Date of Award

January 2026

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Jonathan S. Leventhal

Abstract

BackgroundCutaneous metastases (CM) from cancer are a rare yet deeply distressing diagnosis. Breast cancer is the most common cause of CM in women, accounting for up to 70% of CM diagnoses. Cutaneous metastases may have heterogenous and nonspecific presentations posing a difficult clinical diagnosis, and the discovery of a CM is typically associated with a poor prognosis. First line treatment is focused on slowing the underlying cancer, with limited adjunctive palliative local therapies available for symptomatic lesions. The literature on CM from breast cancer has yet to characterize the complete clinical courses for breast cancer patients who develop CM from presentation and discovery of CM to disease outcome and multidisciplinary management. Research Aims The primary aim of this study was to characterize the characteristics of primary breast cancers and their cutaneous metastases, treatment modalities, and disease response for patients at a tertiary care academic cancer center. Methods Patients with CM from a primary breast cancer were identified through the Joint Data Analytics Team, and dermatology and oncology clinics. Descriptive statistics and survival analyses were performed using Kaplan–Meier curves with log-rank tests using IBM SPSS Statistics version 24.0. Results A total of 56 patients met inclusion criteria. Patients predominantly presented with invasive ductal carcinoma (58.9%). Immunohistochemical staining showed majority HR+/HER2– primary disease (60.7%). CM were most often discovered by patients (75.0%), were nodular in morphology (55.4%) and were located on the breast (46.4%). Concordance in receptor status between primary tumors and CM was observed in the majority of cases (77.5%). Molecular profiling of CM lesions most frequently identified somatic mutations in PIK3CA (14.7%) and TP53 (11.8%). CM detection typically led to changes in systemic therapy (76.8%). Median overall survival from detection of visceral metastases was 56.0 months (95% CI, 45.3–66.6), and 47.1 months (95% CI, 29.8–64.4) from CM diagnosis. Survival from CM diagnosis did not significantly differ by number or morphology of lesions, however, varied significantly by receptor subtype (p=0.005). Statement of scientific impact Our findings suggest among a single cohort, length of survival after diagnosis of CM may be increasing, and genetic profiling of the metastases can inform targeted treatment modalities. Patients should be advised to monitor for skin changes with subsequent expedited workup in a multidisciplinary setting

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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