Luminal A vs. Luminal B stage 1 BC
Comments
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My husband went to grad and med school at UW--the MD/PhD program in Genetics. We lived across the street from Health Sciences, in a student housing complex that was demolished to make way for a parking garage. I didn’t get into UW Law School four blocks away (women were not considered minorities for affirmative action purposes, even though we were only about 10% of the legal profession at the time), so I had to drive 45 miles each way every day to attend law school at Univ. of Puget Sound. (The law school was in S. Tacoma, in a ticky-tacky business park about a mile north of McChord AFB).
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QuinnCat -
I will be getting AC + T.
I really, really wish I could understand why I had an Oncotype of 19, and an awful Mammaprint/Blueprint.
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Hi QuinnCat:
Your ER and PR results seem relatively consistent by IHC and Oncotype single gene score, so the biopsy sample and sample from surgical pathology might both be reasonably representative (no reason why not, in my layperson's view). With no treatment decision on the table, always view things in the most favorable light.
Regarding why they report the numerical score, GenomicHealth provides in a FAQ for professionals (previously quoted by kayb):
"What information do the quantitative ER and PR Scores provide?
The quantitative ER and PR Scores can:
- Help determine the likelihood that an individual patient will derive a substantial benefit from tamoxifen
- Provide additional information for clinical decision making for a patient whose ER protein expression is borderline positive by IHC or reported as uncertain
- Provide further insight into the Recurrence Score result"
In any event, the vast majority (over 90%) of ER results by IHC and Oncotype single gene ER score are deemed concordant. See e.g., the Discussion section of this paper that I cited above for more information:
http://www.nature.com/modpathol/journal/v25/n6/full/modpathol2011219a.html
Providing the specific scores permits the assessment of the potential significance of the numerical score in future retrospective studies, even if archived tissue is no longer available for testing. Also, on-going research is directed to assessing the potential information value of the ER score for various purposes, such as risk of late distant recurrence (beyond 10-yrs) and benefit of extended endocrine therapy. If sound research emerges in the future supporting additional clinical uses of the Oncotype single gene ER score, then patients being tested today will have the score in their report and may be able to use it.
BarredOwl
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I'm so grateful for all the studies and links. I do have a question for you ladies on the chemo. So it appears my numbers aRe equivalent to most of yours. Stage 1A, IDC, 95%er, 5%pr, oncoscore 20 and w/er therapy it says 13% reoccurance. Ki67 =30-35%. No nodes, clean margins, bmx, no ilv, 1 tumor at 1.7cm..... I'm leaning to chemo but....
why did you all choose chemo? I am willing to go through the chmo though the port scares me. What do you think was the tipping point to say yes to chemo? And also is it a particular type That really works best? Like CMF vs. TC?
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Lisey First of all, I'd say was in shock most of the time between biopsy result and first meeting with the MO, post surgery. I don't feel like I actively decided a thing with an oncoscore of 39. You are in the middle ground and I thinkt the Taylor X study would apply to you. Since I was always in the definitely needs chemo group, I didn't give it much thought.
The port is really nothing - the least of the chemo worries, really, well, for me.
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is the TaylorX study out yet? .. last I found no results had been posted.
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I was scared of chemo.. However, chemo was not even close to being as bad as I expected... My lvi was indeterminate and my ki 67 was 25%. My tumor was big at 2.5 cm .. I had it a while misdiagnosed.
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hello all- I have been following this topic and appreciate all of the great research (special thanks to BarredOwl and Kayb) and thoughtful input. My question may be answered or better asked elsewhere, but it comes up in my mind every time I revisit the prognosis and treatment I've undergone.
I had an Onco dx score of 30. (Fairly high ki %). Did BMX, and 6 rounds of TC. I am aware that my OS assumes the inclusion of 5 years of Tamoxifen. I am unsure if I am luminal a or b.
I tried Tamoxifen, but stopped on the advice of MO due to extreme/suicidal depression and 3-4 X high ALT/AST levels, which elevated sharply within 90 days of starting. After a 60 day break I started Anastrazole. Four months later, my mood is more or less stable, but my joint pain (all over but especially knees, feet, wrist and hands) is so extreme I am immobilized almost completely. Without getting into too many details, trust me I've tried many things to reverse this downward spiral, and though terrifed of any recurrence, local or distant, I am now sitting in the bottom of the barrel. I didn't take the pill today.
