Promoting Awareness of Inflammatory Breast Cancer
Spotlight On > SABCS: Breast Cancer
— A deeper grasp of the biology, a focus on trimodal therapy, and new treatments fueling progress
December 3, 2025 - 5 min read
Despite notable advances in understanding inflammatory breast cancer (IBC), diagnosing and treating this disease remains challenging, and prognosis generally trails that of other breast cancers.
IBC accounts for roughly 2%–4% of all breast cancers, yet it contributes to about 7% of breast cancer deaths. Improved recognition and therapeutic progress have begun to shift outcomes, with non-metastatic IBC showing 5-year survival estimates reaching as high as 50%–70% in some recent analyses. Still, about one in three cases are metastatic at diagnosis, and overall survival for IBC remains under four years, markedly shorter than many other breast cancer subtypes.
IBC possesses some distinct clinical features but arises within more common breast cancer categories, most often HER2-positive and, less frequently, triple-negative breast cancer. Hormone receptor–positive disease is less common but tends to carry a poorer prognosis when present.
A primary obstacle in IBC is the absence of a single, well-defined histological or molecular subtype. As Filipa Lynce, MD, of Dana-Farber Cancer Institute, notes, diagnosis hinges on confirming invasive breast cancer plus a set of specific clinical criteria. These criteria include:
- Erythema covering more than one-third of the breast
- A characteristic edema known as peau d’orange
- Often a warm or tender area on the breast
- Enlargement of the breast even without a clearly detectable mass
Dermal involvement, manifesting as erythema and skin dimpling across a substantial portion of the breast, reflects tumor emboli obstructing the lymphatics. Nipple changes such as flattening or inversion are also common. About 75% of IBC patients show dermal lymphatic involvement.
The presentation can vary, but a hallmark is the rapid onset of signs and symptoms within six months of diagnosis.
Breast appearance changes typically begin in one region and then propagate. The timing of these changes matters for diagnosis; for example, if a mammogram previously showed a mass and new skin changes appear after a delay, this timeline is clinically important.
Brain metastases occur more frequently in IBC, contributing to the poorer prognosis. IBC also tends to affect younger women, which may partly explain a higher observed rate of BRCA mutations in this group.
While obesity is a recognized risk factor for breast cancer in general, some studies hint at a stronger association with IBC. However, no definitive causal link or universal biological driver has been established for this subtype.
IBC has not been linked to a single molecular pathway or signature in a conclusive way. Recent work indicates that IBC possesses a biology distinct from other breast cancers. Some investigations have pointed to potential genetic associations, including a 75-gene signature identified by an international consortium that may be linked to IBC.
Despite these insights, clear molecular or genetic targets remain elusive, complicating targeted treatment compared with other breast cancer forms. Nevertheless, trimodal therapy—combining chemotherapy, surgery, and radiation—has emerged as the standard approach due to the disease’s aggressive nature.
Therapy typically starts with systemic chemotherapy, even in estrogen-dependent stage III IBC, because immediate endocrine therapy or surgery is not favored upfront. The aim is to elicit a strong systemic response before pursuing aggressive local treatments, which may include a modified radical mastectomy and intensified radiation (sometimes at doses higher than usual).
Evidence consistently favors trimodal therapy over less intensive strategies. In a national database analysis of 10,197 IBC patients who all underwent surgery, outcomes were best with trimodal therapy: median overall survival was 72 months versus 26 months for surgery alone. Ten-year overall survival rose with treatment intensity: 16.5% for surgery alone, 28.5% with added chemotherapy, and 37.3% with trimodal therapy. From 1998 to 2010, use of trimodal therapy ranged between 58% and 73% of patients.
However, recent trends show a decline in the use of trimodal therapy for IBC, despite strong evidence of its superior outcomes. A separate analysis comparing stage III invasive breast cancers found that IBC patients had worse breast cancer–specific survival and overall survival than other subtypes, and that trimodal therapy usage dropped from 33.9% in 2010 to 24.2% in 2020 (P=0.014).
The goal is clear: ensure every patient diagnosed with IBC is offered trimodality therapy. This decline is concerning, and researchers are actively investigating how to reverse it.
New therapeutic avenues are entering clinical trials, with several centers leading the charge. At Dana-Farber, trials like TRUDI are examining neoadjuvant trastuzumab deruxtecan (Enhertu) in combination with durvalumab (Imfinzi) for stage III, HER2-expressing (including HER2-low) IBC. Another trial, NeoStar, evaluates sacituzumab govitecan (Trodelvy) with pembrolizumab (Keytruda) followed by chemotherapy plus pembrolizumab in stage III HER2-negative IBC.
MD Anderson is a participant in TRUDI and in SWOG1706, which investigates radiotherapy with or without concurrent olaparib (Lynparza). The center also supports a biospecimen registry to build a tissue database for IBC research.
Awareness remains the top priority, according to experts. Early diagnosis can significantly influence outcomes, and ongoing biological and clinical development depends on broad community awareness and patient inclusion in trials. Increasing involvement from funding agencies and pharmaceutical companies is helping to advance research and improve care for IBC.
Ultimately, elevating awareness is crucial not only for early detection but also for driving continued progress in understanding the biology and expanding effective treatment options for this challenging form of breast cancer.
