Rare breast cancer subtypes: histological, molecular, and clinical peculiarities

Abstract

Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good-prognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poor-prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies.

Keywords: Cribriform carcinoma; Medullary carcinoma; Metaplastic carcinoma; Mucinous carcinoma; Pleomorphic lobular cancer; Tubular carcinoma.

Figure 1.

Histological special types of breast cancer. (A): Mucinous carcinoma. (B): Tubular carcinoma. (C): Adenoid cystic carcinoma. (D): Cribriform carcinoma. (E): Medullary carcinoma. (F): Apocrine carcinoma. (G): Lobular pleomorphic carcinoma. (H): Micropapillary carcinoma. (I): Metaplastic spindle cell carcinoma.

Figure 2.

Heterogeneity of breast cancer: histotypes, molecular classification, and immunohistochemical classification. Abbreviations: ER, estrogen receptor; HER2, human epidermal growth factor receptor 2.