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BACKGROUND: For patients with clinically node-positive (cN+) breast cancer undergoing neoadjuvant chemotherapy (NAC), retrieving previously clipped, biopsy-proven positive lymph nodes during sentinel lymph node biopsy [i.e., targeted axillary dissection (TAD)] may reduce false negative rates. However, the overall utilization and impact of clipping positive nodes remains uncertain. PATIENTS AND METHODS: We retrospectively analyzed cN+ ISPY-2 patients (2011-2022) undergoing axillary surgery after NAC. We evaluated trends in node clipping and associations with type of axillary surgery [sentinel lymph node (SLN) only, SLN and axillary lymph node dissection (ALND), or ALND only] and event-free survival (EFS) in patients that were cN+ on a NAC trial. RESULTS: Among 801 cN+ patients, 161 (20.1%) had pre-NAC clip placement in the positive node. The proportion of patients that were cN+ undergoing clip placement increased from 2.4 to 36.2% between 2011 and 2021. Multivariable logistic regression showed nodal clipping was independently associated with higher odds of SLN-only surgery [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.8-6.8, p < 0.001]. This was also true among patients with residual pathologically node-positive (pN+) disease. Completion ALND rate did not differ based on clip retrieval success. No significant differences in EFS were observed in those with or without clip placement, both with or without successful clip retrieval [hazard ratio (HR) 0.85, 95% CI 0.4-1.7, p = 0.7; HR 1.8, 95% CI 0.5-6.0, p = 0.3, respectively]. CONCLUSION: Clip placement in the positive lymph node before NAC is increasingly common. The significant association between clip placement and omission of axillary dissection, even among patients with pN+ disease, suggests a paradigm shift toward TAD as a definitive surgical management strategy in patients with pN+ disease after NAC.
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BACKGROUND AND OBJECTIVES: The ACOSOGZ0011 trial found that overall survival (OS) for patients with 1-2 positive nodes undergoing sentinel lymph node biopsy-alone (SLNB) was noninferior to completion axillary lymph node dissection (ALND), but excluded patients undergoing mastectomy. Our study examined patterns of ALND and its relationship with OS for SLNB-positive patients undergoing mastectomy. METHODS: The National Cancer Database was queried (2010-2017) for patients with cT1-2N0 breast cancer undergoing mastectomy with positive sentinel lymph nodes. Clinical data were compared. RESULTS: Of 20 001 patients, 11 574 (57.9%) underwent SLNB + ALND, and 8427 (42.1%) had SLNB-alone. The SLNB + ALND group had more positive nodes (mean 2.6 vs. 1.3, p < 0.001) and more frequently received nodal radiation (33.4% vs. 28.9%, p < 0.001). Patients diagnosed in later years were less likely to undergo ALND (2010: reference; 2017: odds ratio: 0.29, 95% confidence interval [CI]: 0.25-0.33, p < 0.001). ALND (hazard ratio [HR]: 0.97, 95% CI: 0.89-1.06, p = 0.49) and nodal radiation (HR: 0.92, 95% CI: 0.83-1.02, p = 1.06) were not independently associated with OS. Propensity-score matched 5-year OS was similar (SLNB + ALND: 90.9% vs. SLNB-alone: 90.3%, p = 0.65). CONCLUSION: For patients undergoing mastectomy for cT1-2N0 breast cancer with positive SLNB, SLNB-alone was common and increased over time. Axillary radiation was not routinely delivered in the SLNB-alone group. Completion ALND and nodal radiation were not associated with improved survival.
