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PURPOSE: The role of surgery with curative intent in HER2+ de novo metastatic breast cancer (dnMBC) is uncertain in the era of dual antibody therapy. We sought to determine from existing retrospective data current practice patterns and if an association exists between surgery to the primary tumor and improved survival in HER2+ dnMBC patients treated with dual anti-HER2 blockade, accounting for selection bias. METHODS: This study employed data from the National Cancer Database (NCDB) from the years 2013 to 2015. Study inclusion was limited to adult women with HER2+ dnMBC, who received immunotherapy/biologic response modifier drugs (BRM) as a first line treatment. Patients who received both systemic therapy and surgery to the primary breast tumor and patients who received systemic therapy alone were analyzed in two groups. Chi-square test for discrete variables and Wilcox on Rank-Sum test for numeric variables was used to compare the two groups based on patient, tumor, and treatment characteristics. The primary endpoint was overall survival from the time of diagnosis to the time of death. RESULTS: 928 women with HER2+ dnMBC treated with BRM were identified with 43.5% (n = 404) receiving surgery and 56.5% (n = 524) receiving systemic therapy alone. The 3-year overall survival was superior for the surgery group (74.1%, 95% CI 67.9-79.2%) compared to the no surgery group (53.3%; 95% CI 47.6-58.6%). The no surgery group had median overall survival of 39.8 months (95% CI 34.1-44.9), while the surgery group had not yet reached median overall survival. CONCLUSION: In a group of HER2+ dnMBC patients receiving systemic treatment in the era of dual antibody therapy, patients who underwent surgery had a superior 3-year survival rate than those who did not. There may be a role for a prospective trial in HER2+ dnMBC patients with an excellent response to dual HER2 blockade to investigate the contribution of curative intent local therapy to the primary tumor compared to systemic therapy alone.
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Neoplasias da Mama , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Estudos Prospectivos , Receptor ErbB-2/genética , Estudos Retrospectivos , Trastuzumab/uso terapêuticoRESUMO
PURPOSE: Breast cancer in men (BC-M) is almost exclusively hormone receptor positive. We conducted a large review of the SEER-Medicare linked database to compare endocrine therapy adherence, discontinuation, and survival outcomes of male versus female patients with breast cancer. METHODS: Study data were obtained through the SEER-Medicare linked database. The study included patients age ≥ 65 years-old diagnosed with breast cancer between 2007 and 2015. The primary endpoints were rates of adherence and discontinuation of endocrine therapy (ET). Adherence was defined as a gap of less than 90 days in-between consecutive Medicare prescriptions. Discontinuation was defined as a gap of greater than 12 months in-between Medicare prescriptions. Secondary endpoint was the association of use of ET with overall survival (OS). RESULTS: Of the 363 male patients on ET, 214 patients (59.0%) were adherent to the therapy, and 149 patients (41.0%) were nonadherent. Of the 20,722 females on ET, 10,752 (51.9%) were adherent to the therapy, and 9970 (48.1%) were nonadherent. 39 male patients (10.7%) discontinued therapy, while 324 (89.3%) did not discontinue therapy. 1849 female patients (8.9%) discontinued therapy, while 18,873 (91.1%) patients did not. Men were significantly more adherent than women (p = 0.008), but there was no significant difference in discontinuation among men and women (p = 0.228). Survival was significantly improved in both men (HR 0.77, 95% CI 0.60-0.99, p = 0.039) and women (HR 0.84, 95% CI 0.81-0.87, p < 0.001) on ET. CONCLUSION: Identification of contributing factors impacting adherence and discontinuation is needed to allow physicians to address barriers to long term use of ET.
