**1. Introduction**

Male breast cancer (MBC) is a rare and understudied cancer that accounts for about 1% of all breast cancer cases in the United States [1]. Over the past few decades, the incidence of MBC has been on the rise. In 2022, it was estimated that 2710 new cases and 530 deaths from MBC will occur, representing an increase of 94% and 33%, respectively from estimates for 2000 [2,3]. While substantial efforts have been made in the past 20 years to understand the biologic features, effective treatment modalities, and outcomes for breast cancer, MBC remains largely understudied compared to female breast cancer (FBC) [4,5].

Due to its rarity, most MBC patients in the past have not been included in therapeutic studies, therefore, treatment strategies for MBC have largely been extrapolated from evidence from FBC patients [4–7]. While MBC share similar characteristics with FBC, it has distinct features that may influence treatment outcomes [1,8]. For example, MBC usually occurs at older ages and approximately occur 5 years before FBC [1]. While young MBC patients tend to have better overall survival than older male patients diagnosed with breast cancer, young MBC patients have worse survival outcomes than young FBC patients [9]. The lack of established screening guidelines for breast cancer in men often results in delays in the diagnosis of MBC of about 21 months after the onset of symptoms [6]. Furthermore, MBC patients are less likely to receive conventional treatments that may partly be due to low compliance among MBC patients [10]. Other clinicopathological differences include

**Citation:** Appiah, D.; Mai, M.; Parmar, K. A Prospective Population-Based Study of Cardiovascular Disease Mortality following Treatment for Breast Cancer among Men in the United States, 2000–2019. *Curr. Oncol.* **2023**, *30*, 284–297. https://doi.org/ 10.3390/curroncol30010023

Received: 2 December 2022 Revised: 19 December 2022 Accepted: 23 December 2022 Published: 25 December 2022

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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MBC patients having higher frequency of mutations in BRCA2 tumor suppressor gene compared to BRCA1, having more frequent lymph node metastases, and having a higher proportion of estrogen-receptor positive tumors [1,5,6].

Although inconclusive, several studies have reported worse prognosis for MBC patients compared to FBC patients [4]. Recent registry-based studies have reported lower overall and 5-year survival in MBC compared to FBC patients, with the risk of death in MBC patients being 19% to 43% higher than FBC after controlling for potential confounding factors [4,10]. Clinical characteristics and undertreatments are reported to explain about 63% of the excess mortality for MBC patients [10]. Among MBC patients, racial and ethnic disparities in survival and other clinicopathological characteristics have also been reported with racial and ethnic minority men having lower overall survival compared to non-Hispanic White men [11].

Noncancer death, especially cardiovascular disease (CVD)-related deaths, accounts for a large proportion of deaths in MBC survivors as these two conditions share in common several risk factors [6,12]. Only a few studies have evaluated CVD outcomes in MBC patients [6,12,13]. A recent population-based epidemiologic study reported higher CVD mortality among MBC patients than would have been expected compared to the general population, with the mortality being highest among younger MBC patients aged 35–44 years at diagnosis [6].

Tremendous changes in treatment modalities for breast cancer have occurred over the past five decades that has been suggested to influence cardiovascular outcomes among breast cancer survivors [5,14,15]. The etiology of cardiotoxicity has been reported to vary by the type of cancer therapy. For example, HER2-directed therapeutics and chemotherapeutics such as anthracyclines that are standard-of-care treatment in high-risk individuals have been reported to increase the risk for cardiomyopathy and heart failure [16,17]. However, there is limited evidence on the pertinent roles that treatment for breast cancer plays on CVD outcomes in men. Recent ASCO guidelines on MBC recommend conducting post-treatment surveillance studies to provide evidence-based data for the managemen<sup>t</sup> of breast cancer in men [18]. Therefore, the primary aim of this study was to evaluate the relation between breast cancer treatment and CVD mortality among men in the United States. The secondary aim was to investigate racial and ethnic disparities in the relation of breast cancer treatment and CVD mortality.

## **2. Materials and Methods**
