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INTRODUCTION: Lung cancer is consistently the leading cause of cancer death among women in the United States, yet lung cancer screening (LCS) rates remain low. By contrast, screening mammography rates are reliably high, suggesting that screening mammography can be a "teachable moment" to increase LCS uptake among dual-eligible women. MATERIALS AND METHODS: This is a prospective survey study conducted at two academic institutions. Patients undergoing screening mammography were evaluated for LCS eligibility and offered enrollment in a pilot dual-cancer screening program. A series of surveys was administered to characterize participants' knowledge, perceptions, and attitudes about LCS before and after undergoing dual screening. Data were descriptively summarized. RESULTS: Between August 2022 and July 2023, 54 LCS-eligible patients were enrolled. The study cohort was 100% female and predominantly White (81%), with a median age of 57 y and median of 36 pack-y of smoking. Survey results showed that 98% felt they were at risk for lung cancer, with most (80%) motivated by early detection of potential cancer. Regarding screening barriers, 58% of patients lacked knowledge about LCS eligibility and 47% reported concerns about screening cost. Prior to undergoing LCS, 87% of patients expressed interest in combined breast and lung screening. Encouragingly, after LCS, 84% were likely or very likely to undergo dual screening again and 93% found the shared decision-making visit helpful or very helpful. CONCLUSIONS: Pairing breast and LCS is a feasible, acceptable intervention that, along with increasing patient and provider education about LCS, can increase LCS uptake and reduce lung cancer mortality.
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Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences.
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Carcinoma de Mama in situ , Neoplasias de la Mama , Carcinoma in Situ , Carcinoma Intraductal no Infiltrante , Carcinoma Lobular , Lesiones Precancerosas , Femenino , Humanos , Biopsia , Biopsia con Aguja Gruesa , Carcinoma de Mama in situ/diagnóstico por imagen , Carcinoma de Mama in situ/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/cirugía , Hiperplasia , Estudios Observacionales como Asunto , Lesiones Precancerosas/patologíaRESUMEN
Atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are markers for an increased risk of breast cancer, yet outcomes for these diagnoses are not well-documented. In this study, all breast biopsies performed for radiologic abnormalities over a 10-year period were reviewed. Patients with AH or LCIS were followed for an additional 10 years to assess subsequent rates of cancer diagnosis. Long-term follow-up showed that 25 (7.8%) patients with AH and 5 patients with LCIS (5.7%) developed breast cancer over the follow-up period, a lower rate of breast cancer development than predicted by risk models.
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Carcinoma de Mama in situ , Neoplasias de la Mama , Carcinoma in Situ , Carcinoma Lobular , Mama/patología , Carcinoma de Mama in situ/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Carcinoma in Situ/patología , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/epidemiología , Carcinoma Lobular/patología , Femenino , Humanos , Hiperplasia/patología , Estudios LongitudinalesRESUMEN
PURPOSE: There is very little data on the effect of combining methods to better predict and improve oral antineoplastic adherence in cancer patients. The goal of this study was to evaluate the effectiveness of an intensive pharmacist intervention at the beginning of oral antineoplastic therapy versus nurse-led control group on adherence. METHODS: This was a prospective, randomized, open-label controlled trial performed in a single center hematology/oncology outpatient service to compare the effectiveness of repetitive pharmacist educational intervention on adherence rates measured at four and eight weeks after prescribing oral antineoplastic medication compared to a nurse-led control group. Both groups included investigator pill counts and self-report adherence questionnaires. RESULTS: Two-hundred patients were enrolled between 2009 and 2015. Fourteen of the 101 (14%) patients in the pharmacist group and 7 (7%) of the 99 patients in the nurse-led control group dropped out (p = 0.166). The majority of patients who remained in the study were 90-100% adherent to oral antineoplastic therapy in both groups. The pharmacist group slightly underperformed at Pill Count 2, possibly due to barriers for non-adherence. Statistically significant correlations associated with non-adherence were forgetfulness (p = 0.009), wanting to avoid side effects (p = 0.02), feeling depressed or overwhelmed (p = 0.032), or falling asleep before taking medication (p = 0.048) in both groups. CONCLUSION: The combination of pill count and patient self-report adherence is a way of improving oral antineoplastic adherence. However, significant barriers to adherence were identified such as forgetfulness, wanting to avoid side effects, feeling depressed or overwhelmed, and falling asleep before taking medications.
