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

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  • ShetlandPony
    ShetlandPony Member Posts: 3,063
    edited October 2017
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    Exercise guru, you are already much better-informed than most people. Thank you!

  • exbrnxgrl
    exbrnxgrl Member Posts: 4,950
    edited October 2017
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    "What statistics do not do is provide the crystal ball that tells an individual her or his outcome."

    Shetland pony,

    So very true, yet many continue to view stats as prognostic, or even as some sort of individual ball, as you put it. When their outcome doesn't match what they believe the stats predicted, they become angry. They seem to feel as if the "promise" of a desired outcome was broken. Statistics are good, for the reasons you noted, but are a promise of nothing


  • TWills
    TWills Member Posts: 509
    edited October 2017
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    I read an article about Mindy Cohn too, the article concluded by saying she was now "cancer free". What? I'm so confused. It said after BMX, chemo, and rads it "metastasized and spread". I'm still trying to figure out all of the different terms involved with BC but cancer free seems misleading. Did they mean NED maybe??

  • lisey
    lisey Member Posts: 300
    edited November 2017
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    A new study was just published that sheds a much better light on ER+ recurrance rates

    http://www.breastcancer.org/research-news/distant-recurrence-risk-steady-20-years-later

  • Lucy55
    Lucy55 Member Posts: 2,703
    edited November 2017
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    Lisey ..yes it does ..thanks for posting it .

  • nkb
    nkb Member Posts: 1,561
    edited November 2017
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    Another risk predictor that only goes up to 9 positive lymph nodes-those of us with ILC often have far more than that and are often bilateral at diagnosis.

  • Momine
    Momine Member Posts: 2,845
    edited November 2017
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    That study shows that we are not nuts, but I hope it also makes those DXed with early stage disease feel a little better. The risk is not 30% across the board. Those DXed with stage 1, small tumors, few or no nodes have much better odds than those of us with large tumors and many nodes.

    This study also strengthens my dislike of all the pink survivor rah-rah.

  • marijen
    marijen Member Posts: 2,181
    edited November 2017
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    Would anyone like to give their guess on IDC T0 N1? Occult primary never found so it must have been very small? I’m guessing I’m in the T1N1 category but ...

  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    The purpose of the study shapes the disease characteristics of the patients included in the study. Here is the purpose of this particular study (Pan (2017)):

    "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."

    This was a study of certain patients with "early stage (invasive) breast cancer," which in general refers to Stage IA, IB, IIA, IIB, and IIIA disease, but may or may not include all such patients depending on the inclusion and exclusion criteria of the particular study (see below re exclusion of certain patients with Stage IIIA disease in this study and the inclusion of those with ER+ disease only). Some subset of early stage breast cancer patients have a distant recurrence risk profile that may not warrant extended endocrine therapy (i.e., beyond an initial five years). In contrast, those with more than nine positive axillary nodes would have pN3 disease, which is Stage IIIC disease, with a distant recurrence risk profile that more clearly warrants extended endocrine therapy.

    The patient population in Pan (2017) had specific characteristics in terms of disease and treatments received:

    (1) All of the patients had "ER-positive [invasive] breast cancer".

    (2) "All the patients were scheduled to receive endocrine therapy for 5 years then stop. . ."

    (3) Of the 62,923 women included in the assessment in later years, all "were disease-free after 5 years of scheduled endocrine therapy."

    (4) Some older patients and certain patients with Stage IIIA or later stage disease were excluded:

    "After the exclusion of patients who were 75 years of age or older at the time of diagnosis, those who had a tumor diameter of more than 5.0 cm, those who had more than 9 involved lymph nodes, and those with missing data with respect to age or TN status, a total of 74,194 women (in 78 trials) had entered a study at the time of diagnosis and were included in analyses that began at year 0. We included an additional 10,200 women who had entered the study later (at 2, 3, or 5 years) only in analyses that began at year 5, for a total of 62,923 women in 88 trials who were still being followed at 5 years without recurrence or a second cancer."

