RESUMO
Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Consenso , OncologiaRESUMO
The assessment and categorization of papillary lesions remains one of the most challenging areas in breast pathology. In this review, we will focus on several diagnostic and management issues related to papillary breast lesions that are frequently encountered in daily practice. These include: (i) the distinctions among papillomas with atypia (atypical papillomas), papillomas with ductal carcinoma in situ, and papillary ductal carcinoma in situ; (ii) recent developments in our understanding of encapsulated ('intracystic') papillary carcinomas and solid papillary carcinomas; and (iii) the impact of core needle biopsy on management decisions and specimen evaluation. The role of immunohistochemistry in the evaluation of these lesions, particularly the role of myoepithelial cell markers, will be emphasized.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Biópsia por Agulha , Neoplasias da Mama/terapia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Papilar/terapia , Diagnóstico Diferencial , Feminino , Humanos , Papiloma/diagnóstico , Papiloma/patologiaRESUMO
We correlated quantitative results obtained in 40 invasive breast cancer cases for HER-2 gene amplification by fluorescence in situ hybridization with protein expression by immunohistochemical studies with computer-assisted image analysis. Fluorescence in situ hybridization (FISH) results were quantified as the mean number of fluorescent signals per nucleus, and immunohistochemical slides were read by semiquantitatively assessing membranous immunostaining intensity in tumor cells vs nonneoplastic breast tissue or quantitatively evaluated by image analysis. We found high correlation between immunohistochemical results by semiquantitative scoring and by image analysis. FISH results correlated with immunohistochemical results moderately when the staining intensity of only tumor cells was assessed and significantly better when the difference in staining intensity between tumor cells and nonneoplastic breast tissue was assessed. The correlation with FISH results was further improved when immunohistochemical study was combined with heat-induced epitope retrieval (HIER). Although FISH and immunohistochemical studies assess different aspects of the HER-2/neu gene (amplification vs overexpression), we found good correlation between the diagnostic techniques. The correlation was best when immunohistochemical studies were combined with HIER and assessed as the difference between tumor cells and nonneoplastic breast tissue.
Assuntos
Neoplasias da Mama/diagnóstico , Genes erbB-2 , Processamento de Imagem Assistida por Computador/métodos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Receptor ErbB-2/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Amplificação de Genes , Humanos , Prognóstico , Receptor ErbB-2/imunologiaRESUMO
The goal of this study was to assess whether there are clinical or pathologic differences between radiation-associated breast cancers developing after treatment for Hodgkin's disease and spontaneously arising breast cancers. Clinical and pathologic data were reviewed for 26 Hodgkin's disease patients who received irradiation and subsequently developed breast cancer (cases) and 26 age- and stage-matched patients with sporadic breast cancers (controls). The median age at diagnosis of Hodgkin's disease was 21 years (range 11-40 years), and the median interval between Hodgkin's disease and breast cancer diagnosis was 15 years (range 4-27 years). There were no differences between cases and controls with regard to clinical factors. Cases had a lower frequency of histologic grade III tumors (38% versus 65%, p = 0.09) and moderate to marked mononuclear inflammatory cell reaction (11% versus 35%, p = 0.03). When these covariates were combined, grade III tumors in conjunction with mononuclear inflammatory cell reaction were also seen less frequently in the case group than in the control group (11% versus 31%, p = 0.06). Seven cases developed additional cancers, but no additional cancers developed in the control group (p = 0.01). Patients who developed breast cancers after Hodgkin's disease did not differ from patients with spontaneous breast cancers, with regard to clinical factors. However, the lower frequency of high-grade tumors and moderate to marked mononuclear inflammatory cell reaction among the cases suggests that radiation-associated breast cancers may differ from spontaneously arising cancers in their pathogenesis. Cases appeared to be at increased risk of developing additional cancers, but we cannot exclude surveillance as a possible contributing factor.
