ABSTRACT
PURPOSE: Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort. METHODS: In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data. RESULTS: We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30). CONCLUSION: This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.
Subject(s)
Breast Neoplasms , Meningeal Neoplasms , Humans , Female , Middle Aged , Retrospective Studies , Aged , Adult , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Breast Neoplasms/mortality , Meningeal Neoplasms/secondary , Meningeal Neoplasms/therapy , Meningeal Neoplasms/mortality , Aged, 80 and over , Meningeal Carcinomatosis/secondary , Meningeal Carcinomatosis/therapy , Meningeal Carcinomatosis/mortality , Receptor, ErbB-2/metabolism , PrognosisABSTRACT
Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of 68Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with 18F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of 68Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with 68Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUVmax was significantly higher on 68Ga-FAP-2286 PET than on 18F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: 68Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,68Ga-FAP-2286 PET had consistently higher uptake than 18F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.
Subject(s)
Fluorodeoxyglucose F18 , Gallium Radioisotopes , Neoplasms , Positron-Emission Tomography , Radiometry , Humans , Fluorodeoxyglucose F18/pharmacokinetics , Male , Female , Neoplasms/diagnostic imaging , Neoplasms/metabolism , Positron-Emission Tomography/methods , Middle Aged , Tissue Distribution , Aged , Adult , Radiopharmaceuticals/pharmacokinetics , Aged, 80 and over , QuinolinesABSTRACT
BACKGROUND: Cancer-related cognitive impairment (CRCI) and anxiety co-occur in patients with cancer. Little is known about mechanisms for the co-occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co-occurrence of self-reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co-occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways. METHODS: Patients completed the Attentional Function Index and the Spielberger State-Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration-multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways. CONCLUSIONS: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions.
Subject(s)
Anxiety , Neoplasms , Neurodegenerative Diseases , Self Report , Humans , Female , Male , Middle Aged , Neoplasms/psychology , Neoplasms/complications , Neurodegenerative Diseases/psychology , Aged , Signal Transduction , Cognitive Dysfunction/etiology , AdultABSTRACT
PURPOSE OF REVIEW: In this Perspective we share the personal story of a 33-year-old patient diagnosed with metastatic breast cancer and her journey through fertility preservation, surrogacy, and eventually motherhood, highlighting misconceptions about fertility preservation in this population. RECENT FINDINGS: There are nearly 1 million women under the age of 50 diagnosed and living with cancer in the USA. These patients are met with life-altering decisions, including those that may limit their reproductive ability. While there have been tremendous advances and advocacy in the field of oncofertility, there has been limited focus on patients with advanced stage or metastatic cancer. We describe five key misconceptions surrounding fertility preservation in patients with advanced stage cancer, offering a review of the literature and our approach to challenging topics like desiring fertility preservation in the face of Stage 4 disease, the safety and timing of ovarian stimulation during cancer treatment, and passing away following fertility preservation. We review the importance of assessing perceptions of fertility preservation in patients with metastatic cancer and highlight the lack of research in this area as a call to action.
