Chris Li, MD, PhD, Full Member, Public Health Sciences, FHCRC
Linda Cook, PhD, Full Member, Professor, Department of Epidemiology and Biostatistics, UNM Cancer Center, University of New Mexico
This project directly addresses the PUEDO initiative’s overarching theme of understanding and preventing breast cancer precursors, morbidity, and mortality among Latinas. Our study will evaluate determinants of the incidence and mortality of molecularly defined breast cancer subtypes among women in general and among Latinas specifically. In particular, we are investigating the etiologies and outcomes of two aggressive breast cancer subtypes that disproportionately effect Hispanic women. This work could impact clinical practice and public health in several respects: 1. Identifying modifiable risk factors related to the incidence and mortality of these tumors affords opportunities for prevention and improving survival rates; 2. Development of culturally sensitive targeted screening/education programs for women at high risk for these tumors could lead to earlier diagnosis of these tumors when they are more treatable; and, 3. Determining etiologic pathways relevant to these tumor subtypes at a population level can help inform the development of novel treatment and prevention strategies.
While breast cancer has generally been studied as a single disease, advances in our understanding of the molecular basis for breast cancer indicate that it is a heterogeneous disease that can be divided into distinct molecular subtypes. This project will use clinically available tests to define breast cancer subtypes, whereas Project 4 will fully characterize the molecular subtypes by gene expression profiling. Two of these clinically defined subtypes, triple-negative (TN) [tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor-2 (HER2)] and HER2-overexpressing (H2E) tumors (tumors that are ER-/HER2+) are of considerable clinical and public health importance. TN and H2E breast cancers account for only ~16% and ~9% of all invasive breast cancers, respectively,1-4 but, they are associated with substantially poorer 5-year survival rates (30-80% and 25-80%, respectively) compared with the more common luminal (i.e., ER+) tumors (~90% 5-year survival)5-8. Additionally, these tumors disproportionately impact Hispanic women in addition to other medically disadvantaged populations.7,9-12 Specifically, Hispanic women are ~50% more likely to have TN and H2E tumors compared to non-Hispanic white women.
The molecular classification of tumor subtypes is well defined, and ER, PR, and HER2 status are routinely assessed clinically. In contrast, risk factors for each subtype, especially among Hispanic women, are largely unknown because prior studies have been limited by relatively small sample sizes (n=77-375 TN cases and n=33-116 H2E cases) with only a small number of Hispanic cases. Additionally, no studies have assessed the relationship between established breast cancer risk factors and risk of mortality among TN and H2E patients.1,2,9,13-16 Nonetheless, data published by ourselves and others strongly suggest that established breast cancer risk factors are differentially associated with risks of TN, H2E, and luminal breast cancers. Specifically, parity, breastfeeding, and obesity appear to be more strongly related to TN breast cancer than to luminal disease.
To address the significant gaps in our knowledge regarding the etiologies of H2E and TN breast cancer and factors influencing their prognoses, we propose a population-based case-case study of breast cancer among women aged 20-69 years in the Seattle, Washington and Albuquerque, New Mexico greater metropolitan areas. This study will include 1120 TN, 600 H2E, and 1120 luminal (ER+) invasive breast cancer cases, including 175 TN, 95 H2E, and 175 luminal cases that are Hispanic. With a sample size that is substantially larger than any other published study of these tumors, a focus on the age range over which these tumors are most common, and inclusion of a substantial number of Hispanics, this study will enable us to address the following questions:
Primary Aims to Answer
- How are established breast cancer risk factors, including reproductive factors, body mass index, mammographic density, and a family history of breast cancer, related to risks of TN and H2E breast cancer relative to risk of luminal breast cancer?
- Do the associations between established risk factors and the relative risks of TN and H2E breast cancer differ between Hispanics and non-Hispanics?
- How do established breast cancer risk factors influence risk of mortality in women diagnosed with TN and H2E breast cancers?
Given that most breast cancer risk factors confer elevated risks of breast cancer independent of race/ethnicity, identifying TN and H2E specific risk factors could have broad public health importance and provide important insight into the contributors to the higher incidence rates of these two aggressive types of breast cancer that disproportionately affect Latina women.