Male Breast Cancer: a Review on Diagnosis, Treatment, and Survivorship.

PURPOSE OF REVIEW: Male breast cancer is a relatively uncommon and rare disease that is often managed based on evidence adopted from trials pertaining to female breast cancer due to low accrual rates or exclusion of males. This is despite the known differences in the biology and epidemiology of this condition. This review provides an update regarding the management and surveillance of male breast cancer. RECENT FINDINGS: Men with breast cancer tend to undergo more extensive surgery in the breast and axilla. The outcomes of male breast cancer compared to a similar subtype of female breast cancer appear worse when matched for stage. Systemic therapies remain predominantly based on recommendations for female breast cancer, although tamoxifen is the more optimal endocrine therapy for men than women. Surveillance with mammograms is recommended for patients harboring a breast cancer susceptibility gene but is otherwise not advised for men who have undergone a mastectomy. Notably, the role of other imaging modalities, including ultrasound and magnetic resonance imaging, is minimal. Although the focus on survivorship care among men is low, it is abundantly clear that this is a stigmatizing diagnosis for men, and they suffer from long-term physical and psychological sequelae following a diagnosis and treatment of breast cancer. In summary, providing more gender-inclusive care and advocating for increased representation of men in prospective breast cancer studies and clinical trials may help improve outcomes and provide enhanced support for this population.

Netiquette for social media engagement for oncology professionals.

Social media growth has revolutionized health care, facilitating user-friendly, rapid and global sharing of content. Within oncology, this allows for new frontiers in communication for cancer patients, caregivers and healthcare providers. As more physicians engage in online spaces, it is imperative that there are resources to assist in establishing a professional presence on social media. This article describes how to create a social media identity, best practices for engaging both in patient and caregiver spaces and professional communities, and how to address antagonistic and inappropriate behavior on social media with the goal of helping physicians develop an engaging, productive and enjoyable experience online.

A phase I trial of ganetespib in combination with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer.

BACKGROUND: Targeted therapies in HER2-positive metastatic breast cancer significantly improve outcomes but efficacy is limited by therapeutic resistance. HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90 inhibition can overcome trastuzumab resistance. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. We therefore tested ganetespib, a HSP90 inhibitor, in combination with paclitaxel and trastuzumab in patients with trastuzumab-refractory HER2-positive metastatic breast cancer. METHODS: In this phase I dose-escalation study, patients with trastuzumab-resistant HER2-positive metastatic breast cancer received weekly trastuzumab (2 mg/kg) and paclitaxel (80 mg/m2) on days 1, 8, 15, and 22 of a 28-day cycle with escalating doses of ganetespib (100 mg/m2, 150 mg/m2, and a third cohort of 125 mg/m2 if needed) on days 1, 8, and 15. Therapy was continued until disease progression or toxicity. The primary objective was to establish the safety and maximum tolerated dose and/or recommended phase II dose (RP2D) of this therapy. The secondary objectives included evaluation of the effects of ganetespib on the pharmacokinetics of paclitaxel, and to make a preliminary assessment of the efficacy of the combination therapy. RESULTS: Dose escalation was completed for the two main cohorts without any observed dose-limiting toxicities. Nine patients received treatment. The median prior lines of anti-HER2 therapy numbered three (range 2-4), including prior pertuzumab in 9/9 patients and ado-trastuzumab emtansine (T-DM1) in 8/9 patients. The most common grade 1/2 adverse events (AEs) were diarrhea, fatigue, anemia, and rash. There were no grade 4 AEs related to ganetespib. The overall response rate was 22% (2/9 patients had partial response) and stable disease was seen in 56% (5/9 patients). The clinical benefit rate was 44% (4/9 patients). The median progression-free survival was 20 weeks (range 8-55). CONCLUSION: The RP2D of ganetespib is 150 mg/m2 in combination with weekly paclitaxel plus trastuzumab. The combination was safe and well tolerated. Despite prior taxanes, pertuzumab, and T-DM1, clinical activity of this triplet regimen in this heavily pretreated cohort is promising and warrants further study in HER2-positive metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02060253 . Registered 30 January 2014.

Systemic Therapy for HER2-Positive Central Nervous System Disease: Where We Are and Where Do We Go From Here?