Subject(s)
Breast Neoplasms , Fertility Preservation , Adult , Female , Humans , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Fertility Preservation/methods , Neoplasm Metastasis , Neoplasm Staging , Ovulation InductionABSTRACT
BACKGROUND: Breast cancer patients experienced heightened anxiety during the pandemic. Also, modifications to clinical trial activities allowing for virtual platforms, local assessments, and greater flexibility were introduced to facilitate participation. We sought to evaluate the association between pandemic-related anxiety and willingness to participate in trials and how pandemic-era modifications to trial activities affect the decision to participate. METHODS: We conducted an online survey from August to September, 2021 of patients with breast cancer assessing pandemic-related anxiety; clinical trials knowledge and attitudes; willingness to participate during and before the pandemic; and how each modification affects the decision to participate. Fisher's exact tests evaluated differences in proportions and two-sample t-tests evaluated differences in means. The association of pandemic-related anxiety with a decline in willingness to participate during compared to prior to the pandemic was modeled using logistic regression. RESULTS: Among 385 respondents who completed the survey, 81% reported moderate-severe pandemic-related anxiety. Mean willingness to participate in a trial was lower during the pandemic than prior [2.97 (SD 1.17) vs. 3.10 (SD 1.09), (p < 0.001)]. Severe anxiety was associated with higher odds of diminished willingness to participate during the pandemic compared to prior (OR 5.07). Each of the modifications, with the exception of opting out of research-only blood tests, were endorsed by >50% of respondents as strategies that would increase their likelihood of deciding to participate. CONCLUSIONS: While pandemic-related anxiety was associated with diminished willingness to participate in trials, the leading reasons for reluctance to consider trial participation were unrelated to the pandemic but included worries about not getting the best treatment, side effects, and delaying care. Patients view trial modifications favorably, supporting continuation of these modifications, as endorsed by the National Cancer Institute and others.
Subject(s)
Breast Neoplasms , Clinical Trials as Topic , Pandemics , Patient Participation , Female , Humans , Anxiety/etiology , Breast Neoplasms/therapy , Surveys and QuestionnairesABSTRACT
BACKGROUND: The effect of trastuzumab therapy on left atrial (LA) function remains largely unknown. Our aim was to assess the changes in LA strain parameters longitudinally in patients treated with trastuzumab. METHODS: We retrospectively studied 170 patients with stage I-IV HER2+ breast cancer. All patients had baseline echocardiograms and repeat echocardiograms at 3 months and after 1 year. We measured LA strain at all three time points. Changes in LA strain and strain rate (sr) parameters were evaluated using repeated-measures mixed-effects models. The cohort was stratified according to development of cancer therapeutics-related cardiac dysfunction (CTRCD) during follow-up. RESULTS: The mean age was 52.7 ± 13.8 years, 25.3% had hypertension and 16.0% had metastatic disease. Multiple LA strain parameters (predicted delta value, [95%CI]) showed statistically significant declines in patients who developed CTRCD from baseline to the 3-month follow-up after multivariable adjustment; LA reservoir strain (LAεres ): -4.7%; [-8.1% to -1.3%], p = .007; LA conduit strain (LAεcon ): -2.8%; [-5.3% to -.4%], p = .021); and LAεres sr: -.2/s; [-.3/s to -.09/s], p < .001). In patients who did not develop CTRCD, LA strain parameters declined significantly but to a smaller degree than in the CTRCD group (LAεres : -1.7%; [-3.1% to -.3%], p = .020, LAεcon : -2.2%; [-3.3% to -1.1%], p < .001, and LA booster pump strain : -2.4%; [-3.5% to -1.4%], p < .001). LA strain rates did not decline significantly in the non-CTRCD group. CONCLUSION: Trastuzumab treatment was associated with declines in LA strain parameters in patients with breast cancer. The largest declines were observed in patients who developed CTRCD during treatment.
Subject(s)
Breast Neoplasms , Heart Diseases , Humans , Adult , Middle Aged , Aged , Female , Trastuzumab/adverse effects , Breast Neoplasms/drug therapy , Retrospective Studies , Heart Diseases/complications , Heart Atria/diagnostic imaging , Ventricular Function, LeftABSTRACT
PURPOSE: This study characterizes attitudes and decision-making around the desire for future children in young women newly diagnosed with early-stage breast cancer and assesses how clinical factors and perceived risk may impact these attitudes. METHODS: This is a prospective study in women < 45 years with newly diagnosed stage 1-3 breast cancer. Patients completed a REDCap survey on fertility and family-building in the setting of hypothetical risk scenarios. Patient, tumor, and treatment characteristics were collected through surveys and medical record. RESULTS: Of 140 study patients [median age = 41.4 (range 23-45)], 71 (50.7%) were interested in having children. Women interested in future childbearing were younger than those who were not interested (mean = 35.2 [SD = 5.2] vs 40.9 years [3.90], respectively, p < 0.001), and more likely to be childless (81% vs 31%, p < 0.001). 54 women (77.1% of patients interested in future children) underwent/planned to undergo oocyte/embryo cryopreservation before chemotherapy. Interest in future childbearing decreased with increasing hypothetical recurrence risk, however 17% of patients wanted to have children despite a 75-100% hypothetical recurrence risk. 24.3% of patients wanted to conceive < 2 years from diagnosis, and 35% of patients with hormone receptor positive tumors were not willing to complete 5 years of hormone therapy. CONCLUSION: Many young women diagnosed with early-stage breast cancer prioritize childbearing. Interest in having a biologic child was not associated with standard prognostic risk factors. Interest decreased with increasing hypothetical recurrence risk, though some patients remained committed to future childbearing despite near certain hypothetical risk. Individual risk assessment should be included in family-planning discussions throughout the continuum of care as it can influence decision-making.