    Put another way:

    "We analyzed data from women who had ER-positive breast cancer that had been diagnosed before the age of 75 years and who had T1 disease (tumor diameter, ≤2.0 cm) or T2 disease (tumor diameter, >2.0 to 5.0 cm), fewer than 10 involved nodes (stratified according to a patho-logical nodal status of no nodes [N0], 1 to 3 nodes [N1–3], or 4 to 9 nodes [N4–9]), and no distant metastases. All the patients were scheduled to receive endocrine therapy for 5 years then stop, regardless of actual adherence."

    Note that the exclusion of those with "a tumor diameter of more than 5.0 cm" operates to exclude those with T3 disease (T3 = Tumor greater than 5 cm in largest dimension). Thus, although Stage IIIA includes those with T3 N1 M0 disease or with T3 N2 M0 disease, these particular Stage IIIA patients were excluded from this study.

    BarredOwl

  • muska
    muska Member Posts: 224
    edited November 2017
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    Please note the study results only apply to those who stayed on endocrine therapy for five years. So if you are not on endocrine therapy or stopped it before the five year mark they are not applicable to your case.

  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    I agree that the specific recurrence rates measured in this study do not apply those who do not receive any endocrine therapy, (although I suspect general trends regarding increased risk with tumor size and nodal status would hold). The situation of a person who receives no endocrine therapy and that of a person who receives five years of endocrine therapy and then stops are NOT the same after five years. This is because five years of endocrine therapy has a trailing benefit in later years: "In trials of 5 years of tamoxifen therapy versus no endocrine therapy, the recurrence rate in the tamoxifen group was approximately 50% lower than that in the control group during the first 5 years (the treatment period) and approximately 30% lower during the next 5 years."

    On the other hand, while all patients were assigned to receive five years of endocrine therapy and then stop, not all of the patients actually adhered to their assigned therapy. Here are some additional observations that I posted elsewhere:

    Pan published preliminary results based on a subset of patients (46,138 patients) in a 2016 meeting abstract, per an earlier post of mine.

    A few differences between this study (Pan (2017)) and others come to mind. Prior studies with long-term follow-up, such as Colleoni (2016) were much smaller as compared with this study (Pan (2017)). For example, there were 4,105 patients in Colleoni (2016). In contrast, Pan (2017) included 74,194 women entered at year 0 plus 10,200 added later, with a total of 62,923 patients who were event-free and followed at year 5. Pan notes, "Although a persisting recurrence risk among women with ER-positive breast cancer is well recognized,[13-17,34] our study quantifies the 20-year risk more reliably than previous studies, since it is large and has long follow-up."

    Colleoni (2016) included patients with ER+ or ER- disease, so the patient population was more diverse in hormone receptor status. In Pan (2017), all patients were ER+.

    Another difference is that none of the patients in Colleoni received modern endocrine therapy regimens. Per the accompanying commentary to Colleoni, the regimens would have been one (1) year of tamoxifen with or without prednisone (no longer in use). In contrast, in Pan (2017), patients were enrolled in various EBCCTG clinical trials and were assigned to receive 5 years of endocrine therapy (Tamoxifen, an aromatase inhibitor, or switch regimens). It looks like around 65% of patients received Tamoxifen in Pan (2017).

    [As noted above] re Pan (2017), although trial participants were assigned to five years of endocrine therapy, some may have discontinued treatment early. Pan notes, "All the patients were scheduled to receive endocrine therapy for 5 years then stop, regardless of actual adherence. Most of the patients entered the study at the time of diagnosis, but some entered later, having already received 2 to 5 years of endocrine therapy, but were scheduled to stop therapy at 5 years."

    Regarding adherence, they note: "First, the recurrence rates reported here are in women who were scheduled to receive 5 years of endocrine therapy, not in those who completed treatment. Only a few of the trials in our study provided detailed data with respect to adherence, but a substantial minority of women in trials of 5-year endocrine therapy did not complete their treatment. [Reference 2]" I note that it has been suggested elsewhere that clinical trial participants differ from the general population, in that the former may have increased motivation to adhere to assigned therapy in view of their role as trial participants, receipt of trial support, and reduced treatment costs.

    Pan (2017) includes assessment of the association of various factors with distant recurrence during the first five years and beyond. The factors assessed in Pan (2017) included tumor diameter and nodal status, as well as age, grade, Ki-67, PR status, and HER2 status (although "only 2% of the women in our study received trastuzumab")

    Regarding the particular recurrence rates, keep in mind: "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."

