RESUMO
PURPOSE: To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer. MATERIALS AND METHODS: Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons. RESULTS: Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2. CONCLUSION: A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Mutação em Linhagem Germinativa , Hospitais , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community. METHODS: Patients with stage II to III gastric adenocarcinoma undergoing curative-intent resection (National Cancer Data Base, 2006-2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan-Meier analysis was used to assess survival. RESULTS: There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10-year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline-concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values <.001). The median overall survival was 45.5 months for patients who received guideline-concordant care and 32.0 months for those who did not (P < .001, reference for all ORs: academic programs). CONCLUSIONS: Compliance with guidelines was associated with improved outcomes. Although the rate of compliance with NCCN guidelines is improving, integrated care networks may be an important way of improving the quality of gastric cancer care within the community.
Assuntos
Adenocarcinoma/terapia , Fidelidade a Diretrizes/estatística & dados numéricos , Excisão de Linfonodo/estatística & dados numéricos , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Oncologia/organização & administração , Oncologia/normas , Pessoa de Meia-Idade , Estadiamento de Neoplasias/estatística & dados numéricos , Análise de Regressão , Estudos Retrospectivos , Estatísticas não Paramétricas , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Background: Breast cancer diagnosis and treatment affect quality of life and stress and are associated with fatigue. Meditation interventions are effective strategies for patients with breast cancer but are often limited by poor access, high cost, substantial time commitment, and poor adherence. In this feasibility study, we investigated the use of a portable, wearable, electroencephalographic device for guided meditation practices by breast cancer patients during the period from breast cancer diagnosis until 3 months after surgical treatment. Methods: We enrolled women (age = 20-75 years) who had received a recent diagnosis of breast cancer and planned to undergo surgical treatment. Participants were randomly assigned to perform guided meditation with the device (intervention group) or receive CD-based stress-reduction education (control group). Surveys were used to measure stress, quality of life, and fatigue at baseline, within 4 days before surgery, up to 14 days after surgery, and at 3 months after surgery. Results: In the intervention group, 15 of 17 participants (88.2%) completed the study; in the control group, 13 of 13 participants completed the study (100%). Participants in both groups had less fatigue and stress and improved quality of life at 2 weeks and 3 months after surgery compared with baseline, but there were no significant intergroup differences at any time point. Conclusion: The use of this wearable electroencephalographic device for meditation is a feasible strategy for patients with breast cancer.
Assuntos
Neoplasias da Mama/psicologia , Meditação/psicologia , Dispositivos Eletrônicos Vestíveis/psicologia , Adulto , Idoso , Eletroencefalografia/métodos , Fadiga/psicologia , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Angústia Psicológica , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: The purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer. METHODS: Literature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary risk of cancer is a complex, broad, and dynamic area of medical research. The dominant focus of this guideline is limited in scope to breast cancer. RESULTS: There is a lack of consensus among experts regarding which genes among many should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in many genes. CONCLUSIONS: Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data are reviewed that support genetic testing being offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations. Patients who had genetic testing previously may benefit from updated testing. Genetic testing should be made available to patients without a history of breast cancer who meet National Comprehensive Cancer Network guidelines. Finally, variants of uncertain significance are not clinically actionable and these patients should be managed based on their individual risk factors.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Testes Genéticos/normas , Mutação , Guias de Prática Clínica como Assunto/normas , Cirurgiões/normas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Valor Preditivo dos Testes , Medição de RiscoRESUMO