Here is my question. Since 30-50% of women are unable or unwilling (what's the difference, really?) to complete hormone receptor-directed tx, why is there never any analysis on how stopping (or never starting in the first place) may affect your prognosis statistics?
That is to say, is there any way to re-calculate your risk%s, if you do chemo but not Tamoxifen or an AI?
Sorry to be so long winded, and I apologize if my question is too far off topic, but I wanted to make sure I caught the attention of the sisters here who I admire and trust so much for their ability to research, evaluate, then explain these problems, which seem still so insurmountable even 1 and 1/2 years out from dx and tx. BTW, I have asked my mo this Q, but he became flustered and reverted to the methods he used prior to Oncotype dx availability- which I am loathe to rely on. Thank you.
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Lisey -
Ask to have Mammaprint done...that will futher guide you on chemo decision.
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Laty, They generally say your recurrence risk doubles if you stop hormone therapy early, but looking at the recent studies, it was not doubled; there was a study posted on the main page recently that lists research. I will try to edit and add it if I can.
Quality of life is very important.
http://www.breastcancer.org/research-news/not-taki...
For me, I tolerate them ok; letrozole better than tamoxifen. Until my kids graduate, I will take them if at all possible. Once my kids graduate, quality of life will take precidence and my mind may change
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thanks Kayb and Karen:
When you look at the life math and other calculators, they don't give you the option to enter chemo only. But you can compare chemo + hormonals to no adjuvant tx at all and split the diff I guess. It appears to be 1-2 % difference in my case. Without taking into consideration whatever made my oncotype so high. Not very scientific. I realize there needs to be studies to accurately say but it seems like there are so many of us (30-50% ?) who just can't tolerate them and we just float around, not knowing where we stand. It's scary. It's hard for me to remember what life was really like before all this. I realize also I am getting older. But it has gotten so bad I think I will just have to take my chances.
ETA: looking at kbee's link my risk if I quit would go from 16% (according to chemo plus Tamox predictor) to possible 50% higher? Or say....22%? I guess it's quite pointless to try to figure the math. I know the stats are really 0 and 100%.
Then pops up another question. If I did have a distant recurrence, would I then reconsider AI therapy in that new light? And would it still be effective if I had used it before and stopped?
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I know Hopkins always estimates it is double, but remember.., if you had a 16% chance and it is doubled, the odds are still clearly in your favor.
It is frustrating that studies do not estimate stopping at 1, 2, 3, 4 years... Your risk does not magically go in half from 4 years 364 days to 4 years 365 days. They need to be more accurate I reporting that. It also bothers me that they call it non compliant. It does not consider that they are not tolerated. They would not call someone who reacted severely to an antibiotic non compliant.
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yes exactly. Well I can say it's a point in favor of having done chemo. Overdone probably. But had I not done it and relied on being able to take the anti hormonals for 5-10 I'd be sorry (sorrier)now. I did take that into consideration when deciding on chemo in the intermediate range. Plus I met so many nice people!
A little pill every day didn't seem like it could be that hard.
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Hi Jackbirdie:
General Reminder re Oncotype for invasive disease and receipt of 5-years of endocrine therapy:
The average risk of distant recurrence (10-year risk) associated with a particular Recurrence Score for node-negative patients that is supplied in the Oncotype report was determined in patients who received 5 years of tamoxifen and is thus based on the assumption of receipt of five-years of endocrine therapy. If one declines endocrine therapy, the risk of distant recurrence would be significantly higher than shown on the report.
Jackbirdie, here is what I found about shorter durations of endocrine therapy, for which there is some benefit (though less than with 5-years duration), so you did not suffer needlessly. Some of the studies are very old, and may not reflect the current state of the field.
I have re-capped Kbee's cite from above under (a).
(a) Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence
Chirgwin (2016): http://jco.ascopubs.org/content/early/2016/05/19/JCO.2015.63.8619
Full pdf version available via PatientACCESS option for US $2.00 with registration at Copyright Clearance Center.