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Neoplasias da Mama , Idoso , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Masculino , Medicare , Adesão à Medicação , Programa de SEER , Estados Unidos/epidemiologiaRESUMO
LESSONS LEARNED: Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance. In this single-arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression-free survival of 6.2 months with an acceptable toxicity profile. This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC. BACKGROUND: Capecitabine (Cape) is an oral prodrug of the antimetabolite 5-fluorouracil. Sorafenib (Sor) inhibits multiple signaling pathways involved in angiogenesis and tumor proliferation. SorCape has been previously studied in metastatic breast cancer. METHODS: This single-arm, phase II study was designed to evaluate the activity of SorCape in refractory metastatic colorectal cancer (mCRC). Patients received Sor (200 mg p.o. b.i.d. max daily) and Cape (1,000 mg/m2 p.o. b.i.d. on days 1-14) on a 21-day treatment cycle. Primary endpoint was progression-free survival (PFS) with preplanned comparison with historical controls. RESULTS: Forty-two patients were treated for a median number of 3.5 cycles (range 1-39). Median PFS was 6.2 (95% confidence interval [CI], 4.3-7.9) months, and overall survival (OS) was 8.8 (95% CI, 4.3-12.2) months. One patient (2.4%) had partial response (PR), and 22 patients (52.4%) had stable disease (SD) for a clinical benefit rate of 54.8% (95% CI, 38.7%-70.2%). Hand-foot syndrome was the most common adverse event seen in 36 patients (85.7%) and was grade ≥ 3 in 16 patients (38.1%). One patient (2.4%) had a grade 4 sepsis, and one patient (2.4%) died while on treatment. CONCLUSION: SorCape in this heavily pretreated population yielded a reasonable PFS with manageable but notable toxicity. The combination should be investigated further.
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Neoplasias Colorretais , Desoxicitidina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Desoxicitidina/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Sorafenibe/uso terapêutico , Resultado do TratamentoRESUMO
LESSONS LEARNED: Preclinical studies have demonstrated that Src inhibition through dasatinib synergistically enhances the antitumor effects of oxaliplatin. In this phase II, single-arm study, FOLFOX with dasatinib in previously untreated patients with mPC only showed only modest clinical activity, with a progressive-free survival of 4 months and overall survival of 10.6 months. Continued investigation is ongoing to better understand the role of Src inhibition with concurrent 5-fluorouracil and oxaliplatin in a subset of exceptional responders. BACKGROUND: Src tyrosine kinase activity is overexpressed in many human cancers, including metastatic pancreatic cancer (mPC). Dasatinib is a potent inhibitor of Src family of tyrosine kinases. This study was designed to investigate whether dasatinib can synergistically enhance antitumor effects of FOLFOX regimen (FOLFOX-D). METHODS: In this single-arm, phase II study, previously untreated patients received dasatinib 150 mg oral daily on days 1-14, oxaliplatin 85 mg/m2 intravenous (IV) on day 1 every 14 days, leucovorin (LV) 400 mg/m2 IV on day 1 every 14 days, 5-fluorouracil (5-FU) bolus 400 mg/m2 on day 1 every 14 days, and 5-FU continuous infusion 2,400 mg/m2 on day 1 every 14 days. Primary endpoint was progression-free survival (PFS) with preplanned comparison to historical controls. RESULTS: Forty-four patients enrolled with an estimated median PFS of 4.0 (95% confidence interval [CI], 2.3-8.5) months and overall survival (OS) of 10.6 (95% CI, 6.9-12.7) months. Overall response rate (ORR) was 22.7% (n = 10): one patient (2.3%) with complete response (CR) and nine patients (20.5%) with partial response (PR). Fifteen patients (34.1%) had stable disease (SD). Nausea was the most common adverse event (AE) seen in 35 patients (79.5%). CONCLUSION: The addition of dasatinib did not appear to add incremental clinical benefit to FOLFOX in untreated patients with mPC.