Assuntos
Neoplasias da Mama/epidemiologia , Doença de Hodgkin/epidemiologia , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Induzidas por Radiação/epidemiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Estudos de Casos e Controles , Quimioterapia Adjuvante/estatística & dados numéricos , Criança , Comorbidade , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Humanos , Incidência , Metástase Linfática , Massachusetts/epidemiologia , Mastectomia/estatística & dados numéricos , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/terapia , Prognóstico , Radioterapia Adjuvante/estatística & dados numéricos , Medição de Risco , Fatores de Risco , Taxa de SobrevidaRESUMO
PURPOSE: To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine-needle aspiration biopsy (FNAB) in the diagnosis of nonpalpable breast lesions. MATERIALS AND METHODS: At 18 institutions, 442 women who underwent 22-25-gauge imaging-guided FNAB were enrolled. Definitive surgical, core-needle biopsy, and/or follow-up information was available for 423 (95.7%) of these women. The reference standard was established from additional clinical and imaging information for an additional six (1.4%) women who did not undergo further histopathologic evaluation. The FNAB protocol was standardized at all institutions, and all specimens were reread by one of two expert cytopathologists. RESULTS: When insufficient samples were included in the analysis and classified as positive, the sensitivity and specificity of FNAB were 85%-88% and 55.6%-90.5%, respectively; accuracy ranged from 62.2% to 89.2%. The diagnostic accuracy of FNAB was significantly better for detection of masses than for detection of calcifications (67.3% vs. 53.8%, P =.006) and with US guidance than with stereotactic guidance (77.2% vs. 58.9%; P =.002). CONCLUSION: FNAB of nonpalpable breast lesions has limited value given the high insufficient sample rate and greater diagnostic accuracy of other interventions, including core-needle biopsy and needle-localized open surgical biopsy.
Assuntos
Biópsia por Agulha , Neoplasias da Mama/patologia , Mama/patologia , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Ultrassonografia MamáriaRESUMO
Recent advances in the understanding of the molecular and genetic alterations underlying breast cancer development and progression have provided the opportunity to develop novel therapeutic strategies for this disease. None of these developments has had a greater recent impact on clinicians and pathologists than the recognition of the importance of the HER-2/neu (c-erbB-2) oncogene. Located on chromosome 17, this gene encodes a 185 kD transmembrane glycoprotein with tyrosine kinase activity that functions as a growth factor receptor. Amplification or overexpression of HER-2/neu is seen in approximately 20 to 30% of invasive breast cancers and this has been considered to be an adverse prognostic factor in many studies. However, recent interest in HER-2/neu has largely been focused on its role as a potential target for breast cancer treatment. In particular, recognition of the role of HER-2/neu in breast cancer growth led to the development of a humanized monoclonal antibody directed against the HER-2/neu protein as a therapeutic agent (Herceptin). Clinical studies have further suggested that HER-2/neu status can provide important information regarding sensitivity to certain forms of conventional systemic therapy, particularly anthracyclines. As a result of these developments, there has been increasing demand for pathologists to perform assays for HER-2/neu on current and archived breast cancer specimens. Immunohistochemistry and fluorescence in situ hybridization have emerged as the most viable assays for evaluation of HER-2/neu in routine clinical practice. However, each of these methods has its advantages and disadvantages. Determining the relative merits of these assays and developing clinically meaningful and reproducible systems to report the results are challenges pathologists must now address. The development of a therapeutic agent that directly targets a protein involved in a growth-signaling pathway represents a new paradigm in breast cancer treatment. Therapeutic strategies that target other molecules involved in breast cancer development and progression are on the horizon. It is crucial that pathologists become aware of these advances and assume a pivotal role in the development and application of assays to evaluate these new molecular targets.
Assuntos
Neoplasias da Mama , Genes erbB-2 , Receptor ErbB-2/análise , Animais , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Prognóstico , RatosRESUMO
To compare pathologic features of the cancers arising after different types of benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169 women with a previous benign biopsy result. Lesions were categorized previously as nonproliferative, proliferative without atypia, or atypical hyperplasia. Pathologic features of the cancers were evaluated without knowledge of the previous BBD category. Estrogen and progesterone receptor immunohistochemistry was performed on available tissue blocks. The median times between a benign result and cancer were 100, 124, and 92 months for women with nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia, respectively. Cancers in the 3 groups did not differ significantly in tumor size, axillary lymph node status, or histologic grade, and there was no significant difference in the distribution of histologic types of breast cancer. Lymphatic vessel invasion, extensive intraductal component, and hormone receptor status did not differ among BBD categories. The pathologic features of breast cancers that develop in women with a previous benign biopsy result do not vary according to the histologic category of the previous BBD.