Subject(s)
Breast Neoplasms , Fertility Preservation , Infertility, Female , Humans , Female , Adult , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Prospective Studies , FertilityABSTRACT
OBJECTIVE: HER2 mutations are associated with poor prognosis and are detected in 3-6% of cervical cancers. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, had activity in several HER2-mutant cancer types in the phase 2 SUMMIT basket study. We present updated and final results from the cervical cancer cohort of SUMMIT. METHODS: Eligible patients had HER2-mutant, metastatic or recurrent cervical cancer progressing after platinum-based treatment for advanced/recurrent disease. Patients received neratinib 240â¯mg/day; loperamide was mandatory during cycle 1. Confirmed objective response rate (ORR) was the primary endpoint. Duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), and safety were secondary endpoints. RESULTS: Twenty-two patients were enrolled; 18 (81.8%) had endocervical adenocarcinoma; median two prior systemic chemotherapy regimens (range 1-4). The most common HER2 variant was S310F/Y mutation (nâ¯=â¯13; 59.1%). Four patients had confirmed partial responses (ORR 18.2%; 95% CI 5.2-40.3); 6 had stable disease ≥16â¯weeks (CBR 45.5%; 95% CI 24.4-67.8). Median DoR was 7.6â¯months (95% CI 5.6-12.3). Median PFS was 5.1â¯months (95% CI 1.7-7.2). All-grade diarrhea (90.9%), nausea (54.5%), and constipation (54.5%) were the most common adverse events. Five patients (22.7%) reported grade 3 diarrhea. There were no grade 4 adverse events, no diarrhea-related treatment discontinuations, and two grade 5 adverse events, unrelated to neratinib: dyspnea (nâ¯=â¯1) and embolism (nâ¯=â¯1). CONCLUSIONS: Neratinib resulted in durable responses and disease control in patients with HER2-mutant metastatic/recurrent cervical cancer in SUMMIT. These findings support next-generation sequencing and tailored therapy for select patients with advanced cervical cancer. All responses occurred in patients with endocervical adenocarcinoma. Further assessment of neratinib in this setting is warranted. TRIAL REGISTRATION NUMBER: NCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).