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Antineoplásicos/uso terapéutico , Cumplimiento de la Medicación , Neoplasias/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Atención Ambulatoria , Antineoplásicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Farmacéuticos , Estudios ProspectivosRESUMEN
The mechanism(s) underlying obesity-related postmenopausal (PM) breast cancer (BC) are not clearly understood. We hypothesized that the increased local presence of 'obese' mammary adipocytes within the BC microenvironment promotes the acquisition of an invasive and angiogenic BC cell phenotype and accelerates tumor proliferation and progression. BC cells, treated with primary mammary adipocyte secretome from premenopausal (Pre-M) and PM obese women (ObAdCM; obese adipocyte conditioned-media) upregulated the expression of several pro-tumorigenic factors including VEGF, lipocalin-2 and IL-6. Both Pre-M and PM ObAdCM stimulated endothelial cell recruitment and proliferation and significantly stimulated BC cell proliferation, migration and invasion. IL-6 and LCN2 induced STAT3/Akt signaling in BC cells and STAT3 inhibition abrogated the ObAdCM-stimulated BC cell proliferation and migration. Expression of proangiogenic regulators including VEGF, NRP1, NRP2, IL8RB, TGFß2, and TSP-1 were found to be differentially regulated in mammary adipocytes from obese PM women. Comparative RNAseq indicated an upregulation of PI3K/Akt signaling, ECM-receptor interactions and lipid/fatty acid metabolism in PM versus Pre-M mammary adipocytes. Our results demonstrate that irrespective of menopausal status, cross-talk between obese mammary adipocytes and BC cells promotes tumor aggressiveness and suggest that targeting the LCN2/IL-6/STAT3 signaling axis may be a useful strategy in obesity-driven breast tumorigenesis.
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Adipocitos , Neoplasias de la Mama , Movimiento Celular , Proliferación Celular , Neovascularización Patológica , Obesidad , Factor de Transcripción STAT3 , Femenino , Humanos , Adipocitos/metabolismo , Adipocitos/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Interleucina-6/metabolismo , Lipocalina 2/metabolismo , Lipocalina 2/genética , Menopausia/metabolismo , Invasividad Neoplásica , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Obesidad/metabolismo , Obesidad/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Microambiente TumoralRESUMEN
Hereditary Breast and Ovarian Cancer (HBOC) and Lynch Syndrome (LS) are the most common inherited cancer syndromes identified with genetic testing. Testing, though, commonly reveals variants of uncertain significance (VUSs). This is a retrospective observational study designed to determine the prevalence of pathogenic mutations and VUSs in patients tested for HBOC and/or LS and to explore the characteristics of the VUS population. Patients 18-80 years old that met NCCN criteria for HBOC and/or LS genetic screening were tested between 2006 and 2020 at Mount Auburn Hospital in Cambridge, Massachusetts. A total of 663 patients were included in the study, with a mean age of 50 years old and 90% being females. Pathogenic mutations were identified in 12.5% and VUSs in 28.3%. VUS prevalence was associated with race (p-value = 0.019), being particularly higher in Asian populations. Patients with a personal history of breast cancer or family history of breast or ovarian cancer were more likely to have a VUS (personal breast: OR: 1.55; CI: 1.08-2.25; family breast: OR: 1.68; CI: 1.08-2.60, family ovarian OR: 2.29; CI: 1.04-5.45). In conclusion, VUSs appear to be detected in almost one third patients tested for cancer genetic syndromes, and thus future work is warranted to determine their significance in cancer development.
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BACKGROUND: This study addresses the effectiveness of risk models and screening breast magnetic resonance imaging (MRI) in women who have atypical hyperplasia (AH), lobular carcinoma in situ (LCIS), or a family history of breast cancer, but not a genetic mutation. PATIENTS AND METHODS: A retrospective review of 444 women who had 458 breast screening MRIs at a community teaching hospital over a 12-month period between March 25, 2014 and March 31, 2015 was performed. The patients underwent high risk screening with breast MRIs alternating with mammograms every 6 months. After excluding patients with prior breast or ovarian cancer, genetic mutations, and chest wall radiation, 200 remaining patients constituted the study cohort. Over the following 5 years, the patients were screened with MRIs alternating with mammograms every 6 months. A total of 961 total MRI screenings were performed over the entire 5-year period of the study. RESULTS: A total of 200 women fit the study criteria. Of these 103 had a prior history of AH or LCIS. Over the 5-year period, 60 women dropped out of the screening regimen, 6 patients were diagnosed with breast cancer on screening MRIs, and 2 additional patients were diagnosed with breast cancer on screening mammograms. Surprisingly, the highest Tyrer-Cuzick (T-C) scores did not correlate with increased development of breast cancers in our population. CONCLUSIONS: This study shows that there is wide variation in the results of risk assessment models. Risk models may overestimate breast cancer risk, suggesting that re-evaluation of current risk assessment and screening protocols is warranted.
