Using multiplatform profiling, researchers have identified potentially targetable biomarker aberrations in a large cohort of geriatric breast tumors.1 According to the study, presented at the 2015 Breast Cancer Symposium, these data may help researchers to design clinical trials focusing on geriatric patient populations in the future.
“The triple-negative breast group showed the most differences when comparing younger and elderly patients,” said Paula R. Pohlmann, MD, of Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington DC. “ERBB2 abnormalities in older patients may also warrant further evaluation.”
The study also found that staining for the programmed cell death protein 1 and its ligand (PD-1/PD-L1) was positive in all breast cancer subtypes—not just triple-negative tumors (estrogen receptor–/progesterone receptor–/HER2-negative)—the group that has been the focus of immunotherapy trials with PD-1/PD-L1 inhibitors.
As Dr. Pohlmann reported, geriatric patients are often excluded from clinical trials and are underrepresented in biomarker literature. Because breast cancer is a disease of aging and the number of geriatric patients is rising in the United States, studying older populations of patients with breast cancer may be necessary for the refinement of treatment-selection strategies.
“Our aims were to describe molecular characteristics of breast cancer in geriatric patients,” said Dr. Pohlmann,” and to compare molecular characteristics of tumor samples from geriatric patients with those from younger patients.”
Study Design
This was a cross-sectional retrospective study of biomarker data obtained from samples of patients with breast cancer from 2009 to 2015. All samples underwent local pathology and central review and were tested using multiplatform profiling at Caris Life Sciences: that included immunohistochemistry (IHC), fluorescent or chromogenic in situ hybridization (FISH/CISH), and DNA sequencing for somatic mutations.
Of the 8,720 breast cancer tumors initially identified, researchers separated tumors from patients younger than 70 years and excluded tumors taken from male patients with breast cancer.
The final cohort consisted of 1,189 samples taken from patients older than 70 years (the “geriatric” patients). The remaining 7,531 samples were taken from patients younger than 70 years (the “younger” patients). Tumors came from both primary and metastatic sites.
Molecular Differences
With IHC staining, ER, PR, AR, TOP01, TLE3, Ki67, PTEN, and TOP2A were all detected positive more than 50% of the time. Ki67 was more often positive in younger patient samples, Dr. Pohlmann noted.
The most frequently mutated genes were TP53 and PIK3CA, which were found in greater than 2% of samples. TP53 was more often mutated in younger patients, and PIK3CA was more often mutated in geriatric patients.
TOP2A was more frequently positive among younger patients, although amplification was low overall in both age groups and was almost exclusive to HER2-positive patients.
EGFR was significantly elevated in the triple-negative subgroup, whereas TLE3 was more often elevated in the estrogen receptor–positive/progesterone receptor–positive/HER2-negative group.
ERBB2 was mutated in 12 cases of geriatric breast cancer and in 38 cases among younger patients. “It’s important to mention that we had HER2 positivity in only four of these cases,” Dr. Pohlmann reported.
For HER2-positive patients, although most of the abnormalities were equivalent when comparing younger and geriatric population samples, ERBB2 mutations were more frequent in the geriatric group (12% vs 3%), she indicated. “That being said, the enriched population has a small sample size, so we have to take these results with caution,” added Dr. Pohlmann.
It was also noted that BRCA1 was rarely mutated in the older patient population of triple-negative breast cancer.
PD-L1 tumor cells tested positive in 8% of hormone receptor–positive tumors, 20% of HER2-positive tumors, and 19% of triple-negative geriatric patient samples.
Tumor-infiltrating lymphocytes were PD-1–positive in 39% of hormone receptor–positive, 44% of HER2-positive, and 60% of triple-negative geriatric patient samples.
A lack of patient information about staging, previous treatments, subsequent treatments after molecular profiling, and outcomes was cited as a possible limitation to the study, as was the relatively small number of HER2-positive samples and the lack of definitive clinical validation of cutoff values for each test in breast cancer populations. ■
Disclosure: Dr. Pohlmann owns stock in Immunonet Biosciences and has consulted for OncoPlex Diagnostics and Personalized Cancer Therapy.
Reference
1. Xiu J, Reddy SK, Pohlmann PR: Tumor profiling of 1189 geriatric breast tumors. 2015 Breast Cancer Symposium. Abstract 116. Presented September 25, 2015.