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at an increased risk of developing brain metastases. The incidence and prevalence of central nervous system (CNS) disease are increasing due to improved survival, which can be attributed to better systemic therapies for extracranial disease. The current standard of care for brain metastases includes a combination of surgery and/or radiation. Systemic therapies are typically reserved for patients with intracranial progression following radiation, due to their limited ability to cross the blood-brain barrier. None of the available anti-HER2 agents (trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine (T-DM1)) are currently approved for the treatment of brain metastases. Research is underway evaluating novel anti-HER2 agents, which have demonstrated CNS activity. This article discusses the current data on using anti-HER2 therapies to treat CNS disease as well as the newer anti-HER2 agents, which may overcome the current challenges faced in treating brain metastases in the HER2-positive patient population.

Targeting HER2 in ovarian and uterine cancers: challenges and future directions.

Targeting the human epidermal growth factor receptor 2 (HER2) has yielded major advances in breast cancer treatment. Accordingly, it has generated interest in targeting HER2 to treat gynecologic malignancies. Multiple studies have evaluated the rates of HER2 overexpression and/or amplification in ovarian and uterine cancers. HER2 has also been studied as a prognostic factor but resulting data has been contradictory. Moreover, clinical trials of HER2-directed therapies, including trastuzumab, pertuzumab, and lapatinib in ovarian and uterine cancers have been largely disappointing. Current research on HER2 in gynecologic malignancies has focused on identifying mechanisms of resistance and looking further into how HER2 signaling in gynecologic cancers differs from breast cancer. In this review, we highlight the existing data of targeting HER2 in ovarian and uterine carcinomas, many dating back more than a decade, and discuss future directions in pursuing HER2 as a potential target in these diseases.

Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature.

Hepatitis B reactivation can occur with cytotoxic chemotherapy in patients with hepatitis B and cancer. Reactivation can occur in a patient with chronic hepatitis, an inactive carrier, or one with resolved hepatitis. Clinical presentation may range from subclinical elevation of liver enzymes to fatal fulminant hepatic failure. Mammalian target of rapamycin inhibitors, which include everolimus, are a new generation of targeted agents that are currently approved for many cancers (since March 2009) including advanced hormone receptor positive, human epidermal growth factor receptor 2-negative breast cancer, in conjunction with exemestane (as of July 2012). We are therefore still learning the various adverse events that occur with this new class of agents. Here, we present an unfortunate case of fatal hepatitis B reactivation in a woman with metastatic breast cancer treated with everolimus and exemestane. We have detailed the controversies around hepatitis B screening prior to immunosuppressive therapy. Clinicians and patients should be aware of this rare but fatal complication prior to everolimus use, and a detailed history, screening for hepatitis B and prophylactic antiviral treatment should be considered.

Online Medical Misinformation in Cancer: Distinguishing Fact From Fiction.

It is without question that the Internet has democratized access to medical information, with estimates that 70% of the American population use it as a resource, particularly for cancer-related information. Such unfettered access to information has led to an increase in health misinformation. Fortunately, the data indicate that health care professionals remain among the most trusted information resources. Therefore, understanding how the Internet has changed engagement with health information and facilitated the spread of misinformation is an important task and challenge for cancer clinicians. In this review, we perform a meta-synthesis of qualitative data and point toward empirical evidence that characterizes misinformation in medicine, specifically in oncology. We present this as a call to action for all clinicians to become more active in ongoing efforts to combat misinformation in oncology.

Updates in Neoadjuvant Therapy for Triple Negative Breast Cancer.

Neoadjuvant therapy in breast cancer refers to systemic therapy administered prior to definitive surgery. It was originally developed for patients with locally advanced breast cancer (stage III) with the intention of downstaging unresectable tumors, and decreasing the extent of surgical intervention, including axillary lymph node dissection. For patients with inflammatory breast cancer, neoadjuvant therapy is considered a standard of care. Increasingly, the neoadjuvant setting is being utilized to accelerate drug development and approval in triple negative breast cancer, a diverse and aggressive subgroup for which no approved targeted therapies are currently available. This review discusses the use of pathologic complete response as a clinical trial endpoint, the use of imaging and biomarkers to predict response to therapy, and standard of care treatment for triple negative breast cancer. Finally, we review novel targets and drug trials in the neoadjuvant setting.

American Society of Clinical Oncology Road to Recovery Report: Learning From the COVID-19 Experience to Improve Clinical Research and Cancer Care.

