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BACKGROUND: Breast cancer is a leading cause of cancer-related deaths in females, and the hormone receptor-positive subtype is the most frequent. Breast cancer is a common source of brain metastases; therefore, we aimed to generate a brain metastases prediction model in females with hormone receptor-positive breast cancer. METHODS: The primary cohort included 3,682 females with hormone receptor-positive breast cancer treated at a single center from May 2009 to May 2020. Patients were randomly divided into a training dataset (n = 2,455) and a validation dataset (n = 1,227). In the training dataset, simple logistic regression analyses were used to measure associations between variables and the diagnosis of brain metastases and to build multivariable models. The model with better calibration and discrimination capacity was tested in the validation dataset to measure its predictive performance. RESULTS: The variables incorporated in the model included age, tumor size, axillary lymph node status, clinical stage at diagnosis, HER2 expression, Ki-67 proliferation index, and the modified Scarff-Bloom-Richardson grade. The area under the curve was 0.81 (95 % CI 0.75-0.86), p < 0.001 in the validation dataset. The study presents a guide for the clinical use of the model. CONCLUSION: A brain metastases prediction model in females with hormone receptor-positive breast cancer helps assess the individual risk of brain metastases.

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BACKGROUND: Delays in the initiation of therapy among patients with early stage breast cancer (BC) can negatively affect outcomes. Patients treated with neoadjuvant systemic chemotherapy (NSC) usually display tumors with high-risk features. Considering these high-risk characteristics and the evidence supporting adverse outcomes associated with delays in adjuvant chemotherapy initiation, we sought to determine whether a delay in NSC initiation is associated with overall survival (OS). METHODS: We identified patients diagnosed between January 1995 and December 2015 with invasive primary BC (stage I-III) who received NSC at MD Anderson Cancer Center. Patients were categorized according to their time from BC diagnosis to NSC (in days) into three subgroups: 0-30, 31-60, and ≥61 days. Primary endpoint was OS. Descriptive statistics and Cox's proportional hazard models were used. RESULTS: A total of 5,137 patients were included. Median follow-up was 6.5 years. The 5-year OS estimates according to time to NSC were 87%, 85%, and 83% in patients who received NSC within 0-30, 31-60, and ≥61 days after diagnosis, respectively (p = .006). In multivariable analysis, compared with time to NSC of 0-30 days, delayed NSC ≥61 days was associated with an increased risk of death (31-60 days: hazard ratio [HR] = 1.05 [95% confidence interval (CI) 0.92-1.19]; ≥61 days, HR = 1.28 [95% CI 1.06-1.54]). In stratified analyses, the association between delay in NSC initiation and increased risk of death was statistically significant for patients with stage I and II BC (31-60 days: HR = 1.22 [95% CI 1.02-1.47]; ≥61 days, HR = 1.41 [95% CI 1.07-1.86]) and among patients with HER2-positive tumors ( ≥61 days, HR = 1.86 [95% CI 1.21-2.86]). CONCLUSION: A delay in NSC initiation of more than 61 days after BC diagnosis was associated with an increased risk of death. Early initiation of NSC should be a priority; multidisciplinary teams must focus on coordination of care and patient-centered, timely treatment planning and delivery. IMPLICATIONS FOR PRACTICE: The results of this study showed that a delay in neoadjuvant systemic chemotherapy initiation of more than 61 days after breast cancer diagnosis is associated with an increased risk of death; therefore, efforts must focus on early initiation of therapy, which should be a priority. Multidisciplinary teams must enhance coordination of care and patient-centered, timely treatment planning and delivery.

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BACKGROUND: The current study was performed to identify factors that are present at the time of breast cancer (BC) diagnosis that are associated with a higher rate of central nervous system metastasis (CNSm). METHODS: The authors analyzed a database of patients with a confirmed diagnosis of BC who were referred for a neuro-oncology consultation at the National Cancer Institute in Mexico City, Mexico, from June 2009 to June 2017. Information was collected prospectively and included demographic, pathologic, and clinical data at the time of diagnosis of BC. Bivariate and multivariate logistic regression models were built to estimate the associations between the development of CNSm and the time after BC diagnosis. RESULTS: Among 970 patients with BC, 263 (27%) were diagnosed with CNSm. The median time from BC diagnosis to the development of CNSm was 33 months (interquartile range, 15-76 months). After multivariate analysis, age <50 years at the time of BC diagnosis (odds ratio [OR], 2.5; 95% confidence interval [95% CI], 1.8-3.5 [P < .0001]), human epidermal growth factor receptor 2 (HER2)-positive status (HER2+) (OR, 3.6; 95% CI, 2.1-6.1 [P < .0001]), luminal B/HER2+ subtype (OR, 3.1; 95% CI, 1.9-5.3 [P < .001]), triple-negative subtype(OR, 2.4; 95% CI, 1.5-4 [P = .001]), and Karnofsky performance status ≤70 (OR, 6.6; 95% CI, 4.5-9.6 [P < .0001]) were associated with a higher frequency of CNSm. Brain parenchyma was the most common site of CNSm. The median overall survival after a diagnosis of CNSm was 12.2 months (95% CI, 9.3-15.1 months). CONCLUSIONS: CNSm is not uncommon among patients with BC, particularly in those with neurologic symptoms who require neuro-oncology evaluation and are aged <50 years at the time of diagnosis, have HER2+ or triple-negative subtypes, have a poor Karnofsky performance status, and/or have ≥2 non-CNS metastases.

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Neoadjuvant systemic therapy (NST) has become part of the standard treatment of patients with locally advanced breast cancer. Patients who achieve a pathologically complete response (pCR) after NST have improved outcomes compared with patients with residual disease at the primary tumor site or the lymph nodes. Achieving a pCR after NST correlates with improved disease-free and overall survival; therefore the amount of residual disease is a prognostic predictor, and it is an area of ongoing research. In this article, we review the literature on NST to highlight the importance of pCR as a prognostic indicator. We also review the definition of pCR and describe the association between different patient and tumor characteristics, including the breast cancer subtype classification, and its response to chemotherapy. We expand on the clinical impact of residual disease and comment on the importance of quantifying it and the current treatment recommendations for patients with residual disease after NST.

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PURPOSE: Pathologic angiogenesis has been correlated with tumor growth, dissemination, metastasis, and prognosis in solid tumors including breast cancer. Angiogenesis has also been implicated in the pathophysiology of, and shown to be a therapeutic target in tumors arising in the bone marrow. The status of angiogenesis in the bone marrow of breast cancer patients is unknown. The aim of this study was to estimate the extent of bone marrow angiogenesis in this subset of patients. EXPERIMENTAL DESIGN: We studied 42 women with breast cancer in whom a bone marrow biopsy was done. Bone marrow samples were sorted according to their infiltration status by breast cancer cells. In all bone marrow sections, blood vessels were highlighted by staining endothelial cells with an antibody directed against the CD34-related antigen. A hematopathologist blind to the status of infiltration of breast cancer did the bone marrow vessel count. RESULTS: Nineteen patients (45%) had bone marrow metastasis. The bone marrow microvessel density was significantly higher in patients with bone marrow metastases compared with patients without bone marrow metastases (P < 0.0005). Median bone marrow microvessel density was 2 for the negative bone marrow group, and 15 for the positive bone marrow group. An increased microvessel density was correlated with presence of disease at last follow-up. CONCLUSIONS: This is the first study showing that bone marrow microvessel density is significantly higher in breast cancer patients with bone marrow metastases, when compared with breast cancer patients without evidence of bone marrow metastatic disease. Further research is needed to shed light into the prognostic and therapeutic relevance of this finding.

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