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Adenocarcinoma , Neoplasias Colorretais , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Breast cancer-related lymphedema (BCRL) is a source of postoperative morbidity for breast cancer survivors. Lymphatic microsurgical preventive healing approach (LYMPHA) is a technique used to prevent BCRL at the time of axillary lymph node dissection (ALND). We report the 5-year experience of a breast surgeon trained in LYMPHA and investigate the outcomes of patients who underwent LYMPHA following ALND for treatment of cT1-4N1-3M0 breast cancer. METHODS: A retrospective review of patients with cT1-4N1-3M0 breast cancer was performed in patients who underwent ALND with and without LYMPHA. Diagnosis of BCRL was made by certified lymphedema therapists. Descriptive statistics and lymphedema surveillance data were analyzed using results of Fisher's exact or Wilcoxon rank-sum tests. Logistic regression and propensity matching were performed to assess the reduction of BCRL occurrence following LYMPHA. RESULTS: In a 5-year period, 132 patients met inclusion criteria with 76 patients undergoing LYMPHA at the time of ALND and 56 patients undergoing ALND alone. Patients who underwent LYMPHA at the time of ALND were significantly less likely to develop BCRL than those who underwent ALND alone (p = 0.045). Risk factors associated with BCRL development were increased patient age (p = 0.007), body mass index (BMI) (p = 0.003), and, in patients undergoing LYMPHA, number of positive nodes (p = 0.026). CONCLUSIONS: LYMPHA may be successfully employed by breast surgeons trained in lymphatic-venous anastomosis at the time of ALND. While research efforts should continue to focus on prevention and surveillance of BCRL, LYMPHA remains an option to reduce BCRL and improve patient quality of life.
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Neoplasias da Mama , Linfedema , Cirurgiões , Axila , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Linfedema/etiologia , Linfedema/prevenção & controle , Linfedema/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
BACKGROUND: Undergoing cancer screening is a debatable topic in patients with cognitive impairment. In this study, we aimed to examine the utilization and predictors of breast and colorectal cancer screening among screening eligible, cognitively impaired individuals. METHODS: We analyzed the 2018 and 2019 National Health Interview Survey data (n = 12,965 and 24,782, respectively) on individuals eligible for breast or colorectal cancer screening. We calculated the percentage of cancer screening eligible individuals who received mammogram or colonoscopy by cognitive impairment status. We used multivariable logistic regression to examine whether having a recent mammogram or colonoscopy differed by cognitive impairment status, adjusting for covariates. RESULTS: We observed a significantly lower percentage of mammogram use in the screening eligible, cognitively impaired (mild or severe) versus unimpaired women. Adjusting for the covariates, the cognitively impaired women, mild (odds ratio [OR] = 0.85; p = 0.015) or severe (OR = 0.54; p < 0.001), were less likely to have had a recent mammogram compared to the cognitively unimpaired women. Although statistically non-significant, the percentage of colonoscopy use in the screening eligible, cognitively impaired individuals were slightly higher than that in the cognitively unimpaired individuals. In the regression analysis, we found the cognitively impaired men, mild (OR = 0.79; p < 0.001) or severe (OR = 0.69; p = 0.038), were less likely to have had a recent colonoscopy compared to the cognitively unimpaired men. More studies are needed to examine the multilevel factors that underpin the difference in cancer screening utilization in this vulnerable population. CONCLUSION: Our results highlight the need for additional research to address utilization and effectiveness of cancer screening in individuals with cognitive impairment.
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Neoplasias da Mama/diagnóstico , Disfunção Cognitiva , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Idoso , Colonoscopia/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , Mamografia/estatística & dados numéricos , Pessoa de Meia-IdadeRESUMO
PURPOSE: Chemotherapy education provided by nurses to patients is a fundamental component of high-quality cancer care. The Quality Oncology Practice Initiative (QOPI ®) provides guidance on treatment-related aspects of chemotherapy education (diagnosis, goals, regimen, schedule, adverse events, follow-up), but recommendations on practical lifestyle issues lack evidence and standardization. METHODS: An anonymous, voluntary, uncompensated survey was distributed in October 2019 to 12,995 oncology certified nurses who report working in adult outpatient clinic/infusion room settings. An electronic survey was designed to determine current practice in nurse-patient counseling related to lifestyle and behavior during chemotherapy treatment. RESULTS: Survey responses were obtained from 1243 oncology certified nurses (9.6%). Nurses reported that their education practice was influenced by their institution and coworkers (other nurses or oncologists). Most nurses (> 50%) reported counseling on all topics asked. Most frequently counseled topics included water intake, infection monitoring, alcohol consumption, exercise, and mucositis. Less frequently counseled topics included hair dye, laundry practices, and mask wearing (pre-pandemic). CONCLUSION: This study highlighted that chemotherapy nurses routinely counsel patients on important topics that lack evidence-based recommendations. In the absence of evidence, nurses rely on learned education practices, most commonly institutional guides or recommendations adopted from other nurses or oncologists. On important topics that lack evidence, expert panel review and development of consensus guidelines could standardize and improve the education process for both oncology nurses and patients.