This report presents the American Society of Clinical Oncology's (ASCO's) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.

The efficacy of trabectedin in treating ovarian cancer.

INTRODUCTION: The majority of women with epithelial ovarian cancer present with advanced stage disease and there is a critical need for novel drugs and treatment strategies to improve outcomes. Trabectedin is a unique cytotoxic agent with a complex mechanism of action. It binds to guanines in the N2 position in the minor groove of DNA and its cytotoxicity involves DNA repair pathways and transcription regulation. Trabectedin's activity is also related to the drug-induced changes of the tumor microenvironment. It has been shown to improve progression-free survival in combination with pegylated liposomal doxorubicin in patients with platinum-sensitive relapsed ovarian cancer. The most common adverse events experienced with trabectedin are nausea, vomiting, fatigue, neutropenia and transaminitis. Studies of biomarkers that are predictors of trabectedin benefit are underway. Areas covered: This review covers trabectedin's mechanism of action and pharmacology, the clinical development of the drug in ovarian cancer, ongoing trials, and the use of biomarkers to predict efficacy to trabectedin. Expert opinion: Ongoing phase III trials with biomarker studies will help to elucidate the patient population that will best benefit from trabectedin and pave the way for personalized treatment decisions and potential future approval of trabectedin in the United States.

Family-building After Breast Cancer: Considering the Effect on Adherence to Adjuvant Endocrine Therapy.

Adherence to endocrine therapy (ET) is a longstanding problem in breast cancer (BC) survivorship care, particularly among younger women. Younger patients have reported lower ET initiation rates and greater rates of early discontinuation and are considered an "at risk" group for nonadherence. For women who hope to have children in the future, concerns about premature menopause and the implications of postponing childbearing for the 5 to 10 years of ET are widespread. Preliminary evidence suggests that prioritizing fertility, along with concerns about side effects, leads to ET noninitiation and early discontinuation. Clinical efforts to improve adherence might need to consider patients' family-building goals during the course of treatment and to appropriately counsel patients according to their priorities and family-building intentions. Educational materials about family building after cancer are still not consistently available or provided. Helping patients to access trusted informational resources and decision support tools, in conjunction with medical counseling, will promote informed decisions regarding ET adherence and pregnancy that are medically appropriate. Such shared patient-provider decision-making about ET adherence and pregnancy could help to maximize patient autonomy by incorporating their values, preferences, and priorities into decisions, using providers' medical expertise.

Hyperactivated mTOR and JAK2/STAT3 Pathways: Molecular Drivers and Potential Therapeutic Targets of Inflammatory and Invasive Ductal Breast Cancers After Neoadjuvant Chemotherapy.

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data showed strong activation of the phosphatidylinositide-3-kinase/mammalian target of rapamycin (mTOR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, and expression of inflammatory cytokines and tumor-associated macrophages (TAMs). PATIENTS AND METHODS: Archival tumor tissue from 3 disease types (IBC treated with neoadjuvant chemotherapy [NAC], n = 45; invasive ductal carcinoma [IDC] treated with NAC [n = 24; 'treated IDC'; and untreated IDC [n = 27; 'untreated IDC']) was analyzed for the expression of biomarkers phospho-S6 (pS6) (mTOR), phospho-JAK2 (pJAK2), pSTAT3, interleukin (IL)-6, CD68 (monocytes, macrophages), and CD163 (TAMs). Surrounding nontumor tissue was also analyzed. RESULTS: Biomarker levels and surrogate activity according to site-specific phosphorylation were shown in the tumor tissue of all 3 disease types but were greatest in IBC and treated IDC and least in untreated IDC for pS6, pJAK2, pSTAT3, and IL-6. Of 37 IBC patients with complete biomarker data available, 100% were pS6-positive and 95% were pJAK2-positive. In nontumor tissue, biomarker levels were observed in all groups but were generally greatest in untreated IDC and least in IBC, except for JAK2. CONCLUSION: IBC and treated IDC display similar levels of mTOR and JAK2 biomarker activation, which suggests a potential mechanism of resistance after NAC. Biomarker levels in surrounding nontumor tissue suggested that the stroma might be activated by chemotherapy and resembles the oncogenic tumor-promoting environment. Activation of pS6 and pJAK2 in IBC might support dual targeting of the mTOR and JAK/STAT pathways, and the need for prospective studies to investigate combined targeted therapies in IBC.