Hershman commentary (2016): http://jco.ascopubs.org/content/early/2016/05/19/JCO.2016.67.7336.full
BC.org summary: http://www.breastcancer.org/research-news/not-taking-hormonal-tx-leads-to-more-recurrence
(b) (2-years tamoxifen in post-menopausal women) Randomized Trial of Two versus Five Years of Adjuvant Tamoxifen for Postmenopausal Early Stage Breast Cancer - OLDER STUDY
Swedish Breast Cancer Cooperative Group (1998): http://jnci.oxfordjournals.org/content/88/21/1543.full.pdf
(c) (2-years in pre-menopausal women) Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial
Ekholm (2016): http://jco.ascopubs.org/content/early/2016/05/05/JCO.2015.65.6272.full
BC.org summary: http://www.breastcancer.org/research-news/2-yrs-of-tamoxifen-offers-long-term-benefits
(d) Tamoxifen for early breast cancer: an overview of the randomised trials - OLDER STUDY
EBCTCG (1998): http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)11423-4/abstract
(e) FDA label for Nolvadex (Tamoxifen citrate), discussing the content of (d) I think
"Adjuvant Breast Cancer:
Overview:
The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) conducted worldwide overviews of systemic adjuvant therapy for early breast cancer in 1985, 1990, and again in 1995. In 1998, 10-year outcome data were reported for 36,689 women in 55 randomized trials of adjuvant NOLVADEX using doses of 20-40 mg/day for 1-5+ years. Twenty-five percent of patients received 1 year or less of trial treatment, 52% received 2 years, and 23% received about 5 years. Forty-eight percent of tumors were estrogen receptor (ER) positive (> 10 fmol/mg), 21% were ER poor (< 10 fmol/l), and 31% were ER unknown. Among 29,441 patients with ER positive or unknown breast cancer, 58% were entered into trials comparing NOLVADEX to no adjuvant therapy and 42% were entered into trials comparing NOLVADEX in combination with chemotherapy vs. the same chemotherapy alone. Among these patients, 54% had node positive disease and 46% had node negative disease.
Among women with ER positive or unknown breast cancer and positive nodes who received about 5 years of treatment, overall survival at 10 years was 61.4% for NOLVADEX vs. 50.5% for control (logrank 2p < 0.00001). The recurrence-free rate at 10 years was 59.7% for NOLVADEX vs. 44.5% for control (logrank 2p < 0.00001). Among women with ER positive or unknown breast cancer and negative nodes who received about 5 years of treatment, overall survival at 10 years was 78.9% for NOLVADEX vs. 73.3% for control (logrank 2p < 0.00001). The recurrence-free rate at 10 years was 79.2% for NOLVADEX versus 64.3% for control (logrank 2p < 0.00001).
The effect of the scheduled duration of tamoxifen may be described as follows. In women with ER positive or unknown breast cancer receiving 1 year or less, 2 years or about 5 years of NOLVADEX, the proportional reductions in mortality were 12%, 17% and 26%, respectively (trend significant at 2p < 0.003). The corresponding reductions in breast cancer recurrence were 21%, 29% and 47% (trend significant at 2p < 0.00001).
Benefit is less clear for women with ER poor breast cancer in whom the proportional reduction in recurrence was 10% (2p = 0.007) for all durations taken together, or 9% (2p = 0.02) if contralateral breast cancers are excluded. The corresponding reduction in mortality was 6% (NS). The effects of about 5 years of NOLVADEX on recurrence and mortality were similar regardless of age and concurrent chemotherapy. There was no indication that doses greater than 20 mg per day were more effective."
BarredOwl
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Kayb- thanks. I see that now. I appreciate you pointing that out.
BarredOwl- as always, comprehensive and very helpful. Thank you for taking the time.
It is interesting that the result I now get from the life math is quite different than from my oncotype info, adjusting for the failure to complete anti hormonal tx. As I said before, I understand that in the case of my tumor sample, there must be underlying factors, not present in the average life math assumption, which my tumor presented, thus producing the higher score. I guess I'm just going to have to live with the greater risk. And hope that the intolerable SEs I am experiencing now are not permanent- and that they recede and I can find my way back to some QOL.
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I know my chances are better if I go back on AI, but I feel so good off the medication.
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For those wishing to continue endocrine therapy, even for the same AI, different generics may have different inactive ingredients, and some members have found they tolerate an AI from one generic manufacturer better than another.