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Neoplasias , Enfermeiros Clínicos , Adulto , Aconselhamento , Exercício Físico , Humanos , Neoplasias/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Frail elderly women with nonmetastatic hormone receptor-positive breast cancer often receive primary endocrine therapy. Limited data are available on the outcomes associated with this population and treatment approach. METHODS: We selected patients with an initial primary diagnosis of stage I-III ER-positive breast cancer from 2001 to 2015 in Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Patients were excluded if they received surgery, radiation, chemotherapy, or other targeted drug treatment including anti-HER2 agents. Two Cox proportional-hazards models were constructed to determine the predictors of breast cancer-specific survival and overall survival after a cancer diagnosis. RESULTS: A total of 552 patients were identified, with 82.1% of the patients being 80 years or older and 81.7% of patients being non-Hispanic White. PR positive (OR 1.77; 95% CI 1.09-2.85; p = 0.025) and tumor size larger than 50 mm (OR 1.99; 95% CI 1.05-3.75; p = 0.035) were associated with higher adherence to endocrine therapy. In the multivariable Cox analyses, patients who were adherent of endocrine therapy had significantly worse survival (HR 1.40; 95% CI 1.17-1.69; p < 0.001). The other two factors associated with worse survival were larger tumor size and more comorbidities. The competing risk model demonstrated no statistically significant difference between patients who were adherent to endocrine therapy and those who were not in terms of risk of dying from breast cancer. CONCLUSION: In elderly women with localized ER-positive breast cancer, there were no statistically significant differences in breast cancer-specific or overall mortality between those who were adherent to endocrine therapy and those who were not.
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Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/mortalidade , Bases de Dados Factuais , Programa de SEER/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
This article presents current best knowledge to assess the projected outcomes benefit of adding multi-modality surveillance imaging to standard follow-up care for breast cancer patients at high risk (>30%) for developing future metastases. This analysis is motivated by recent preliminary clinical studies that have suggested that augmenting systemic treatment of early-stage metastases with targeted surgery and/or radiosurgery achieves significant overall survival and disease-free survival benefit. Our primary aims are to: (a) describe the clinical motivation and scan parameters needed to identify the early onset of metastatic progression in breast cancer patients for effective surgical or radiosurgical treatment; (b) estimate the anticipated survival benefit for high-risk patients under this recommended protocol; and (c) estimate the radiation risks associated with the repeated body imaging of this protocol.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Mortalidade , Tomografia por Emissão de Pósitrons , RadiocirurgiaRESUMO
OBJECTIVES: Knowledge of women's health is important for physicians in various specialties, but training often is inadequate. The objective of this project was to develop, implement, and evaluate a women's health curriculum for medical students at the University of Florida College of Medicine in Gainesville. METHODS: After reviewing previous pertinent literature and assessing institutional factors, we developed an interdisciplinary women's health elective for medical students. We present the curricular design for the course. The 2-week elective explores women's health topics such as disease prevention, screening, breast health, osteoporosis, and cardiovascular health. Teaching methodology includes case-based lectures, reading assignments, and clinic sessions at multiple sites. RESULTS: Senior medical students worked in a variety of clinical settings and were assigned a women's health project, a pretest before starting the elective, and a posttest after completion of the course. A statistically significant increase was seen in the students' mean posttest (98.8%) versus pretest (85.6%) scores (difference 13.1%; 95% confidence interval 7.3-19.0, P < 0.0001). CONCLUSIONS: Designing curricula that promote lifelong professional competency in the field of women's health can be challenging. At the University of Florida, we have successfully created and implemented a medical student elective in women's health using local resources and expertise. This elective satisfies important women's health training requirements, has been well received by our students, and has resulted in increased women's health-specific knowledge. The experience at our institution may be useful for other programs interested in developing a women's health curriculum geared toward medical students utilizing minimal resources.
