Adenomyosis and Endometrial Cancer: Cause or Coincidence?

Adenomyosis and Endometrial Cancer: Untangling the Relationship Between Two Complex Gynecological Conditions

In recent years, the medical community has grappled with understanding the intricate relationship between adenomyosis and endometrial cancer, two conditions that frequently overlap yet whose interplay remains enigmatic. Adenomyosis, characterized by the presence of endometrial glandular tissue within the myometrium, has traditionally been viewed as a benign gynecologic disorder primarily affecting women in their reproductive years. Meanwhile, endometrial cancer stands as the most common malignancy of the female reproductive tract, with risk factors spanning from hormonal imbalances to genetic predispositions. The critical question posed by contemporary research is whether adenomyosis biologically contributes to the onset and progression of endometrial cancer or simply coexists without influencing the malignant process.

A landmark retrospective cohort study published in BMC Cancer provides fresh insight into this controversy, analyzing a robust sample of 388 endometrial cancer patients treated between 2019 and 2024. The researchers employed stringent diagnostic criteria to identify adenomyosis, specifying the infiltration of endometrial glands and stroma at a depth of at least 2.5 millimeters into the myometrium. This allowed for a clear demarcation between patients with and without adenomyosis, thereby enabling a precise comparison regarding clinical outcomes and pathological features.

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Interestingly, the study revealed that 18.8% of endometrial cancer patients harbored coexisting adenomyosis, a finding that aligns with previous reports but underscores the regularity of this phenomenon. Patients with adenomyosis were notably younger in age and less likely to have reached menopause compared to their counterparts. This demographic skew suggests that adenomyosis may be more prevalent in a different hormonal milieu, potentially implicating estrogenic effects as a shared underlying factor in the pathophysiology of both conditions.

Adjuvant therapy, often administered postoperatively to reduce cancer recurrence, was significantly less frequent among patients with adenomyosis. This may reflect either a lower perceived risk profile or variations in tumor characteristics; however, the study found no meaningful differences between the two groups in terms of tumor grade, histological subtype, or molecular classification based on The Cancer Genome Atlas (TCGA) subtypes. This molecular neutrality challenges any assumption that adenomyosis imparts aggressive biological behavior to endometrial tumors.

A particularly intriguing observation was the increased prevalence of concurrent endometrial hyperplasia in patients with adenomyosis—64.4% compared to 32.4% in the non-adenomyosis group. Endometrial hyperplasia, a recognized precursor lesion to carcinoma, typically arises from prolonged estrogen stimulation unopposed by progesterone. The heightened frequency of hyperplasia in adenomyosis patients hints at a shared hormonal or microenvironmental pathway that may subtly predispose to neoplastic changes, though the lack of differences in survival outcomes tempers expectations about its clinical significance.

The clinical endpoints of progression-free and overall survival did not differ significantly between patients with and without adenomyosis. Despite the lower utilization of adjuvant therapy among adenomyosis patients, their survival trajectories paralleled those without the condition. Notably, the follow-up periods—approximately four to five years—provide a substantial window to capture disease recurrence and mortality, lending weight to the conclusion that adenomyosis does not influence the malignant course of endometrial cancer.

This neutrality bears clinical implications. It suggests that the presence of adenomyosis should not necessarily alter surgical planning, adjuvant treatment decisions, or prognostication in endometrial cancer management. Physicians can be reassured that adenomyosis is unlikely to worsen outcomes or indicate a more aggressive tumor phenotype. However, the authors caution that the relatively low recurrence rates encountered may limit the statistical power to detect minor effects, underscoring the need for larger multicenter prospective studies to validate these findings.

From a biological standpoint, these results prompt a reassessment of proposed mechanisms linking adenomyosis and endometrial carcinogenesis. While both conditions involve aberrations in endometrial glandular cells, the study’s data imply that adenomyosis itself does not drive tumor initiation or progression. Instead, it may reflect a parallel pathological process influenced by common hormonal or genetic factors rather than a direct causal relationship. This distinction is crucial when considering targeted therapies or biomarkers that rely on understanding the tumor microenvironment.

The study also sheds light on reproductive factors and age dynamics. Patients with adenomyosis were younger and less commonly menopausal, possibly suggesting that estrogen dominance in premenopausal women contributes to adenomyotic changes. Since endometrial cancer typically arises post-menopause, this co-occurrence in younger women may represent an incidental intersection of two separate disease pathways rather than one fostering the other.

Furthermore, the study meticulously applied molecular subtyping via TCGA categories, revealing no significant differences between adenomyosis and non-adenomyosis groups. This cutting-edge genomic classification, which stratifies tumors based on mutational landscapes, offers a refined lens to assess tumor behavior beyond traditional histology. The lack of variation reinforces the concept that adenomyosis does not shape or influence the molecular evolution of endometrial cancer cells.

Clinicians should also consider the impact of adjuvant therapy practices and patient demographics elucidated by this research. With adenomyosis patients receiving fewer adjunctive treatments but maintaining comparable outcomes, there lies a potential avenue to tailor therapy more precisely, avoiding overtreatment without compromising efficacy. This could improve quality of life and reduce healthcare burdens.

The study’s rigorous methodology—covering over five years of patient data and employing comprehensive histopathological evaluations—adds robustness to its conclusions. Even so, the authors acknowledge the retrospective design’s limitations, specifically regarding unmeasured confounders and the inability to perform multivariate Cox regression analyses due to low event counts. These caveats invite cautious interpretation and subsequent confirmatory studies.

Parallel to this clinical research, molecular investigations into the microenvironment of adenomyosis might uncover subtle influences on tumor initiation or immune modulation that escaped detection in survival analyses. The intersection of chronic inflammation, hormonal signaling, and cellular invasion characteristic of adenomyosis could, in theory, create a permissive niche for oncogenic transformation, yet this study’s findings argue against any substantial contribution.

In summary, this pioneering study offers compelling evidence that adenomyosis does not exert a significant biological role in the progression or prognosis of endometrial cancer. Its presence should be considered an incidental co-occurrence rather than a driver of malignancy. This insight refocuses the clinical approach to managing patients harboring both conditions and refines our understanding of their pathogenesis.

Future research will need to integrate molecular profiling, hormonal assessments, and longitudinal follow-up to unravel any nuanced interactions between adenomyosis and endometrial tumor biology. For now, the evidence supports clinical equipoise, alleviating concerns regarding adenomyosis as a potential risk modifier in endometrial cancer.

Subject of Research: The investigation focuses on the interplay between adenomyosis and endometrial cancer, specifically assessing whether adenomyosis contributes biologically to cancer progression or simply coexists incidentally.

Article Title: Adenomyosis and endometrial cancer: determining its role as a biological contributor or incidental coexistence

Article References:
Shiwali, V., Tang, Y., Xue, M. et al. Adenomyosis and endometrial cancer: determining its role as a biological contributor or incidental coexistence. BMC Cancer 25, 984 (2025). https://doi.org/10.1186/s12885-025-14389-1

Image Credits: Scienmag.com

DOI: https://doi.org/10.1186/s12885-025-14389-1

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