Luminal B Breast Cancer: Molecular Characterization, Clinical Management, and Future Perspectives

Abstract

Gene expression profiling has reshaped our understanding of breast cancer by defining and characterizing four main intrinsic molecular subtypes: human epidermal growth factor receptor 2-enriched, basal-like, luminal A, and luminal B subtypes. Luminal B breast cancer has been reported to have lower expression of hormone receptors, higher expression of proliferation markers, and higher histologic grade than luminal A. It also exhibits worse prognosis and has a distinct profile of response to hormone therapy and chemotherapy. Although luminal cancers share similarities, the studies conducted in recent years using next-generation sequencing technology show that luminal A and B breast cancers should be perceived as distinct entities, with specific oncogenic drivers, rather than more proliferative varieties of luminal tumors. This review discusses the definition and molecular characterization of luminal B breast cancer and presents the available clinical evidence for chemotherapy and endocrine therapy patterns of response. It also provides an overview of ongoing research on molecularly targeted agents for this disease.

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

“…However, molecular studies have shown that luminal B is not simply a more proliferative variant of luminal A, because both luminal A and B cancers have their own specific oncogenic drivers. 80 The IHC definition for this subgroup is less well defined. Originally, ER þ and PR À , 81 or ER þ and HER2 þ , 82 was used, but later most investigators used ER þ and HER2 À to describe this subtype if the score of Ki-67 was 14% or higher, 25,52 or higher than 20%.…”

Predictive and prognostic significance of CD8+ tumor-infiltrating lymphocytes in patients with luminal B/HER 2 negative breast cancer treated with neoadjuvant chemotherapy

“…Overall, the results of the present study may have important clinical implications. Considering the prognosis of luminal B/HER 2-negative cancer and the various profiles of hormonal and chemotherapy sensitivity, immunobiological stratification according to the expression of CD8 + TILs may improve the management of these patients (4,6). In addition, this type of immunological profiling may represent the first step towards a more improved understanding of the potential function of antitumor immune responses in mediating the clinical outcome of NC.…”

“…It has been reported that luminal B BC exhibits a lower expression of hormone receptors, higher expression of proliferation markers and higher histologic grade compared with luminal A cancer (3,5). Furthermore, patients with luminal B cancer exhibit worse prognosis and have a distinct profile of response to hormonal and chemotherapy (4), and numerous efforts have been made to improve survival rates through early diagnosis and multiple therapies (6). However, the limitations of the current therapeutic modalities and advances in molecular diagnostics have resulted in increasing requirements for defining novel prognostic and predictive tools (7).…”

“…Breast cancer (BC) is the most common type of female malignancy in Saudi Arabia with evidence of an increased annual incidence from 23.5 cases/100,000 people in 2000 to 34.5 cases/100,000 people in 2010 (1,2 Although the luminal types of cancer share similarities, previously conducted studies using next-generation sequencing technology have revealed that luminal A and B BC should be perceived as distinct subtypes, with specific oncogenic drivers, rather than more proliferative varieties of the luminal tumor subtype (4). It has been reported that luminal B BC exhibits a lower expression of hormone receptors, higher expression of proliferation markers and higher histologic grade compared with luminal A cancer (3,5).…”

“…Few studies have addressed the predictive and/or prognostic significance of CD8 + TIL in patients with the luminal subtypes of BC (3,4,19,20).…”