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Carcinoma de Mama in situ , Neoplasias de la Mama , Neoplasias Ováricas , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Hiperplasia , Masculino , MamografíaRESUMEN
BACKGROUND: It is estimated that there are 3.8 million breast cancer survivors in the United States. Addressing survivors' post-treatment needs is critical to providing quality healthcare. METHODS: A standardized questionnaire for breast cancer survivors was employed to assess the health status, challenges, and concerns of our breast cancer patients at their survivorship visits, which were conducted 4 months after surgery. All patients were seen in the breast center at one community hospital over a 6-year period. RESULTS: Responses to a standardized questionnaire that was administered to 505 consecutive breast cancer patients at their survivorship visits 4 months after surgery were evaluated. The most striking finding was that 35% reported symptoms of insomnia, 26% had persistent fatigue, and 19% experienced fatigue that interfered with their usual activities. There was a significant association between symptoms of insomnia and radiation treatment (P = .004), pain (P < .001), hormone therapy (P < .01), and side effects of hormone therapy (P < .0001). There was also a significant association between fatigue and pain (P < .001) as well as side effects from hormone treatment (P = .0036). CONCLUSIONS: Over a third (35%) of breast cancer patients suffer from insomnia, while over a quarter (26%) complain of fatigue at their survivorship assessments. Contributing factors include radiation treatment, pain, and hormonal therapy. Careful assessment and treatment of fatigue and symptoms of insomnia in breast cancer patients is needed to improve quality of life for survivors.
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Neoplasias de la Mama , Supervivientes de Cáncer , Trastornos del Inicio y del Mantenimiento del Sueño , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Fatiga/etiología , Femenino , Hormonas , Humanos , Dolor , Calidad de Vida , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Sobrevivientes , SupervivenciaRESUMEN
OBJECTIVES: A comprehensive decision aid (DA) for women ≥70 years with Stage I ER+/HER2-negative breast cancer was developed to support locoregional and systemic treatment decision-making. We aimed to test the acceptability of this novel DA in women newly-diagnosed with breast cancer. MATERIALS AND METHODS: Women ≥70 diagnosed with Stage I, ER+/HER2- breast cancer were recruited from three Boston-area hospitals. They underwent baseline interviews after initial surgical consultation, reviewed the DA, and were surveyed <2 weeks later to determine DA acceptability (e.g., was it helpful?), changes in decisional conflict, stage of decision-making, and knowledge. Participants could optionally complete a three-month follow-up. Paired t-tests and McNemar's tests were used for statistical comparisons, and thematic analyses were conducted to identify themes in participants' open-ended comments. RESULTS: Thirty-three of 56 eligible patients approached completed the baseline and acceptability surveys, and 25 completed the three-month follow-up. Participants' mean age was 74.7 years (±3.8). Nearly all participants (n = 31, 94%) strongly agreed that the DA was helpful and felt that the DA prepared them for treatment decision-making, with a mean decision preparation score of 4.1 (out of 5.0); 6% (n = 2) found it very anxiety provoking. Knowledge improved with a mean of 9.0 out of 14 questions correct at baseline to 10.6 correct on the acceptability survey (p < 0.0001). CONCLUSIONS: A DA tailored to women ≥70 with Stage I, ER+, HER2- breast cancer increased knowledge and was perceived to be helpful by older women. A randomized controlled trial is needed to evaluate its efficacy.
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Neoplasias de la Mama , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Toma de Decisiones , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Receptores de Estrógenos , Encuestas y CuestionariosRESUMEN
Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of atypical hyperplasia and >13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification of women at increased risk of developing breast cancer.
