New Research on ILC and new multigene prognostic test
I just saw this article on ILC and a new multigene test in development the authors are calling "LobSig" that has more prognostic validity than the existing multigene tests like Oncotype for ILC.
https://www.nature.com/articles/s41523-019-0113-y
** If someone wants to look at Figure 3 and have a conversation about it, let me know. My reading of it is that Oncotype only had one case in which there was a "low" Oncotype score and an ILC death (one case second from the bottom) - whereas the LobSig had 4 such missed detections (LobSig giving a low risk score for cases that ended up with an ILC death). But, maybe I'm misreading it or over-interpreting this figure's importance. (Maybe they're saying the Oncotype is less predictive because the "medium" scores in Oncotype include some ILC deaths?)
Comments
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That is such an interesting and exciting article. I couldn't read it all tonight, but will read again when I'm fresh in the morning. Thanks for posting it.
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Finally. Thank you, Australian researchers! It gives me hope that our children and grandchildren will be better off.
I said it in 2011. I did not believe Oncotype was valid for ILC. I was undertreated.
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Interesting, my coworker who was diagnosed about the same time I was, she had 1 cm ILC near the chest wall her oncodx score was 4. Not 6 months later they discovered the cancer in her bones near the hip.
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That is definitely scary to hear of MBC when the situations seemed so benign. I'm glad I'm doing chemo plus OS and AI. Thank you for reinforcing that!
I will read the article!
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Lojo thanks for the article. Im pretty smart but I am definitely going to need my medical oncologist (whom I dont have as of yet) to explain that article. Either way sounds like its too early to be used but may help future women who develop ILC
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Lojo- Figure 3- it looks to me like Lob sig had 5 cases of Low Risk people who died of ILC, while Oncotype had 1. It also looks like 4 Intermediate Risk people in the Oncotype column died of ILC and they were all High Risk with Lob sig.
What I do find interesting is the number of people who would be labeled high risk by Oncotype who would change to Low under Lob Sig if they were used independently. One challenge in analyzing this is that the people who had high risk Oncotype scores probably had chemo, so how would you determine whether their longevity was caused by having a low risk cancer versus having chemo?
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I had a 34 on the oncodx test, I believe they sent my ILC tumor. It was a suprise since I was barely grade 2, mitotic score 1. But my er 95% and pr 0% likely drove my score up. I didn't do chemo I did 4 years AI drugs. Eight years NED. Wonder what the Lob Sig would have shown.
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Meow13- that is really interesting! Yes, definitely wonder what Log Sig would have said for you!
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I wonder what it would have said for ME.
Interestingly, the recent refinements to Oncotype that take into account menopausal status would have put me in the chemo-could-be-helpful group, because I was premenopausal with Oncotype 16 (low category but barely). I would have done OS + AI at least. But in 2011 all three MOs I consulted told me that would be overtreatment.
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Shetland Pony- your 2011 stats are rather similar to mine including the ITC, except that my tumor was 3cm (plus I had 3 other smaller tumors). I think you would have been in the non-chemo group for the new TAILORx results because you'd be classified "low risk" because of tumor size.
My MO was originally thinking chemo would be overtreatment for me, but I think that the new results put her into the "maybe it will be helpful group". It is so hard to decide since ILC solid tumors don't respond as well to adjuvant chemo. From my point of view it is possible that aggressive ILC ITC's and micromets could respond to chemo.
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I believe the TailorX results would have put me in the group for chemo or OS + AI, OnTarget. See below. Unless there is some refinement tool that applies that I do not know about. I always notice other ILC patients and reading your stats have been glad you did chemo and OS. I agree that aggressive ILC does respond to chemo. While early stage classic ILC (ER+PR+Her2-) is very hormone-driven, as it progresses it can mutate into a different beast that is more responsive to chemo. Furthermore, I read one study that suggested ITCs in ILC may actually be micromets, because the ILC growth pattern can be single file rather than clumps. In other words, should isolated tumor cells really be considered node-negative in ILC?
