Endocrine Therapy in Epithelial Ovarian Cancer (EOC) New Insights in an Old Target: A Mini Review

Introduction: Endocrine therapy with tamoxifen and aromatase inhibitors has been used in Estrogen Receptor (ER) positive breast cancer for decades. Epithelial ovarian cancer, in particular serous Low- and High Grade Subtypes (LGSOC, HGSOC), shows a similar high ER expression and represents therefore a potential target for endocrine therapy. Many treatments have been evaluated in phase II clinical trials in heavily pretended patients, but the overall tumor response and agent superiority (tamoxifen vs. aromatase inhibitors) remains unclear. Methods: We present a literature review of endocrine therapy for ovarian cancer and emphasize the role of endocrine maintenance therapy with letrozole after standard of care. Results: Endocrine therapy appears to be an eligible and cost effective treatment option with good quality of life in the adjuvant and recurrent treatment of advanced ovarian cancer. The trend shows the highest effect in histological subtypes with the highest ER expression (LGSOC and HGSOC).

Reply to technical comment on: Biskup E, et al. Oncological patients in the intensive care unit: prognosis, decision-making, therapies and end-of-life care

The comment very positively emphasises that the trends described in the review article are indeed global and apply to various hospital environments – not only American, European, Asian, but also Mexican.

Efficacy of adjuvant chemotherapy with carboplatin for early triple negative breast cancer: a single center experience

Background Anthracycline- and taxane-based adjuvant chemotherapies are the most frequently used systemic treatments for women with triple negative breast cancer (TNBC). Adding platinum derivatives in the neo-adjuvant setting has been shown to not only improve the pCR rates, but also the 3 year DFS for TNBC patients; however, data on platinum derivatives in the adjuvant setting are limited. Methods We conducted a retrospective, single-center study in a Swiss breast cancer cohort to evaluate the role of carboplatin in addition to standard adjuvant therapy (anthracyclines and/ or taxanes) in early TNBC patients. All patients with stage I-III TNBC who underwent primary breast surgery between 2004 and 2014 were included. Results Eighty-three patients were included in the analysis. Stage and grade were well balanced between patients treated with standard chemotherapy (N=54; cohort A) or standard chemotherapy plus carboplatin (N=29; cohort B). The median time to local relapse (LRFS) was 15.0 months in cohort A versus 16.0 months in cohort B (p=0.655). The median time to distant relapse (DRFS) was 29.5 months in cohort A versus 25.0 months in cohort B (p=0.606) There was also no difference in overall survival between the two cohorts (mean overall survival 98 and 91 months, respectively; p=0.208). Discussion Our data suggest that in an unselected cohort of early TNBC patients, the addition of carboplatin in the adjuvant setting may not be beneficial with respect to relapse-free and overall survival. Further prospective trials to evaluate the addition of platinum in the adjuvant setting are warranted, especially to define subgroups of TNBC patients, which might benefit from carboplatin therapy.BACKGROUND Anthracycline- and taxane-based adjuvant chemotherapies are the most frequently used systemic treatments for women with triple negative breast cancer (TNBC). Adding platinum derivatives in the neo-adjuvant setting has been shown to not only improve the pCR rates, but also the 3 year DFS for TNBC patients; however, data on platinum derivatives in the adjuvant setting are limited. METHODS We conducted a retrospective, single-center study in a Swiss breast cancer cohort to evaluate the role of carboplatin in addition to standard adjuvant therapy (anthracyclines and/ or taxanes) in early TNBC patients. All patients with stage I-III TNBC who underwent primary breast surgery between 2004 and 2014 were included. RESULTS Eighty-three patients were included in the analysis. Stage and grade were well balanced between patients treated with standard chemotherapy (N=54; cohort A) or standard chemotherapy plus carboplatin (N=29; cohort B). The median time to local relapse (LRFS) was 15.0 months in cohort A versus 16.0 months in cohort B (p=0.655). The median time to distant relapse (DRFS) was 29.5 months in cohort A versus 25.0 months in cohort B (p=0.606) There was also no difference in overall survival between the two cohorts (mean overall survival 98 and 91 months, respectively; p=0.208). DISCUSSION Our data suggest that in an unselected cohort of early TNBC patients, the addition of carboplatin in the adjuvant setting may not be beneficial with respect to relapse-free and overall survival. Further prospective trials to evaluate the addition of platinum in the adjuvant setting are warranted, especially to define subgroups of TNBC patients, which might benefit from carboplatin therapy.

Immunotherapy in Gynecologic Cancers

During the last years, significant progress in the understanding of signaling pathways of immune cells has revive the field of immune therapy for cancer. In this chapter, we explain the recent immunotherapy-based strategies for the treatment of gynecological cancers including cervical cancer, endometrial cancer, ovarian cancer, and vulvar cancer. This work will mainly focus on emerging clinical data on immune checkpoint inhibitors. But also data on adoptive T cell therapies and vaccines will be presented. It is anticipated that in future biomarker-guided randomized trials will provide better approaches in terms of response and resistance to immune therapy. The use of combination therapy for gynecological cancer might be one possible approach to overcome resistance.