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Competência Clínica , Currículo , Educação de Graduação em Medicina/métodos , Saúde da Mulher , Feminino , Florida , Humanos , Desenvolvimento de Programas , Avaliação de Programas e Projetos de SaúdeAssuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Ovário/efeitos dos fármacos , Tamoxifeno/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Adesão à Medicação , Ovário/fisiopatologia , Sobrepeso/fisiopatologia , Pré-MenopausaRESUMO
Purpose: In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes. Patients and Methods: A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12-month time points. Results: Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever-smokers but not in never-smokers. Conclusion: Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.
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The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel-based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non-hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient-reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (n = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel-based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.
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Antineoplásicos , Neoplasias , Testes Farmacogenômicos , Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/genética , Testes Farmacogenômicos/economia , Testes Farmacogenômicos/estatística & dados numéricos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Oncologia/métodos , Sistemas de Apoio a Decisões Clínicas , FarmacogenéticaRESUMO
Leptomeningeal spread of cancer is rare, difficult to both diagnostically confirm and treat, and associated with a poor prognosis. The blood-brain barrier largely prevents sufficient penetration of systemic therapy to be effective. Direct administration of intrathecal therapy has thus been used as an alternative treatment option. We present a case of breast cancer complicated by leptomeningeal spread. Intrathecal methotrexate was initiated, and the manifestation of systemic side effects suggested systemic absorption. This was subsequently confirmed by blood work showing detectable methotrexate levels following intrathecal administration as well as resolution of symptoms with reduction in the dose of methotrexate administered.
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Neoplasias da Mama , Neoplasias Meníngeas , Humanos , Feminino , Metotrexato/uso terapêutico , Neoplasias Meníngeas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Absorção Fisiológica , Injeções EspinhaisRESUMO
Pregnancy-associated cancer is defined as malignancy diagnosed during gestation or up to 1 year post partum. Treatment of cancer during pregnancy is complicated by the risk of harm to the fetus and limitations in safety data. Postpartum patients receiving chemotherapy, tyrosine-kinase inhibitors or hormonal agents should avoid breast feeding to avoid drug excretion in breast milk. Patients who will receive cytotoxic chemotherapy should be advised of the potential impact on their future fertility and offered fertility-preservation options. Breast cancer is the most common pregnancy-associated malignancy and is most frequently either invasive ductal or lobular carcinoma. Breast lymphoma is an exceedingly rare diagnosis that typically presents with unilateral disease in the seventh decade of life. Here, we present the case of a woman who presented with bilateral breast masses during the second trimester of pregnancy and was ultimately diagnosed with primary breast Burkitt's lymphoma.
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Neoplasias da Mama , Linfoma de Burkitt , Gravidez , Feminino , Humanos , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Neoplasias da Mama/patologia , Aleitamento MaternoRESUMO
Immune-mediated herb-induced liver injury (HILI) is an acute or chronic inflammatory liver disease precipitated by a hepatotoxic agent with a presentation similar to acute autoimmune hepatitis. It is distinguished in clinical course from true autoimmune hepatitis by remission on drug discontinuation and immunosuppressive treatment. We report a potential case of immune-mediated HILI associated with artemisinin use, an herb underlying first-line malarial treatments, in a woman undergoing radiotherapy for right-sided pelvic sarcoma. A probable association in this case is supported by causality assessment using the updated Roussel Uclaf Causality Assessment Method (score of 6). She achieved clinical improvement with a course of oral corticosteroids and remained stable without relapse following discontinuation. Increased awareness of this complication is imperative, as literature to date only documents direct hepatocellular and cholestatic liver injury from artemisinin use, and should augment clinician counsel regarding complementary medicine administration, especially in high-risk individuals like those with cancer.