Assuntos
Biópsia , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/patologia , Axila , Neoplasias da Mama/química , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Hiperplasia , Linfonodos/patologia , Invasividade Neoplásica , Receptores de Estrogênio/análise , Receptores de Progesterona/análiseRESUMO
Most breast carcinomas in situ (CIS) are easily categorized as ductal (DCIS) or lobular (LCIS). However, some CIS have indeterminate histologic features (CIS-IF). Prior studies have shown that E-cadherin protein expression is lost in lobular but not ductal carcinomas. Therefore, evaluation of examples of CIS-IF for E-cadherin expression by immunohistochemistry might be useful in helping to define their nature. To address this, we studied histologic features and E-cadherin expression by immunohistochemistry in 89 cases of breast CIS (28 LCIS, 33 DCIS, 28 CIS-IF). CIS-IF cases were divided into three groups based on histology: Group 1 cases had all the cytologic and architectural features typical of LCIS but showed areas of comedo-type necrosis (n = 6). Group 2 cases were CIS lesions characterized by small, uniform neoplastic cells either growing in a solid pattern with focal microacinar-like structures but with cellular dyshesion, or growing in a cohesive mosaic pattern but with occasional intracytoplasmic vacuoles (n = 17). Group 3 cases showed marked cellular pleomorphism and nuclear atypia but had the dyshesive growth pattern characteristic of LCIS (n = 5). E-cadherin staining was scored as negative, positive, or mixed (mixture of negative and positive tumor cells). All 28 cases of LCIS were E-cadherin negative, and all 33 DCIS cases were E-cadherin positive by immunohistochemistry. All cases from CIS-IF group 1 and group 3 were negative for E-cadherin, suggesting a closer kinship to LCIS than to DCIS. In contrast, CIS-IF group 2 cases were heterogeneous with respect to E-cadherin staining. Six (35.3%) cases were E-cadherin negative (more akin to LCIS), 5 (29.4%) cases were E-cadherin positive (akin to DCIS), and 6 (35.3%) cases had both E-cadherin-positive and E-cadherin-negative tumor cells, suggesting a mixed DCIS/LCIS phenotype. Our findings suggest that E-cadherin immunostaining is of value in helping to characterize breast carcinomas in situ with indeterminate features. However, validation of these observations will require clinical outcome studies.
Assuntos
Neoplasias da Mama/patologia , Caderinas/análise , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Neoplasias da Mama/classificação , Carcinoma in Situ/química , Carcinoma in Situ/classificação , Carcinoma Ductal de Mama/química , Carcinoma Lobular/química , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-IdadeRESUMO
There has long been a pressing clinical need to identify prognostic and predictive factors for patients with breast cancer. Although numerous candidate biological and molecular markers have been identified during the last two decades, traditional factors such as lymph node status, tumor size, histologic type, histologic grade, and hormone receptor status remain the most useful indicators of prognosis and therapeutic response. A major obstacle to the translation of research advances into clinically useful prognostic and predictive markers has been the considerable methodologic variability used in the evaluation of the newer markers. It is now generally accepted that, to be useful in patient management, a putative prognostic or predictive marker must have clinical importance, independence, significance, and standardization with regard to methods, interpretation, and reporting. It is hoped that recognition and adoption of these criteria will serve to clarify the value of newer biologic and molecular markers.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Biomarcadores/análise , Neoplasias da Mama/classificação , Neoplasias da Mama/genética , Genes erbB-2/genética , Genes p53/genética , Humanos , Metástase Linfática , Tumores de Vasos Linfáticos/fisiopatologia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
Evidence from clinical follow-up studies has indicated that there is a relationship between the presence of histologically proven benign breast disease and breast cancer risk, and that the risk varies according to the histological category of benign breast disease and hormonal status. The risk associated with these histological factors appears to be equal in both breasts, suggesting that these factors are best considered markers of generalized increased breast cancer risk rather than direct precursor lesions. A number of interesting observations gleaned from the Nashville Study, the Breast Cancer Detection Demonstration Project and the Nurses' Health Study, among other studies, provide evidence of an interaction between these histological risk factors and estrogen in determining the level of breast cancer risk. In the National Surgical Adjuvant Breast Project P-1 trial, tamoxifen was associated with an 86% reduction in breast cancer risk among a small subset of women with biopsy-proven atypical hyperplasia. Taken together, these observations strongly suggest that there is an interaction between estrogen and histological factors in determining breast cancer risk, and that it may be possible to reduce the risk associated with these histological risk factors using antiestrogen therapy.