    BarredOwl

    ---------

    Note: "Approximately three quarters of those with node-positive disease had undergone chemotherapy."

  • muska
    muska Member Posts: 224
    edited November 2017
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    Thank you, BarredOwl.

    Speaking of general trends maybe you can clarify for those of us who have little training in statistics what the below risks translate into for an average BC ER+ woman diagnosed at 50? I think I read somewhere every year adds 1 or 1.5% to the risk. As per the below table if she has 41% risk of distant recurrence at 70 years old, what age would this risk reach 75% and 90%? I understand that data is not there but assuming the trend holds after 20 years...

    Cumulative risk of distant recurrence at 20 years was:

    • 13% for T1 cancer with zero positive lymph nodes
    • 20% for T1 cancer with one to three positive lymph nodes
    • 34% for T1 cancer with four to nine positive lymph nodes
    • 19% for T2 cancer with zero positive lymph nodes
    • 26% for T2 cancer with one to three positive lymph nodes
    • 41% for T2 cancer with four to nine positive lymph nodes


  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    I have no training in statistics either. :)

    By the way, I think that you have misstated the conclusion above. Those are not the cumulative rates at 20 years (from year 0 to 20), but are the cumulative rate over years 5 to 20 among those who were disease-free after five years per Pan: "However, even among women with T1N0 disease, the cumulative risk of distant recurrence was 13% during years 5 to 20." The graph is at zero starting at year 5.

    As you note, they didn't measure beyond 20 years, and I don't think it is appropriate to assume that the rates remain constant forever. In fact, some of the annual distant recurrence rates do not appear to be constant over years 5 to 20.

    The ~1% to ~1.5% annual distant recurrence rate applies to the node-negative patients only (T1, N0 and T2, N0) and specifically for years 5-20 in whom the annual distant recurrence rates in five year increments were:

    T1, N0: 0.8%; 1%; 1%.

    T2, N0: 1.6%; 1.4%; 1.3%.

    Compare:

    T1, N4-9: 3.2%; 2.6%; 2.2%.

    T2, N4-9: 4.5%; 3.3%; 1.7%.

    My layperson impression would be that the annual distant recurrence rate is already falling off somewhat over time in some groups.

    Note also data in the Supplemental Appendix showing that recurrence rates appear to vary according to age at diagnosis. Thus, extrapolating from rates determined in a group as a whole based solely on TN status to a person of a specific age may not be appropriate.

    Lastly, for those who received tests such as the Oncotype test or MammaPrint test, certain test results would indicate that a person may have a lower than average risk (or higher than average risk) than that based on TN status alone.

    BarredOwl

  • marijen
    marijen Member Posts: 2,181
    edited November 2017
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    Thank you BarredOwl for all your analysis.


  • Artista964
    Artista964 Member Posts: 376
    edited November 2017
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    Grade 3 responds best to chemo is what I was told.

  • lisey
    lisey Member Posts: 300
    edited November 2017
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    BB, I was 41 when diagnosed and a T1, low PR, with an Oncotype of 20. grade 2, with 30% Ki. I was told not to do chemo, but they left it my choice. I then did the mammaprint as a second opinion and it said 'low risk, luminal A" so no chemo.

    Grade has nothing to do with size, only with the amount of cells dividing, tubules, nucleus and Mitosis etc. You could have a large tumor and be a grade 1 or a tiny tumor and be grade 3.

  • nkb
    nkb Member Posts: 1,561
    edited November 2017
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    The other thing i will add is that IIIC is a relatively new stage. You can see that people staged awhile ago as IIIA would now be cataorized as IIIC. I was told that my chance of being alive in 10 years was 28%- however that was based on the algorithm’s worse case scenario which was unilateral Breast cancer of 6 cm with 9 positive lymph nodes. Mine was bilateral with many more positive nodes- not sure how to extrapolate from there.

  • runor
    runor Member Posts: 1,613
    edited November 2017
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    Solfeo, you NAILED it! We have all been thrown into the sea on Not Knowing. We are all paddling to keep our heads above the water, looking for something to hang onto and hoping there are no sharks circling below our flailing feet. I read all these posts. I look for something to soothe my shattered nerves. It's not going to happen. I have been handed the cancer notice. It's my "You've been served" moment of mortality. Now, to me it feels like a waiting game, no matter the studies, no matter the statistics, no matter the loving people here who have taken the time to try and reassure me. WE DO NOT KNOW. No one does.

