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BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer. Although mammography is known to have low sensitivity for ILC, there are no data to guide the optimal surveillance after treatment. We explored surveillance strategies after breast-conserving surgery (BCS) for ILC and determined the proportion of imaging-detected recurrences versus interval cancers. METHODS: From an institutional database of 813 women, we retrospectively identified patients who underwent BCS for stage I-III ILC and subsequently had a recurrence. We categorized patients by surveillance strategy and determined the modality of recurrence detection. Interval cancer rates for local recurrences were compared across surveillance strategies using the Chi-square test. We evaluated overall survival with the log-rank test and a Cox proportional hazards model. RESULTS: We included 58 patients with ILC who had a recurrence after BCS. Of these, 22 (37.9%) had local recurrence, 27 (46.6%) had distant recurrence, and 9 (15.5%) had both local and distant recurrence. Most patients underwent routine mammographic surveillance (65.2%), with 19.6% having supplemental breast magnetic resonance imaging (MRI) and 15.2% having no surveillance. The interval cancer rate was significantly higher in the mammographic surveillance group compared with the MRI surveillance group (61.9% vs. 16.7%; p < 0.001). CONCLUSION: In this study of patients with recurrence after BCS for primary treatment of stage I-III ILC, we found that most local recurrences were not detected by surveillance mammography. These data support further investigation of supplemental imaging beyond mammography specifically for patients with ILC who undergo BCS.
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BACKGROUND: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. MATERIALS AND METHODS: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. RESULTS: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. CONCLUSION: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.
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BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.
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Neoplasias de la Mama , Ganglio Linfático Centinela , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela/métodos , Terapia Neoadyuvante/métodos , Axila/patología , Estudios Prospectivos , Metástasis Linfática/patología , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Escisión del Ganglio LinfáticoRESUMEN
BACKGROUND: Surgical treatment of invasive lobular carcinoma (ILC) is challenging due to its diffuse growth pattern, and the positive margin rate after mastectomy is poorly described. METHODS: We retrospectively determined the positive margin rate in those with stage I-III ILC undergoing mastectomy. We evaluated the relationship between management strategy and recurrence free survival (RFS). RESULTS: In 357 patients, the positive margin rate was 10.6% overall and 18.7% in those with T3 tumors. Having a positive margin was associated with significantly shorter RFS on multivariate analysis (p = 0.01). Undergoing additional local treatment (radiation or re-excision) for a positive margin was significantly associated with improved RFS (p = 0.004). Older women with positive margins were significantly less likely to undergo additional local therapy. CONCLUSIONS: Even mastectomy fails to clear margins in a high proportion of patients with large ILC tumors, a finding which may warrant testing neoadjuvant strategies even prior to planned mastectomy.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Femenino , Humanos , Incidencia , Márgenes de Escisión , Mastectomía , Mastectomía Segmentaria , Recurrencia Local de Neoplasia/patología , Estudios RetrospectivosRESUMEN
BACKGROUND. There is a paucity of data and consensus guidelines on the utility of preoperative MRI for planned bilateral prophylactic mastectomy. OBJECTIVE. The purpose of this study was to evaluate the utility of breast MRI performed in high-risk patients for the indication of planned bilateral prophylactic mastectomy, with attention given to the diagnostic performance for breast cancer detection. A secondary aim was to assess the potential impact of breast MRI findings on the decision to perform sentinel lymph node biopsy at the time of prophylactic mastectomy. METHODS. A retrospective database review identified MRI examinations performed at an academic medical center from August 2003 to January 2020 for the indication of planned bilateral prophylactic mastectomy. Patient demographics, imaging findings, operative details, and pathology were recorded. BI-RADS category 1 and 2 assessments were considered negative examinations, and BI-RADS category 3, 4, and 5 assessments were considered positive examinations. Descriptive statistics and performance metrics were calculated. RESULTS. The final cohort included 53 patients (mean age, 45 years). Most (35/53; 66.0%) studies were baseline examinations. Of the 53 patients, 31 (58.5%) had negative MRI examinations and 22 (41.5%) had positive MRI examinations. MRI detected two malignancies (one invasive lobular carcinoma and one high-grade ductal carcinoma in situ), both of which were assessed as BI-RADS category 4. The patient with invasive lobular cancer underwent sentinel lymph node biopsy at the time of mastectomy, which showed metastasis. Breast MRI had sensitivity of 100.0% and specificity of 60.8% for overall breast cancer detection and sensitivity of 100.0% and specificity of 59.6% for invasive cancer detection. CONCLUSION. Preoperative MRI for planned bilateral prophylactic mastectomy detected all cancers, indicating a potential role for MRI in impacting surgical decision making. CLINICAL IMPACT. Given the high NPV for cancer, our results suggest that lymph node biopsy may be safely avoided in patients with a negative MRI examination. This is clinically relevant because sentinel nodes cannot be identified after mastectomy.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Imagen por Resonancia Magnética/métodos , Cuidados Preoperatorios/métodos , Mastectomía Profiláctica/métodos , Mama/diagnóstico por imagen , Mama/cirugía , Bases de Datos Factuales , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Estudios Retrospectivos , Riesgo , Resultado del TratamientoRESUMEN
