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OBJECTIVES: The response to HER2-targeted neoadjuvant chemotherapy (NAC) in HER2-positive (+) breast cancer can be quantified using residual cancer burden (RCB) pathologic evaluation to predict relapse free/overall survival. However, more information is needed to characterize the relationship between patterns of HER2 testing results and response to NAC. We evaluated clinicopathologic characteristics associated with RCB categories in HER2+ patients who underwent HER2-directed NAC. METHODS: A retrospective chart review was conducted with Stage I-III HER2+ breast cancer cases following NAC and surgical resection. HER2 immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH), histologic/clinical characteristics, hormone receptor status, and RCB scores (RCB-0, RCB-I, RCB-II, and RCB-III) were evaluated. RESULTS: 64/151 (42.4%) patients with HER2+ disease had pathologic complete response (pCR). Tumors with suboptimal response (RCB-II and RCB-III) were more likely to demonstrate less than 100% HER2 IHC 3+ staining (p < 0.0001), lower HER2 FISH copies (p < 0.0001), and lower HER2/CEP17 ratios (p = 0.0015) compared to RCB-I and RCB-II responses. Estrogen receptor classification using ≥10% versus ≥1% staining showed greater association with higher RCB categories. CONCLUSIONS: HER2+ characteristics show differing response to therapy despite all being categorized as positive; tumors with less than 100% IHC 3+ staining, lower HER2 FISH copies, and lower HER2/CEP17 ratios resulted in higher RCB scores.
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BACKGROUND: Although breast cancer (BC) is uncommon in women age ≤ 35 years, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPVs). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC. MATERIALS AND METHODS: This was a retrospective study of women diagnosed with BC at age ≤ 35 years at Allina Health System from 2000 through 2017 (n = 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor, and human epidermal growth factor receptor 2), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan-Meier curves were conducted for RFS and OS. RESULTS: With mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had HRPVs. There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in luminal B-like cancers followed by triple negative and human epidermal growth factor receptor 2-positive cancers (P = .041). Pregnancy-associated BC diagnoses, angiolymphatic invasion, and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly one-third of patients did not receive germline genetic testing. CONCLUSIONS: Similar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion, and cancer stage were associated with reduced OS.
Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Supervivencia sin Enfermedad , Mutación de Línea Germinal , Adulto , Neoplasias de la Mama/genética , Femenino , Humanos , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: Preoperative breast magnetic resonance imaging (B-MRI) staging in newly diagnosed breast cancer increases detection of synchronous contralateral findings, but may result in false-positive outcomes. This study objective was to identify women more likely of having mammographically occult, MRI detected contralateral breast cancer (CBC). METHODS: We performed a retrospective review of patients who had preoperative B-MRI prior to surgery from 2010 to 2015 and collected patient imaging and clinicopathologic data. Multivariate logistic regression was used to identify predictors of CBC. RESULTS: MRI resulted in contralateral findings in 201 of 1894 patients (10.6%). Overall 3.2% (60 of 1894) had synchronous CBC detected on B-MRI. The majority of CBCs (n = 60) were stage 0 or IA (85.0%), hormone receptor positive (94.9%), human epidermal growth factor receptor 2 (HER2/neu) negative (89.7%), and low/intermediate pathological grade (87.2%). Women more likely to have CBC were older (P < .001), had lobular index cancer (P = .03), and estrogen receptor (ER)+ (P = .027) or progesterone receptor (PR)+ (P = .002) tumors. On multivariate analysis (receiver operating characteristic curve area = 0.75), PR + status (P = .022), and older age (P = .004) were predictive of CBC. CONCLUSIONS: Preoperative MRI is most effective in detecting early stage, hormone receptor-positive CBC in older women.