Assuntos
Doenças Mamárias/complicações , Neoplasias da Mama/etiologia , Doenças Mamárias/tratamento farmacológico , Doenças Mamárias/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Seguimentos , Humanos , Hiperplasia , Receptores de Estrogênio/metabolismo , Fatores de RiscoRESUMO
BACKGROUND: A history of proliferative benign breast disease has been shown to increase the risk of developing breast carcinoma, but, to the authors' knowledge, how postmenopausal exogenous female hormone use, in general, has affected breast carcinoma risk among women with a history of proliferative breast disease with or without atypia has not been well established. METHODS: In the current case-control study, nested within the Nurses' Health Study, benign breast biopsy slides of 133 postmenopausal breast carcinoma cases and 610 controls with a history of benign breast disease, were reviewed. Reviewers had no knowledge of case status. RESULTS: Women with proliferative disease without atypia had a relative risk for postmenopausal breast carcinoma of 1.8 (95%, confidence interval [CI]: 1.1 to 2.8), and women with atypical hyperplasia had a relative risk of 3.6 (95%, CI: 2.0 to 6.4) compared with women who had nonproliferative benign histology. Neither current postmenopausal use of exogenous female hormones nor long term use for 5 or more years further increased the risk of breast carcinoma in the study population beyond that already associated with their benign histology. CONCLUSIONS: Women who had proliferative benign breast disease, with or without atypia, were at moderately to substantially increased risk of developing postmenopausal breast carcinoma compared with women who had nonproliferative benign conditions. In the current study, postmenopausal exogenous female hormone use in general did not further increase the breast carcinoma risk for women with proliferative benign breast disease. However, the analysis did not exclude the possibility of increased risk with a particular hormone combination or dosage.
Assuntos
Neoplasias da Mama/patologia , Terapia de Reposição de Estrogênios/efeitos adversos , Biópsia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Saúde da MulherRESUMO
PURPOSE: To estimate the possible efficacy of axillary radiation therapy (AXRT) following a positive sentinel node biopsy (SNB), we evaluated the risk of regional nodal failure (RNF) for patients with clinical Stage I or II, clinically node-negative invasive breast cancer treated with either no dissection or a limited dissection (LD) defined as removal of 5 nodes or less followed by AXRT. MATERIALS AND METHODS: From 1978 to 1987, 292 patients underwent AXRT in the absence of axillary dissection; 126 underwent AXRT following LD. The median dose to the axilla was 46 Gy. The median dose to the supraclavicular fossa was 45 Gy. Among patients found to have positive nodes on LD, adjuvant chemotherapy and tamoxifen were administered to 81% and 7% of subjects, respectively. All patients had potential 8-year follow-up. RESULTS: Six of the 418 patients (1. 4%) developed RNF as a first site of failure within 8 years. Among these 6 patients (1.4%) with RNF as the first site of failure, 4 had simultaneous distant and regional recurrences; and 2 had isolated axillary failures. Three of the 292 patients (1%) with no axillary dissection, none of 84 patients with pathologically negative nodes and 3 of 42 patients (7%) with pathologically involved nodes had RNF as a first site of failure. Radiation pneumonitis developed in 5 patients (1.2%), brachial plexopathy in 5 (1.2%) and arm edema in 4 (1.2%). In all cases, radiation pneumonitis and brachial plexopathy were transient. CONCLUSION: These results imply that AXRT may be an effective and safe alternative to completion dissection for treatment of the axilla following a positive SNB. Further studies comparing these two options in specific patient subgroups are needed.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Linfonodos/patologia , Irradiação Linfática , Idoso , Axila , Biópsia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
PURPOSE: Tangential (2-field) radiation therapy to the breast and lower axilla is typically used in our institution for treating patients with early-stage breast cancer who have 0-3 positive axillary nodes, as determined by axillary dissection, whereas a third supraclavicular/axillary field is added for patients with 4 or more positive nodes. However, dissection may result in complications and added expense. We, therefore, assessed whether clinical or pathologic factors of the primary tumor could reliably predict, in the absence of an axillary dissection, which patients with clinically negative axillary nodes have such limited pathologic nodal involvement that they might be effectively treated with only tangential fields. This would eliminate both the complications of axillary dissection and the added complexity and potential morbidity of a supraclavicular/axillary field. METHODS AND MATERIALS: In this study, 722 women with clinical Stage I or II unilateral invasive breast cancer of infiltrating ductal histology, with clinically negative axillary nodes, at least 6 lymph nodes recovered on axillary dissection, and central pathology review were treated with breast-conserving therapy from 1968 to 1987. Pathologic nodal status was assessed in relation to clinical T stage, the presence of lymphatic vessel invasion (LVI), age, histologic grade, and the location of the primary tumor. RESULTS: LVI, T stage, and tumor location were each significantly correlated with nodal status on univariate analysis. Ninety-seven percent of LVI-negative patients had 0-3 positive axillary nodes compared to 87% of LVI-positive patients. There was no association between T stage and extent of axillary involvement within LVI-negative and LVI-positive subgroups. In a logistic regression model, only LVI remained a significant predictor of having 4 or more positive nodes, although tumor size was of borderline significance. The odds ratio for LVI (positive vs. negative) as a predictor of having 4 or more positive nodes was 3.9 (95% CI, 2.0-7.6). CONCLUSION: For patients with clinical T1-2, N0, infiltrating ductal carcinomas, the presence of LVI is predictive of having 4 or more positive axillary nodes. Only 3% of patients with clinical T1-2, N0, LVI-negative breast cancers had 4 or more positive nodes on axillary dissection. Such patients may be reasonable candidates for treatment with tangential radiation fields in the absence of axillary dissection.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Linfonodos/patologia , Análise de Variância , Axila , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Análise de RegressãoRESUMO
