here is an “expert commentary“ on the above paper from Practice Update. Dr. Anderson makes the point I’ve been thinking about in regards to HER-2 positive BC...QUOTE “In the era prior to trastuzumab, a tumor being HER2/neu-positive was simply bad news for the patient.“

And that included early stage cases, too. The ONLY reason we HER2++ people are showing up in the “better” prognostic groups in this study is because effective treatment was found. Just underscores what we already know...research is needed, better treatments are needed. And, hopefully , this staging system could play a part too, especially in exploring the non-drug approaches and making doctors more willing to consider them for us.

https://www.practiceupdate.com/C/104220/56?elsca1=emc_enews_topic-alert

Written by Benjamin O. Anderson MD, FACS

The TNM classification for staging cancer was developed in the 1940s by Prof. Pierre Denoix at the Institute Gustave Roussy.1 The purpose of cancer staging systems is to accurately and concisely summarize the extent of disease and its related prognosis to facilitate communication between providers and patients to enable individualized treatment decisions.2In the early 20th century, treatment options were limited, especially in relation to systemic therapies, making anatomic staging based on the extent of disease the overriding factor predicting cancer prognosis. Today, drug treatment has revolutionized cancer outcomes, calling into question the value of anatomic staging based on tumor size and nodal status. The most recent 8th edition of the AJCC Cancer Staging Manual created a new "prognostic staging" scheme for breast cancer that, in addition to tumor size and nodal status, adjusts for biologic features (hormone receptor status, HER2/neu oncogene expression, tumor grade) as they are related to predicted drug response.3

Stage IV cancer characterized by distant metastatic disease historically was considered invariably fatal, making subdivision of this staging group of limited utility as treatment with curative intent would be highly improbable to change the invariably poor outcome that distant metastatic disease predicted. Today, the situation is evolving as modern therapies demonstrate favorable outcomes that in the past were only seen in anecdotal cases. For example, the CLEOPATRA trial showed significant improvement in overall survival with pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer, compared with placebo, trastuzumab, and docetaxel.4 These highly favorable outcomes due to the development of HER2-targeted therapies speak to the need to refine stage IV cancer staging as the line between nonmetastatic and metastatic breast cancer is becoming increasingly blurred.

Plichta and colleagues performed a technically superior analysis of patients from the National Cancer Database who presented with de novo metastatic breast cancer. These investigators were able to subdivide de novo stage IV breast cancer into three subgroups (IVA, IVB, IVC) based on tumor biology and extent of metastatic disease.5 To advance this level of refinement is entirely logical and in alignment with the original purpose of the TNM staging system as conceived by Denoix 80 years ago. At the same time, it should be noted that what has changed is not the biology of breast cancer but the therapies that are available to treat it. Prognostic staging is only relevant when patients have access to and receive the treatments that permit the favorable results seen today. In the era prior to trastuzumab, a tumor being HER2/neu-positive was simply bad news for the patient. When these new highly effective treatments are unavailable or inaccessible due to healthcare disparities, the novel modifications in cancer staging serve to amplify the healthcare inequities that sadly continue to live with us in the 21st century.