Weight-centric prevention of cancer.

Background: The link between excess adiposity and carcinogenesis has been well established for multiple malignancies, and cancer is one of the main contributors to obesity-related mortality. The potential role of different weight-loss interventions on cancer risk modification has been assessed, however, its clinical implications remain to be determined. In this clinical review, we present the data assessing the effect of weight loss interventions on cancer risk. Methods: In this clinical review, we conducted a comprehensive search of relevant literature using MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies from inception to January 20, 2024. In this clinical review, we present systematic reviews and meta-analysis, randomized clinical trials, and prospective and retrospective observational studies that address the effect of different treatment modalities for obesity in cancer risk. In addition, we incorporate the opinions from experts in the field of obesity medicine and oncology regarding the potential of weight loss as a preventative intervention for cancer. Results: Intentional weight loss achieved through different modalities has been associated with a reduced cancer incidence. To date, the effect of weight loss on the postmenopausal women population has been more widely studied, with multiple reports indicating a protective effect of weight loss on hormone-dependent malignancies. The effect of bariatric interventions as a protective intervention for cancer has been studied extensively, showing a significant reduction in cancer incidence and mortality, however, data for the effect of bariatric surgery on certain specific types of cancer is conflicting or limited. Conclusion: Medical nutrition therapy, exercise, antiobesity medication, and bariatric interventions, might lead to a reduction in cancer risk through weight loss-dependent and independent factors. Further evidence is needed to better determine which population might benefit the most, and the amount of weight loss required to provide a clinically significant preventative effect.

Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study.

INTRODUCTION: Accurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice. METHODS AND ANALYSIS: In this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs. ETHICS AND DISSEMINATION: This study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT05214144; Pre-results.

Breast cancer and gender-affirming hormone therapy for transgender and gender-diverse (TGD) individuals.

Transgender and gender-diverse (TGD) individuals are at risk for breast cancer, but are less likely to undergo screening mammograms and appear to suffer poorer cancer-related outcomes than cisgender women. Gender-affirming hormone therapy (GAHT) may be lifesaving for TGD individuals from the perspective of affirming their core identities; however, the effects of GAHT on cancer development, progression, and outcomes are poorly understood.

Preparing Hematology/Oncology Fellows for Success: Implementing an Annual Career Development and Research Retreat.

Multiple factors, including job satisfaction, personality traits, and training experiences, influence the career trajectory of hematology/oncology fellows. In an effort to expose hematology/oncology fellows to (1) the various careers in oncology, (2) a diverse group of speakers for future mentorship, and (3) research opportunities, and grant writing experience, we established an annual career development and research retreat. During the retreat, we engaged speakers who covered a range of career trajectories, including academic, private practice, industry, government, and administrative paths. We introduced clinicians and researchers with a track record of providing top-notch mentorship to fellows with aligning interests and detailed research opportunities and grant writing. The sessions were led by senior fellows, and we adopted an in-person and virtual hybrid model to allow speakers from various institutions to participate. Feedback from participants, as gathered through surveys, indicated positive responses: all respondents reported that this retreat was "extremely" or "very helpful," and a majority expressed their intent to pursue academic careers. The curriculum and structure of this retreat may help to inform the development of fellowship career development and research retreats at other institutions.

Sexual Dysfunction in Patients With Metastatic Breast Cancer.

BACKGROUND: Sexual well-being is a key determinant of quality of life. Sexual dysfunction in patients with metastatic breast cancer (MBC) is understudied. PATIENTS AND METHODS: Patients were eligible for this study if they participated in the Mayo Clinic Breast Disease Registry (MCBDR), had a diagnosis of de novo MBC, and responded to a question about sexual dysfunction at the baseline MCBDR survey. Participants reported their sexual dysfunction on a scale of 0 (no dysfunction) to 10 (severe dysfunction) at baseline and then annually for 4 years. Participants answered additional sexual symptom questions in years 2 and 4. Associations between patient attributes and the presence and severity of sexual dysfunction, changes in sexual dysfunction from baseline to subsequent surveys, and associations between specific sexual symptoms and severity of sexual dysfunction were assessed. RESULTS: One hundred three patients with de novo MBC answered the sexual dysfunction question at baseline. The prevalence of any sexual dysfunction (score of 1-10) was 56.3% at baseline (n = 103), 57.1 % at year 1 (n = 77), 80.4% at year 2 (n = 46), 65.8% at year 3 (n = 38), and 85% at year 4 (n = 20). Vaginal dryness was reported by approximately 49% and 39% of patients in years 2 and 4 respectively. Vaginal dryness was associated with higher severity of sexual dysfunction. CONCLUSIONS: Self-reported sexual dysfunction is frequent in women with de novo MBC. Vaginal dryness is a frequently reported treatable symptom associated with higher severity of sexual dysfunction. Clinicians should assess patients with MBC for sexual dysfunction and discuss potential treatment strategies.

