The term triple negative breast cancer (TNBC) was coined in the mid 2000s to describe a subset of human breast cancers that lacked expression of oestrogen (ER), progesterone (PR) and human epidermal growth factor receptor (HER2) proteins.
Initially perceived as a clinical entity, closely related to the basal like tumours described by Perou et al, subsequent studies revealed a heterogeneous group of tumours with marked variation in morphology, molecular characteristics, clinical behaviour and response to treatment.
Broadly speaking TNBC can be classified into three main groups; high grade, low grade and low grade precursor lesions that may progress to high grade tumours, each group also displaying morphological and molecular heterogeneity.
The high grade TNBC group includes invasive breast cancer, no special type (IBC NST). Some of these IBC NST tumours contain prominent tumour infiltrating lymphocytes (TILs), most notably the medullary pattern. High TILs counts are associated with improved prognosis, a superior response to neoadjuvant chemotherapy (NACT) and are also associated with increased PDL1 expression which has therapeutic significance in the metastatic setting.
Some types of metaplastic breast carcinoma also categorise as high grade TNBC (discussed separately).
Invasive apocrine carcinoma is a special type breast cancer, frequently triple negative, with a unique steroid receptor profile; this tumour is typically ER and PR negative but expresses androgen receptor. This tumour displays luminal molecular characteristics, reflected in its clinical behaviour and response to NACT with a lower rate of complete pathological response than is observed in other TNBCs. Applying the TNBC classification developed by Lehmann et al, invasive apocrine carcinoma is classified as a luminal androgen receptor tumour (LART).
Our understanding of the heterogeneity of TNBC continues to evolve with accompanying advancement of specific personalised treatment regimes.

Microglandular adenosis (MGA) is a rare lesion composed of small tubules lacking a myoepithelial layer with an infiltrative growth pattern. MGA and atypical MGA can act as a precursor lesion for triple negative breast cancer, including high grade NST cancers and rarer salivary special type breast cancers such as acinic cell carcinoma. MGA can cause a diagnostic challenge by being mistaken for invasive triple negative breast cancer on core biopsy. Post neoadjuvant chemotherapy MGA can be mistaken for residual invasive disease, and distinguishing between the two can be difficult. A case of MGA in a post neoadjuvant chemotherapy breast excision is presented, with discussion around how to recognise the diagnosis.

Rare forms of triple negative breast cancer (TNBC), including secretory carcinoma, tall cell carcinoma with reversed polarity and mucinous cystadenocarcinoma will be discussed. Cases will be presented and differential diagnoses will be addressed. Some of these tumours have unique features and are associated with particular genetic alterations. Incorporating morphological, immunohistochemical and molecular pathology findings aids accurate diagnosis of these rare tumours. Many of these tumours are associated with relatively indolent biological behaviour, in contrast to typical TNBCs. Recognition of these ‘low-grade’ forms of TNBC guides tailored clinical decision-making regarding de-escalation of adjuvant treatment.

The routine use of neoadjuvant chemotherapy following a diagnosis of triple negative invasive breast carcinoma eliminates the opportunity for a “second look” at the tumor in the excision specimen before patients receive treatments that carry the risk of significant morbidity, and even mortality.
Thus, it is imperative to ensure that other types of triple negative tumors have been excluded.
This session will review important morphologic clues and discuss practice patterns that can help prevent potentially catastrophic errors.