Comment

Despite recent advances in breast cancer research, we still know little about the mechanisms that lead to metastatic breast cancer (MBC). However, treatment options for patients have increased based on results of recent randomized clinical trials in this setting. Today we have much hope, yet many questions remain unanswered. Conducting a fully academic and international study such as AURORA is very challenging, yet ever more crucial to advancing knowledge about MBC.

The combination of an endocrine agent with a CDK4/6 inhibitor is the standard of care in the first-line setting for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Randomized trials have demonstrated similar and significant improvements in progression-free survival using the three available CDK4/6 inhibitors and led to regulatory approval. However, mature overall survival data now suggest potential differences among the various agents, suggesting an evolution in selection preferences.

Multigenic tests represent an essential tool for the selection of adjuvant therapy in estrogen-positive/HER2-negative (ER + /HER2-) early breast cancer (BC). The workflow of these tests, either if they are externalized or carried out in-house, generates a workload for the pathology laboratories, that is often underestimated and may affect timely therapy initiation. Here, we describe the evolving role of pathology laboratories in using multigenic tests and, more in general, in providing adequate tissue for molecular analyses. Moreover, we propose a “reflex testing” model, in which pathologists, based on pre-specified and shared criteria, are expected to action multigene testing independently of multidisciplinary team discussion in ER + /HER2- BC patients, in order to optimize turnaround time and proper therapy intervention.

In the setting where the ongoing evolution of management of the axilla in breast cancer is being driven by better understanding of different sub-types of the disease, and of how these respond to chemotherapy, here we discuss management of the axilla in breast cancer patients who present with T1 or T2 N1 disease, while making the distinction between triple negative and HER2 positive tumors as one group, and hormone receptor positive/HER2 negative tumors as a second group.

PARP inhibitors have been approved for the treatment of metastatic breast cancer in germline BRCA mutation (gBRCAm) carriers. The recent OlympiA trial demonstrated improved progression-free and distant disease-free survival with adjuvant olaparib for gBRCAm carriers with HER2-negative high-risk early-stage breast cancer. The current article addresses some for the questions raised by OlympiA regarding how to incorporate PARP inhibitors into the treatment of early-stage breast cancer as well as future directions for PARP inhibitors in breast cancer treatment and prevention.

In recent years, several trials of breast cancer treatment have failed to demonstrate a survival benefit for some previously routine surgical therapies in selected patient groups. As each of these therapeutic approaches has been deemed of low value deimplementation has varied significantly. This demonstrates that effective de-escalation in breast cancer surgery relies on more than the availability of data from randomized controlled trials and other high-quality evidence, but is also influenced by various stakeholders, social expectations, and environmental contexts.

FANCM protein truncating variants (PTVs) are emerging as risk factors for ER-negative and triple negative breast cancer. Here, we discuss evidence that greatest risk associates with PTVs, such as p.Arg658*, that extensively truncate the 2048 amino acid FANCM protein. Moreover, risks associated with other less-truncating FANCM PTVs such as p.Gln1701* and p.Gly1906Alafs12* may be amplified by additional gene variants acting as modifiers. Further studies need to be conducted taking into considerations these aspects.

In the global health emergency caused by the COVID-19, clinical trial management has proven to be critical for the pharmaceutical industry, sponsors, and healthcare professionals. Our experience as a sponsor managing interventional oncology clinical studies has provided us with some data and insights. Though limited by sample size, our data emphasize the importance of quickly adopting measures that first prioritize patient safety and data validity, then consider contingency measures such as telemedicine, virtual medical review, and remote monitoring. Successful adaptations of healthcare and patient management in response to COVID-19 have been fundamental to ensuring continuing clinical cancer research.