Retrospective cohort study of CDK4/6-inhibitor-induced alopecia in breast cancer patients.

PURPOSE: Dermatologic adverse events commonly result in the interruption of oncologic treatment, and targeted therapies are the most frequently interrupted class of anticancer agents. Alopecia is a common cutaneous adverse event reported with CK4/6i therapy. Though the clinical characteristics and therapeutic response of EIA have been well documented, few studies have characterized alopecia in patients treated with CDK4/6i. METHODS: This study analyzed a retrospective cohort of 28 breast cancer patients diagnosed with endocrine-induced alopecia (EIA) or CDKiA. Comparative analysis of the clinical characteristics of alopecia and therapeutic response to minoxidil was conducted. Therapeutic response to minoxidil (LDOM or topical [5%] solution or foam) was assessed by both Dean Scale and qualitative clinical improvement by comparison of pretreatment and posttreatment clinical images by single-blinded, board-certified academic dermatologists (ST and BD). RESULTS: CDKiA was clinically similar to androgenetic alopecia and specific vertex involvement was more common in patients treated with CDK4/6i + ET than endocrine monotherapy (n = 7 [70.0%] vs n = 4 [36.4%]; p = 0.04), respectively. After 4-6 months of minoxidil, there was a moderate to significant qualitative alopecia improvement in 80% of CDKiA patients versus 94.4% of EIA patients. Additionally, superior improvement of mean Dean Score grade was observed in EIA (with change from pre- to posttreatment - 0.44; p = 0.0002). CONCLUSION: Compared to endocrine monotherapy, patients on combination CDK4/6i + ET had greater extent of vertex involvement and were more recalcitrant to minoxidil. The preferential vertex involvement observed in CDKiA suggests that combination therapy with minoxidil and topical antiandrogens with poor systemic absorption should be studied in this setting.

Advances in the care of breast cancer survivors.

Breast cancer survivors may experience significant after effects from diagnoses of breast cancer and cancer directed therapies. This review synthesizes the evidence about optimal management of the sequelae of a diagnosis of breast cancer. It describes the side effects of chemotherapy and endocrine therapy and evidence based strategies for management of such effects, with particular attention to effects of therapies with curative intent. It includes strategies to promote health and wellness among breast cancer survivors, along with data to support the use of integrative oncology strategies. In addition, this review examines models of survivorship care and ways in which digital tools may facilitate communication between clinicians and patients. The strategies outlined in this review are paramount to supporting breast cancer survivors' quality of life.

Measuring symptoms and toxicities: a 35-year experience.

PURPOSE: When conducting trials aimed at the improvement of cancer-related and/or cancer treatment-related toxicities, it is important to determine the best means of measuring patients' symptoms. METHODS: The authors of this current manuscript have an extensive experience with the conduct of symptom-control clinical trials. This experience is utilized to provide insight into the best means of measuring symptoms caused by cancer and/or cancer therapy. RESULTS: Patient-reported outcome data are preferable for measuring bothersome symptoms, for determining toxicities caused by treatment approaches, and offer more accurate and detailed information compared with health care practitioners recording their impressions of patient experiences. Well-validated patient friendly measures are recommended when they are available. When such are not readily available, face-valid, single-item numerical rating scales are effective instruments to document both treatment trial outcomes and cancer treatment side effects/toxicities. CONCLUSION: The use of numerical rating scales are effective means of measuring symptoms caused by cancer, by cancer treatments, and/or alleviated by symptom control treatment approaches.

Germline BRCA-Mutated HER2-Negative Advanced Breast Cancer: Overcoming Challenges in Genetic Testing and Clinical Considerations When Using Talazoparib.

Genetic testing is essential to the diagnosis and management of patients with breast cancer. For example, women who carry mutations in BRCA1/2 genes have an increased lifetime risk of breast cancer and the presence of these mutations may sensitize the patient to treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. Two PARP inhibitors are approved by the US Food and Drug Administration for patients with germline BRCA-mutated advanced breast cancer (olaparib and talazoparib). The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer (Version 2.2023) recommend that all patients with recurrent or metastatic breast cancer (mBC) be assessed for the presence of germline BRCA1/2 mutations. However, many women eligible for genetic testing do not receive it. Here, we provide our perspectives on both the importance of genetic testing and the challenges patients and community clinicians may face when trying to access genetic testing. We also present a hypothetical case study involving a female patient with germline BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative mBC to highlight potential clinical considerations on the use of talazoparib, including the decision to initiate therapy, dosing considerations, potential drug-drug interactions, and managing side effects. This case illustrates the benefits of a multidisciplinary approach to managing patients with mBC and involving the patient in the decision-making process. This patient case is fictional and does not represent events or a response from an actual patient; this fictional case is for educational purposes only.