Ductal carcinoma in situ (DCIS) is a risk factor for the subsequent development of invasive breast cancer. High-risk features include age <45 years, size >5 cm, high-grade, palpable mass, hormone receptor negativity, and HER2 positivity. We have previously shown that immune infiltrates are positively associated with these high-risk features, suggesting that manipulating the immune microenvironment in high-risk DCIS could potentially alter disease progression. Patients with high-risk DCIS were enrolled in this 3 × 3 phase 1 dose-escalation pilot study of 2, 4, and 8 mg intralesional injections of the PD-1 immune checkpoint inhibitor, pembrolizumab. Study participants received two intralesional injections, three weeks apart, prior to surgery. Tissue from pre-treatment biopsies and post-treatment surgical resections was analyzed using multiplex immunofluorescence (mIF) staining for various immune cell populations. The intralesional injections were easily administered and well-tolerated. mIF analyses demonstrated significant increases in total T cell and CD8+ T cell percentages in most patients after receiving pembrolizumab, even at the 2 mg dose. T cell expansion was confined primarily to the stroma rather than within DCIS-containing ducts. Neither cleaved caspase 3 (CC3) staining, a marker for apoptosis, nor DCIS volume (as measured by MRI) changed significantly following treatment. Intralesional injection of pembrolizumab is safe and feasible in patients with DCIS. Nearly all patients experienced robust total and CD8+ T cell responses. However, we did not observe evidence of cell death or tumor volume decrease by MRI, suggesting that additional strategies may be needed to elicit stronger anti-tumor immunity.
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Localization of metastatic axillary lymph nodes in breast cancer patients is an increasingly common procedure performed by radiologists. In 2014, the National Comprehensive Cancer Network guidelines stated that "clinically positive axillary lymph node (s) should be sampled by FNA or core biopsy and clipped with image-detectable marker; clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy". Since then, multiple studies have further supported targeted axillary surgery after neoadjuvant chemotherapy (NAC), with excision of the clipped metastatic axillary node in addition to the sentinel node (s). Requests for image guided localization of clipped axillary nodes will continue to increase and likely become the standard of care. However, when lymph nodes have decreased in size after NAC, or when small deep lymph nodes are sampled, the clipped node can be difficult to identify under ultrasound at the time of localization. When the target node is questionable, we have found it valuable to place an intermediary clip, and use an axillary mammographic view to confirm this intermediary clip co-localizes with the intended target. With this confirmation, safe, accurate localization can then be performed. We describe 3 cases of intermediary clip placement facilitating successful localization of previously clipped axillary lymph nodes.
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Neoplasias de la Mama , Biopsia del Ganglio Linfático Centinela , Axila/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico por imagen , Terapia Neoadyuvante , Estadificación de Neoplasias , Instrumentos QuirúrgicosRESUMEN
BACKGROUND: Although rates of total skin-sparing (nipple-sparing) mastectomies are increasing, the oncologic safety of this procedure has not been evaluated in invasive lobular carcinoma (ILC). ILC is the second most common type of breast cancer, and its diffuse growth pattern and high positive margin rates potentially increase the risk of poor outcomes from less extensive surgical resection. METHODS: We compared time to local recurrence and positive margin rates in a cohort of 300 patients with ILC undergoing either total skin-sparing mastectomy (TSSM), skin-sparing mastectomy, or simple mastectomy between the years 2000-2020. Data were obtained from a prospectively maintained institutional database and were analyzed by using univariate statistics, the log-rank test, and multivariate Cox proportional hazards models. RESULTS: Of 300 cases, mastectomy type was TSSM in 119 (39.7%), skin-sparing mastectomy in 52 (17.3%), and simple mastectomy in 129 (43%). The rate of TSSM increased significantly with time (p < 0.001) and was associated with younger age at diagnosis (p = 0.0007). There was no difference in time to local recurrence on univariate and multivariate analysis, nor difference in positive margin rates by mastectomy type. Factors significantly associated with shorter local recurrence-free survival were higher tumor stage and tumor grade. CONCLUSIONS: TSSM can be safely offered to patients with ILC, despite the diffuse growth pattern seen in this tumor type.
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Neoplasias de la Mama , Carcinoma Lobular , Mamoplastia , Neoplasias de la Mama/cirugía , Carcinoma Lobular/cirugía , Humanos , Mastectomía , Recurrencia Local de Neoplasia/cirugía , Pezones/cirugía , Tratamientos Conservadores del Órgano , Estudios RetrospectivosRESUMEN
OBJECTIVE. The objective of this study was to evaluate the feasibility of using a magnetic seed system for preoperative localization of axillary lymph nodes in patients with breast cancer. MATERIALS AND METHODS. We performed a retrospective analysis that included patients with breast cancer who underwent preoperative magnetic seed localization of axillary lymph nodes at our institution between January 1, 2017, and January 1, 2019. Magseed (Endomag) is a nonradioactive inducible magnetic seed that is induced to become a magnet when under the influence of its detector in the operating room. Clinical history, prior axillary sampling and clip placement, and procedure details and surgical outcomes were determined from a search of our PACS and electronic medical records. RESULTS. Thirty-five patients (34 women and one man) composed our study cohort. The mean patient age was 56 years (range, 32-78 years). One patient underwent two separate consecutive localizations for two separate operations, and another patient had bilateral lesions, for a total of 37 axillary lymph node localizations. One case of seed misplacement occurred during the ultrasound-guided localization procedure, resulting in immediate placement of a second seed, for a total of 38 Magseeds placed. All seeds were placed under ultrasound guidance. The mean number of days from seed placement to surgery was 5 days (range, 0-31 days). Thirty-seven of 38 Magseeds (97%) were documented to be successfully retrieved in the operating room. CONCLUSION. Magseed localization appears to be a safe, nonradioactive way to accurately localize axillary lymph nodes preoperatively.
