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BACKGROUND: This study investigated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST) in patients with initially high nodal burden. METHODS: In the multicenter retrospective cohort, 388 individuals with cN1-3 breast cancer who underwent NAST and had SLNB followed by completion axillary lymph node dissection were included. In an external validation cohort, 267 patients with HER2+ or triple-negative breast cancer (TNBC) meeting similar inclusion criteria were included. Primary outcome was the false-negative rates (FNRs) of SLNB according to the MRI response and subtypes. We defined complete MRI responders as patients who experienced disappearance of suspicious features in the breast and axilla after NAST. RESULTS: In the multicenter retrospective cohort, 130 (33.5%) of 388 patients were of cN2-3, and 55 (14.2%) of 388 patients showed complete MRI responses. In hormone receptor-positive HER2- (n = 207), complete and non-complete responders had a high FNRs (31.3% [95% CI 8.6-54.0] and 20.9% [95% CI 14.1-27.6], respectively). However, in HER2+ or TNBC (n = 181), the FNR of complete MRI responders was 0% (95% CI 0-0), whereas that of non-complete responders was 33.3% (95% CI 20.8-45.9). When we validated our findings in the external cohort with HER2+ or TNBC (n = 267), of which 34.2% were cN2-3, the FNRs of complete were 7.1% (95% CI 0-16.7). CONCLUSIONS: Our findings suggest that SLNB can be a reliable option for nodal status evaluation in selected patients who have responded well to NAST, especially in HER2+ and TNBC patients who show a complete MRI response.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela , Neoplasias de la Mama/patología , Terapia Neoadyuvante , Neoplasias de la Mama Triple Negativas/patología , Estudios Retrospectivos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patologíaRESUMEN
INTRODUCTION: The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST. METHODS: This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model. RESULTS: Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42-2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12-4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%). CONCLUSIONS: SLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.
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Axila , Neoplasias de la Mama , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Terapia Neoadyuvante , Micrometástasis de Neoplasia , Biopsia del Ganglio Linfático Centinela , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/mortalidad , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Terapia Neoadyuvante/métodos , Adulto , Anciano , Pronóstico , Ganglios Linfáticos/patología , Ganglio Linfático Centinela/patologíaRESUMEN
BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela , Carcinoma Intraductal no Infiltrante/cirugía , Metástasis Linfática , Neoplasias de la Mama/cirugía , Estudios Retrospectivos , MastectomíaRESUMEN
PURPOSE: We aimed to identify factors associated with the extent of brain metastases in patients with breast cancer to help distinguish brain oligometastases (1-4 brain metastases) from extensive metastases (5 or more brain metastases). METHODS: This retrospective observational study included 100 female patients diagnosed with brain metastases from breast cancer at a single institution between January 2011 and April 2022. Patient demographics and tumor characteristics were compared between the brain oligometastases group and the extensive metastases group. Multivariable logistic regression analysis was performed to determine the independent factors, including age at initial diagnosis, initial stage, breast cancer subtype, detection time of brain metastases, and de novo or recurrent status of the metastatic disease. In a subgroup analysis of patients with brain oligometastases, demographic and tumor characteristics were compared between patients with single and two-four brain metastases. RESULTS: Of the 100 patients, 56 had brain oligometastases, while 44 had extensive brain metastases. The multivariable logistic regression analysis revealed that only the de novo/recurrent status of metastatic breast cancer was significantly associated with the extent of brain metastasis (p = 0.023). In the subgroup analysis of 56 patients with brain oligometastases, those diagnosed at an earlier stage were more likely to have a single brain metastasis (p = 0.008). CONCLUSION: Patients with de novo metastatic breast cancer are more likely to develop extensive brain metastases than those with recurrent metastatic breast cancer. This insight could influence the development of tailored approaches for monitoring and treating brain metastases, supporting the potential advantages of routine brain screening for patients newly diagnosed with stage IV breast cancer.