BarredOwl
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Jackbirdie - I also get treatment in Oregon (southern). Just wondering. I know my MO there says she has some patients that just cannot tolerate hormone blockers - suicidal thoughts being one SE. I can't imagine. I just wanted to say that on my first 7 months of Exemestane I woke up every morning feeling like a 90 year old woman in the joints. After that, I would get swelling hands and trigger fingers, but almost 4 years later, most of that has subsided - well, except the brain fog. Being a witness to my mother's BC journey, as a teenager, put the fear of stage IV in me at a rather early age and I think I would endure almost anything (maybe) to keep BC away. I have no intent of minimizing your symptoms,,,. they are probably much worse than mine. My point is that some of these SEs do go away, or lessen with time, and I have oft read that on BCO.
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thanks Quinncar and others- I know nobody is minimizing my symptoms. It is a very hard decision. I have two very dear friends in st IV right now and I can't even tell them because I know they are trying everything they can to stay alive. It makes me feel selfish to even consider this. Many days I don't leave the house. The only time I don't hurt a lot is when I don't move. I live aIone and I think the isolation makes it worse. I have, perhaps temporarily, lost the use of my left wrist which is a pain. I'm not suicudal anymore since stopping Tamoxifen. I am bipolar and am restricted as to many meds that might make me feel better.
I guess my plan is to take a break and see if I feel better. If so, I might be willing to try another. I have tried different brands of the generic. Things have steadily gotten worse. My mo said he would try exemesrane next.
I also plan to research and try some supplements, I have taken glu/chon and curcurin in the past. But I want to try and separate the variables before I change or try anything new.
I really appreciate everyone listening and offering feedback. I am at a really low point at a time I had hoped I would be getting my life back.
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One thing that is helping with the pain if CBD oil. If you google Charlotte's Web, you'll see it's available in all 50 states since the Feds changed the rules on 'hemp'. CBD had NO THC, so doesn't mess with your head, but it definitely helpful with pain and joints. It's also what they give to children with seizures, so it's not something I consider worse than a vitamin supplement. I use a company here in CO that I've seen their facility, and understand they are what they say they are.
By the way, Meeting with the Onc tomorrow, will insist on the mammaprint, but now all this talk of Tamoxifen and AI SE makes me think I should just do the Chemo to be safe.
The only other thing I was considering is the fact that the oncotype doesn't account for Mastectomy / vs Lumpectomy. Wouldn't Mastectomies of said tumors (so long as there are really good margins) make that percentage change than if it were a Lumpectomy with Rad? -
Jackbirdie,
I know your pain! I stayed on anastrozole for a year and finally told oncologist I just couldn't do it anymore and my quality of life was more important. She convinced me to try Femara (letrozole). Why oh why did I wait a year? What a difference it has made. It took about two weeks for the residual anastrozole to leave my body but no more joint pain after two weeks.Have a discussion with your oncologist and hopefully you can get the same relief I have had. Good luck.
Jo
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The only other thing I was considering is the fact that the oncotype doesn't account for Mastectomy / vs Lumpectomy. Wouldn't Mastectomies of said tumors (so long as there are really good margins) make that percentage change than if it were a Lumpectomy with Rad?
Lisey I took a long enough break from BCO that my BC knowledge has greatly diminished, but I do believe there was a study recently that gave lumpectomies better odds than mastectomies - counterintuitive, but they are very close and probably within the margin of error. I don't think radiation was a factor.
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I tried both anastrozole and exemestane. With anastrozole my pain got so bad I felt I couldn't move out of bed. Then exemestane I quit when my eye dried out. That was it, i will not lose my eye sight. I feel so much better but still have tinnitus after all this treatment.
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After 6 months on letrozole, I developed a trigger thumb (had one on my other hand long before bc, surgery cured it), lowered metabolism (dieted my way down to my pre-letro weight and hoping to hold the line), mild night sweats (thank you, A/C), and acceleration of ripening of preexisting cataracts. I do have some startup hip pain when getting up from a long session in the recliner, and hobble like a 90-yr-old, but 20 steps later I’m fine. I notice my symptoms are the least on the Roxane generic, then Femara (have most of a 3-mo stash bought online from Canada), and worst on Teva. Unwilling to try other formulations as their laundry lists of inactive ingredients (and potential allergens/sensitizers) are longer. I have at least 4.5 yrs. to go, but thus far it’s doable and a small price to pay. There are always cortisone shots and tendon-release surgery for trigger thumb, better posture in my recliner for my hip (as well as arnica gel), increasing my exercise and doubling down on diet, and cataract surgery (which I was going to need anyway).