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Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Mastectomia , Mastectomia Simples , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Axila/patologia , Linfonodos/cirurgia , Linfonodos/patologiaRESUMO
BACKGROUND: The management of high-risk breast lesions diagnosed on image-guided core biopsy remains controversial. We implemented a high-risk breast conference attended by breast pathologists, imagers, and surgeons to prospectively review all contemporary cases in order to provide a consensus recommendation to either surgically excise or follow on imaging at 6-month intervals for a minimum of 2 years. METHODS: Between May, 2015 and June, 2019, 127 high-risk lesions were discussed. Of these 127 cases, 116 had concordant radiology-pathology (rad-path) findings. The remaining 11 patients had discordant rad-path findings. Of the 116 concordant cases, 6 were excluded due to lack of the first imaging follow-up until analysis. Of the remaining 110 patients, 43 had atypical ductal hyperplasia (ADH), 12 had lobular carcinoma in situ (LCIS), 19 had atypical lobular hyperplasia (ALH), 33 had radial scar (RS), 2 had flat epithelial atypia (FEA), and 1 had mucocele-like lesion (ML). We recommended excision for ADH if there were > 2 ADH foci or < 90% of the associated calcifications were removed. For patients with LCIS or ALH, we recommended excision if the LCIS or ALH was associated with microcalcifications or the LCIS was extensive. We recommended excision of RS when < 1/2 of the lesion was biopsied. We recommended all patients with FEA and ML for 6-month follow-up. RESULTS: Following conference-derived consensus for excision, of the 27 ADH excised, 9 were upgraded to invasive carcinoma or ductal carcinoma in situ. Of the six LCIS cases recommended for excision, none were upgraded. Nine excised radial scars revealed no upgrades. Additionally, 3 patients with ADH, 2 with ALH, 1 with LCIS, and 2 with RS underwent voluntary excision, and none were upgraded. All other patients (13 with ADH, 5 LCIS, 17 ALH, 22 RS, 2 FEA and 1 ML) were followed with imaging, and none revealed evidence of disease progression during follow-up (187-1389 days). All 11 rad-path discordant cases were excised with 2 upgraded to carcinoma. CONCLUSIONS: The results of this prospective study indicate that high-risk breast lesions can be successfully triaged to surgery versus observation following establishment of predefined firm guidelines and performance of rigorous rad-path correlation.
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Neoplasias da Mama , Carcinoma in Situ , Carcinoma Intraductal não Infiltrante , Carcinoma Lobular , Biópsia com Agulha de Grande Calibre , Mama/diagnóstico por imagem , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/patologia , Feminino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/patologia , Estudos ProspectivosRESUMO
BACKGROUND: To determine whether patients with benign papilloma diagnosed on core biopsy can be spared from surgery. METHODS: We prospectively reviewed 150 consecutive core biopsy-diagnosed papilloma cases at a multi-specialty high-risk breast lesion conference to determine whether surgical excision was necessary. Of these 150 cases, 148 had concordant radiologic-pathologic features. Six were excluded due to lack of the first imaging follow-up until analysis. 112 were benign papillomas; 17 were papillomas involved by atypical ductal hyperplasia (atypical papilloma); 6 papillomas had ADH in adjacent tissue but not involving the papilloma; 2 papillomas were involved by atypical lobular hyperplasia (ALH); and 5 papillomas had ALH in adjacent tissue. Two were radiology-pathology (rad-path) discordant. RESULTS: Thirty-nine of the 112 benign papillomas were excised with no upgrade to carcinoma; 73 were followed with no disease progression during follow-up (185-1279 days). Fifteen of 17 atypical papillomas were surgically excised with 4 (26.7%) upgraded to carcinoma. Four of the 6 patients with ADH adjacent to a benign papilloma underwent excision with 2 upgrades to carcinoma. None of the patients with papilloma, which was either involved by ALH or had ALH in adjacent tissue had upgrade or disease progression during follow-up (204-1159 days). Finally, the two cases with discordant path-rad discordant were excised with no upgrade. CONCLUSIONS: Our data confirm that rad-path concordant benign papillomas diagnosed on core biopsy do not require surgery. It also supports the value of a formal multi-specialty review of all benign papilloma cases to create a consensus management plan.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Papiloma , Radiologia , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Papiloma/diagnóstico , Papiloma/cirurgiaRESUMO
BACKGROUND AND METHODS: Apocrine adenocarcinoma is a rare subtype of breast cancer. We sought to compare the characteristics and survival of patients diagnosed with triple-negative apocrine adenocarcinoma to those of patients diagnosed with triple-negative invasive ductal carcinoma. Utilizing data from the National Cancer Database between 2004 and 2013, 70 524 eligible female patients with triple-negative breast cancer were identified including 566 patients with apocrine adenocarcinomas and 69 958 patients with invasive ductal carcinoma. Descriptive statistics for each variable were reported. A comparison of each covariate between the study cohorts was assessed in univariate and multivariate analysis. Cox proportional models were used to calculate hazard ratios. Additionally, the propensity score matching method was implemented to reduce treatment selection bias. RESULTS: Patients with triple-negative apocrine tumors were more likely to be older, Caucasian, and have smaller, moderately to well-differentiated tumors. Multivariable analysis noted a significantly improved survival for patients with triple-negative apocrine carcinoma (TNAC) vs triple-negative invasive ductal carcinoma (TNBC) (hazard ratio [HR] 0.65 [95% confidence interval [CI] [0.53-0.81], P = 0 < .001). Propensity score matching analysis confirmed a significant difference in overall survival for patients with TNAC in comparison to TNBC (HR 0.79 [95% CI [0.63-1.00], P = .05). DISCUSSION: Triple-negative apocrine adenocarcinomas have a modestly improved long-term survival when compared with triple-negative invasive ductal cancers.
