Field cancerization, accelerated aging, and immunosuppression: the rapid rise of hormone-sensitive and early-onset breast cancer

Q: 为什么传统因素不足以解释近年乳腺癌发病率的上升？

仅靠筛查增强与生活方式改变无法完整解释总体发病率，尤其是特定种族与地理亚群中、以及ER+与早发型乳腺癌的持续增长。

Q: 作者提出的核心假设是什么？

作者认为激素敏感型与早发型乳腺癌上升可体现为对环境的慢性累积暴露，尤其是内分泌干扰物（EDCs）对乳腺组织生物学的深刻改变。

Q: EDCs可能通过哪些机制影响早发型乳腺癌风险？

EDCs会改变雌激素受体信号、重塑表观遗传景观，并破坏免疫监视；这些作用在宫内、产后、青春前期和青春期等高度可塑阶段可推动更早的癌症发生。

Sep 23, 2026

Uploaded by Asher

Breast cancer etiology has traditionally emphasized genetic mutations, hormonal dynamics, and tissue aging, yet recent decades show a sustained increase in estrogen receptor–positive (ER+) tumors and a striking rise in early-onset breast cancer even without family history. Screening and lifestyle changes do not fully explain the growing incidence, prompting a perspective that chronic, cumulative environmental exposure—especially endocrine-disrupting chemicals—remodels breast tissue biology, including field cancerization, epigenetic states, and immune surveillance. The work reviews historical trends and geographic clustering to support this mechanistic framework.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Historical perspective and current trends

Geographic clustering and environmental exposure

npj | breast cancer Review | Published in partnership with the Breast Cancer Research Foundation | | | | --- | --- | --- | | [https://doi.org/10.1038/s41523-025-00840-w](https://doi.org/10.1038/s41523-025-00840-w) | | | | Field cancerization, accelerated aging, and immunosuppression: the rapid rise of hormone-sensitive and early-onset breast cancer
Check for updates | | | | Meadow Parrish1, Nicole Traugh1, Meloryn Seraj1 & Charlotte Kuperwasser1,2 | | | | Breast cancer etiology traditionally emphasizes genetic mutations, hormonal dynamics, and tissue aging. However, recent decades have seen a steady rise in breast cancer with a growing proportion of these tumors exhibiting estrogen receptor–positive (ER +) phenotypes along with an alarming rise in early-onset breast cancer occurring in individuals without a family history of the disease. While increased screening and lifestyle changes explain part of this trend, they do not fully account for the rising incidence, particularly among speciﬁc racial and geographic subgroups. We hypothesize that this rising trend in hormone-sensitive and early-onset cancers is a manifestation of chronic, cumulative environmental exposures, particularly to endocrine-disrupting chemicals (EDCs), that profoundly alter breast tissue biology. Since EDCs alter estrogen receptor signaling, the epigenetic landscape, and disrupt immune surveillance, we hypothesize that this may underpin the rising incidence of hormone-sensitive early-onset breast cancers through a mechanism that affects ﬁeldcancerization and hormone-mediated aging. | | | | Historical perspective and current trends
Since the 1970s, breast cancer incidence trends have been understood through genetic predispositions, cumulative hormone exposure, and increased mammography screening. Lifestyle changes including earlier menarche, delayed childbirth, obesity, and hormone replacement therapy usage have also contributed to the rise of breast cancers1–7. However, these factors alone cannot explain epidemiological studies showing that each new generation carries a slightly higher risk of breast cancer than the prior one2,8–11. Moreover, these factors cannot explain the alarming increases speciﬁcally in estrogen receptor-positive (ER + ) breast cancers, but also in early-onset breast cancers (<50 years old), or the shift in breast cancer subtypes in younger women particularly among Hispanic American, Asian American, and Paciﬁc Islander populations2, 10.
Traditionally, early-onset breast cancers were linked with exposure to radiation around the time ofmenarche12, or linked with inherited mutations in cancer causing genes (eg. BRCA1/2, TP53, ATM, PALB etc)13–17. Earlyonset breast cancers were also predominantly characterized by estrogen receptor-negative (ER-) proﬁles18–20. However, recent trends have shown a shift in the presentation ofthese cancers with an increasing number ofearly- | onset breast cancers identiﬁed as ER+ and the vast majority with no family history21. This change underscores a possible evolution in the biological mechanisms underlying the formation ofthese cancers. Most notably, earlyonset breast cancer incidence has been shown to be enriched in the Northeast, Midwest, and Southeast United States22.
In this perspective, we argue that the risingtrends in hormone-sensitive and early-onset cancers, is a manifestation of chronic and cumulative environmental exposures that profoundly alter breast tissue biology. Speciﬁcally, the continuous exposure to endocrine disrupting chemicals(EDCs) permeates highly plastic and susceptible stages of breast development, overwhelming intrinsic tumor‑suppressive programs. In utero, post-natal, peri-pubertal, and pubertal exposures to EDCs remodel the breast epigenome, accelerate tissue‑speciﬁc aging, and impair immunosurveillance, leading to increased cancer development and especially early-onset breast cancers.
Geographic clustering and environmental exposure
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FAQs

为什么传统因素不足以解释近年乳腺癌发病率的上升？

仅靠筛查增强与生活方式改变无法完整解释总体发病率，尤其是特定种族与地理亚群中、以及ER+与早发型乳腺癌的持续增长。

作者提出的核心假设是什么？

作者认为激素敏感型与早发型乳腺癌上升可体现为对环境的慢性累积暴露，尤其是内分泌干扰物（EDCs）对乳腺组织生物学的深刻改变。

EDCs可能通过哪些机制影响早发型乳腺癌风险？

EDCs会改变雌激素受体信号、重塑表观遗传景观，并破坏免疫监视；这些作用在宫内、产后、青春前期和青春期等高度可塑阶段可推动更早的癌症发生。

Sep 23, 2026

Uploaded by Asher