Will 30% of Early Stage (1-IIIA) go on to metastasize??

I was just telling someone in a PM yesterday that I go through periods of obsessing over the numbers, and wanting to nail down my risk to the decimal point. Other times I think what is the point of worrying about an unknown because there's nothing I can do to change it. I'm not speaking for anyone else, but the latter is what I strive for because I think it is the better choice in terms of my mental health.

The kind of studies that really bother me are the ones that suggest my recurrence risk might be different than originally thought, in a way that would have changed my treatment choices if the new information had been available at the time. This was not one of those. It might be relevant to someone with certain stats who chose to forego antihormonal therapy, but if you fall into that category you probably wouldn't have made that choice to begin with.

As BarredOwl has pointed out, the women in the study only took the meds for five years. With many of us expecting to continue for ten years the statistics will change, presumably for the better. It remains to be seen whether some people might benefit from even longer therapy, but the way things stand right now even ten years would be overkill for some women, and not worth the risk of the side effects.

Here is the text of the publicly available abstract, bold and parentheticals added by me:

http://www.nejm.org/doi/full/10.1056/NEJMoa1701830?query=featured_home&#iid=f02

BACKGROUND

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment.

METHODS

In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients' outcomes during the period from 5 to 20 years.

RESULTS

Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status [Tumor Size and Nodal Status]. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively.

CONCLUSIONS

After 5 years [in those assigned to 5 years] of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)

Regarding your MO's estimate, more individualized "recurrence risk" estimates should include information about:

(a) assumptions being made about treatment(s) received (in your case, residual recurrence risk after chemotherapy plus 5 yrs Tam);

(b) nature of "recurrence" risk (e.g., local recurrence? locoregional recurrence? and/or distant recurrence?) (needs clarification)

(c) time-frame (e.g., 5-years from diagnosis? 10-years from diagnosis? other?) (needs clarification).

You can check your notes or ask your oncologist what time-frame he was talking about, and what type of "recurrence" risk he was providing.

If you wish, you can also request a more detailed explanation about how the estimate was derived.

Often (but not always), 5-year or 10-year distant recurrence estimates are provided in connection with treatment decisions regarding chemotherapy, HER2-targeted therapy, and/or an initial five years of endocrine therapy (i.e., risk over years 0 to 5; risk over years 0 to 10).

If a person receives a 10-year distant recurrence risk estimate (residual risk after all treatments), it is quite likely to differ from the paper's reported distant recurrence risks over 20 years (a longer time-frame (twice as long)) or the risk during years 5 to 20 (a longer time-frame (15 years) and a different window of time). So you may be comparing apples and oranges in terms of time-frame.

Estimates received in connection with treatment decisions may also be more tailored to individual disease features and specific treatments than in this study. The treatments received can matter. And other factors may modulate recurrence risk to some extent, such that one's recurrence risk profile may actually be higher or lower than the averages reported for this large and relatively diverse "ER+" group.

Thus, the specific rates reported here may not be the best or most accurate estimates of individual risk, because they did not consider all relevant factors for each estimate, are not segregated by treatments received, some patients did not complete assigned endocrine therapy, and not all participants received treatment in accordance with current standards of care (e.g., particularly for HER2-positive disease). The Discussion notes: "However, long follow-up means that most of the patients received the breast-cancer diagnosis well before 2000. Since then, the prognosis for women in particular TN categories has somewhat improved owing to earlier diagnosis, more accurate tumor staging, and better surgical, radiation, and systemic therapies."

Hope that helps.

BarredOwl

Georgia1, I also experience varying views of statistics from day to day. The [edit: first graph in the] node-negative (N0) Oncotype report provides a 10-year Distant recurrence risk (after 5 yrs Tam), as measured in a group of patients who were all assigned to 5 years Tamoxifen, as you have appreciated.

BBINACT: Please note that the abstract refers in the alternative to: " . . the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively." Those figures are from Figure 4D and are a combined risk estimate, not purely contralateral risk. Specifically, this is a risk of "any breast cancer event", which the paper defined as "the rate of any breast-cancer event (distant recurrence, loco-regional recurrence, or contralateral new primary tumor, regardless of unrelated deaths)".

The paper also comments: " . . the risk of contralateral breast cancer, which continued at a rate of approximately 0.3% per year after the cessation of endocrine therapy, independent of age or TN status."