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Glândulas Apócrinas/patologia , Carcinoma Ductal de Mama/mortalidade , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Programa de SEER , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Adulto JovemRESUMO
BACKGROUND: Recurrence score (RS) testing in early-stage, ER-positive breast cancer is used to predict the benefit of adjuvant chemotherapy for disease recurrence and overall survival. TAILORx results decreased the ambiguity of "intermediate risk" RS by creating a binary classification system. We aimed to determine how women ≥ 70 years with intermediate RS were redistributed post-TAILORx and to identify predictors of low RS. METHODS: Patients ≥ 70 years with early-stage, node-negative, ER-positive breast cancers in the National Cancer Database(2006-2014) were included. "Pre-TAILORx" RS were classified as low (0-17), intermediate (18-30), and high (> 30). "Post-TAILORx" RS were classified as low (0-25) and high (> 25). RESULTS: In total, 14,925 women were included. Average age was 74 years. 60% (n = 9009) had low pre-TAILORx RS, 31% (n = 4635) intermediate, and 9% (n = 1281) high. Of 4635 patients with intermediate RS, 72% (n = 3660) were reclassified to low RS. Only 12% (n = 1783) of patients received chemotherapy. Of patients with pre-TAILORx intermediate RS who received chemotherapy, 55% (n = 417) would have been spared chemotherapy by being reclassified with low RS post-TAILORx. The strongest predictor of post-TAILORx low RS was tumor grade; 95% of well-differentiated had low RS, compared with 56% of poorly/undifferentiated tumors (p < 0.001). Smaller tumor size also was associated with low RS. Age was not associated with RS. CONCLUSIONS: With post-TAILORx RS criteria, the vast majority of patients ≥ 70 years can be classified as low-risk and unlikely to benefit from chemotherapy. Given that the elderly have greater rates of chemotherapy-associated complications, reconsideration of routine RS testing in patients ≥ 70 years is warranted. Tumor grade and size also may inform the decision to omit RS testing.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Guias de Prática Clínica como Assunto/normas , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Bases de Dados Factuais , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
BACKGROUND: The authors determined the impact of postmastectomy radiotherapy (PMRT) on overall survival (OS) among patients with pT3N0M0 breast cancer in the National Cancer Data Base. METHODS: A total of 3437 patients with pT3N0M0 breast cancer who initially were treated with mastectomy between 2003 and 2011 were identified. Of these women, 1644 (47.8%) received PMRT (67% treated with chest wall RT alone and 33% treated with chest wall and regional lymph node irradiation). Univariable and multivariable analyses were conducted to identify characteristics associated with PMRT and OS. In addition, propensity score matching and interaction effect testing also were performed. RESULTS: PMRT was associated with age <40 years, private insurance coverage, treatment facility location within 10 miles of the patient's home zip code, Charlson-Deyo comorbidity score of 0, tumor size ≥7 cm, and treatment with chemotherapy or hormone therapy (all P<.05). PMRT was associated with improved 5-year OS (86.3% for patients treated with PMRT vs 66.4% for patients not treated with PMRT; P<.01). In addition to PMRT (hazard ratio, 0.72; 95% confidence interval, 0.59-0.87 [P<.01]), age ≤50 years, treatment at an academic/research program, Charlson-Deyo comorbidity score of 0, tumor size <7 cm, chemotherapy receipt, and hormone therapy receipt were associated with improved OS on multivariable analyses (all P<.05). Interaction testing found that PMRT improved OS independent of age, facility type, Charlson-Deyo comorbidity score, tumor grade and size, surgical margin status, and receipt of chemotherapy or hormone therapy (all P>.1). Finally, propensity score matching analysis confirmed the impact of PMRT on OS (P = .02). It is interesting to note that regional lymph node irradiation did not improve OS versus chest wall RT alone (P = .09). CONCLUSIONS: Among patients with pT3N0M0 breast cancer in the National Cancer Data Base, PMRT was found to be associated with improved OS regardless of surgical margin status, tumor size, and receipt of systemic therapy. Cancer 2017;123:2829-39. © 2017 American Cancer Society.
