the value of ki67, mitotic rates, and stages in relation to MBC

I’m curious about this too. My ki67 went up from first diagnosis. From 60’s to 70’s. I felt like I could feel the cancer growing the second time.

42young as to the relationship between ki67 and Oncotype - there are several studies that show a direct linear correlation between ki67 and Oncotype score, here is one https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241562/

My oncologist's office mistakenly ordered OncotypeDX report for me (I was Stage IV de novo so a recurrence score was useless) and my score was 89, so there was definitely correlation for me with both scores super high.

Candy my research has been mainly focused on the Luminal B aspect of high ki67, and specifically my combination of PR-/HER2+ and high ki67, which would be different than your ER+/PR+/HER2-. It is a factor in Luminal B treatment and prognosis - for example even though we are ER+, if we are also PR- and HER2+ we don't typically respond to hormonal therapy and there are a few of us here who have never been prescribed hormonal/endocrine therapy for that reason. And although we typically respond better than Luminal A to chemo, we actually don't respond as well as HER2+ and TN do.

You'll find extensive research on treatments and prognosis by looking at the Luminal B molecular sub-type, but I'm not sure how much you'll find specifically on the combination of ER+/PR+/HER2- with high ki67 because that is a less common combination. You would be Luminal A except for your high ki67. You might fall into one of those gray areas.

Candy I've done so much research on the topic that I feel like I could probably write a book at this point haha! I have been dealing with some de novo resistance to different lines of treatment so I've been trying to understand why (likely a combination of some of it due to being strongly Luminal B and some because IBC is often inherently resistant to treatment - like I said, I got hit with the triple whammy as far as aggressiveness and resistance).

Yes, typically someone who is ER+ PR+ HER2- would also have a low ki67 or other measure of proliferation, which is Luminal A. That's an indolent, slower-growing cancer that usually responds well to hormonal treatment for a few years. Most (but not all) Luminal B's are PR-, and often have low ER,. But it's the high grade, high ki67, high number of nodes involved, sometimes a specific gene expression if the PAM50 model is used, that determines Luminal B vs A, not just the IHC. But I should mention that not everyone is using the same definition (what I've stated is what is most commonly used), and I could definitely write a book on that topic. One example - some researchers think that all HER2+ should be classified as Luminal B because it's more aggressive by nature, even if it doesn't have high proliferation score. Other researchers think all HER2+ should be classified as HER2-Enriched just because the treatment is different. So the first thing you need to check when researching is what definition is being used.

This might help - they are starting to further define the molecular subtypes and some studies refer to LumB1 as ER+/HER2-.Ki67+ and LumB2 as ER+/HER2+, so in that case you would be Luminal B1 and I would be Luminal B2.

The whole field of molecular subtyping is fairly new and constantly undergoing change as they learn more. Originally it was proposed that 14 be used as the cutoff for determining a "high" ki67, then it was adjusted to 20 as they noticed a difference in how the cancer behaved, and more recently I've seen 25 used as the value.

Candy, our tumors are so heterogenous that it is possible that different tumors or parts of tumors could have different levels of cell proliferation. I have dormant lesions in my liver but also active ones. Some of the dormant lesions have been asleep for years. I have never had an inactive tumor biopsied but would suspect that the proliferation rate would look quite different than my active tumors.

As far as future progressions and biopsies go, my thought is that you would gain more value using your biopsy sample for a genetic panel (such as Foundation One or Caris), which will show you actionable mutations, alterations or amplifications of various genes and indicate which drugs are linked to those actionable items. Often there is not enough sample to do all the underlying tests one may want performed. If you know from the outset your cancer is aggressive, it will continue to be treated as aggressive cancer for the most part. A variance in Ki score at this point will probably not have much if any bearing on your treatment plan.

Although the prognosis is better for Luminal A, there are other factors that go into your prognosis - overall health, quality of your care, age, treatments and the need or preference to take breaks from treatments, desire to live, etc. I don't recall specific stats offhand but when I have looked into them in the past, I was surprised as to how close the survival rates were between the two groups over certain periods of time - I recall seeing a 5-8% difference or something relatively small like that. And the difference may not be as meaningful once one crosses the Stage 4 threshold than it would be at looking into the likelihood of progression for someone who is early stage and Luminal A v. Luminal B. The more aggressive cancers tend to respond to treatment better than slower growing cancers as many treatments target fast growing cells so there is some benefit to having an aggressive cancer. It is not all bad news for Luminal B.

As we all know, a lot of this is a crap shoot and statistics do not matter for any one individual who may respond differently than others of the same profile. Statistically, I shouldn't have been diagnosed at 30 and then with mets at 38. The likelihood is a fraction of a %. On the flip side, I was a few weeks away from death when diagnosed with mets in 2014. I was diagnosed due to uncontrollable hypercalcemia and had to be hospitalized for that. I had mets in essentially all of my bones as well as a liver full of mets. Hypercalcemia is an indicator of late stage breast cancer and has a "grave" prognosis, with most patients living no more than several months. However, I am still kicking over 4.5 years later. Don't get too caught up in the stats.

I'll echo everything JFL said, the answer isn't as simple as you'd like it to be. You could be Lum B but if you're strongly ER+ instead of only weakly positive, you might get years on hormone/endocrine treatment. If you're HER2+ you could get years on targeted therapy. There are so many different factors that play into it. At least most of us have some decent treatments available, unlike TN which is also aggressive but doesn't yet have any specific treatment for their subtype. It really depends on how your cancer specifically respond to treatments and there's still so much that they are learning.

Ignore the stats. When I was first diagnosed, my doctor gave a prognosis of 60 days because it was spreading so fast, and he told my husband to call my family in. I'm still here 22 months later. The median OS for Stage IV de novo IBC is still only 21 months, and I beat that too even though I've been struggling with resistance problems . Just focus on living. Keep your body as strong and healthy as possible so it's in good shape to handle treatment. Don't worry about the possible problems unless and until they become a reality.

What it DOES mean for me, because it has been documented several times that my cancer spreads almost right before their eyes (again probably the combination of being IBC and high proliferation score), is that my doctors don't waste any time if I have any symptoms so they can jump on it as quickly possible. My scan and biopsy requests are always marked stat (we only scan when I have symptoms), they usually fit me in for scan/biopsy the next day at the latest and the report is sitting on my doctor's desk via courier by the next morning at the latest. Example Monday at my infusion I casually mentioned that I had been having headaches for a month and wasn't sure if I should be worried, and Tuesday morning they had me in for brain scan. It's kinda nice in a way because I never have to wait long for anything, even though the reason for it is a little scary. But again, that's based on how fast mine has spread every time in the past, not just the numbers.