BarredOwl

[Edited typo in Figure number]

BBINACT..what was your oncotype? Remember that someone diagnosed 20 years ago wouldn’t have had that test. My doctors put a lot of value in that tes

Those numbers for cbc don't apply to those of us with genetic mutations. I have a high risk of cbc thanks to check2. That's why I chose to remove my right, healthy breast.

Statistics statistics.

Someone told me the other day that for the UK population as a whole, the chances of living to be 100 years old are the same for a new born as they are for a 90 year old (apparently it’s about one in 3 in the UK and I’m guessing probably similar in the US).

So if you are a baby born today you have a 2/3 chance of dying in the next 99 years, and a 1/3 chance of not dying before your 100th birthday, but if you are 90 today you have a 2/3 chance of dying in the next 9 years and the same 1/3 chance of making it to 100 as the new born.

But these odds only apply to the population overall. They don’t apply to individuals. I know a few people in their nineties and also some small babies and just knowing them as individuals and knowing their personal circumstances makes you realise that the individual odds on them reaching 100 or not will be different to the 1/3 and 2/3 which applies to the general population. Genetics, nutrition, life choices, existing conditions, general health etc etc will all have the effect of nudging individuals towards the survivors or non-survivors groups in each case

It all depends on how you look at it. We are each in a statistical sample size of 1 after all so looking at the odds overall is a bit limited. Having had a BC diagnosis reduces our odds of reaching 100 significantly which is annoying as I had always planned to die aged 110. I’m 51 now BTW.

Sorry for rambling...

X

BBINACT, for me personally my risk of a new cancer is 29% over 20 years. It doesn't predict recurrence.

I was told by BS the CTC test can cause false positives and false negatives. Didn't know they actually test the cancer cells like in solfeo's case. CTC means circulating tumo cells. It can find cancer eleven months before it shows up in symptoms. There's a study. I brought it to my BS I wanted itfor my occult primary. He said he would take a blood sample at surgery, three surgeries later, no test. I was lied to from the begining. He left the study on the exam room counter, that should have told me his intentions.

Marijen makes a good point. I'm not sure if all labs grow the cells and test the oncogenes. My blood was sent to a specialized lab in Greece, and that is why there was no hope of getting insurance to pay for it.

Was it worth the money? Probably not because it didn't change anything except my level of anxiety about recurrence, but I do like knowing there may be reason for me to continue antihormonals longer than would usually be recommended. I won't take any drugs without good reason, and if not for the CTCs it would have been hard to decide if I should continue the meds for more than five years.

muska - It didn't change my treatment at all in the eyes of the medical doctors. It didn't give the naturopath anything more to do either, because when I went on tamoxifen I had to stop taking most supplements. I did do high dose vitamin C IVs for a year. That wouldn't kill a tumor (regardless of what you may hear) but may have had some effect on the individual CTCs in the blood. Who knows what had already landed because my cancer was missed for so long.

BBINACT - To answer your question about chemo, I did have the chemosensitivity testing as well, of both conventional and natural substances. I know the cells responded well to chemo, but they were also killed by tamoxifen and Vitamin C so I chose that route. Each person would have to weigh the risks and benefits for herself, and most likely without the help of your doctor.

marijen, I'm not sure if you were directing that to me, but maybe I need to clarify. The cells were killed by the vitamin C in the lab. That much I know for sure. IVs are the only way to get blood levels high enough to match the conditions that killed my CTCs in the lab. I did receive high dose Vitamin C IVs for a year to hopefully address the floaters, but that wouldn't kill something that had already found a home. I chose not to test again to see if I still have CTCs, because I feel I have done all I am willing to do about it.

The CTCs were tested for a lot of different substances. It will seem more clear when you look at the report but the website is still down.

I think what you've done so far is OK. You're IA right? With nearly five years of AI You're fine w/o chemo in MHO.

Thanks Solfeo, it’s all good. $800 not too much if anyone thinks they need it, it was helpful for you. I’ll try to find the study I gave to BS

Hi Lisey - I actually had a low level, just barely above the threshold they are able to test. They have a way to grow them in the lab so there are enough to run all of these tests on. There is a paper that explains how they do it, but it is a PDF and I don't think the link will work. I will try but if it isn't clickable try to copy and paste the address.

http://www.atmctx.com/files/8813/9325/1196/14A_REASON_WE_USE_RGCC_cancer_test_2.13.14.pdf