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Neoplasias da Mama/radioterapia , Mastectomia , Radioterapia Adjuvante , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Seguro Saúde , Linfonodos , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Parede Torácica , Adulto JovemRESUMO
PURPOSE: Racial disparity of breast cancer in each subtype and substage is not clear. METHODS: We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. RESULTS: African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2- stages III and IV breast cancer and HR-/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2- stage II cancer and HR-/HER2- stage II cancer. CONCLUSION: AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.
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Negro ou Afro-Americano/genética , Neoplasias da Mama/epidemiologia , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptores de Progesterona/genética , População Branca/genéticaRESUMO
BACKGROUND: Racial disparity is often identified as a factor in survival from breast cancer in the United States. Current data regarding survival in patients treated in the Department of Defense Military Healthcare System is lacking. METHODS: The Department of Defense Automated Central Tumor Registry (ACTUR) was queried for all women diagnosed with Stage I or II breast cancer from January 1, 1996 through December 31, 2008. Statistical analyses evaluated demographics, surgical treatment, tumor stage, and survival rates. RESULTS: There were 8,890 patients meeting inclusion criteria. Patients who were younger, Asian American (versus white or black), lower T and/or N stage had significantly improved survival rates. Interestingly, white and black patients demonstrated similar survival in this study. Patients with a longer period of time between diagnosis and treatment had no decrement in survival. As would be expected, patients with a longer recurrence free period enjoyed longer survival. CONCLUSIONS: Survival from early stage breast cancer is equivalent between white and black patients in the Department of Defense Healthcare System. This finding is contrary to reports from our civilian counterparts and may be indicative of improved access to care and overall improved cancer surveillance.
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População Negra/estatística & dados numéricos , Neoplasias da Mama/mortalidade , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Militares/estatística & dados numéricos , Recidiva Local de Neoplasia/mortalidade , População Branca/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/etnologia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etnologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Sistema de Registros/estatística & dados numéricos , Taxa de Sobrevida , Estados UnidosRESUMO
BACKGROUND: A practice standard in sentinel lymph node (SLN) mapping in breast cancer is intradermal injection of technetium-99m sulfur colloid (Tc-99m), resulting in significant patient discomfort and pain. A previous randomized controlled trial showed that adding lidocaine to Tc-99m significantly reduced radioisotope injection-related pain. We tested whether 1 % lidocaine admixed with Tc-99m affects feasibility of SLN mapping. METHODS: Between January 2006 and April 2009, 140 patients with early breast cancer were randomly assigned (1:1:1:1) to receive standard topical 4 % lidocaine cream and intradermal Tc-99m (control) or to one of three other study groups: topical placebo cream and injection of Tc-99m containing sodium bicarbonate (NaHCO3), 1 % lidocaine, or both. All SLN data were collected prospectively. RESULTS: Study groups were comparable for clinicopathological parameters. As previously reported, the addition of 1 % lidocaine to the radioisotope solution significantly improved patient comfort. Overall SLN identification rate in the trial was 93 %. Technical aspects of SLN biopsy were similar for all groups, including time from injection to operation, first SLN (SLN 1) gamma probe counts, ex vivo counts for SLN 1 and SLN 2, and axillary bed counts. SLN identification rates were comparable statistically: control (96 %), lidocaine (90 %), sodium bicarbonate (97 %), and sodium bicarbonate-lidocaine (90 %). The control group had a significantly higher SLN 2/SLN 1 ex vivo count ratio, and the number of SLNs detected was significantly reduced in the lidocaine versus no-lidocaine groups (p < 0.05). CONCLUSIONS: Addition of 1 % lidocaine to standard radioisotope solution for SLN mapping in breast cancer is associated with fewer SLNs detected, but it does not appear to compromise SLN identification.
