Breast cancers, other than invasive carcinomas NST, may belong to one of a number of major categories as follows: special types of invasive breast carcinoma, epithelial-myoepithelial tumours, fibroepithelial tumours, mesenchymal tumours and lymphomas. In this review, these BC subtypes will be described as they are important for understanding both clinical behaviour and in directing treatment. Some of the rarer subtypes will not be addressed here in detail. Several good articles have recently been published which cover these subtypes in more detail for the interested reader [2, 3], and several are also covered in other chapters in this book (► Chaps. 46 and 47).

The second most frequent histological subtype of BC, and the most frequent special type of BC, is invasive lobular carcinoma (ILC, 10–12% of all BCs) (◘ Fig. 15.2). It has a particular clinical behaviour pattern which corresponds to its particular genotype: mutation or loss of the gene for E-cadherin, a cellular adhesion molecule (CDH1) [4]. Lobular carcinomas tend to have a more diffuse pattern of spread within the breast making them difficult to clinically and radiologically characterise (tumour size often underestimated both clinically and on imaging). They also may be mammographically occult so magnetic resonance imaging (MRI) is often advocated to fully characterize these lesions before offering conservation surgery. They are also more likely to be multifocal [5] which again justifies the use of preoperative MRI [6]. Lobular breast cancers tend to be histological grade 2, to be oestrogen receptor (ER) positive, to be HER-2 negative and to have an unusual pattern of metastatic spread where they are more likely to infiltrate the viscera (stomach, bladder, bowel, etc.) than other breast tumour subtypes [7].

Among the BC types other than invasive ductal or lobular carcinoma, some are characterized by a particularly good or poor prognosis. Tubular, colloid (mucinous), adenoid cystic or secretory breast carcinomas, in general, have a good prognosis, so most of them can be effectively controlled by first-line surgery and anti-oestrogens (+/− adjuvant radiotherapy if appropriate), without the need for systemic chemotherapy [2, 3, 8]. For example, tubular carcinomas are usually small, node negative, low grade and ER+ and have an excellent prognosis compared to other invasive carcinomas of NST [9]. In contrast, micropapillary, metaplastic and pleomorphic lobular breast carcinoma has an intrinsically aggressive behaviour pattern and poor prognosis [10–12].

Medullary breast carcinoma is a very rare BC subtype but deserves special attention as it was the first type of BC which demonstrated that a dense lymphocytic infiltration in a high-grade cancer can be associated with a favourable prognosis. It was first described almost 60 years ago [13] and named medullary because of its close resemblance to a lymph node. However, besides its high-grade and dense lymphocytic infiltrate, this BC subtype is also characterized also by syncytial architecture and circumscribed margin. This combination is now considered classically to denote a «true» medullary BC, whereas other BCs rich in tumour-infiltrating lymphocytes (TILs) belong mostly to two other categories, atypical medullary BC and BC with medullary features. «True» medullary BC is a rare tumour (comprising less than 0.5% of all BCs), has the «triple-negative» phenotype (ER-, PR-, HER2-) and is TP53-mutated. It has been demonstrated, during the past 10 years, that most medullary BCs or BCs with medullary features are triple negative or HER2+. The triple negative ones frequently arise in patients having a germline BRCA1 mutation [14]. If this mutation is not present, other hereditary mutations may be found, mostly in genes involved in DNA damage repair (DDR) [15]. In addition, such tumours may have numerous other anomalies in the DDR pathway and are said to have «BRCAness», i.e. pathobiological features typical of BCs associated with BRCA1 mutation [16]. The presence of BRCAness is usually assessed by several molecular assays and is demonstrated to be associated with increased tumour sensitivity to DNA-damaging agents like platinum salts and/or to the inhibitors of poly (ADP-ribose) polymerase (PARP) [17–19]. These molecular features influence the therapeutic approach to BC, as tumours with BRCAness can often be successfully treated by neoadjuvant therapies containing DNA-damaging agents, which allows for a reduction tumour burden («downstaging») and subsequent breast conservative surgery. A high number of tumour-infiltrating lymphocytes (TILs) in a BC, the most striking «medullary feature», have been demonstrated in several recent studies to be a powerful prognostic and predictive biomarker in BC [20]; however, at the time of writing this chapter, no clinical decisions regarding BC can be made on the basis of TIL level – they can only be used for selection of patients for clinical studies of neoadjuvant chemo- or immunotherapies.

Inflammatory breast cancer is characterized by tumour infiltration into the dermal lymphatic vessels causing oedema of the skin overlying the breast. This diagnosis is principally clinical, as the «orange peel» breast skin texture (peau d’orange) is observed clinically and can be documented by a skin biopsy [1]. This subtype of BC has a very unfavourable prognosis and is treated initially by neoadjuvant systemic chemotherapy [21] (see ► Chap. 48, locally advanced breast cancer).

Other rare tumour types include desmoid tumours, phyllodes tumour, primary sarcoma and lymphoma (most of which are dealt with elsewhere in this book (► chaps. 46 and 47).