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Neoplasias Encefálicas , Neoplasias de la Mama , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Persona de Mediana Edad , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Adulto , AncianoRESUMEN
Background Nipple-sparing mastectomy (NSM) is usually contraindicated in patients with nonmass enhancement (NME) extension to the nipple at breast MRI. However, little is known about the feasibility of NSM when NME extension to the nipple resolves after neoadjuvant chemotherapy (NAC). Purpose To evaluate whether NSM is an appropriate surgical procedure for patients in whom NME extension to the nipple resolves after NAC. Materials and Methods This retrospective study included 383 women with NME at baseline MRI who underwent NAC followed by mastectomy between January 2007 and March 2022 at a single institution. NME extension to the nipple was assessed using breast MRI before NAC (hereafter, pre-NAC) and after NAC (hereafter, post-NAC). In 326 women who underwent mastectomy with removal of the nipple-areolar complex, the rate of pathologic analysis-confirmed tumor invasion of the nipple compared with NME extension to the nipple at post-NAC breast MRI was evaluated. Tumor involvement of the nipple was also assessed in those with complete pathologic response at posttreatment MRI. Furthermore, the outcomes in 57 women undergoing NSM were investigated, particularly in patients with NME extension to the nipple at initial diagnosis. Results Of the 326 women who underwent mastectomy with removal of the nipple-areolar complex (mean age, 49 years ± 9.4 [SD]), 217 patients (67%) showed NME extension to the nipple on pre-NAC MRI scans. Among the 153 women (70%) in whom the NME extension to the nipple resolved after NAC, the rate of pathologic analysis-confirmed tumor invasion of the nipple was 2.6% (four of 153 women; 95% CI: 0, 6.5). No pathologic analysis-confirmed tumor invasion of the nipple was detected in 31 women with complete response at MRI. Of the 57 women who underwent NSM, 12 (21%) with resolution of NME extension to the nipple after NAC had no relapse during the median follow-up of 31 months (range, 11-80 months). Conclusion Pathologic analysis-confirmed tumor invasion of the nipple was rare in women with resolution of nonmass enhancement extension to the nipple after neoadjuvant chemotherapy (NAC). Therefore, nipple-sparing mastectomy could be feasible in this population, especially in those with complete MRI response to NAC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Lee in this issue.
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Neoplasias de la Mama , Mamoplastia , Femenino , Humanos , Persona de Mediana Edad , Mastectomía/métodos , Pezones/diagnóstico por imagen , Pezones/cirugía , Pezones/patología , Terapia Neoadyuvante , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Estudios de Factibilidad , Recurrencia Local de Neoplasia/patología , Imagen por Resonancia Magnética , Mamoplastia/métodosRESUMEN
PURPOSE: Radiation-induced anti-tumor responses occur in the immune system, particularly in peripheral blood mononuclear cells (PBMCs), which are overly sensitive to ionizing radiation. Irradiation of PBMCs is associated with inflammation. We assessed the association between radiotherapy (RT)-induced changes in peripheral blood cells, utilizing the lymphocyte-to-monocyte ratio (LMR), and survival outcome in breast cancer patients who underwent breast-conserving surgery followed by adjuvant RT. METHODS: LMR values were obtained from retrospective data, and serial sampling of blood before the first and last RT sessions was performed. The cut-off point was analyzed using the Youden index and receiver operating characteristic curve. Recurrence-free survival (RFS) and overall survival (OS) were the main outcomes. RESULTS: Patients with RT-induced low LMR had significantly shorter RFS (hazard ratio [HR] 2.730; 95% confidence interval [CI], 1.607-4.636, P = 0.0002) and OS (HR 2.890; 95% CI 1.410-5.924, P = 0.0038). The results were more robust in the subgroup of patients who received chemotherapy. Multivariate analysis showed that lymph node metastasis and RT-induced low LMR were associated with poor RFS (HR 1.763; 95% CI, 1.017-3.059, P = 0.044) and OS (HR 2.254; 95% CI, 1.060-4.796, P = 0.035). CONCLUSION: This study demonstrates that RT-induced low LMR is a valid prognostic marker for recurrence and survival in breast cancer patients undergoing RT.