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Anestésicos Locais/administração & dosagem , Neoplasias da Mama/patologia , Lidocaína/administração & dosagem , Linfonodos/diagnóstico por imagem , Biópsia de Linfonodo Sentinela/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor/etiologia , Dor/prevenção & controle , Cintilografia , Compostos Radiofarmacêuticos/efeitos adversos , Coloide de Enxofre Marcado com Tecnécio Tc 99m/efeitos adversosRESUMO
BACKGROUND: Patient and socioeconomic factors both contribute to disparities in post-mastectomy reconstruction (PMR) rates. We sought to explore PMR patterns across the US and to determine if PMR rates were associated with Medicaid expansion. METHODS: The NCDB was used to identify women who underwent PMR between 2004-2016. The data was stratified by race, state Medicaid expansion status, and region. A multivariate model was fit to determine the association between Medicaid expansion and receipt of PMR. RESULTS: In comparison to Caucasian women receiving PMR in Medicaid expansion states, African American (AA) women in Medicaid expansion states were less likely to receive PMR (OR .96 [.92-1.00] P < .001). Patients in the Northeast (NE) had better PMR rates vs any other region in the US, for both Caucasian and AA women (Caucasian NE ref, Caucasian-South .80 [.77-.83] vs AA NE 1.11 [1.04-1.19], AA-South (.60 [.58-.63], P < .001). Interestingly, AA patients residing in the NE had the highest receipt of PMR 1.11 (1.04-1.19), even higher than their Caucasian counterparts residing in the same region (ref). Rural AA women had the lowest rates of PMR vs rural Caucasian women (.40 [.28-.58] vs .79 [.73-.85], P < .001]. DISCUSSION: Racial disparities in PMR rates persisted despite Medicaid expansion. When stratified by region, however, AA patients in the NE had higher rates of PMR than AA women in other regions. The largest disparities were seen in AA women in the rural US. Breast cancer disparities continue to be a complex problem that was not entirely mitigated by improved insurance coverage.
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Neoplasias da Mama , Medicaid , Neoplasias da Mama/cirurgia , Feminino , Disparidades em Assistência à Saúde , Humanos , Cobertura do Seguro , Mastectomia , Patient Protection and Affordable Care Act , Estados UnidosRESUMO
BACKGROUND: Receptor status in breast cancer is known to be related to survival. However, the relationship between breast cancer subtype, preferential sites of metastasis, and overall survival is not clear. METHODS: A total of 414,528 patients from the National Cancer Database (2010-2013) were examined. All patients received surgery and systemic treatments. Breast cancer was subtyped based on hormonal receptor (HR) and HER2 status. RESULTS: HR-/HER2+ breast cancer patients had the highest overall rate of metastasis while HR+/HER2- had the lowest. HR+/HER2+ cancer had the most frequent metastasis to the bone, and HR-/HER2+ to brain, liver, lung and multiple sites. Generally, patients with brain or multiple metastasis had the worst overall survival (OS) across different subtypes. Patients with bone oligometastasis tend to have better OS than patients with metastasis to other site but significantly worse OS than patients without any metastasis. CONCLUSIONS: This large study exhibits how breast cancer subtype plays a role in the rate and site of metastasis as well as in overall survival. Surveillance and treatment strategies should be tailored on the risk and potential site of metastases based upon receptor subtype.
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Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Programa de SEER/estatística & dados numéricos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/terapia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
BACKGROUND: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup. RESULTS: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P < .01) and had fewer T1a tumors (11% vs. 13%; P = .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P < .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P = .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P = .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .043). CONCLUSION: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions.