Subject(s)
Adenocarcinoma , Quinolines , Uterine Cervical Neoplasms , Humans , Female , Receptor, ErbB-2/genetics , Treatment Outcome , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Quinolines/adverse effects , Diarrhea/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adenocarcinoma/drug therapyABSTRACT
PURPOSE: We hypothesized that eribulin combined with cyclophosphamide (EC) would be an effective combination with tolerable toxicity for the treatment of advanced breast cancer (ABC). METHODS: Patients with histologically confirmed metastatic or unresectable ABC with any number of prior lines of therapy were eligible to enroll. In the dose escalation cohort, dose level 0 was defined as eribulin 1.1 mg/m2 and cyclophosphamide 600 mg/m2, and dose level 1 was defined as eribulin 1.4 mg/m2 and cyclophosphamide 600 mg/m2. Eribulin was given on days 1 and 8 and cyclophosphamide on day 1 of a 21-day cycle. In the dose expansion cohort, enrollment was expanded at dose level 1. The primary objective was clinical benefit rate (CBR), and secondary objectives were response rate (RR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: No dose-limiting toxicities were identified in the dose escalation cohort (n = 6). In the dose expansion cohort, an additional 38 patients were enrolled for a total of 44 patients, including 31 patients (70.4%) with hormone receptor-positive (HR +)/HER2- disease, 12 patients (27.3%) with triple-negative breast cancer (TNBC), and 1 patient (2.3%) with HR + /HER2 + disease. Patients had a median age of 56 years (range 33-82 years), 1 prior line of hormone therapy (range 0-6), and 2 prior lines of chemotherapy (range 0-7). CBR was 79.5% (35/44; 7 partial response, 28 stable disease) and the median DOR was 16.4 weeks (range 13.8-21.1 weeks). Median PFS was 16.4 weeks (95% CI: 13.8-21.1 weeks). The most common grade 3/4 adverse event was neutropenia (47.7%, n = 21). Fourteen of 26 patients (53.8%) with circulating tumor cell (CTC) data were CTC-positive ([Formula: see text] 5 CTC/7.5 mL) at baseline. Median PFS was shorter in patients who were CTC-positive vs. negative (13.1 vs 30.6 weeks, p = 0.011). CONCLUSION: In heavily pretreated patients with ABC, treatment with EC resulted in an encouraging CBR of 79.5% and PFS of 16.4 weeks, which compares favorably to single-agent eribulin. Dose reduction and delays were primarily due to neutropenia. The contribution of cyclophosphamide to eribulin remains unclear but warrants further evaluation. NCT01554371.
Subject(s)
Breast Neoplasms , Neutropenia , Polyether Polyketides , Triple Negative Breast Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Cyclophosphamide/adverse effects , Furans/therapeutic use , Ketones/adverse effects , Neutropenia/drug therapy , Receptor, ErbB-2 , Treatment Outcome , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/etiologyABSTRACT
PURPOSE: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. PATIENTS AND METHODS: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. RESULTS: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. CONCLUSIONS: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.
Subject(s)
Breast Neoplasms , Recombinant Fusion Proteins , Female , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bayes Theorem , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Neoadjuvant Therapy , Paclitaxel/adverse effects , Receptor, ErbB-2/metabolism , Receptor, TIE-2 , Trastuzumab/adverse effectsABSTRACT
BACKGROUND: Comorbidities and symptoms in metastatic breast cancer patients impact treatment decisions and influence prognosis and quality of life. The objective of this study is to examine the concordance between physician documentation and patient reports of comorbidities and symptoms to understand their comparative effectiveness. METHODS: New patients with metastatic breast cancer completed an electronic intake survey assessing patient health history and symptoms. Physician documentation across 54 comorbidities and 42 symptoms was abstracted from notes for the corresponding clinic visits between November 2016 and March 2020. Concordance between patient reports and medical records for each condition and hazards ratios for each patient versus physician reported comorbidity and symptom were assessed. RESULTS: A total of 168 patients were included in the analysis (age, median = 56 years, range = 29-86 years; 131 white [78.9%]). Twenty-three of 54 comorbidities had a moderate to high level of agreement between patients and physicians (κ ≥ 0.40). Physicians documented higher numbers of comorbidities that can be objectively measured which also had higher concordance (e.g., diabetes [κ = 0.83] and hypertension [κ = 0.79]) while patients reported higher numbers of comorbidities that are more subjective which also had lower concordance (anxiety [κ = 0.30], GERD [κ = 0.36]). One physician-documented and two patient-reported comorbidities were significantly associated with survival (p < 0.05). Only 2 of 42 symptoms had a moderate to high level of agreement between patients and physicians. One physician-documented and nine patient-reported symptoms were significantly associated with decreased survival (p < 0.05). CONCLUSION: Agreement between patients' and physicians' reporting of comorbidities varies substantially, and patient reports can complement physician documentation. Physicians significantly underreported symptoms versus patients; thus, concordance was also low. Multiple patient-reported symptoms were predictive of survival; thus, incorporating them can provide more informative estimates of predicted survival.