An evaluation of the effect of lithium on taxane-induced neuropathy.

PURPOSE: No medications are known to protect against chemotherapy-induced peripheral neuropathy (CIPN). Pre-clinical models suggest that lithium may lessen taxane-induced neuropathy. Our aim was to use clinical data to assess whether concurrent lithium usage decreased the frequency or severity of CIPN in patients receiving taxane chemotherapy. METHODS: A retrospective analysis was performed using the electronic health record at Mayo Clinic to identify all patients prescribed concurrent lithium and paclitaxel. Four controls were matched to each case based on clinical variables. Neuropathy severity was graded from available patient and clinician reports. Rates of any neuropathy, dose reduction for CIPN, and treatment discontinuation for CIPN were compared. Conditional regression analysis was performed with propensity score matching. RESULTS: Six patients, receiving concurrent lithium and paclitaxel, were included in the analysis, and compared to 24 control cases. A similar number of paclitaxel cycles were administered to both groups. Any neuropathy was experienced by 33% (2/6) of patients receiving lithium and 38% (9/24) patients who did not receive lithium (p = 1.000). There was no difference in neuropathy severity (p = 0.8565), rate of chemotherapy dose reduction (17% vs. 17%, p = 1.000), or treatment discontinuation (17% vs 4%, p = 0.3655) for CIPN. In the propensity score analysis, the odds ratio for developing any neuropathy was 0.63 (95% confidence interval, 0.06 to 6.96, p = 0.7079). CONCLUSIONS: Lithium does not appear to significantly lessen the risk of neuropathy for patients receiving paclitaxel. IMPLICATIONS FOR CANCER SURVIVORS: Targeted approaches for preventing CIPN are desperately needed. Despite sound scientific rationale, the current study did not identify neuroprotective properties of lithium.

A five arm natural history study of nasal vestibulitis.

INTRODUCTION: Nasal symptoms are frequently reported by patients undergoing chemotherapy. METHODS: Eligible patients planning to receive paclitaxel, docetaxel, nab-paclitaxel, bevacizumab without a concomitant taxane, or "other" (non-taxane, non-bevacizumab) chemotherapy regimens were invited to participate in this prospective study. Patients reported nasal symptoms prior to each dose of chemotherapy. RESULTS: The percentage of patients (95% CI) who reported nasal symptoms was the same for patients who received bevacizumab or nab-paclitaxel, 82.6% (61.2%, 95.1%). There were no significant differences among the proportions of patients experiencing nasal symptoms within the paclitaxel, nab-paclitaxel, and bevacizumab cohorts. Patients in the nab-paclitaxel cohort were more likely to experience symptoms than those in the non-taxane non-bevacizumab cohort or docetaxel cohort (p = 0.001, p = 0.001). Patients in the bevacizumab cohort were more likely to experience nasal symptoms than those in the non-taxane non-bevacizumab cohort (p = 0.03). CONCLUSION: Nasal vestibulitis symptoms are common in patients receiving chemotherapy, especially those receiving paclitaxel, docetaxel, and bevacizumab. Further investigations into treatments of this symptom complex are warranted.

Integrating 4 Measures to Evaluate Physical Function in Patients with Cancer (In4M): Protocol for a prospective study.

Introduction: Accurate, patient-centered evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterize the longitudinal measurement characteristics of physical function assessments, including clinician-reported physical function (ClinRo), patient-reported physical function (PRO), performance outcome tests (PerfO) and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice. Methods and analysis: In this prospective study, we are enrolling 200 English- and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive standard of care intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centered health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity, and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multi-modal physical function data collection in real-world patients with cancer will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform, and PROs. Ethics and dissemination: This study has received approval from IRBs at Mayo Clinic, Yale University, and the U.S. Food & Drug Administration. Results will be made available to participants, funders, the research community, and the public. Registration Details: The trial registration number for this study is NCT05214144. Strengths & Limitations: This study addresses an important unmet need by characterizing the performance characteristics of multiple patient-centered physical function measures in patients with cancerPhysical function is an important and undermeasured clinical outcome. Scientifically rigorous capture and measurement of physical function constitutes a key component of cancer treatment tolerability assessment both from a regulatory and clinical perspective.This study will include patients with lymphoma or breast cancer receiving a broad range of cytotoxic chemotherapy regimens. While recruitment will occur at two academic sites, patients who ultimately receive treatment at local community sites will be included.A patient-centered health data aggregating platform facilitates the delivery of patient-reported outcome measures and collection of wearable data to researchers, while reducing patient burden compared to traditional patient-generated data collection and aggregation methodsHeterogeneity in patient willingness or comfort engaging with mobile products including smartphones and wearables, enrollment primarily at large academic centers, and the modest sample size are potential limitations to the external validity of the study.