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Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Mastectomia Segmentar/estatística & dados numéricos , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante/estatística & dados numéricos , Programa de SEER/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is generally treated with HER2-targeted therapy combined with chemotherapy. Patients with HER2+ and estrogen receptor-positive (ER+) cancer are additionally treated with long-term hormone therapy. This study examined the metastatic pattern and prognosis of both ER+/HER2+ and ER-/HER2+ breast cancer. PATIENTS AND METHODS: A total of 54,147 patients with HER2+ breast cancer from the National Cancer Data Base (NCDB, 2010-2013) and 31,946 patients with HER2+ breast cancer from the Surveillance, Epidemiology, and End Results Program (SEER, 2010-2014) were examined. Sites of metastasis and overall survival (OS) were examined in the NCDB, while OS and breast cancer-specific survival were examined in the SEER database. RESULTS: Compared to ER-/HER2+ breast cancer, ER+/HER2+ breast cancer was more likely to metastasize to bone but less likely to brain, liver, and lung and less likely to result in multiple metastases. In univariate analysis based on the NCDB, patients with ER-/HER2+ breast cancer had worse OS in all metastasis subsets, including patients who received HER2-targeted therapy. This poor survival for ER-/HER2+ persisted in patients with metastasis to bone and lung, and multiple metastases. In multivariate analysis adjusting for age, tumor grade, surgery, chemotherapy, HER2-targeted therapy, and hormone therapy, ER-/HER2+ patients with bone metastasis still had worse OS. In the SEER, ER-/HER2+ patients had both worse OS and breast cancer-specific survival in univariate analysis. CONCLUSION: This large study showed patients with ER+/HER2+ and ER-/HER2+ breast cancers had different metastatic patterns. Patients with ER-/HER2+ breast cancer may require more aggressive treatment.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Programa de SEER , Taxa de SobrevidaRESUMO
A number of cancers present with synchronous or metachronous hepatic metastases. Historically, many of these patients were considered unresectable and were treated with either systemic chemotherapy or supportive care. Today, a variety of options exist for the management of hepatic metastases. Newer agents for systemic therapy continue to be introduced and are providing improved progression-free and overall survival and increased resectability of liver metastases. However, complete surgical resection of isolated hepatic metastases remains the optimal management for these patients. Surgical interventions can be offered to patients with hepatic-only metastases. Hepatic artery chemotherapy represents an adjunct for those patients undergoing resection and can improve survival. This benefit may be even more pronounced when combined with systemic chemotherapy. Newer generation biologic agents can improve results. New therapeutic modalities to treat lesions that are unresectable include ablative techniques such as radiofrequency ablation (RFA) and cryoablation. This article will examine modalities of diagnosis of hepatic metastases and highlight the data regarding hepatic resection for metastases of several types of primary cancers, the rationale for, and efficacy of, hepatic arterial chemotherapy, in both the postoperative adjuvant setting and in unresectable liver disease, and review the current literature for ablative techniques in the treatment of liver metastases.
Assuntos
Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Terapia Combinada , Humanos , Neoplasias Hepáticas/secundárioRESUMO
We have previously reported the identification and characterization of a novel BRCA1/2 interacting protein complex, BRCC (BRCA1/2-containing complex). BRCC36, one of the proteins in BRCC, directly interacts with BRCA1, and regulates the ubiquitin E3 ligase activity of BRCC. Importantly, BRCC36 is aberrantly expressed in the vast majority of breast tumors, indicating a potential role in the pathogenesis of this disease. To further elucidate the functional consequence of abnormal BRCC36 expression in breast cancer, we have done in vivo silencing studies using small interfering RNAs targeting BRCC36 in breast cancer cell lines, i.e., MCF-7, ZR-75-1, and T47D. Knock-down of BRCC36 alone does not affect cell growth, but when combined with ionizing radiation (IR) exposure, it leads to an increase in the percentage of cells undergoing apoptosis when compared with the small interfering RNA control group in breast cancer cells. Immunoblot analysis shows that inhibition of BRCC36 has no effect on the activation of ATM, expression of p21 and p53, or BRCA1-BARD1 interaction following IR exposure. Importantly, BRCC36 depletion disrupts IR-induced phosphorylation of BRCA1. Immunofluorescent staining of BRCA1 and gamma-H2AX indicates that BRCC36 depletion prevents the formation of BRCA1 nuclear foci in response to DNA damage in breast cancer cells. These results show that down-regulation of BRCC36 expression impairs the DNA repair pathway activated in response to IR by inhibiting BRCA1 activation, thereby sensitizing breast cancer cells to IR-induced apoptosis.