Subject(s)
Breast Neoplasms , Physicians , Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Female , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Quality of Life , Comorbidity , Patient Reported Outcome MeasuresABSTRACT
While adjuvant treatment with the selective-estrogen receptor modulator (SERM) tamoxifen has been the standard of care for pre-menopausal patients with hormone receptor (HR) positive breast cancer, recent trials showed a benefit of aromatase inhibitors (AI) and ovarian function suppression (OFS) for some patients. The approach to endocrine therapy has not been well studied in pre-menopausal patients with invasive lobular carcinoma (ILC). We identified 202 pre-menopausal patients with HR positive stage I-III ILC in an institutional database. We investigated factors associated with endocrine therapy type and determined changes in systemic therapy from 1990-2021. We evaluated associations between endocrine therapy type and disease-free survival (DFS) with a multivariate Cox proportional hazards model. Of 202 patients, most (69.3%) were prescribed a SERM (99.3% tamoxifen). Those who received an AI had significantly higher stage disease. Over time, use of OFS and AI increased significantly in stage II or III cases (from 0% in 1990 to 56% after 2015 for stage II; from 0% to 80% after 2015 for stage III). Concurrently, adjuvant chemotherapy use significantly decreased in stage II cases (from 67% to 19%). In an exploratory multivariable model, longer duration of AI compared to tamoxifen was associated with significantly improved DFS (HR 0.31; 95% CI 0.11-0.86; p = 0.025). While most pre-menopausal patients received adjuvant tamoxifen, the use of OFS and AIs increased significantly over time. The association between AI use and improved DFS may be consistent with prior randomized trials and warrants further investigation into predictive factors to guide treatment selection.
ABSTRACT
PURPOSE: National mandates require cancer centers provide comprehensive survivorship care. We created an 8-session, group intervention, the Survivorship Wellness Group Program (SWGP), that covered 8 topics: nutrition, physical activity, stress, sleep/fatigue, sexuality/body image, emotional wellbeing/fear of cancer recurrence, spirituality/meaning, and health promotion/goal setting. This study examined the acceptability and preliminary outcomes of SWGP. METHODS: We evaluated SWGP using questionnaire data collected at program entry and 15-week follow-up. Questionnaires assessed acceptability and impact on anxiety, depression, quality of life, and perceived knowledge of topics. Enrollees who consented to participate in research and completed the baseline and 15-week follow-up were included in the analysis (N = 53). We assessed acceptability and preliminary outcomes using paired-samples t-tests. Due to the COVID-19 pandemic, SWGP transitioned to telehealth partway through data collection. Post-hoc analyses compared outcomes by intervention delivery. RESULTS: Participants completed an average of 7.44/8 classes. Participants reported a mean response of 3.42/4 regarding overall program satisfaction and 90.6% reported being "very likely" to recommend SWGP. SWGP was associated with decreases in anxiety and depression; increases in physical, emotional, functional, and overall quality of life; and increases in knowledge of all health behavior domains. No outcomes differed significantly between delivery in person versus telehealth. CONCLUSIONS: SWGP offers an acceptable and replicable model for cancer centers to meet national survivorship care guidelines. IMPLICATION FOR CANCER SURVIVORS: SWGP provides a comprehensive service for cancer survivors post-treatment, and was associated with better quality of life, fewer mental health symptoms, and increased knowledge in multiple domains of wellness.
Subject(s)
Cancer Survivors , Neoplasms , Humans , Cancer Survivors/psychology , Survivorship , Quality of Life/psychology , Pandemics , Exercise , Neoplasms/therapy , Neoplasms/psychologyABSTRACT
The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.