BACKGROUND: Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in breast cancer and stratified them into categories reflecting the strength of published evidence. MATERIALS AND METHODS: Factors were ranked according to previously established College of American Pathologists categorical rankings: category I, factors proven to be of prognostic import and useful in clinical patient management; category II, factors that had been extensively studied biologically and clinically, but whose import remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected about existing prognostic factors, and (3) improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included TNM staging information, histologic grade, histologic type, mitotic figure counts, and hormone receptor status. Category II factors included c-erbB-2 (Her2-neu), proliferation markers, lymphatic and vascular channel invasion, and p53. Factors in category III included DNA ploidy analysis, microvessel density, epidermal growth factor receptor, transforming growth factor-alpha, bcl-2, pS2, and cathepsin D. This report constitutes a detailed outline of the findings and recommendations of the consensus conference group, organized according to structural guidelines as defined.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Feminino , Genes erbB , Genes p53 , Humanos , Excisão de Linfonodo , Metástase Linfática , Mitose , Patologia Clínica , Ploidias , Prognóstico , Receptores de Superfície Celular/metabolismo , Sociedades Médicas , Estados UnidosRESUMO
PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.
Assuntos
Neoplasias da Mama/terapia , Mastectomia Segmentar , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
BACKGROUND: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal-lobular histology. METHODS: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and > or = 6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular features; these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. RESULTS: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and 13% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. CONCLUSIONS: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.
Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Mastectomia Segmentar , Idoso , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/radioterapia , Terapia Combinada , Feminino , Humanos , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma. However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention. METHODS: Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of > or =60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate for the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months. RESULTS: One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS. CONCLUSIONS: Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma. [See editorial counterpoint and reply to counterpoint on pages 978-81 and 982-3, this issue.]
Assuntos
Neoplasias da Mama/cirurgia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Carcinoma in Situ/mortalidade , Carcinoma in Situ/radioterapia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/radioterapia , Terapia Combinada , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/radioterapia , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
PURPOSE: To investigate if extracapsular extension (ECE) of axillary lymph node metastases predicts for a decreased rate of disease-free survival or an increased rate of regional recurrence of breast carcinoma. METHODS: The study population consisted of 368 patients with T1 or T2 breast cancer and pathologically-positive lymph nodes treated with breast-conserving therapy between 1968 and 1986. The median number of sampled lymph nodes was 10. Median follow-up time for the surviving patients was 139 months (range 70-244). Twenty percent of the patients were treated with supraclavicular RT, and 64% received both axillary and supraclavicular RT, with a median dose to the nodes of 45 Gy. The following factors were evaluated: presence of ECE, number of sampled lymph nodes (LN), number of involved LN, size of primary tumor, histologic grade of tumor, presence of lymphatic vessel invasion (LVI), presence of an extensive intraductal component (EIC), radiation dose, use of adjuvant chemotherapy, and age of patient. Recurrences were reported as the 5-year crude sites of first failure, and were divided into breast recurrences (LR), regional nodal failure (RNF, defined as isolated axillary, supraclavicular, or internal mammary recurrence), and distant metastases (DM). RESULTS: One hundred twenty-two patients (33%) had ECE and 246 patients did not. The median number of LN with ECE was 1 (range 1-10) and 20% of patients had ECE in > or =4 LN. Patients with ECE tended to be older (median age 51 vs. 47, p = 0.01), and had a higher number of involved LN (median 3 vs. 2, p = 0.005) than patients without ECE. Forty-three percent of patients with ECE had > or =4 involved LN compared to 15% of patients without ECE (p<0.0001). Models of ECE and the above factors revealed no significant correlation between ECE and either disease-free or overall survival. There was no statistically significant increase in local, regional nodal, or distant failures in patients with ECE as compared to patients without ECE. CONCLUSION: In this population of patients with nodal involvement, the presence of ECE correlates with the number of involved LN but does not appear to add predictive power to models of local, regional, or distant recurrence when the number of positive LN is included.