Early Is As Early Does

What is “early breast cancer?”  By convention, most clinicians use the term to describe breast cancer diagnosed at an early stage, usually Stage 0-II.  However, some would argue that Stage II is not particularly “early.”  Our goal in screening is to minimize the number of Stage II, III, and IV cancers while maximizing Stage I (Stage 0 in situ disease is a more controversial goal).  Stage I breast cancers are “invasive” tumors that are smaller than 2.0cm with lymph nodes negative.

“Early diagnosis” implies early-stage, but has other implications as well.  The ubiquitous statement that “early diagnosis is the key” implies that a screening intervention, be it a focused self-exam or a radiologic image, can detect a tumor earlier than what would have occurred naturally when a lump becomes obvious.  And this is where things get murky.  What does “early” mean, and with it, what does “earlier” mean?

Certainly, “early” does NOT mean early by the calendar.  In fact, it can be argued that the duration of a cancer residing in the breast prior to diagnosis is inversely proportional to its aggressiveness.  A slow-growing tumor that is late to spread might be existing in the breast for many years, while a very aggressive tumor can appear within a few months of a normal mammogram. Better to have the breast cancer that’s been sitting silently for years with very slow growth than the one that pops up this quickly.

So, if it’s not the calendar that marks “early,” what is it?  While tumor size is an important indicator of “early,” and thus predictive of curability, there is another component — biology.  Each tumor has its own set of built-in instructions that are not evident through the traditional staging system.  Eventually, we will abandon the current system of anatomic staging (and perhaps even the organ where cancer arose) and tumors will be described by this internal system of instruction, based on the genetics and biology of the tumor cells as well as how these instructions interact with the host.  Therapies will be designed accordingly, and we will no longer be discussing “early stage” disease.

In the meantime, however, tumor size and its biology go hand-in-hand, with biology already dictating whether or not “early diagnosis” (through screening) does any good.  For screening to work, the intervention must reliably find cancer earlier than what would occur naturally, but that’s not all — the biology must be vulnerable.  Oddly, the most aggressive cancers might not be vulnerable to early detection, having disseminated lethal cells throughout the body from the git-go.  On the other hand, some cancers grow so slowly that early detection might look good on paper, but the cancer would still have been eradicated successfully if the patient had waited until the lump became palpable.

Critics of breast cancer screening, in fact, claim that those are the only two types of biology — 1) systemic early on, prior to early detection through screening, and 2) localized to the breast and cured without screening.  Most of us, however, believe that breast cancer has a wide spectrum of different biologies, and that some breast cancers are vulnerable to early detection a la Goldilocks — not too hot and not too cold — but just right, such that early detection identifies tumors that are local at the point in time when screening occurs, but left to their own devices, would have later become systemic.

And while the lay public might think this “Goldilocks biology” is true for ALL breast cancers, in fact, using mathematical models beyond the scope here, one can easily show that this vulnerable biology is driving only a MINORITY of breast cancers.  Otherwise, four decades of mammographic screening would have had a stronger impact on breast cancer deaths overall.  Still, we screen to capture this vulnerable group of breast cancers.

So, do we need “earlier” detection?  Probably not.  We already have the tools to find breast cancer at 5mm (0.5cm), or “early Stage I,” which should translate to a 95% cure rate. But this cannot be done in most patients with mammograms alone.  What we desperately need is more reliable detection — identifying the cancers that are currently being missed by mammography.

It is unsettling to think that these critical tools to help mammography are sitting idle most of the time – screening ultrasound, MRI and molecular imaging. Cost and feasibility are prohibiting widespread application of these tools that, together, could lower breast cancer mortality to a greater degree than mammography. Strange – for once, we don’t need more R&D or any technologic “breakthroughs” – we need to figure out a way to make these tools cost-effective.

My proposal since 1993 has been the development of an intermediate, inexpensive screening tool to be used post-mammography, identifying patients who need a second form of imaging in spite of a negative mammogram. For a detailed look at progress in this area, I encourage you to read my book on mammographic screening, detailed elsewhere on this web site. There, I offer the history of mammography, how it got to the point of such intense controversy, and how we can revolutionize screening so that a Stage II, III or IV diagnosis is a rarity.