“A total of 40% of women who were 50 years of age or younger had a recurrence score of 15 or lower, which was associated with a low rate of recurrence with endocrine therapy alone. Exploratory analyses indicated that chemotherapy was associated with some benefit for women 50 years of age or younger who had a recurrence score of 16 to 25 (a range of scores that was found in 46% of women in this age group). A greater treatment effect from adjuvant chemotherapy has been noted in younger women,7 which may be at least partly explained by an antiestrogenic effect associated with premature menopause induced by chemotherapy.27 We did not collect data on chemotherapy-induced menopause. It remains unclear whether similar benefits could be achieved with ovarian suppression plus an aromatase inhibitor instead of chemotherapy.28,29“
N Engl J Med 2018; 379:111-121
DOI: 10.1056/NEJMoa1804710Sorry to go off the topic of the thread, but my point is that ILC is indeed different from IDC and needs its own prognostic tests such as the new LogSig. I hope it becomes available to clinicians stat!
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Hi ShetlandPony, I was primarily looking at Table 2 from the 2019 study results which lists the people under 50 with low clinical risk at a 4.6% chance of distant recurrence without chemo and 4.8% with chemo, for a total chemo benefit of -.2%.
https://www.nejm.org/doi/full/10.1056/NEJMoa190481...
"Clinical risk was defined as low if the tumor was 3 cm in diameter or smaller and had a low histologic grade, 2 cm or smaller and had an intermediate grade, or 1 cm or smaller and had a high grade; the clinical risk was defined as high if the low-risk criteria were not met."
People with high clinical risk who were under 50 on the other hand had an 11.9% chance of distant recurrence without chemo and a 5.5% chance with chemo, for an absolute chemo benefit of 6.5%.

N Engl J Med 2019; 380:2395-2405
DOI: 10.1056/NEJMoa1904819Also, slightly contradictory to what they said in the quote you have above, they have a table which shows that there was less chemo benefit in women under 40. Women who were 41-45 had chemo benefit, and then women aged 46-50 had more chemo benefit. What I heard them say is that they believe that chemo causing menopause is greater in women aged 46-50, less in 41-45 but still there, and that under 40 chemo won't cause permanent menopause. They associated the ovarian suppression caused by chemo induced menopause with the increased benefit from chemo, not the cytotoxicity of chemo.
One thing I find which disagrees with their theory is the women who were 51-55 before menopause. If their theory of ovarian suppression is correct, the hazard ratio for women who are 51-55 should be even higher than the 46-50 women. But weirdly enough it is below 1. That makes me feel better about choosing chemo- their theory may not be correct, and chemo may be very beneficial. Add that to OS + AI, and I hope all the bases are covered!
Figure 3.

The thought that ITC's in ILC are actually micromets is pretty scary- and it is a great question.
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So complex. It sounds to me like they are speculating as to whether ovarian supression in chemo in women closer to menopause years could be part of the reason chemo was more beneficial but that is only part of the equation with the rest unknown. I really think its hard bc no study is perfect and I truly think every womans body probably responds a little differently to chemo as it does to its ability to dispose of cancer cells on its own.
Not referring to this study but I always thought cancer in younger women tended to be more aggressive in general and because they had the cancer younger, thus their chances for recurrence in their lifetime could be higher because they had more years to live until older age.
Im sure chemo has some benefit regardless of these stats. It just needs to be weighed with other health concerns to see if the benefit is worth the risk you might gain. OnTarget I think your bases are covered. ShetlandPony this must be frustrating as hell to feel you were under-treated. How are you doing now? My mom had stage iv idc w mets to the liver and that was 12 years ago. Did chemo and AI. Shes doing well. Shes now 70.
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Trying, were your mom’s liver mets de novo (from the beginning of metastatic breast cancer) or did they appear later? I am glad she is doing well! I am doing well, considering, as I have just reached five years with liver mets and pretty good quality of life. Frustrating doesn’t begin to describe the horror that “could have” and “might have” produce. I scream inside my head. Then I decide to keep calm and carry on — what else can I do? That’s why I am so glad ILC is finally getting studied.
Thank you for that detailed reply, OnTarget. I will think more about it and hopefully continue our discussion.
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shetlandpony, her liver mets were found from the beginning on imaging. Scary bc it only looked like a stage 1 breast tumor (IDC.) Weirdly the liver biopsy showed it was BC but triple negative when her primary breast tumor was er and pr + and her2 neg. No one knows how that happened. She had chemo first then bmx, and nothing new was found at all and primary responded (or chemo eliminated it). Liver ablation did the rest and AI meds for years.
I agree glad ILC is getting studied. I admit when I heard mine was ILC I was really scared because studies that say its so different and hides more than IDC. I have a few conditions that chemo could aggravate so it would really have to be of clear benefit to do it. Im less than thrilled that oncotype may not even be accurate for ILC. Weighing stats and studies to try to save your life to me feels a bit like russian roulette...
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