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Artemisininas , Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Hepatite Autoimune , Feminino , Humanos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Recidiva Local de Neoplasia , Artemisininas/efeitos adversosRESUMO
BACKGROUND: Thymic epithelial tumors are rare and include thymomas and thymic carcinomas. There is scarce literature characterizing prognostic factors and long-term outcomes in these tumors. AIMS: This review aims to describe disease features of thymomas and thymic carcinomas and to report clinical differences among thymoma histological subtypes. METHODS AND RESULTS: A retrospective chart review was performed at the University of Florida Shands Hospital, a tertiary care academic medical center in Gainesville, Florida, USA. The review included clinical data of adults with thymic epithelial tumors diagnosed between 2001 and 2021. Significant associations among demographics, histology, stage, and outcomes were investigated. Thymoma subgroup analysis was performed using histological subtype and sex. Forty patients with thymoma and seven patients with thymic carcinoma were included in the final analysis. Among those with thymomas, patients with subtype B1, B2, or B3 tumors were younger, had larger tumors, and presented with higher stage disease when compared to those with subtypes A or AB. Tumor recurrence was most common in subtype B2 and B3 tumors (50.0% and 16.7% vs. 0%; p < .01). However, there was no significant difference in overall survival between histologic subtypes. Compared to females, males with thymomas had superior overall survival (103.0 vs. 62.9 months; p = .021) despite presenting with larger tumors (9.8 vs. 5.8 cm; p = .041). Concomitant myasthenia gravis was associated with increased recurrence but not worsened mortality. Compared to thymomas, patients with thymic carcinoma presented with higher-stage disease and had poorer 5-year survival (50.0% vs. 93.1%; p < .01). CONCLUSION: This study affirmed pathologic stage and resectability as prognostic factors for thymic epithelial tumors. New findings include inferior overall survival in female patients and higher recurrence rates in those with thymomas and concomitant myasthenia gravis.
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Miastenia Gravis , Neoplasias Epiteliais e Glandulares , Timoma , Neoplasias do Timo , Adulto , Masculino , Humanos , Feminino , Timoma/diagnóstico , Timoma/cirurgia , Timoma/complicações , Prognóstico , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/complicações , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/complicações , Miastenia Gravis/complicações , Miastenia Gravis/diagnósticoRESUMO
PURPOSE: Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC). PATIENTS AND METHODS: From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. RESULTS: One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy. CONCLUSION: Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Capecitabina/uso terapêutico , DNA Tumoral Circulante/genética , Terapia Neoadjuvante , Medicina de Precisão , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Tomada de Decisão Clínica , Intervalo Livre de Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Neoplasia Residual , Seleção de Pacientes , Valor Preditivo dos Testes , Fatores de Tempo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Most cases of metastatic breast cancer (MBC) arise as a recurrence of a previously treated early breast cancer. Distinct from recurrent MBC is de novo MBC (dnMBC), which describes patients who present with distant sites of disease at initial diagnosis and is reviewed here. dnMBC represents approximately 3% to 6% of new breast cancer diagnoses in high-income countries. This incidence has not declined despite decades of widespread use of population-based mammography screening. Overrepresentation of both biologically aggressive tumors and patients negatively impacted by social determinants of health are characteristics of dnMBC. Survival has generally been superior for patients with dnMBC compared with those with recurrent MBC, although it is similar to that for patients with recurrent MBC with long disease-free intervals. Subgroups of patients with dnMBC who experience prolonged survival include those with human epidermal growth factor receptor-2-positive disease or hormone receptor-positive bone-only disease. Opportunities to decrease dnMBC presentation may include novel screening modalities suited for biologically aggressive breast tumors and improved access to health care. Recognizing that there will remain some women diagnosed with dnMBC, refining our ability to identify those likely to be long-term survivors could allow for appropriate escalation or de-escalation of care. Finally, evaluation of tumor genomics in robust sample sizes has the potential to advance our knowledge of the biology of dnMBC as an entity distinct from recurrent MBC.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Incidência , Prognóstico , Taxa de SobrevidaRESUMO
Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.