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Neoplasias de la Mama , Monocitos , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Humanos , Leucocitos Mononucleares , Linfocitos/patología , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To investigate the added diagnostic value of abbreviated breast magnetic resonance imaging (MRI) for suspicious microcalcifications on screening mammography. METHODS: This prospective study included 80 patients with suspicious calcifications on screening mammography who underwent abbreviated MRI before undergoing breast biopsy between August 2017 and September 2020. The abbreviated protocol included one pre-contrast and the first post-contrast T1-weighted series. MRI examinations were interpreted as either positive or negative based on the visibility of any significant enhancement. The positive predictive value (PPV) was compared before and after the MRI. RESULTS: Of the 80 suspicious microcalcifications, 33.8% (27/80) were malignant and 66.2% (53/80) were false positives. Abbreviated MRI revealed 33 positive enhancement lesions, and 25 and two lesions showed true-positive and false-negative findings, respectively. Abbreviated MRI increased PPV from 33.8 (27 of 80 cases; 95% CI: 26.2%, 40.8%) to 75.8% (25 of 33 cases; 95% CI: 62.1%, 85.7%). A total of 85% (45 of 53) false-positive diagnoses were reduced after abbreviated MRI assessment. CONCLUSIONS: Abbreviated MRI added significant diagnostic value in patients with suspicious microcalcifications on screening mammography, as demonstrated by a significant increase in PPV with a potential reduction in unnecessary biopsy. KEY POINTS: ⢠Abbreviated breast magnetic resonance imaging increased the positive predictive value of suspicious microcalcifications on screening mammography from 33.8 (27/80 cases) to 75.8% (25/33 cases) (p < .01). ⢠Abbreviated magnetic resonance imaging helped avoid unnecessary benign biopsies in 85% (45/53 cases) of lesions without missing invasive cancer.
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Neoplasias de la Mama , Calcinosis , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Detección Precoz del Cáncer , Femenino , Humanos , Imagen por Resonancia Magnética , Mamografía , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Incorporating dual human epidermal growth factor receptor 2 (HER2) blockade into neoadjuvant systemic therapy (NST) led to higher response in patients with HER2-positive breast cancer. However, axillary response to treatment regimens, including single or dual HER2 blockade, in patients with clinically node-positive breast cancer remains uncertain. Our study aimed to examine the pathologic axillary response according to the type of NST, that is, single or dual HER2 blockade. In our study, 546 patients with clinically node-positive, HER2-positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into three groups: chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab. The primary outcome was the axillary pathologic complete response (pCR). Among 471 patients undergoing axillary lymph node dissection, the axillary pCR rates were 43.5%, 74.5% and 68.8% in patients who received chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab, respectively. There was no difference in axillary pCR rates between patients who received single or dual HER2 blockade (P = .379). Among patients receiving chemotherapy + trastuzumab, patients without breast pCR had the greatest risk for residual axillary metastases (relative risk, 9.8; 95% confidence interval, 3.2-14.9; P < .0001). In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node-positive, HER2-positive breast cancer; furthermore, dual HER2-blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node-positive patients treated with HER2-targeting therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ganglios Linfáticos/patología , Terapia Neoadyuvante/métodos , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Axila , Biomarcadores de Tumor , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Ganglios Linfáticos/metabolismo , Metástasis Linfática , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trastuzumab/administración & dosificaciónRESUMEN
BACKGROUND: Our study evaluated the association between body mass index (BMI) and absolute lymphocyte count (ALC) in breast cancer patients and healthy females. Additionally, we determined the prognostic value of these factors in breast cancer. METHODS: We retrospectively identified 1225 primary invasive breast cancer patients and 35,991 healthy females. Factors including BMI and complete blood count associated with disease-free survival (DFS) were assessed using a multi-variable Cox proportional hazard model. RESULTS: BMI and ALC were positively correlated in breast cancer patients and healthy females (both P < 0.001). In multi-variable analysis, overweight or obese participants had worse DFS (hazards ratio [HR], 1.98; 95% confidence interval [CI], 1.34-2.92; P = 0.001) than underweight or normal-weight individuals, but patients with high ALC had better DFS than those with low ALC (HR, 0.43; 95% CI, 0.29-0.65; P < 0.001). After risk stratification according to BMI/ALC, high-risk patients with high BMI/low ALC had worse DFS than others (HR, 2.48; 95% CI, 1.70-3.62; P < 0.001). CONCLUSIONS: BMI and ALC were positive correlated, but their effect on breast cancer prognosis was opposite. Patients with high BMI/low ALC had worse DFS than others. Underlying mechanisms for effect of BMI/ALC on breast cancer prognosis should be studied in the future.