Subject(s)
Cancer Survivors , Neoplasms , Adult , Humans , Survivorship , Neoplasms/diagnosis , Neoplasms/therapy , Neoplasms/psychology , Survivors , Cancer Survivors/psychology , ImmunizationABSTRACT
BACKGROUND: To evaluate the efficacy of crofelemer, a first in class anti-secretory anti-diarrheal agent, to manage neratinib-induced diarrhea in patients with early-stage breast cancer taking adjuvant neratinib. PATIENTS AND METHODS: This single center, open label trial enrolled patients with Stage 2 to 3 HER2+ breast cancer taking adjuvant neratinib. One cohort took prophylactic crofelemer 125 mg bid and loperamide in the first 2 cycles, and as needed in subsequent cycles. The second cohort took dose-escalated neratinib with loperamide as needed (DE cohort). The primary endpoint was incidence of grade ≥ 3 diarrhea in the first 2 cycles. RESULTS: Seven patients in the crofelemer cohort and 4 in the DE cohort were enrolled. In the first 2 cycles, 2 patients (29%) in the crofelemer cohort and 2 patients (50%) in the DE cohort experienced grade 3 diarrhea lasting 1 day on average. After cycle 2, no additional patients in either cohort had grade 3 diarrhea. Five of 7 patients controlled diarrhea with crofelemer alone. There were no grade 4 diarrhea events in either cohort. Three patients in the crofelemer cohort dose-reduced neratinib due to diarrhea in the first 2 cycles. Patients in the crofelemer cohort had an average of 0.58 diarrhea episodes/day. 82% experienced constipation, all grade 1. CONCLUSIONS: This is the first study to investigate crofelemer for neratinib-induced diarrhea and demonstrates crofelemer activity in this setting. Further investigation of crofelemer for diarrhea secondary to cancer treatment is needed.
Subject(s)
Breast Neoplasms , Quinolines , Female , Humans , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/drug therapy , Diarrhea/chemically induced , Diarrhea/epidemiology , Loperamide/adverse effects , Quinolines/adverse effects , Receptor, ErbB-2/therapeutic useABSTRACT
BACKGROUND: Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD). METHODS: This multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the phase I; the phase II was limited to HER2-positive breast cancer. RESULTS: Intrathecal trastuzumab was well-tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80 mg were included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for phase II dose treated patients was 8.3 months (95% CI 5.2-19.6). The phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2-20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable cerebrospinal fluid (CSF) concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations. CONCLUSION: This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients.
Subject(s)
Breast Neoplasms , Meningeal Carcinomatosis , Humans , Female , Trastuzumab/adverse effects , Receptor, ErbB-2/metabolism , Breast Neoplasms/pathology , Meningeal Carcinomatosis/drug therapy , Meningeal Carcinomatosis/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
Background: Little is known about the genetic characteristics associated with exercise in women undergoing breast cancer surgery. Purpose: In a sample of women who were evaluated prior to breast cancer surgery (n = 310), we evaluated for differences in demographic and clinical characteristics between patients who did and did not exercise on a regular basis and evaluated for associations between polymorphisms in genes for pro- and anti-inflammatory cytokines, their receptors, and their transcriptional regulators. Methods: Patients completed an investigator-developed exercise questionnaire. Based on the recommended level of exercise (≥150 minutes/week), survivors were classified into no exercise (NoEx), less exercise (LessEx), or recommended exercise (RecEx) groups. Candidate gene analyses were done to identify relationships between polymorphisms and exercise group membership (i.e., NoEx vs. RecEx). Only 23.5% of the total sample met the recommendations for regular exercise. Results: Compared to the RecEx group (n = 78), patients in the NoEx group (n = 120) had less education; were less likely to report being White or Asia/Pacific Islander; more likely to report a lower household income; had a higher body mass index (BMI), had a poorer functional status; had a higher comorbidity burden; were more likely to self-report high blood pressure; and were more likely to have received neoadjuvant chemotherapy. Polymorphisms in IFNGR1 and NFKB1 were associated with membership in the NoEx group. Conclusions: While they warrant replication, our findings suggest that variations in cytokine-related genes may play a role in exercise behavior, and that clinicians need to assess for barriers to regular exercise and educate patients on its benefits.