OBJECTIVE. The purpose of this study is to prospectively compare the size of invasive breast cancer before and after neoadjuvant chemotherapy (NAC) at breast MRI and molecular breast imaging (MBI) and to assess the accuracy of post-NAC MBI and MRI relative to pathologic analysis. SUBJECTS AND METHODS. Women with invasive breast cancer greater than or equal to 1.5 cm were enrolled to compare the longest dimension before and after NAC at MRI and MBI. MBI was performed on a dual-detector cadmium zinc telluride system after administration of 6.5 mCi (240 MBq) 99mTc-sestamibi. The accuracy of MRI and MBI in assessing residual disease (invasive disease or ductal carcinoma in situ) was determined relative to pathologic examination. RESULTS. The longest dimension at MRI was within 1.0 cm of that at MBI in 72.3% of cases before NAC and 70.1% of cases after NAC. The difference between the longest dimension at imaging after NAC and pathologic tumor size was within 1 cm for 58.7% of breast MRI cases and 59.6% of MBI cases. Ninety patients underwent both MRI and MBI after NAC. In the 56 patients with invasive residual disease, 10 (17.9%) cases were negative at MRI and 23 (41.1%) cases were negative at MBI. In the 34 patients with breast pathologic complete response, there was enhancement in 10 cases (29.4%) at MRI and uptake in six cases (17.6%) at MBI. Sensitivity, specificity, positive predictive value, and negative predictive value after NAC were 82.8%, 69.4%, 81.4%, and 71.4%, respectively, for MRI and 58.9%, 82.4%, 84.6%, and 54.9%, respectively, for MBI. CONCLUSION. Breast MRI and MBI showed similar disease extent before NAC. MBI may be an alternative to breast MRI in patients with a contraindication to breast MRI. Neither modality showed sufficient accuracy after NAC in predicting breast pathologic complete response to obviate tissue diagnosis to assess for residual invasive disease. Defining the extent of residual disease compared with pathologic evaluation was also limited after NAC for both breast MRI and MBI.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Imagem Molecular/métodos , Invasividade Neoplásica/diagnóstico por imagem , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tecnécio Tc 99m SestamibiRESUMO
Importance: Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens. Objective: To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab. Design, Setting, and Participants: Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico. Women 18 years or older with invasive operable HER2-positive breast cancer were enrolled from September 15, 2007, to December 15, 2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked on October 15, 2017, and analysis was completed on December 15, 2017. Interventions: Patients randomized to arm 1 received 500 mg/m2 of fluorouracil, 75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by the combination of 80 mg/m2 of paclitaxel and 2 mg/kg (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks. Patients randomized to arm 2 received the same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks. Women with hormone receptor-positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion. Main Outcomes and Measures: The primary outcomes were DFS and OS and pCR in the breast and nodes. Results: Two hundred eighty-two women with HER2-positive breast cancer were enrolled in the trial, and 2 withdrew consent before treatment. Among the remaining 280 women, the median age was 50 years (range, 28-76 years), 232 (82.9%) were white, 29 (10.3%) were black, 8 (2.9%) were Asian, 4 (1.4%) were American Indian or Alaskan Native, and 7 (2.5%) did not report race/ethnicity. There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival rates did not differ with respect to treatment arm (stratified log-rank P = .96; stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95% CI, 0.56-1.83). Overall survival did not differ with respect to treatment arm (stratified log-rank P = .73; stratified HR [arm 2 to arm 1], 1.17; 95% CI, 0.48-2.88). Conclusions and Relevance: Across a median follow-up of 5.1 years (range, 26 days to 6.2 years), pCR, DFS, and OS did not differ with respect to sequential or concurrent administration of FEC with trastuzumab. Trial Registration: ClinicalTrials.gov identifier: NCT00513292.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Receptor ErbB-2/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Progressão da Doença , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Paclitaxel/administração & dosagem , Intervalo Livre de Progressão , Porto Rico , Fatores de Risco , Fatores de Tempo , Trastuzumab/administração & dosagem , Estados UnidosRESUMO
BACKGROUND: Placement of a clip in the positive node in patients presenting with node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) allows resection of the clipped node at SLN surgery and improves the accuracy of surgical staging. We sought to evaluate our experience with SLN surgery with resection of the clipped node since incorporation into our practice. METHODS: With Institutional Review Board approval, we evaluated all breast cancer patients with a percutaneous biopsy-positive axillary lymph node, clipped at the time of diagnosis, who underwent NAC followed by surgery. RESULTS: Fifty-six node-positive patients were identified. Eighteen patients (32.1%) underwent axillary dissection without sentinel lymph node (SLN) surgery, and 38 patients underwent SLN surgery (18 patients underwent SLN surgery alone, and 20 patients underwent SLN surgery and axillary lymph node dissection). In 25 patients, preoperative localization of the clipped node with an 125I radioactive seed was attempted. This was performed by ultrasound guidance in 18 cases (72%), computed tomography (CT) guidance in two cases (8%), and was unable to be localized in five cases (20%). In all 20 seed-localized cases, the seed and the clipped node were resected along with additional SLNs. In 14 patients without seed localization (nine not attempted, five unable to be localized), the clipped node was resected in 11 cases (79%)-as one of the SLNs (6), by intraoperative ultrasound (4), or by palpation (1). Overall, the clipped node was resected in 31/34 (91%) cases. CONCLUSION: Preoperative ultrasound localization of the clipped node was successful in 72% of cases. Alternatively, the clipped node can be identified by preoperative CT, routine SLN surgery, intraoperative ultrasound, or palpation.
Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Terapia Neoadjuvante , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Reações Falso-Negativas , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo , Linfonodos/diagnóstico por imagem , Linfonodos/efeitos dos fármacos , Pessoa de Meia-Idade , Inoculação de Neoplasia , Prognóstico , Tomografia Computadorizada por Raios X , Ultrassonografia MamáriaRESUMO
OBJECTIVE: The purpose of this study was to examine additional diagnostic workup and costs generated by addition of a single molecular breast imaging (MBI) examination to screening mammography for women with dense breasts. SUBJECTS AND METHODS: Women with mammographically dense breasts presenting for screening mammography underwent adjunct MBI performed with 300 MBq (99m)Tc-sestamibi and a direct-conversion cadmium-zinc-telluride dual-head gamma camera. All subsequent imaging tests and biopsies were tracked for a minimum of 1 year. The positive predictive value of biopsies performed (PPV3), benign biopsy rate, cost per patient screened, and cost per cancer detected were determined. RESULTS: A total of 1651 women enrolled in the study. Among the 1585 participants with complete reference standard, screening mammography alone prompted diagnostic workup of 175 (11.0%) patients and biopsy of 20 (1.3%) and yielded five malignancies (PPV3, 25%). Results of combined screening mammography plus MBI prompted diagnostic workup of 279 patients (17.6%) and biopsy of 67 (4.2%) and yielded 19 malignancies (PPV3, 28.4%). The benign biopsy rates were 0.9% (15 of 1585) for screening mammography alone and 3.0% (48 of 1585) for the combination (p < 0.001). The addition of MBI increased the cost per patient screened from $176 for mammography alone to $571 for the combination. However, cost per cancer detected was lower for the combination ($47,597) than for mammography alone ($55,851). CONCLUSION: The addition of MBI to screening mammography of women with dense breasts increased the overall costs and benign biopsy rate but also increased the cancer detection rate, which resulted in a lower cost per cancer detected than with screening mammography alone.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/economia , Detecção Precoce de Câncer/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Mamografia/economia , Imagem Molecular/economia , Tomografia por Emissão de Pósitrons/economia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Compostos Radiofarmacêuticos/economia , Tecnécio Tc 99m Sestamibi/economia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Neoadjuvant chemotherapy with trastuzumab for patients with HER2-positive breast cancer can produce a pathological complete response in the breast in 30-65% of patients. We investigated the effect of the timing of trastuzumab administration with anthracycline and taxane neoadjuvant chemotherapy. METHODS: This randomised trial was done at 36 centres in the USA and Puerto Rico. Women with operable HER2-positive invasive breast cancer were randomly assigned (1:1) with a biased coin minimisation algorithm, stratified for age, tumour size, and hormone receptor status. Neither patients nor investigators (except for a cardiac safety review panel) were masked to treatment assignment. Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group. Surgery, including evaluation of the axilla, was done within 6 weeks of completion of neoadjuvant treatment. The primary outcome was the percentage of patients who had a pathological complete response in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00513292. FINDINGS: From Sept 15, 2007, to Dec 15, 2011, 282 women were enrolled (140 in the sequential group, 142 in the concurrent group). Two patients in the sequential group withdrew consent before starting treatment. 78 of 138 (56·5%, 95% CI 47·8-64·9) patients who received sequential treatment had a pathological complete response in the breast versus 77 of 142 (54·2%, 95% CI 45·7-62·6) who received concurrent treatment (difference 2·3%, 95% CI -9·3 to 13·9). No treatment-related deaths occurred. The most common severe toxic effects were neutropenia (35 [25·3%] of 138 patients in the sequential group vs 45 [31·7%] of 142 patients in the concurrent group) and fatigue (six [4·3%] vs 12 [8·5%]). Left ventricular ejection fraction dropped below the institutional lower limit of normal at week 12 in one (0·8%) of 130 patients who received sequential treatment and four (2·9%) of 137 patients who received concurrent treatment; by week 24, it had dropped below this limit in nine (7·1%) of 126 patients and in six (4·6%) of 130 patients, respectively. INTERPRETATION: Concurrent administration of trastuzumab with anthracyclines offers no additional benefit and is not warranted. FUNDING: US National Cancer Institute.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Mastectomia , Terapia Neoadjuvante/métodos , Receptor ErbB-2/análise , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Mastectomia/métodos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Porto Rico , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Trastuzumab , Resultado do Tratamento , Estados UnidosRESUMO
This quality improvement pilot study evaluated the effect of massage therapy on pain, anxiety, and overall well-being in women who received mastectomies at a busy hospital practice. Participants reported a significant reduction in pain, stress, and muscle tension, as well as an increase in relaxation. Oncology nurses should consider the feasibility of massage therapy as a valuable nonpharmcologic pain management strategy.