The significant decrease in breast cancer deaths achieved by organized mammography screening programs and treatment of breast cancer at an early phase is a remarkable achievement in clinical cancer research. A remaining challenge is to recognize the breast cancers we are still failing to manage effectively, even when women attend screening regularly and receive modern therapeutic regimens. Many of these fatal tumours originate in the major lactiferous ducts through the carcinogenic process of neoductgenesis with the formation of invasive neoducts. The proposed name for these malignancies is ductal adenocarcinoma of the breast (DAB). Using imaging biomarkers correlated with large format histopathology, we sought to identify the DAB subgroups with the highest fatality.

All histologically proven breast cancer cases (n = 3587) in women of all ages, diagnosed in our Institution from January 2008-June 2022 and followed up through 2023, were prospectively classified into their apparent site of tumour origin using imaging biomarkers mammographic tumour features. These have been correlated with large format histopathology and long-term, patient outcome. Breast cancers originating from the major lactiferous ducts (DAB) formed a subgroup of 570 consecutive cases, which were further subdivided according to their imaging biomarkers. The frequency of occurrence of the combined necrosis producing cases, the combined fluid producing cases and the non-calcified architectural distortion type DAB cases were compared with the death rate within each of these combined subgroups.

Patients with the necrosis-producing DAB subtypes had a significantly elevated, 4.33-fold risk of breast cancer-specific death (95% CI: 1.73–10.84) compared with the fluid-producing DAB subtypes. Patients with the non-calcified architectural distortion DAB subtype had a non-significant 2.51-fold higher risk (95 % CI: 0.87–7.23 compared with the fluid-producing DAB subtypes. The majority of breast cancer deaths, 51/67 (76 %), were in the 317 women having fragmented casting type calcifications on the mammogram. Biopsied axillary node and distant metastases of some fatal cases revealed structures closely resembling neoducts.

Perception and recognition of the imaging biomarkers of the DAB subgroups are necessary first steps in controlling these malignancies, since these biomarkers indicate the site of tumour origin and have documented prognostic value. Reliable imaging-histopathologic correlation of these extensive, diffusely invasive malignancies calls for the use of a large section histopathology technique. The duct-like structures of each DAB subgroup are newly formed invasive neoducts produced by the carcinogenic process of neoductgenesis; they are not pre-existing ducts and can metastasize to the lymph nodes and to distant organs. These observations challenge the use of the term ductal carcinoma in situ (DCIS) for these DAB cases. Until the medical community recognizes that neoductgenesis is an invasive, not an in situ carcinogenic process, we are unlikely to achieve a significant reduction in its high fatality rate.