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Axila/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Marcadores Fiduciales , Metástasis Linfática/diagnóstico por imagen , Magnetismo , Adulto , Anciano , Axila/patología , Neoplasias de la Mama/patología , Estudios de Factibilidad , Femenino , Humanos , Metástasis Linfática/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Cuidados Preoperatorios , Estudios RetrospectivosRESUMEN
BACKGROUND: Obesity and high breast density both increase breast cancer risk but paradoxically are inversely related. Bariatric surgery decreases breast cancer risk, but its impact on mammographic breast density is not well understood. OBJECTIVES: We investigated how mammographic density changes after bariatric surgery and whether this change is related to weight loss. SETTING: University of California, San Francisco Medical Center. METHODS: We reviewed records from 349 prospectively collected patients who underwent bariatric surgery between 2013 and 2015 and identified 42 women with pre- and postoperative screening mammograms within 1.5 years of surgery. We recorded body mass index (BMI), height and Breast Imaging Reporting and Data System density and calculated BMI loss and total weight loss. Data were analyzed in Stata 14.2. RESULTS: Average age was 54.2 years, mean preoperative BMI was 43.8 kg/m2, mean BMI lost was 30.9%, and total weight loss was 31.1% at 1.3 years. Over one-third had a change in mammographic breast density, which increased 93.3% of the time (P < .001). Amount of weight loss was not associated with a density change. Patients with the lowest mammographic density preoperatively were most likely to have a density change (P = .02). CONCLUSIONS: Most women with a mammographic change had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Baseline breast density was associated with a density change, but amount of weight loss was not. These findings suggest the metabolic effects of bariatric surgery have an effect on breast parenchyma independent of absolute BMI reduction or weight loss.
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Cirugía Bariátrica/estadística & datos numéricos , Densidad de la Mama/fisiología , Mamografía/estadística & datos numéricos , Obesidad/cirugía , Pérdida de Peso/fisiología , Índice de Masa Corporal , Peso Corporal/fisiología , Femenino , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
[This corrects the article DOI: 10.1038/s41523-018-0074-6.].
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Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.
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The problem of overdiagnosis and overtreatment has been highlighted in breast cancer and many other cancer types, most notably prostate cancer. Addressing this problem presents an opportunity to continue the evolution of breast cancer care. Advances in technology, such as molecular subtyping, have increased the understanding of breast cancer biology and the range of associated behavior, and have provided tools that allow greater personalization of treatment. This article identifies 3 areas of breast cancer care where opportunity currently exists to refine management strategies and help decrease overtreatment and overdiagnosis: the use of adjuvant-external beam radiation in invasive breast cancer, the application of aggressive treatment for all ductal carcinoma in situ, and the authors' approach to breast cancer screening. Personalizing treatment based on patient and tumor characteristics holds promise for minimizing harms and maximizing benefits. This approach will allow continual improvement and ultimately result in providing the right treatment for each patient.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Intraductal no Infiltrante/terapia , Uso Excesivo de los Servicios de Salud/prevención & control , Terapia Combinada , Detección Precoz del Cáncer , Femenino , Humanos , RiesgoRESUMEN
Invasive lobular carcinoma (ILC) accounts for approximately 5 to 20 per cent of all breast cancers and is often multicentric. Despite pre- and intraoperative assessments to achieve negative margins, ILC is reported to be associated with higher rates of positive margin. This cross-sectional study examined patients with breast cancer treated at our institution from 2000 to 2010. The objective was to investigate the rate of re-excision resulting from positive or close margin (1 mm or less) in patients who underwent breast-conserving surgery (BCS) for ILC compared with invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). Of the 836 patients treated, 416 patients underwent BCS. The rate of re-excision after BCS for ILC was 35.1 versus 17.7 per cent for IDC and 20.0 per cent for DCIS (P = 0.04). Re-excisions were more often performed for positive margin in patients with ILC (11 of 37 [29.7%]) versus IDC (36 of 334 [10.8%]) and DCIS (five of 45 [11.1%];(P = 0.004). In this single-institution review, BCS for ILC had significantly higher rates of re-excision as a result of positive margins when compared with IDC and DCIS. Tumor size greater than 2 cm and lymph node involvement were identified as factors associated with positive surgical margin in ILC. The higher possibility of positive margins and the need for additional procedures should be discussed with patients undergoing BCS for ILC.