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Neoplasias de la Mama/mortalidad , Obesidad/epidemiología , Sobrepeso/epidemiología , Delgadez/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Neoplasias de la Mama/sangre , Estudios de Casos y Controles , Femenino , Humanos , Recuento de Linfocitos , Persona de Mediana Edad , Obesidad/complicaciones , Sobrepeso/complicaciones , Pronóstico , República de Corea , Estudios Retrospectivos , Análisis de Supervivencia , Delgadez/complicacionesRESUMEN
PURPOSE: The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients. METHODS: Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI). RESULTS: Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival. CONCLUSIONS: We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival.
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Antígeno B7-H1 , Neoplasias de la Mama Triple Negativas , Genómica , Humanos , Inmunohistoquímica , PronósticoRESUMEN
Background Although nonmass enhancement (NME) extension to the nipple at preoperative MRI frequently leads to sacrifice of the nipple-areolar complex (NAC), its correlation with pathologically confirmed NAC involvement is unclear. Purpose To evaluate the diagnostic accuracy of using NME extension to the subareolar region at breast MRI to predict pathologic nipple involvement and the eligibility for nipple-sparing mastectomy. Materials and Methods From November 2017 to November 2019, the authors prospectively enrolled participants with breast cancer and NME within 2 cm of the nipple at breast MRI who underwent surgery that included removal of the NAC. The authors evaluated NME extensions that were ipsilateral and contiguous with the biopsy-proven tumor lesions on images acquired during the early contrast phases. Pathologic nipple involvement and the distance from the nipple to the nearest cancer cell were evaluated by using serial vertical sectioning of the area extending from the entire NAC to the tumor. The primary end point was the positive predictive value (PPV) of NME, which was calculated as follows: (number with pathologic nipple invasion and NME extension to the nipple at breast MRI/number with NME extension to the nipple at breast MRI) × 100. Results Of 64 women (mean age, 52 years ± 9.8 [standard deviation]), 49 (77%) had NME extension to the nipple at breast MRI. The PPV of NME extension to the nipple was 86% (42 of 49 women; 95% CI: 73, 94). Among the 15 participants without NME extension to the nipple, only one (7%) had pathologic nipple involvement. The diagnostic accuracy of using NME extension to the nipple was 88% (56 of 64 women; 95% CI: 77, 95). The radiologic distance correlated well with the pathologic distance (Spearman correlation coefficient = 0.71, P = .003). Conclusion Nonmass enhancement extension to the nipple base at preoperative MRI has a high positive predictive value for identifying tumor involvement of the nipple, a contraindication to nipple-sparing mastectomy. © RSNA, 2021 Online supplemental material is available for this article.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Imagen por Resonancia Magnética/métodos , Pezones/diagnóstico por imagen , Pezones/patología , Adulto , Anciano , Mama/diagnóstico por imagen , Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , República de CoreaRESUMEN
PURPOSE: Insertion of radiopaque markers is helpful for tumor localization in patients receiving neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS). The aim of this retrospective study was to investigate the pathologic margin status in patients with single or double marker insertion. METHODS: We reviewed the records of 130 patients with marker insertion prior to NAC followed by BCS from January 2016 to September 2019. Under ultrasonography guidance, single or double markers were inserted to localize a tumor in the breast. The incidence of additional resection after frozen biopsy and re-excision after permanent pathologic diagnosis was analyzed. RESULTS: In a total of 130 patients, 104 had a single marker in the center of the tumor and 26 had double markers at the periphery of the tumor before NAC. Among 69 patients with residual invasive tumors after NAC, there was no difference in the additional resection rate after frozen biopsy (single vs. double markers; 14.3% vs. 38.5%, P = .059) or the re-excision rate after final pathologic diagnosis (0% vs. 7.7%, P = .188). After propensity score matching for tumor size and subtypes, the two groups showed no differences in the additional resection rate after frozen biopsy (7.7% vs. 19.2%, P = .139) or the re-excision rate (0% vs. 3.8%, P = .308). After a median follow-up of 19 months (range 8-48 months), local recurrence-free survival did not differ between the two groups (log-rank P = .456). CONCLUSIONS: Number of inserted markers for tumor localization did not affect the pathologic margin status after BCS.
