In a world where medical science constantly pushes boundaries, a troubling question persists: why do Black patients with certain cancers often face worse outcomes than White patients, even when their medical care seems identical? This isn’t just a statistical blip; it’s a profound challenge to our understanding of equitable healthcare. A groundbreaking study published in Biophotonics Discovery offers a compelling new perspective, suggesting the very structure of tissues surrounding tumors—specifically, collagen—might be a crucial, overlooked factor. This research points to subtle biological variations that could influence how a tumor behaves and whether it spreads, moving beyond common assumptions about genetics or care quality.
For years, doctors have relied on various methods to predict if a patient’s cancer will spread, a process known as metastasis. This spread is often the deadliest aspect of cancer. Yet, existing prediction tools have shown concerning inaccuracies for Black patients. Consider the widely used 21-gene test for breast cancer: its accuracy in predicting metastasis and guiding chemotherapy decisions is compromised for Black American patients. This means some might undergo unnecessary, harsh chemotherapy, while others could miss a vital opportunity to prevent their cancer from spreading. The urgent need for universally accurate prognostic tools is clear.
This new study delves into the “tumor microenvironment,” the intricate network surrounding a tumor that influences its growth and spread. Collagen, a key protein in our connective tissues, is a major player in this environment. It’s not merely a passive support structure; collagen actively influences cancer cell behavior, and cancer cells, in turn, can reshape the collagen around them. These physical changes in collagen can even trigger chain reactions within the body that accelerate tumor growth and progression.
The scientists focused on two cancer types: invasive ductal carcinoma (IDC), the most common breast cancer, and stage I colon adenocarcinoma (CRC). Their innovative approach utilized second-harmonic generation (SHG) imaging, a sophisticated technique that reveals the internal organization and packing of collagen fibers. Unlike standard imaging, SHG doesn’t just locate collagen; it uncovers the subtle patterns within its tiny fibers. SHG acts like a microscopic scanner, deciphering these hidden structural details.
Researchers specifically measured two collagen features: the “forward-to-backward scattering ratio” (F/B ratio) and “fiber angle variability” (FAV). The F/B ratio indicates how light scatters off collagen fibers, reflecting their internal structure, including diameter and packing. Prior studies have linked this ratio to patient outcomes in some breast and colon cancers. Fiber angle variability (FAV) measures the consistency of collagen fiber angles; a lower FAV suggests a more organized structure. Both measurements offer insights into a tumor’s potential for spread.
How the Study Was Conducted
The research sought to determine if SHG-based measurements (F/B and FAV) differed between Black/African American (BAA) and White/Caucasian American (WCA) patients, providing critical information for future clinical trials aiming for diverse patient representation.
Patient samples were obtained from the University of Rochester Medical Center (URMC) pathology archives. These were preserved “formalin-fixed paraffin-embedded (FFPE) tumor blocks,” routinely collected after surgeries. The blocks were meticulously cut into thin slices (about 5 micrometers, roughly one-tenth the width of a human hair) and stained for microscopic examination.
The colorectal cancer (CRC) group included 88 patients (77 White, 11 Black) with stage I colon adenocarcinoma diagnosed between 2001 and 2012. The larger invasive ductal carcinoma (IDC) group comprised 243 patients (223 White, 20 Black) with estrogen-receptor-positive (ER+) IDC, diagnosed between 1999 and 2011 and prescribed tamoxifen. Patient data, though not always complete for every variable, was carefully recorded. All tissue samples were validated by trained pathologists, and the study adhered to ethical guidelines, approved by the URMC’s Institutional Review Board.
SHG imaging involved using a laser to excite collagen fibers, with detectors collecting scattered light from both forward and backward directions. This generated “F” (forward) and “B” (backward) images. Three image pairs were captured from both the “tumor bulk” (main tumor) and the “tumor-stroma interface” (where the tumor meets surrounding healthy tissue). The tumor-stroma interface is particularly relevant in breast cancer prognosis.
Computer algorithms analyzed these images. For the F/B ratio, algorithms identified collagen pixels and calculated the mean ratio of forward to backward scattered light. For FAV, software pinpointed individual collagen fibers and measured their angles. Statistical analyses were then performed to identify significant differences.