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/surgery , Receptors, Cytokine/genetics , Polymorphism, Single Nucleotide , Exercise , Genes, RegulatorABSTRACT
PURPOSE: Pseudocirrhosis is a term used to describe changes in hepatic contour that mimic cirrhosis radiographically, but lack the classic pathologic features of cirrhosis. This radiographic finding is frequently found in patients with metastatic breast cancer (MBC), but the risk factors and clinical consequences are poorly understood. METHODS: In this retrospective study, we identified patients with MBC and pseudocirrhosis who were treated at a single center from 2002 to 2021. We used chart extraction and radiology review to determine demographic characteristics, treatment history, imaging features, and complications of pseudocirrhosis. RESULTS: 120 patients with MBC and pseudocirrhosis were identified with the following BC subtypes: hormone receptor (HR) positive, HER2 negative (n = 99, 82.5%), HR+/HER2+ (n = 14, 11.7%), HR- /HER2+ (n = 3, 2.5%), and triple negative (TNBC; n = 4, 3.3%). All patients had liver metastases and 82.5% (n = 99) had > 15 liver lesions. Thirty-six patients (30%) presented with de novo metastatic disease. Median time from MBC diagnosis to pseudocirrhosis was 29.2 months. 50% of patients had stable or responding disease at the time of pseudocirrhosis diagnosis. Sequelae of pseudocirrhosis included radiographic ascites (n = 97, 80.8%), gastric/esophageal varices (n = 68, 56.7%), splenomegaly (n = 26, 21.7%), GI bleeding (n = 12, 10.0%), and hepatic encephalopathy (n = 11, 9.2%). Median survival was 7.9 months after pseudocirrhosis diagnosis. Radiographic ascites was associated with shorter survival compared to no radiographic ascites (42.8 vs. 76.2 months, p = < 0.001). CONCLUSIONS: This is the largest case series of patients with MBC and pseudocirrhosis. Nearly all patients had HR+ MBC and extensive liver metastases. Survival was short after pseudocirrhosis and prognosis worse with radiographic ascites.
Subject(s)
Breast Neoplasms , Liver Neoplasms , Humans , Female , Breast Neoplasms/pathology , Retrospective Studies , Ascites , Prognosis , Liver Neoplasms/secondary , Receptor, ErbB-2ABSTRACT
OBJECTIVES: Palpitations are common and have a negative impact on women's quality of life. While evidence suggests that inflammatory mechanisms may play a role in the development of palpitations, no studies have evaluated for this association in patients with breast cancer who report palpitations prior to surgery. The purpose of this pilot study was to evaluate for associations between the occurrence of palpitations and single nucleotide polymorphisms (SNPs) in genes for pro- and anti-inflammatory cytokines, their receptors, and transcriptional regulators. METHODS: Patients were recruited prior to surgery and completed a self-report questionnaire on the occurrence of palpitations. Genotyping of SNPs in cytokine genes was performed using a custom array. Multiple logistic regression analyses were done to identify associations between the occurrence of palpitations and SNPs in fifteen candidate genes. RESULTS: Of the 82 SNPs evaluated in the bivariate analyses, eleven SNPs in 6 genes were associated with the occurrence of palpitations. After controlling for functional status, the occurrence of back pain, and self-reported and genomic estimates of race/ethnicity, 3 SNPs in 3 different genes (i.e., interleukin (IL) 1-beta (IL1B) rs1143643, IL10 rs3024505, IL13 rs1295686) were associated with the occurrence of palpitations prior to surgery (all p ≤ .038). CONCLUSIONS: While these preliminary findings warrant replication, they suggest that inflammatory mechanisms may contribute to the subjective sensation of palpitations in women prior to breast cancer surgery.