Hair loss during and after breast cancer therapy.

For patients diagnosed with breast cancer, alopecia can be a distressing side effect of treatment. Major surgeries, cytotoxic chemotherapy, and endocrine therapy may result in several different types of alopecia. This article reviews the underlying mechanisms, etiology, prevention strategies, and treatment options for chemotherapy-induced alopecia, telogen effluvium, and endocrine-induced alopecia. Here, we aim to provide breast oncologists with a review of the types of hair loss related to cancer therapy and current preventative and treatment options to facilitate informative patient counseling.

Evidence-Based Guidance for Breast Cancer Survivorship.

Breast cancer survivorship care includes management of lingering physical symptoms, supports to address the emotional toll exacted by a cancer diagnosis and cancer therapies, monitoring and optimization of cardiac and bone health, general wellness promotion, reproductive health care, surveillance for cancer recurrence, care coordination, and efforts to mitigate health disparities.

Late Breast Cancer Survivorship: Side Effects and Care Recommendations.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.

Natural history of nasal vestibulitis associated with paclitaxel, docetaxel, and other chemotherapy agents: a Minnesota Cancer Clinical Trials Network (MNCCTN) study.

PURPOSE: To describe the natural history of nasal vestibulitis in patients receiving taxane chemotherapy, including incidence, severity, and associated symptoms. METHODS: Eligible patients with minimal or no baseline nasal symptoms were enrolled in this natural history study at initiation of a new chemotherapy regimen. Patients completed nasal symptom logs each time they received a chemotherapy dose. This manuscript reports upon the patients who received paclitaxel, docetaxel, or non-taxane non-bevacizumab chemotherapy. The proportions of patients within each cohort reporting any treatment-emergent nasal symptoms were estimated, with corresponding exact 95% confidence intervals. A cumulative incidence function was estimated within the chemotherapy cohorts to calculate the cumulative incidence rate of treatment-emergent nasal vestibulitis, treating death and disease progression as competing risks. RESULTS: Of the 81 evaluable patients, nasal symptoms were reported by 76.5% (58.8%, 89.3%) receiving paclitaxel, 54.2% (32.8%, 74.5%) receiving docetaxel, and 47.8% (26.8%, 69.4%) receiving non-taxane and non-bevacizumab chemotherapy. Of the three pairwise chemotherapy group comparisons, both the tests comparing the cumulative incidence function between the paclitaxel and non-taxane non-bevacizumab chemotherapy cohorts and between the paclitaxel and docetaxel cohorts achieved statistical significance at the 5% level with a higher incidence of treatment-emergent nasal vestibulitis in the paclitaxel cohort in both comparisons (P = 0.026 and P = 0.035, respectively). These significant differences were retained in the cumulative incidence function regression analysis controlling for age, smoking history, allergies, and asthma. Most patients in the paclitaxel cohort reported nasal symptoms as moderate or severe (56%). CONCLUSION: Patients receiving paclitaxel chemotherapy experience a high incidence of nasal symptoms.

Breast Cancer in Adolescent and Young Adult Women Under the Age of 40 Years.

In the United States, one in 196 women is diagnosed with breast cancer under the age of 40 years. Adolescents and young adults (AYAs), of age 15-39 years at diagnosis, experience a number of unique challenges when confronting breast cancer. The incidence of invasive breast cancer has increased among AYA women in the United States since 2004, and most of this change is due to an increase in young women diagnosed with distant disease. AYAs are more likely than older women to present with aggressive subtypes and advanced disease, and they often require systemic staging at diagnosis. Clinical trials should be considered whenever possible, particularly in AYAs with locally advanced or metastatic disease at diagnosis and those with disease progression or recurrence. A significant proportion of AYAs carry germline cancer predisposition mutations, which necessitates prompt genetic testing for all AYAs at diagnosis and may influence choice of local therapy. Suppression of ovarian function, as an adjunct to chemotherapy, may improve breast cancer survival in AYAs. To provide optimal care for AYAs with breast cancer, clinicians should engage multidisciplinary teams that offer fertility preservation, genetic counseling, physical and occupational therapy, nutrition, and psychosocial support, along with medical expertise in tailoring cancer-directed therapy and symptom management toward young women.