Inflammatory breast cancer

Inflammatory breast cancer is a clinical diagnosis, staged T4d: rapid onset over six months or less of erythema and oedema covering at least a third of the breast, often with warmth, heaviness and peau d'orange, with or without a palpable mass. Tumour emboli in the dermal lymphatics on a skin punch biopsy support the diagnosis but are not required, and their absence does not exclude it. Because the picture mimics mastitis, women are often given antibiotics first; any presumed infection that does not settle within a week or two in a woman who is not breastfeeding needs imaging and biopsy. Staging includes PET-CT or CT and bone scan, because roughly a third of patients in registry series have distant metastases at diagnosis. Compared with other breast cancers a higher share are HER2-positive or triple-negative and fewer are hormone receptor-positive, and no mutation unique to the inflammatory phenotype has been found.

Treatment is trimodality and the order is fixed. Systemic therapy comes first: an anthracycline and taxane, with trastuzumab and pertuzumab throughout for HER2-positive disease and a pembrolizumab-based regimen for triple-negative disease by extrapolation from KEYNOTE-522, since inflammatory cases were few in the landmark trials. Response on examination and imaging then permits a modified radical mastectomy with axillary dissection; breast conservation, sentinel node biopsy alone, skin-sparing incisions and immediate reconstruction are avoided because the disease is in the skin lymphatics. Post-mastectomy radiotherapy to the chest wall and regional nodes follows in every patient, with bolus to bring the dose to the skin and a higher dose for poor responders. Endocrine therapy, completion of a year of HER2 therapy with trastuzumab emtansine or trastuzumab deruxtecan if disease remained, and olaparib or capecitabine for residual triple-negative disease follow the rules of non-inflammatory cancer.

Outcomes have improved but remain the worst of any breast presentation: before chemotherapy the disease was almost uniformly fatal within a few years of surgery, and even with trimodality treatment well under half of patients are alive at five years in registry series, with pathological complete response the strongest predictor of who will be. The MD Anderson programme that began giving chemotherapy before surgery in the 1970s and the dedicated inflammatory breast cancer clinics that followed have defined the standards, and an international expert consensus in 2011 fixed the diagnostic criteria; trials restricted to inflammatory disease remain scarce, so most evidence is borrowed. Whether immunotherapy and antibody-drug conjugates close the gap, whether radiotherapy can be intensified safely, and what drives the inflammatory phenotype are the open questions.