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Neoplasias de la Mama , Terapia Neoadyuvante , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Humanos , Márgenes de Escisión , Mastectomía Segmentaria , Recurrencia Local de Neoplasia , Estudios RetrospectivosRESUMEN
OBJECTIVE: To develop a nomogram and validate its use for the intraoperative evaluation of nodal metastasis using shear-wave elastography (SWE) elasticity values and nodal size METHODS: We constructed a nomogram to predict metastasis using ex vivo SWE values and ultrasound features of 228 axillary LNs from fifty-five patients. We validated its use in an independent cohort comprising 80 patients. In the validation cohort, a total of 217 sentinel LNs were included. RESULTS: We developed the nomogram using the nodal size and elasticity values of the development cohort to predict LN metastasis; the area under the curve (AUC) was 0.856 (95% confidence interval (CI), 0.783-0.929). In the validation cohort, 15 (7%) LNs were metastatic, and 202 (93%) were non-metastatic. The mean stiffness (23.54 and 10.41 kPa, p = 0.005) and elasticity ratio (3.24 and 1.49, p = 0.028) were significantly higher in the metastatic LNs than those in the non-metastatic LNs. However, the mean size of the metastatic LNs was not significantly larger than that of the non-metastatic LNs (8.70 mm vs 7.20 mm, respectively; p = 0.123). The AUC was 0.791 (95% CI, 0.668-0.915) in the validation cohort, and the calibration plots of the nomogram showed good agreement. CONCLUSIONS: We developed a well-validated nomogram to predict LN metastasis. This nomogram, mainly based on ex vivo SWE values, can help evaluate nodal metastasis during surgery. KEY POINTS: ⢠A nomogram was developed based on axillary LN size and ex vivo SWE values such as mean stiffness and elasticity ratio to easily predict axillary LN metastasis during breast cancer surgery. ⢠The constructed nomogram presented high predictive performance of sentinel LN metastasis with an independent cohort. ⢠This nomogram can reduce unnecessary intraoperative frozen section which increases the surgical time and costs in breast cancer patients.
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Neoplasias de la Mama/cirugía , Metástasis Linfática/diagnóstico por imagen , Nomogramas , Adulto , Anciano , Área Bajo la Curva , Axila , Neoplasias de la Mama/patología , Elasticidad , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Metástasis Linfática/patología , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Ganglio Linfático Centinela/diagnóstico por imagen , Ultrasonografía Mamaria/métodos , Adulto JovenRESUMEN
BACKGROUND: There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer. METHODS: This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991). RESULTS: Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5-21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications. CONCLUSIONS: Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period.
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Neoplasias de la Mama/radioterapia , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Radioterapia/efectos adversos , Radioterapia/métodos , Adulto , Anciano , Neoplasias de la Mama/cirugía , Femenino , Humanos , Periodo Intraoperatorio , Corea (Geográfico) , Mastectomía Segmentaria , Persona de Mediana Edad , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Intraoperative radiotherapy (IORT) with a 50-kV x-ray is used for a tumor bed boost during breast-conserving surgery. This study evaluated the anatomicosurgical factors associated with cancellation of planned IORT. METHODS: Patient eligibility for the study included age of 20 years or older, compatibility for lumpectomy, and ductal carcinoma in situ or stages 1-3 invasive carcinoma. All the patients underwent magnetic resonance imaging (MRI) and multidisciplinary team evaluations. Resection margins were assessed by frozen pathology. Pre- and intraoperative variables were compared between the IORT and IORT-cancellation groups. RESULTS: A total of 434 patients underwent surgeries for IORT between August 2014 and December 2017. For 90 of these patients, IORT was canceled because of repeated positive margins leading to a large cavity or total mastectomy (n = 27), insufficient cavity-skin distance (n = 14), satellite lesions leading to a large cavity or total mastectomy (n = 12), MRI findings of a large primary tumor or uncertain margins leading to a large cavity (n = 6), cavity geometry unsuitable for IORT (n = 6), subareolar tumor extension (n = 6), tumor abutting the pectoralis muscle (n = 3), patient refusal (n = 5), intraoperative confirmation of bilateral breast cancer (n = 3) or benign pathology (n = 3), device malfunction (n = 3), or scheduling difficulty (n = 2). A tumor larger than 2 cm (P = 0.014) and the presence of satellite lesions (P = 0.014) were independent predictors of IORT cancellation. CONCLUSIONS: Surgical procedures resulting in large cavities were the leading cause of IORT cancellation. Multidisciplinary evaluations using MRI were critical for completion of IORT procedures.
