by Luana DeAngelis, YCT Founder
Recently I attended San Antonio breast cancer symposium as a patient advocate, and the session titled “Treatment on the Edges: Discordance Between Stage and Biology” was standing room only! Literally, the entire back of the room was packed and people were sitting in the isles to hear what was being said about pathological discordance and treatment variables. I got the feeling that this was a very important session to attend and reporting on it was essential.
As a patient advocate I work with survivors to help them ask the right questions and understand their treatment choices. Navigating pathology especially with breast cancer is quite tricky, even for doctors. For all of us, helping patients to understand why their doctor is recommending treatments that can be very harsh is so important.
In this session two doctors discussed this topic using the Bad stage, good biology vs. Low stage, bad biology. The first doctor spoke of how to avoid overtreatment of large cancers that will not be affected by chemotherapy, and the second spoke about guidelines for small tumors and the use of chemotherapy in these cases.
With concordant pathology stage is bad, risk levels are high and biology is adverse, so standard chemotherapy is automatically given. In these cases, it is apparent that a tumor needs systemic treatment like chemotherapy, but in other cases not so much. This discussion was about what to do in the other cases.
What should drive decisions when high staging co-exists with good biology?? Or low staging co-exists with bad biology? This is called discordance, and it’s the biggest issue for breast cancer doctors.
Two doctors took us step by step through their reasoning and the literature, which they base their treatment decisions on. Though statistics on people who do not take treatment are no longer kept, the session was opened with an old but well-annotated University of Chicago database on surgery alone and no systemic therapy. It was concluded that many patients live a normal life expectancy free of recurrence after surgical treatment alone. But how do doctors identify these patients?
In following surgery alone patients up to 30 years and beyond breast cancer survival plateaus at about 20 years, with only 1.3% of recurrences after that point. Even in the large tumors without treatment there is a plateau, at least 20-25% will survive long term free of recurrence even without adjuvant treatment. Who are the patients that are probably cured without systemic therapy? Who needs it? That is the question! We cannot yet reliably identify these people despite all of our advances. However we are taking big steps.
Genomic assays like Oncotype and Mammoprint show a definitive correlation between recurrence scores and long-term outcomes when following patients. The studies on these genomic tumor pathology tests were conclusive that they are very important in predicting effectiveness of treatment and how people will fare long term. It can be beneficial to have these tests for people who fit into the category of being eligible, if you’re going to use the information. However, there are a group of tumors that need creative treatment and have higher risk even when they sit in a ‘lower recurrence score’ category.
The problem with gene assays is that they are not always concordant with estrogen receptor scores, usually with a very high estrogen score it is thought a better treatment option is endocrine suppressors, but then a genetic assay may come back with a high recurrence score. Or you could have a tiny tumor that formerly wouldn’t need additional treatment, and you get back a high recurrence score. In these cases looking at additional factors is necessary.
People diagnosed young 35 or less, always seem to fare worse long term and for those patients chemo is always recommended. If a tumor has the molecular subtype pure luminal A and estrogen is the dominant pathway with a low proliferation grade, chemotherapy is relatively ineffective (but the reverse is true in triple negative or Basil like groups). In luminal B tumors there are not a lot of guidelines. Luminal B tumors are estrogen driven and often high-grade, these biological subtypes often differ in their degree of sensitivity to chemotherapy. Therein lies the rub! In these cases the avoidance of chemo may be justified if they are HER2 negative with a low proliferation rate by a 21 gene assay recurrence score.
Doctors also look at a slew of other factors to help them decide, and the other indicators with significant relevance right now are: HER2+ is an independent prognostic indicator as well as High Ki67 from hospital pathology. Additionally, the presence of vascular invasion or lymphatic invasion is important, though it occurs in only roughly 5% of tumors. A good pathologist is pertinent, because the risk of death is doubled in these cases, doctors look at this factor independently of recurrence scores.
Only the Oncotype test has been prospectively validated thus far. It seems that low risk patients treated with endocrine therapy alone do extremely well –those with a low recurrence score did better on tamoxafen or other estrogen suppressor alone. Chemo had no advantages vs. no systemic therapy in these groups. The grade of the tumor was most predictive of negative outcomes thus far, and that never changed in its significance, whereas ER positive or negative status can lose its significance.
We’ve discovered in breast cancer research and advances in the past few years that genetics trumps staging, and doctors struggle in daily practice to decide when a small cancer looks bad enough to consider additional systemic treatment.
Because even in small tumors we can see adverse biology, assessing the ‘acceptable’ risks is always an important issue for doctors and patients. Oncotype and Mammoprint capture proliferation and give important information for hormone positive cancers.
In small cancers 40% will have an intermediate or high recurrence score, previously these would not be treated. 25% of these small cancers have a high genomic risk, but only 7% are considered high risk by our previously standard assessment tool adjuvant online.
In the presence of low recurrence scores patients will do very well, but for the other small cancers the risk of death in ten years can be as high as 10.5% and that seems to be a good threshold for considering systemic treatment.
International meetings like San Antonio Breast Cancer Symposium help doctors put together all the data and advance their clinical practice so that they can know more succinctly when to treat or discuss treatment with their patients in the face of such a complex and compelling disease. Once the breast cancer community can agree on what exactly is adverse biology, perhaps new standards will be instituted to make these decisions less trying on the doctors and the patients.