Impressive long-term response with chemo-endocrine therapy in a premenopausal patient with metastatic breast cancer. A case report

Rationale: Patients with, or who develop, metastatic breast cancer have a 5-year relative survival of about 25%. Endocrine therapy clearly improves outcomes in patients with estrogen receptor-positive breast cancer. In the metastatic setting, the primary goal of treatment is to maintain long-term disease control with good quality of life. Rarely, exceptional responders achieve durable disease control, and potential cures cannot be ruled out.Patient Concerns: We report the case of a 39-year-old woman with primary breast cancer and associated synchronous bone metastases, who experienced a disease response of 12 years with hormonal therapy as maintenance after first line chemotherapy, with a good toxicity profile.Diagnosis: The patient was diagnosed with estrogen receptor + human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer with synchronous bone metastases.Interventions: This patient was treated with chemotherapy for 6 cycles as a first-line therapy following by endocrine treatment given as a maintenance therapy.Outcomes: Our patient experienced a progression-free survival >12 years with an exceptionally good quality of life.Lessons: Our anecdotal experience highlights the existence of exceptional responders among patients with hormone receptor-positive metastatic breast cancer, who achieve clinical remission and durable disease control with endocrine therapy. Being able to identify these patients could help in the selection of the best treatment option among the many available

Can cyclin-dependent kinase 4/6 inhibitors convert inoperable breast cancer relapse to operability? A case report

BACKGROUND Pathological complete response (pCR) is rare in hormone receptor-positive (HR+) HER2-negative breast cancer (BC) treated with either endocrine therapy (ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures. The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced pCR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a pCR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified as endocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable

Cell-Free DNA Variant Sequencing Using CTC-Depleted Blood for Comprehensive Liquid Biopsy Testing in Metastatic Breast Cancer

Keup and colleagues provide liquid biopsy preliminary results by sequencing variants in circulating tumor cells (CTCs) and cell-free deoxyribonucleic acid (cfDNA) "all from one tube" format, in order to use the same blood sample under the same isolation conditions of both analytes to reach an unbiased comparability and consistency. We appreciated the attempt of the authors to improve technical procedures in liquid biopsy research area, but we wanted to raise several issues related to cfDNA detection, reporting our research experience. This is a feasibility study as the authors analyzed only one sample from a small case series at an advanced line of treatment. In the clinical practice to monitor the disease and predict the treatment response, the analysis should be done at multiple time points. We have previously demonstrated that the quantity and the integrity of the cfDNA are not useful to determine the evolution of early breast cancer (bc), maybe due to the fact that cfDNA is not strictly related to cancer but also to an inflammatory status. Given that a high content of cfDNA could reflect inflammatory processes, we decided to investigate the role of stimulator of interferon gene (STING), an important regulator of cancer cell growth and senescence, in bc tissue in relation to cfDNA. STING biomarker analyzed by immunohistochemistry on tumor tissue could reflect a circulating inflammatory status and needs to be further investigated, not only on CTCs but also on cfDNA. One of the major issues of cfDNA is to decide what to analyze on it, in terms of type of cells and genetic alterations. Considering that multiple tests could be done to study gene copy number alterations, mutations, and variant fusions, the proper molecular test should be chosen, on the basis of the clinical need, starting from the treatment choice to disease monitoring

Precision medicine: PI3K targeting in advanced breast cancer

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Ribociclib and Endocrine Therapy in Breast Cancer

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Letter Re: Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology

A shockable rhythm influences the ouctome of cardiac arrest

COVID-19: Relative Risk of Non-Vaccinated to Vaccinated Individuals

Following the outbreak of the COVID-19 pandemic, Italy has implemented an extensive vaccination campaign involving individuals above the age of 12, both sexes. The public opinion and the medical community alike questioned the usefulness and efficacy of the vaccines against SARS-CoV-2. The widespread opinion was that the vaccines protected individuals especially against serious conditions which could require intensive care and may lead to the death of the patient rather than against the possibility of infection. In order to quantify the effect of the vaccination campaign, we calculated the relative risks of non-vaccinated and vaccinated individuals for all possible outcomes of the disease: infection, hospitalization, admission to intensive care and death. Relative risk was assessed by means of likelihood ratios, the ratios of the probability of an outcome in non-vaccinated individuals to the probability of the same outcome in vaccinated individuals. Results support the hypothesis that vaccination has an extensive protective effect against both critical conditions and death. Nonetheless, the relative magnitude of the protection in vaccinated individuals compared to those non-vaccinated appears to be higher against the former outcome than the latter, for reasons which need to be investigated further

COVID-19 Biomarkers for Critically Ill Patients: A Compendium for the Physician

Background: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of knowledge regarding known COVID-19 in critical patients. We searched PubMed® using the Boolean operators and identified all results on the PubMed® database of all studies regarding COVID-19 biomarkers. We selected studies regarding endothelium, cytokines, bacterial infection, coagulation, and cardiovascular biomarkers. Methods: We divided the results into four essential paragraphs: “Cytokine storm”, “Endothelium dysfunction and coagulation biomarkers in COVID-19”, “Biomarker of sepsis”, and Cardiovascular lung and new perspectives. Results: The assessments of the severe COVID-19 prognosis should monitor, over time, IL-6, soluble Von Willebrand factor (VWF), P-selectin, sCD40L, thrombomodulin, VCAM-1, endothelin- Troponin, D-dimer, LDH, CRP, and procalcitonin. Metabolomic alterations and ACE2 receptors represent new perspectives. Discussion and Conclusions: Early identification of critically ill patients has been crucial in the first COVID-19 pandemic wave for the sustainability of the healthcare emergency system and clinical management. Only through the early identification of the most severe patients can they be provided with the most appropriate treatments

Immunotherapy: The end of the "dark age" for metastatic triple-negative breast cancer?

The lack of effective therapies for metastatic triple-negative breast cancer (mTNBC) highlights the need for the development of novel treatment strategies. The cornerstone of treatment has long been represented by chemotherapy. Relevant evidence has recently emerged regarding the efficacy of immune checkpoint inhibitors, with the demonstration of a statistically significant improvement of progression-free survival with the addition of atezolizumab to nab-paclitaxel in the first-line treatment of mTNBC, accompanied by a substantial overall survival benefit in the PD-L1-positive subgroup. Despite this, it is necessary to identify the biomarkers that could allow a better selection of patients and combination regimens