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Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Determinación de la Elegibilidad , Cuidados Intraoperatorios , Mastectomía Segmentaria/métodos , Radioterapia Adyuvante/estadística & datos numéricos , Adulto , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/radioterapia , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Mastectomía Simple , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
PURPOSE: Neoadjuvant chemotherapy (NAC) is being increasingly used to treat locally advanced breast cancer and to conserve the breast. In triple-negative breast cancer and HER2-positive breast cancer, a high density of tumor-infiltrating lymphocytes (TILs) is an important predictor of NAC response. Thus far, it remains unclear whether the TIL scores in core needle biopsies (CNBs) are closely representative of those in the whole tumor section in resected specimens. This study aimed to evaluate the concordance between the TIL scores of CNBs and resected specimens of breast cancer. METHODS: A total of 220 matched pairs of CNBs and resected specimens of breast cancer were included. Stromal TILs were scored on slides stained with hematoxylin and eosin. Clinicopathologic parameters and the agreement of the TIL scores between CNBs and resected specimens were statistically analyzed. RESULTS: The average TIL score was approximately 4.4% higher for the resected specimens than for the CNBs. When the tumors were divided into two groups according to a 60% TIL score cut-off (low and intermediate TIL vs. high TIL), 8.2% showed discordance between the CNB and resected specimen. The overall intraclass correlation coefficient (ICC) value of the TIL score was 0.895 (95% confidence interval, 0.864-0.920, P < 0.001), and all molecular subtypes showed ICC values over 0.8 (P < 0.001). The ICC values were > 0.9 when ≥ 5 cores were included in the CNBs. Tumors with discordant TILs were characterized by histologic grade III, ER negativity, high proliferative index, and HER2 and triple-negative subtypes. A high proliferative index was an independent risk factor for TIL discordance. CONCLUSIONS: The TIL score in CNB specimens is a reliable value that reflects the TIL status of the entire tumor in resected specimens of breast cancer. More than five CNB cores may accurately predict the TIL score of the entire tumor.
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Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Biopsia con Aguja Gruesa , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Humanos , Inmunohistoquímica , Mastectomía/métodos , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Fenotipo , Estudios RetrospectivosRESUMEN
BACKGROUND: Recent studies have shown that tumors with extensive tumor-infiltrating lymphocytes (TILs) have a higher probability of pathologic complete response, even in luminal/human epidermal growth factor 2 (HER2)-negative breast cancer. We compared TIL levels and the 21-gene recurrence score (RS) in estrogen receptor (ER)-positive/HER2-negative breast cancer. METHODS: We evaluated the percentage of stromal TILs in 198 ER-positive/HER2-negative patients in whom RS was obtained by examining slides of surgical specimens by standardized methodology proposed by the international TIL Working Group. TIL levels were categorized as high (≥ 60%), intermediate (11-59%), or low (≤ 10%). All tumors were treatment-naïve. RESULTS: Ninety-seven (49.0%), 88 (44.4%), and 13 patients (6.6%) had low, intermediate, and high TIL levels, respectively. There was a significant but weak correlation between continuous RS and continuous TIL levels (Pearson's R = 0.201, p = 0.004). The mean RS was significantly highest in high TIL tumors (17.8 ± 10.7 in low TIL tumors, 19.4 ± 8.7 in intermediate TIL tumors, and 26.2 ± 8.2 in high TIL tumors; p = 0.014). However, when we compared categorized RS and TIL levels, we found that tumors with high TIL levels tended to have higher RS (≥ 26) but it was not significant (p = 0.155). Furthermore, multivariate analysis revealed that high RS was not an independent factor associated with high TIL levels. Chemo-endocrine therapy was more frequently performed among patients with high TILs and less frequently among those with low or intermediate TILs (p < 0.001). CONCLUSIONS: Despite of a weak correlation between continuous TIL levels and RS, we found that tumors with high TIL levels tended to have a higher RS in ER-positive/HER2-negative breast cancer. Further study is warranted considering the clinical outcomes.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Linfocitos Infiltrantes de Tumor/metabolismo , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Modelos Logísticos , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can reveal the metabolic activity of malignant tumors. Recent advances gained from molecular studies suggest that tumor biology can be a good predictor of prognosis in breast cancer. We compared the ability of maximum standardized uptake values (SUVmax) derived by FDG-PET with tumor burden in predicting tumor recurrence for patients with breast cancer. METHODS: 496 patients with breast cancer who underwent preoperative FDG-PET between April 2004 and May 2009 were retrospectively identified. SUVmax was obtained by FDG-PET, and the cutoff point was defined using a time-dependent receiver operating characteristic curve for recurrence-free survival (RFS). The primary endpoint was RFS. RESULTS: In multivariate analysis for RFS, SUVmax carried independent prognostic significance (hazard ratio, 2.39; 95% confidence interval, 1.20 to 4.76; P = 0.012). When the patients were classified into four groups according to the combined factors of tumor size (≤2 cm versus >2 cm) and SUVmax (<4 versus ≥4), RFS differed significantly (P < 0.001). Similarly, SUVmax had prognostic value in combination with nodal status (negative versus positive) or stage (I versus II and III) (P < 0.001 and P = 0.001, respectively). In hormone receptor-positive disease, SUVmax remained a significant prognostic factor for RFS based on multivariate analysis. CONCLUSIONS: Our results highlight the prognostic value of FDG-PET in prediction of tumor relapse for patients with breast cancer. Particularly in patients with hormone receptor-positive disease, the tumor metabolic information provided by FDG-PET is more significantly correlated with prognosis than tumor burden.