Assuntos
Proteína BRCA1/metabolismo , Neoplasias da Mama/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Apoptose/fisiologia , Apoptose/efeitos da radiação , Proteína BRCA1/antagonistas & inibidores , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Reparo do DNA/fisiologia , Regulação para Baixo , Expressão Gênica , Humanos , Fosforilação/efeitos da radiação , RNA Interferente Pequeno/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/biossíntese , Ubiquitina-Proteína Ligases/genéticaRESUMO
Patients often receive axillary ultrasound-biopsy (AUS-B) before clinical evaluation. One positive biopsy in the absence of palpable disease rarely indicates additional nodal involvement, but it eliminates patients from being managed by the American College of Surgeons Oncology Group Z0011 trial criteria. To determine which patients may benefit from AUS-B, we analyzed whether characteristics on AUS were associated with large-volume axillary disease and, thus, the need for axillary lymph node (LN) dissection. A retrospective review identified patients who met Z0011 criteria and underwent AUS. Clinicopathologic and ultrasound characteristics were compared between patients with ≤2 versus ≥3 positive LNs. Two hundred and seven patients with cT1-2N0 tumors underwent preoperative AUS and breast-conserving surgery. On multivariate analysis, three AUS combinations were associated with ≥3 positive LNs: cortical thickness (CT) > 4 mm + loss of fatty hilum + round shape (P = 0.0218), CT > 4 mm + loss of fatty hilum (P = 0.0211), and CT > 4 mm + round shape (P = 0.0155). Preoperative axillary LN biopsy in patients with a single abnormal LN characteristic on AUS may be unnecessary because a positive finding will eliminate management according to Z0011 criteria. Cortical thickness >4 mm combined with any other abnormal characteristic was associated with ≥3 positive LNs, supporting the performance of AUS-B in this population.
Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Mastectomia Segmentar , Oncologia , Biópsia de Linfonodo Sentinela , Sociedades Médicas , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Linfonodos/patologia , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos , Estados UnidosRESUMO
BACKGROUND: Standard methods of palliative gastrojejunostomy lead to delayed gastric emptying in up to 67% of patients. Partial stomach-partitioning gastrojejunostomy (PSPG) allows for the preferential passage of ingested material into the jejunum while maintaining endoscopic access to the diseased region and obviating the risk of leakage after antrectomy. METHODS: A retrospective examination of all patients undergoing PSPG from February 1999 through November 2004 was undertaken. Successful palliative bypass was based on the patient's ability to tolerate a regular diet. RESULTS: Thirty-nine patients underwent PSPG during the study period. All patients had locally advanced or metastatic gastrointestinal tract tumors. Sixteen patients presented with obstructive symptoms. The majority of patients (97%) were tolerating a regular diet at their last follow-up. CONCLUSIONS: PSPG is an alternative method of providing palliative bypass and allows for excellent palliation with delayed gastric emptying rates lower than that of standard gastrojejunostomy procedures.
Assuntos
Duodenopatias/cirurgia , Neoplasias Gastrointestinais/complicações , Gastrostomia/métodos , Obstrução Intestinal/cirurgia , Jejunostomia/métodos , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: This phase II trial assessed the activity and tolerability of a daily oral dose of 500 mg gefitinib (ZD1839, Iressa) in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma, and explored the clinical value of determining the status of the epidermal growth factor receptor (EGFR). EXPERIMENTAL DESIGN: Primary measure of efficacy was progression-free survival at 6 months. Mutations in exons 18 to 21 of EGFR and/or immunohistochemical expression of EGFR were evaluated in tumor specimens from patients enrolled in this trial as well as from patients not treated with gefitinib. RESULTS: Twenty-seven of 30 (90%) patients were eligible and evaluable for analysis of gefitinib efficacy and toxicity. Of these, four survived progression-free >6 months with one objective response (4%). The most commonly observed grade 3 toxicities were dermatologic (15%, 4 of 27) and diarrhea (30%, 8 of 27). Specimens from 26 of 26 or 25 of 26 patients were evaluable for immunohistochemical or mutation analysis, respectively. The response rate for patients with EGFR-positive tumors was 9% (1 of 11). EGFR expression was associated with longer progression-free survival (P = 0.008) and possibly longer survival (P = 0.082). The patient with the only objective response had a mutation in the catalytic domain of the tumor's EGFR (P = 0.04). Among 32 invasive tumors from patients not treated with gefitinib, one exhibited a catalytic domain mutation. CONCLUSIONS: Gefitinib was well tolerated but had minimal activity in unscreened patients with recurrent ovarian or primary peritoneal carcinoma. Prescreening patients for activating mutations in EGFR may improve response rate to gefitinib. This report is the first to document activating mutations in catalytic domain of EGFR in 3.5% (2 of 57) of ovarian cancers.