Optimal Choice of Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer: Clinical Insights.

The neoadjuvant setting provides immense opportunities for translational research and drug development. The acceptance of pathological complete response (pCR) as a surrogate endpoint for clinical benefit has led to the widespread use of neoadjuvant treatment. Optimal neoadjuvant therapies are determined based on their ability to achieve the highest rates of pCR. Predicted rates of pCR for triple negative breast cancer (TNBC) treated with sequential taxane/anthracycline regimens range from 35% to 48%. With the addition of a platinum agent pCR rates of 55% are predicted. Further increases have been observed with the addition of immune checkpoint inhibitors to this standard chemotherapy backbone. In the pivotal KEYNOTE-522 clinical trial pCR rates of 65% and 69% were reported for chemotherapy plus pembrolizumab in the overall and PD-L1-positive subgroup respectively. The role of the neoadjuvant chemotherapy is less clear in hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer. In general, HR-positive cancers have the least chance of achieving a pCR after neoadjuvant chemotherapy, especially if they are low-grade. If neoadjuvant chemotherapy is given for high-risk HR-positive, HER2-negative breast cancer, standard adjuvant anthracycline/taxane regimens are appropriate. Optimum endocrine therapy is the standard-of-care in the adjuvant setting regardless of pCR. There are several genomic signatures available to guide decisions regarding adjuvant chemotherapy use however these assays are not routinely used in the neoadjuvant setting. For high-risk patients meeting the criteria for the monarchE trial adjuvant abemaciclib in addition to endocrine therapy is associated with an improvement in disease free survival (DFS) at 3 years. Based on the OlympiA trial patients with germline BRCA mutations should be considered for adjuvant olaparib therapy. In this article we review neoadjuvant clinical trials that guide optimum treatment options for TNBC and HR-positive, HER2-negative breast cancer.

SKAP2-BRAF fusion and response to an MEK inhibitor in a patient with metastatic melanoma resistant to immunotherapy.

A woman in her 40s presented to the emergency department with headache and unintentional weight loss in September 2018. Investigations revealed a widely metastatic pan-negative melanoma of unknown primary. She had multiple lines of treatment including combination immunotherapy and chemotherapy. Next-generation sequencing identified an SKAP2-BRAF fusion protein, and she was commenced on an MEK inhibitor in September 2019 with a partial response seen on restaging scans after 6 weeks and a dramatic fall in her lactate dehydrogenase from 2248 IU/L to 576 IU/L. Unfortunately, the response was not maintained and she died from progression of her cancer in January 2020. SKAP2-BRAF fusions have a dimerisation domain that paradoxically activates the mitogen-activated protein kinase pathway, resulting in hyperproliferation if first-generation or second-generation BRAF inhibitors are used. Our knowledge is limited regarding the complex effects of targeted therapy in rare BRAF fusion proteins.

Virtual oncology clinics during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in radical changes in the delivery of healthcare worldwide. Our oncology service (at an Irish national cancer centre) rapidly transitioned to the use of telemedicine or virtual clinics (VC) to minimise potential risk of exposure to COVID-19 amongst an immunosuppressed, high-risk population. Our study aimed to evaluate the use of VC in this setting. METHODS: An 18-point questionnaire was designed to investigate the patient experience of VC during the COVID-19 pandemic in Ireland and compliance with guidelines developed in Ireland to conduct VC and the role of VC in the future. Questionnaires were distributed following the receipt of verbal consent from patients during the VC. Descriptive statistics were utilised for data analysis using SPSS®. RESULTS: One hundred and four patients returned completed surveys (n = 104/164, 63% response rate). Overall satisfaction levels were high with most patients (n = 58/100, 58%; no answer provided (NAP), n = 4) equally satisfied or nearly equally satisfied with VC in comparison to a usual clinic encounter. The majority of patients felt that there should be a role for VC in the future (n = 84/102, 82%; NAP, n = 2). The majority of patients (n = 61/99, 61%; NAP, n = 5) were very relieved to avoid a hospital visit due to perceived risk of potential exposure to COVID-19. CONCLUSION: The majority of oncology patients were satisfied with a VC encounter. VC may have a role in the future of medical care in Ireland post the COVID-19 pandemic.

Are we reaping what we sow? Gender diversity in surgery: a survey of medical students.

BACKGROUND: A survey of medical students from the Royal College of Surgeons in Ireland (RCSI) at Dublin, Perdana and Penang in Malaysia was undertaken in an attempt to explore attitudes towards a career in surgery and document potential differences between male and female students' perceptions of a surgical career. METHOD: A hyperlink to an online, anonymised questionnaire was distributed to medical students in 3rd, 4th and final year at three RCSI campuses. Basic descriptive statistics were used to describe the responses to individual questions and appropriate statistical tests used to compare male and female responses to questions. RESULTS: A total of 464 completed questionnaires were analysed. Almost 40% (n=185) were male and 60% (n=279) were female. Males were significantly more influenced by remuneration than females (p<0.001) towards a choice of surgical career. Females were significantly more influenced in their choice of surgical career by part-time work (p<0.001), parental leave (p<0.001), working hours (p<0.001) and length of residency (p=0.003). During surgical attachments, females were significantly more likely to admit feeling intimidated than males (p=0.002) and males more likely to report feeling confident (p<0.001). Ninety-six per cent of students felt they would be more likely to pursue a career in which they had identified a positive role model, with female medical students three times more likely to have identified a female role model than males. CONCLUSION: According to our study, preference for a career in surgery declines with advancing years in medical school for both males and females. Medical students report high levels of feeling intimidated or ignored during their surgical placements, and enthusiasm for surgery reduces during medical school with exposure to this. These findings, along with the importance of role modelling, add further urgency to the need to address factors which make surgery less appealing to female medical graduates.

Extended Adjuvant Endocrine Therapy in Hormone Receptor-Positive Early Breast Cancer.

Despite meaningful, incremental improvements in detection, local treatment and adjuvant systemic treatments for breast cancer, there remains a significant risk of late relapse in hormone receptor (HR)-positive disease. 5 years of tamoxifen or an aromatase inhibitor for all patients with HR-positive early breast cancer is considered standard; however, there are now data to support an extended approach using up to 10 years of treatment. This review will provide some historical background on endocrine therapy and summarize the key clinical trials that demonstrate the small absolute benefit of extended adjuvant therapy. We provide suggested treatment algorithms for both premenopausal and postmenopausal patients and an overview of ongoing adjuvant trials.