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Solid Malignancies in Individuals With Down Syndrome: A Case Presentation and Literature Review

Scott V. Bratman, Kathleen C. Horst, Robert W. Carlson, and Daniel S. Kapp

Individuals with Down syndrome (DS) are at elevated risk for acute leukemia, whereas solid tumors are uncommon, and most types, including breast cancers, have significantly lower-than-expected age-adjusted incidence rates. This article reports on a man with DS and breast cancer, thought to be the first in the literature, and presents the management of his cancer. The literature on malignancies in patients with DS is reviewed and the major epidemiologic studies that have examined the spectrum of cancer risk in individuals with DS are summarized. Potential environmental and genetic determinants of cancer risk are discussed, and the potential role of chromosomal mosaicism in cancer risk among patients with DS is explored. Trisomy of chromosome 21, which causes DS, provides an extra copy of genes with tumor suppressor or repressor functions. Recent studies have leveraged mouse and human genetics to uncover specific candidate genes on chromosome 21 that mediate these effects. In addition, global perturbations in gene expression programs have been observed, with potential effects on proliferation and self-renewal.

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Phyllodes Tumors of the Breast: Natural History, Diagnosis, and Treatment

Melinda L. Telli, Kathleen C. Horst, Alice E. Guardino, Frederick M. Dirbas, and Robert W. Carlson

Phyllodes tumors of the breast are unusual fibroepithelial tumors that exhibit a wide range of clinical behavior. These tumors are categorized as benign, borderline, or malignant based on a combination of histologic features. The prognosis of phyllodes tumors is favorable, with local recurrence occurring in approximately 15% of patients overall and distant recurrence in approximately 5% to 10% overall. Wide excision with a greater than 1 cm margin is definitive primary therapy. Adjuvant systemic therapy is of no proven value. Patients with locally recurrent disease should undergo wide excision of the recurrence with or without subsequent radiotherapy.

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Delays in Care Associated With Non–English-Speaking Patients With Breast Cancer

Katy E. Balazy, Cecil M. Benitez, Paulina M. Gutkin, Clare E. Jacobson, Rie von Eyben, and Kathleen C. Horst

Background: Breast cancer care requires coordination between multiple diagnostic and treatment modalities. Disparities such as age, race/ethnicity, and socioeconomic status are associated with delays in care. This study investigates whether primary language is associated with delays in breast cancer diagnosis and treatment before and through radiotherapy (RT). Patients and Methods: This study was an institutional retrospective matched-cohort analysis of women treated with breast RT over 2 years. A total of 65 non–English-speaking (NES) patients were matched with 195 English-speaking (ES) patients according to stage, age, and chemotherapy delivery. Key time intervals along the breast cancer care path from initial findings through RT were recorded. Data were analyzed in a mixed model with matching as the random effect. The impact of race and insurance status was analyzed in addition to language. Results: Significant delays were found for NES patients, which varied by race. NES Latina patients experienced the longest delay, with a mean total care-path time of 13.53 months (from initial findings to end of RT) versus 8.18 months for all ES patients (P<.0001). Specifically, their mean total care-path time was 5.97 months longer than that of ES Latina patients (P=.001) and 5.80 months longer than that of ES White patients (P<.0001). In addition, NES Latina patients had a significantly longer total care-path time than NES patients of other races/ethnicities (P=.001). Delays were specifically seen between initial clinical or radiographic findings and diagnostic mammogram (P=.001) and between biopsy and resection (P=.044). Beyond language, race/ethnicity was itself associated with delays between resection and start of RT (P=.032) and between start and end of RT (P=.022). Conclusions: Language is associated with pre-RT delays in breast cancer care, especially for NES Latina patients. Delays are most pronounced before diagnostic mammograms, but they also exist before resection and RT. Future work should target NES patients to assist their progress along the care path.

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Outcomes Following Neoadjuvant Chemotherapy for Breast Cancer in Women Aged 40 Years and Younger: Impact of Pathologic Nodal Response

Margaret M. Kozak, Clare E. Jacobson, Rie von Eyben, Erqi L. Pollom, Melinda Telli, and Kathleen C. Horst

Purpose: We sought to evaluate whether pathologic nodal response was predictive of outcomes in women aged ≤40 years with breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: A total of 220 patients treated with NAC between 1991 and 2015 were retrospectively reviewed. Pathologic complete response (pCR) was defined as no evidence of residual invasive tumor in the breast and lymph nodes (LNs) (ypT0/Tis ypN0); partial response if there was no tumor in the LNs but residual tumor in the breast (ypT+ ypN0) or residual tumor in the LNs (ypT0/Tis ypN+); and limited response if there was residual tumor in both the breast and the LNs (ypT+ ypN+). Kaplan-Meier and Cox proportional hazards analyses were performed to identify factors predictive for overall survival (OS). Results: A total of 155 patients were included. Following NAC, 39 patients (25.2%) achieved pCR, 57 (36.8%) achieved a partial response (either ypT+ ypN0 or ypT0/Tis ypN+), and 59 (38.1%) had a limited response. A total of 22 patients (14.2%) experienced local failure, 20 (12.9%) experienced regional failure, and 59 (38.1%) experienced distant failure. Median OS for patients who achieved pCR was not reached, and was significantly worse for patients who had residual disease in the breast and/or LNs (P<.001). No difference in OS was seen among patients who had residual disease in the breast alone versus those who remained LN-positive (97 vs 83 months, respectively; P=.25). Subset analysis did not reveal differences in OS based on year of treatment or cN1 disease at the time of initial diagnosis. Conclusions: Women aged ≤40 years who achieved pCR had excellent outcomes; however, those who achieved a pathologic response in the LNs but had residual disease in the breast continued to have outcomes similar to those who remained LN-positive.