New Strategies in Breast Cancer: The Significance of Molecular Subtypes in Systemic Adjuvant Treatment for Small T1a,bN0M0 Tumors

摘要

Abstract Awareness of breast cancer heterogeneity has strikingly increased in the past decade in parallel with the development of high-throughput molecular tests. Beyond the clear usefulness of antiestrogen treatment in luminal tumors and trastuzumab in HER2-positive tumors, breast cancer subtypes may have additional clinical and predictive roles that can be relevant to clinical practice. In this article, we discuss the significance of molecular subtypes in the systemic treatment of early-stage breast tumors smaller than 1 cm (T1a,bN0M0) and suggest new strategies for future treatment recommendations for these patients. Background Screening and increased awareness have led to a rise in the detection of T1 breast tumors that are generally estimated to have a low risk of recurrence after loco-regional treatment (1-4). However, even small tumors can have an aggressive behavior. This population suffers from low representation in clinical trials, which leads to a situation where medical oncologists lack high-level evidence that can guide them in the treatment of these patients. Tumor size and nodal involvement remain among the most important clinicopathologic prognostic factors in breast cancer, which puts T1a,bN0 (<1 cm) tumors in a group with a generally low risk of recurrence. Information on T1a,bN0 from large population databases of untreated patients demonstrates relatively low cancer-related mortality rates at 15 years (<10%), with much higher death rates from other causes in women older than 50 years (5, 6). However, it has been shown that about 25% of all relapses of small lobular/ductal cancers occur beyond 10 years (7). High grade, young age, high proliferation, and vascular invasion are considered adverse prognostic signs even among T1a,bN0 tumors, suggesting a potential benefit of more aggressive therapy in women diagnosed with tumors harboring any or all of these features (8-11). Furthermore, the classification of breast cancers into different subtypes (luminal A, luminal B, triple negative, and HER2 positive), appears also to affect prognosis and treatment decisions in such early cases (10,12,13). This classification was first based only on histology features [estrogen receptor (ER), progesterone receptor, and HER2] but later it was shown that the differences are also reflected by the mRNA expression profiles (14,15).