    Maybe some people take comfort in numbers. I do not. I am a skeptic. According to one of those calculators my overall lifetime risk of ever getting breast cancer was 8%. Wow. I got the shitty end of the stick there. Then I had a radial scar and only a tiny percentage of them are ever cancer. Wow, again with the shitty end of the stick. Then my lumpectomy went wrong and I had two surgeries in one day and the morphine they gave me almost killed me. I tell you, I'm afraid to leave the house these days cause something is going to fall on my head! I have made a liar of every statistic out there. I'm not feeling the hope. But I read it all anyway hoping for something hopeful. I know, that makes no sense.

  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    That said, the Pan (2017) study seems reasonably relevant to the topic of this thread. It may be of significant interest to some newer members for whom it may not be old hat.

    As this type of study goes, the size of the study population, the length of follow-up (20 years), plus the receipt of more modern endocrine therapy regimens are notable. Yet the study population is relatively diverse in some ways, so depending on a variety of factors, one's actual risk may differ somewhat from the reported group averages.

    For 5-year and 10-year recurrence risks, other studies may be more tailored in terms of disease characteristics and therapies received.

    I often read complaints about how the general public does not understand the on-going recurrence risk and the related worries and fears faced by those diagnosed with "early stage" invasive breast cancer. This study, which has been featured in lay news reports, illustrates the nature of the problem.

    BarredOwl

  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    Regarding evolving definitions of stage, as I noted on the previous page, the paper said:

    "We analyzed data from women who had ER-positive breast cancer that had been diagnosed before the age of 75 years and who had T1 disease (tumor diameter, ≤2.0 cm) or T2 disease (tumor diameter, >2.0 to 5.0 cm), fewer than 10 involved nodes (stratified according to a pathological nodal status of no nodes [N0], 1 to 3 nodes [N1–3], or 4 to 9 nodes [N4–9]), and no distant metastases. All the patients were scheduled to receive endocrine therapy for 5 years then stop, regardless of actual adherence."

    Results are reported according to tumor size and number of positive nodes (0; 1 to 3; 4 to 9). With the above information re inclusion and exclusion criteria, including information about the tumor sizes and the number of involved nodes of patients included in this study, (and receipt of endocrine therapy,) most should be able to figure out whether the study might be potentially relevant to their situation or not.

    For those who are interested in the results and decide to purchase a copy of the full paper, be certain to also download a copy of the Supplementary Appendix, which contains a large amount of data.

  • marijen
    marijen Member Posts: 2,181
    edited November 2017
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    I am glad to see this new information and don’t find it old hat at all. I prefer to know the details and the additional information BarredOwl has supplied, rather than a confusing lump sum. And at the same time I can hold in my mind that in the end we are not statistics. We may or may not beat the odds. Time will tell but I find it adds hope, especially when new studies will be even better. Thanks as always BarredOwl

  • nkb
    nkb Member Posts: 1,561
    edited November 2017
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    BarredOwl- good point re the staging. I now realize you did point that out before- thank you for all this info quite interesting.

  • runor
    runor Member Posts: 1,613
    edited November 2017
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    My comment in no way meant to disparage Barred Owl's work here. I appreciate her posts, even though I still find all the numbers and information confuzzling.

  • TWills
    TWills Member Posts: 509
    edited November 2017
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    I do as well, I can't make heads or tails of it.

  • cive
    cive Member Posts: 265
    edited November 2017
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    Blame your AI for the confuzzling.  Shocked

  • Artista964
    Artista964 Member Posts: 376
    edited November 2017
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    I'm not on an AI and I'm confused.

  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    For those who are confused, please specify what you are confused about.

    By the way, some did not complete their endocrine therapy, which is a weakness of the study.

  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    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.)


  • TWills
    TWills Member Posts: 509
    edited November 2017
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    Does it matter what types of treatments we've had? there are so many factors. My MO had me somewhere around a 7% reoccurance risk with my planned treatments. That's with 5 years of tamoxifen.

  • BarredOwl
    BarredOwl Member Posts: 261
    edited March 2018
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    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