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Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Lobular/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Carga Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Estudios de Cohortes , Técnicas de Apoyo para la Decisión , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Estudios RetrospectivosRESUMEN
This study aimed to develop a machine learning-based prediction model for predicting multi-gene assay (MGA) risk categories. Patients with estrogen receptor-positive (ER+)/HER2- breast cancer who had undergone Oncotype DX (ODX) or MammaPrint (MMP) were used to develop the prediction model. The development cohort consisted of a total of 2565 patients including 2039 patients tested with ODX and 526 patients tested with MMP. The MMP risk prediction model utilized a single XGBoost model, and the ODX risk prediction model utilized combined LightGBM, CatBoost, and XGBoost models through soft voting. Additionally, the ensemble (MMP + ODX) model combining MMP and ODX utilized CatBoost and XGBoost through soft voting. Ten random samples, corresponding to 10% of the modeling dataset, were extracted, and cross-validation was performed to evaluate the accuracy on each validation set. The accuracy of our predictive models was 84.8% for MMP, 87.9% for ODX, and 86.8% for the ensemble model. In the ensemble cohort, the sensitivity, specificity, and precision for predicting the low-risk category were 0.91, 0.66, and 0.92, respectively. The prediction accuracy exceeded 90% in several subgroups, with the highest prediction accuracy of 95.7% in the subgroup that met Ki-67 <20 and HG 1~2 and premenopausal status. Our machine learning-based predictive model has the potential to complement existing MGAs in ER+/HER2- breast cancer.
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In patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, achievement of pathologic complete response (pCR) is a known prognostic indicator after neoadjuvant systemic therapy (NAST). We investigated the clinicopathological factors associated with pCR in patients with HER2-positive breast cancer treated with dual HER2-blockade. In this retrospective study, 348 patients with HER2-positive breast cancer who received NAST with docetaxel and carboplatin, combined with trastuzumab and pertuzumab (TCHP), were included. Of the 348 patients with HER2 protein expression data, 278 (79.9%) had HER2 immunochemistry (IHC) 3+. Data on tumor-infiltrating lymphocyte (TIL) levels were available for 305 patients, showing a median TIL level of 20% (IQR 5-50), among which 121 (39.7%) had high TIL levels (≥30%). Estrogen receptor (ER) status (77.9% in ER-negative vs. 47.5% in ER-positive; p < 0.001), HER2 protein expression (71.6% in IHC 3+ vs. 34.3% in IHC 2+; p < 0.001), and TIL levels (71.9% in high vs. 57.6% in low; p = 0.011) were significantly associated with the pCR rate. In addition, we observed a significant link between numerical TIL levels (per 10% increment) and the pCR rate. After adjusting other clinicopathologic factors, ER status (low expression [defined as 1-9% expression] or negative), HER2 IHC 3+ and numerical TIL levels (per 10% increment), and high TIL levels (≥30%) were found to be independent predictors of pCR. Notably, in ER-negative breast cancer, the treatment response was excellent, irrespective of HER2 expression and TIL levels. Conversely, in ER-positive cases, low ER expression, HER2 IHC 3+, and numerical TIL levels or high TIL levels emerged as independent predictors of pCR. Our results suggest that ER expression, HER2 protein expression, and TIL levels serve as valuable predictors of the treatment response to neoadjuvant TCHP.