Key Discoveries
The study’s findings are both illuminating and a call for action. While most clinical characteristics like age or sex showed no significant racial differences in the CRC group, the breast cancer cohort revealed a higher average BMI among Black patients, aligning with existing research.
A consistent finding was that the F/B ratio was notably higher at the tumor-stroma interface compared to the tumor bulk in both CRC and IDC. This indicates a structural distinction in collagen at the tumor’s edge versus its core.
The most profound discovery came from comparing optical measurements across racial groups. In the CRC cohort, there was a trend suggesting a difference in the F/B ratio between Black and White patients, both at the tumor-stroma interface and within the tumor bulk. This points to a potential, though not yet statistically definitive, racial variation in colon cancer collagen structure.
For breast cancer (IDC), the results were more conclusive and significant. The F/B ratio at the critical tumor-stroma interface was distinctly different between Black and White patients. Specifically, Black breast cancer patients had a lower average F/B ratio (12.39) compared to White patients (15.36) at this crucial boundary. This is a significant revelation, showing that the way light interacts with collagen—reflecting its internal structure—differs by race in breast cancer. This disparity could mean that current prognostic tools, largely calibrated on data from White patients, might not fully capture the complete biological picture for Black patients.
Interestingly, fiber angle variability (FAV) showed no significant differences between Black and White patients in either cancer type. This implies that while the internal packing of collagen fibers (F/B) may vary by race, the overall organization of these fibers (FAV) does not. This distinction highlights the F/B ratio as a particularly important area for further research.
These findings strongly indicate that the relationship between the F/B ratio and cancer metastasis may indeed vary by patient race. This underscores a potential need for developing race-specific prognostic algorithms. To enhance the accuracy of cancer metastasis prediction for all patients, especially those from underrepresented groups, predictive models might need to account for these subtle yet significant biological differences in collagen structure.
Towards More Equitable Cancer Care
The findings from this study by Elias et al. are a stark reminder that biological differences, some subtle and some profound, can exist between racial groups and can impact disease progression and the effectiveness of diagnostic tools. These differences are not about blaming individuals or suggesting inherent inferiority, but rather about acknowledging biological realities that may be influenced by a complex interplay of genetics, environment, lifestyle, and other yet-to-be-understood factors. It’s about building a more precise and equitable healthcare system for everyone. The path forward is clear: future clinical studies must actively include more participants from underrepresented groups to ensure that new prediction methods are accurate and effective for all patients, ultimately improving health outcomes across the board.
Paper Summary
Methodology
This study investigated if optical measurements (F/B ratio and fiber angle variability, FAV) from collagen, using second-harmonic generation (SHG) imaging, differed by race (Black/African American and White/Caucasian American) in breast and colon cancer patients. Researchers analyzed preserved tumor tissue samples (FFPE blocks) from 88 colon cancer patients (11 Black, 77 White) and 243 breast cancer patients (20 Black, 223 White). Measurements were taken from the main tumor and its boundary with healthy tissue to understand collagen structure and organization.
Results
The study found significant differences in the F/B ratio, indicating collagen structure, between Black and White patients in breast cancer at the tumor’s edge, with Black patients having lower values. A similar trend was observed in colon cancer, though not statistically definitive. The F/B ratio was consistently higher at the tumor-stroma interface than within the main tumor for both cancers. However, fiber angle variability (FAV), which measures collagen organization, did not show significant racial differences in either cancer type.
Limitations
The study acknowledges limitations including a relatively small representation of minority patients, which may affect how broadly the findings apply. The use of preserved tissue might yield different results compared to fresh tissue, and imaging artifacts from glass slides could potentially influence measurements. Additionally, some patient clinical data was incomplete.
Funding and Disclosures
The paper is published under a Creative Commons Attribution 4.0 International License. No specific funding sources or conflicts of interest were explicitly mentioned within the provided document excerpts.
Publication Information
Authors: Tresa M. Elias, Danielle E. Desa, Edward B. Brown IV, Showmick Paul, Gabriel A. Ramirez, Bradley M. Turner, Kelley Madden, Raul S. Gonzalez, Anna Weiss, and Edward B. Brown III Journal: Biophotonics Discovery Volume: 2, Issue: 2 Article Number: 022703 Publication Date: April 30, 2025 DOI: 10.1117/1.BIOS.2.2.022703