What’s Your Stage?-Notes on biologic factors in the 8th Edition Cancer Staging Manual

Breast cancer illus

Read on as our Director of Education, Martha McCormick, explains the 8th Edition Cancer Staging Manual as it pertains to a breast cancer diagnosis.

A breast cancer diagnosis generates complex feelings, fears and questions. It also brings a whole new language and terminology to learn. The vocabulary of Breast Cancer includes words such as Oncotype, Bilateral, Lymphedema, and acronyms like DCIS, LCIS, HER2, and BRCA. Another word that becomes important is “Stage”. You learn that you don’t just have Breast Cancer. You have Stage 0, I, II, or higher Breast Cancer.

Classification by staging of Breast Cancer began in 1959 and is used worldwide. It classifies as TNM based on size of primary tumor (T), lymph node involve­ment (N), and metastasis to other parts of the body (M). The first Staging Manual for Breast Cancer was published in 1977. It’s purpose was to provide a consistent way for descriptions of particular cancers to be communicated, to assist in treatment decisions and prognosis, and to allow for comparisons.

Today, few would describe their Breast Cancer simply as Stage I, Stage II, etc. They would say “Stage II, Triple Negative” or Stage I, HER2 positive, or Stage I, ER positive, etc. These additional characteristics, known as “biologic factors,” are noted because they are significant for determining treatment and prognosis.

Since the first staging manual was issued, it has been reviewed several times to address scientific and medical progress. The last review in 2010 considered the increasingly utilized biologic factors and prognostic indicators but decided that there was not enough evidence to include them in staging. Years later, in preparation for the 8th edition, it was determined that sufficient research-based evidence existed to warrant inclusion.

Reviewers acknowledged that biologic factors such as grade, hormone receptors, HER2 status and genomic panels have become at least as important as tumor size, lymph node involvement and metastasis in predicting survival. Therefore, in the new edition, adopted in 2018, biologic factors are part of the equation.

So what changes in 2018 and what does not?

The main thing that does not change is that anatomic designations of TNM are still the foundation of the staging framework; indicative that not everyone worldwide has the advantage of genomic testing, tests for hormone receptor status, etc. TNM designation remains an important baseline that can apply anywhere, regardless of the availability of advanced testing and treatment.

The 8th edition classification now incorporates biologic factors as predictors of outcome. These include: Tumor grade, hormone receptor status, and HER2 status; indicators which are known to impact prognosis and treatment options.

Tumor Grade describes the extent to which cancer cells resemble or differ from normal cells in appearance and pro­liferation (how fast they are dividing, growing and dying). Lower grade cancer cells are more similar to normal cells so they proliferate more slowly than higher grade cells, which are less similar to normal cells and proliferate more rapidly. Tumor grade can be an indication of how aggres­sive a particular cancer is and influence how it is treated.

Hormone receptor status indicates the extent to which the individual cancer is affected by Estrogen and Progesterone in the body. Breast cancer that is hormone receptor positive can be treated by therapies that remove or block the hormones. There are different treatment options available for Breast Cancer that is hormone receptor negative.

Another important receptor is the Human Epidermal growth factor Receptor 2 (HER2). HER2 is a protein that promotes growth of cancer cells. Patients who are HER2 positive may have the option of targeted treatments that are often effective; whereas HER2 negative status patients are not eligible for these same treatments. When a negative HER2 status is added to a negative estrogen and a negative proges­terone status, that is considered Triple Negative Breast Cancer, for which there are fewer treatments available currently.

Genomic tests such as the Oncotype DX can be incorporated into evaluation and treatment as appropriate. The Oncotype DX tests Breast Cancer tissue from women whose cancer is estrogen receptor positive. For those estrogen receptor positive cancers of TNM stage 1 - IIIa, the Oncotype DX test can help determine whether chemotherapy would be of benefit and the likelihood of the cancer recurring. For estrogen receptor positive DCIS, stage 0, the test can help determine the likelihood of local (same breast) recurrence and determine the appropriate course of treatment.

Utilization of Genomic Tests, particularly the Oncotype DX, has become increasingly common and evidence as to the value of such tests for managing disease has progressed to the point where results are being factored into guidelines.

Will the staging classification change?

Breast Cancer has been identified as TNM Stage 0 – Stage IV for many years and new classifications will continue to stage breast cancer similarly. However, with the in­corporation of biologic factors to TNM staging, some Breast Cancers could be staged higher or lower. Some cancers, where TNM alone indicates a certain stage, may be upstaged or downstaged based on biologic factors that indicate it is more or less aggressive than others.

It is important to note that it is the classification of the staging that is changed - NOT the treatments. If you were previously a stage IIb you would have received a specific course of treatment based on the TNM factors and on the status of other biologic factors - such as grade, hormone receptor and HER2 status. Treatment with the old staging and the new would likely be identical. Accordingly if you are a long-term survivor, diagnosed and treated before the biologic factors were recognized, your treatment would simply have been based on the what was known and the standard of care at that time.

What if I was diagnosed before 2018 but I am still in treatment? Will my cancer be restaged now?

No, your cancer will not be restaged. The 8th edition goes into practice in 2018. It does not look back.

Could my cancer actually be a higher or lower stage with the new criteria? Does that make a difference?

Some breast cancers might be staged higher or lower in some specific instances. Cancers with certain biologic factors that are known to be more aggressive and/or cur­rently have fewer treatment options such as Triple Negative Breast Cancer may now be staged higher to better reflect the impact of the Triple Negative status. Cancers that might be larger but are hormone positive indicating effective treat­ment options, and/or less aggressive, may be staged lower than previously, also to reflect the impact of those biologic factors and as­sociated treatment options.

If you are told that your Breast Cancer is Stage II, for example, that number itself is less important than understanding why it is that stage and the possible treatment options. Your treatment and prognosis are based on anatomic TNM and known (at the time) biologic factors. That has not changed. Only the staging classification is changed to account for mounting evidence of biologic and other factors on the many variations and progression of this disease. Up until now, the biologic factors have not been classified – just added on as descrip­tors. Now that their impact is recognized as significant in measurable and predictable ways, they are part of the classification and add to its usefulness.

Are there other changes in the Eighth Edition?

There are a number of incremental changes in measure­ments and definitions that reflect ongoing knowledge, evidence and specificity in how the staging system is utilized, and how various breast cancers are treated.

Earlier TNM staging reflected characteristics that could be seen and measured at the time. In recent years, additional characteristics have come to light concerning predictable aggressiveness and response to treatment of different types of breast cancer and these are being factored into the clas­sification when evidence warrants.

-Martha M. McCormick, MS, EdS

Director of Education, To Life!