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Biomarcadores de Tumor/orina , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/orina , Metaloproteasas/orina , Proteínas ADAM/orina , Proteína ADAM12 , Análisis de Varianza , Carcinoma in Situ/enzimología , Carcinoma in Situ/orina , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Humanos , Modelos Logísticos , Metaloproteinasa 9 de la Matriz/orina , Proteínas de la Membrana/orina , Persona de Mediana Edad , Lesiones Precancerosas/enzimología , Lesiones Precancerosas/orina , Medición de RiesgoRESUMEN
Restitution is the process by which superficial interruptions in the gastrointestinal mucosa are repaired by the flattening and spreading of epithelial cells surrounding the damage. During this process, mucosal epithelial cells undergo extensive reshaping and cytoskeletal remodeling. K(+) channels, located primarily on the basolateral surface of gut epithelial cells, are central to both actin polymerization, via their control of membrane potential, and cell volume regulation. We questioned whether K(+) channels are involved in restitution using an in vitro model of intestinal epithelium, monolayers of the human colon carcinoma cell line T84. We report that pharmacologic K(+) channel inhibition accelerates wound healing in T84 cell monolayers. Both Ca(++)-dependent and constitutively active channels are involved, as indicated by the sensitivity to clotrimazole, charybdotoxin, and barium. The ability of clotrimazole to accelerate wound resealing was also observed in Caco-2 cell sheets. Pharmacologic stimulation of K(+) channel activity had no effect on the repair rate. Analysis of the resealing process by time lapse and confocal microscopy revealed that K(+) channel inhibitors abolished the initial wound retraction, briefly accelerated the repair rate, and altered the shape of the cell sheet abutting the injury during the early phase of resealing. We hypothesize that K(+) channel inactivation interrupts the coregulation of f-actin polymerization and volume control that is initiated by the healing process.
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Caribdotoxina/farmacología , Clotrimazol/farmacología , Células Epiteliales/metabolismo , Canales de Potasio/efectos de los fármacos , Bario/farmacología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Neoplasias del Colon/patología , Células Epiteliales/efectos de los fármacos , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Microscopía Electrónica , Valores de Referencia , Sensibilidad y Especificidad , Células Tumorales Cultivadas , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND AND AIMS: Cancer progression is in large part dependent on the complex process of cell invasion, involving adhesion, motility, and enzymatic proteolysis. Overexpression of the Src proto-oncogene (c-Src), a nonreceptor tyrosine kinase, has been implicated in the progression of both colon and breast cancer. Our group has previously reported that overexpression of c-Src leads to a significant gain in invasive cell behavior in vitro. In this study, we sought to assess the relative importance of epidermal growth factor (EGF) stimulation and c-Src overexpression in conferring an invasive phenotype. METHODS: Breast carcinoma cells and colon epithelial cells which naturally express low levels of c-Src were used for these studies. The cells were transfected so that they overexpressed c-Src; the mock-transfected parent lines were used as controls. Transfectants were tested for changes in invasion patterns after Src inhibition and EGF stimulation. RESULTS: Invasion assays in both cell systems confirmed the importance of c-Src in determining invasive potential. A significant correlation was shown between c-Src kinase protein and cell invasion. Furthermore, Src inhibition significantly inhibited invasion in a dose-dependent manner. To clarify the relative contribution of EGF and c-Src to cell invasion, the ability of cells to invade through growth-factor-reduced matrigel, with or without EGF added, was compared to invasion through intact matrigel. The breast and colon cell lines behave quite differently in this regard. In the colon model, overexpressed c-Src is critical for cell invasion and stimulation with EGF is synergistic with c-Src overexpression. Conversely, the breast carcinoma cells transfected with c-Src were unable to invade without EGF stimulation and did not demonstrate the same synergistic relationship between c-Src and EGF. Instead, our results indicate that in BT474 breast carcinoma cells, EGF can substitute for c-Src in promoting breast cancer cell invasion. CONCLUSIONS: Because most breast carcinomas overexpress c-Src, it behooves one to question the extent to which reducing the amount of EGF and consequent EGFR activity will decrease invasion. In this study, the effects of EGF on cell invasion were determined in light of a single alteration in c-Src expression. Our results show that EGF enhances the impact of c-Src overexpression on invasion. In breast cancer cells, EGF is capable of inducing invasion to the same extent as c-Src overexpression. This suggests that anti-EGFR therapies will be efficacious in retarding breast carcinoma invasion and metastasis.