When pondering chemo vs. AIs or tamoxifen, it’s not a balanced “either-or.” If you have a hormone-receptor positive cancer, you’re going to need some sort of anti-estrogen therapy no matter what, totally independent of chemo. If you have a cancer which pathological analysis reveals is aggressive (i.e., characterized by rapidly-dividing cells), then chemo is indicated. If you don’t need chemo you will still need that endocrine therapy; but if you do need chemo it won’t exempt you from the need for endocrine therapy. It’s not like the choice between BMX w/o rads and LX + rads. Sorry.
Only justification for avoiding AIs or tamox with an ER+ cancer is if you have comorbidities that would make it too dangerous, must take a life-sustaining drug that is contraindicated with it (e.g., severe clinical depression with suicidal tendencies treatable only with an antidepressant contraindicated with AIs or tamox), or endocrine therapy makes your QOL so awful that you’d rather roll the dice and do without it. Some here have come to that difficult decision after unsuccessfully trying every possible AI (or can’t find an effective antidepressant that doesn’t thwart their endocrine therapy).
Hate to be a cop-out, but the ball is in your court.
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Hi Lisey:
"The only other thing I was considering is the fact that the oncotype doesn't account for Mastectomy / vs Lumpectomy. Wouldn't Mastectomies of said tumors (so long as there are really good margins) make that percentage change than if it were a Lumpectomy with Rad?"
The trials used to develop the risk data shown in the graphs on node-negative Oncotype reports were NSABP B-14 and NSABP B-20, and were described in one publication:
"Patients in both trials had lumpectomy plus axillary node dissection or modified radical mastectomy as their surgical procedure. All lumpectomy-treated patients were required per protocol to receive standard breast irradiation. However, chest wall irradiation after mastectomy was not allowed per protocol. Similarly, regional nodal irradiation was not allowed, irrespective of surgical procedure. As a result, there were two types of initial locoregional (LR) treatment in the two trials: lumpectomy plus breast irradiation (L + XRT) or mastectomy."
Note that (lumpectomy plus radiation) or (mastectomy alone) are primarily local treatments, and are comparably effective with respect to overall survival.
In the appropriate case, the risk of distant recurrence is addressed by administration of systemic treatments, such as chemotherapy, HER2-targeted therapies, and/or endocrine therapy.
The main benefit of chemotherapy is in addressing the risk of distant metastasis. The Oncotype test for invasive disease provides a means of assessing the risk of distant metastasis in connection with deciding whether to add systemic chemotherapy to endocrine therapy. Specifically, in node-negative patients, the Recurrence Score is associated with an average risk of recurrence of breast cancer at a distant site at 10 years after diagnosis with receipt of a 5-year course of tamoxifen (See Graph 1 on your report). In the validation studies***, recurrence in the ipsilateral (same) breast, local recurrence, and regional recurrence were not considered events or censoring events. With that study design and focus (recurrence at a distant site), it seems to me that the specific local treatment would not be a separate consideration in deciding on whether to add chemotherapy to endocrine therapy. However, please confirm it with your team.
BarredOwl
***Node-negative validation studies establishing certain correlations with Recurrence Score featured in graphs in Oncotype node-negative report:
Paik (2004): http://www.nejm.org/doi/full/10.1056/NEJMoa041588#t=article
Paik (2006): http://jco.ascopubs.org/content/24/23/3726.full
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Ladies, I just returned from the oncologist and have news and questions from my experts (you guys!)
1) I like this oncologist. She immediately said she doesn't like the 'gray area' and wants a mammaprint done so that I can have a black and white result. She says her odds are on not needing chemo. She also doubts I'm luminal B but says the mammaprint will tell us for sure. She staged me at 1A, even though the mets is an unknown, she offered a PET, but said with my margins and no nodes she doesn't think it's needed but is willing to order anytime I want one.
2) She said my overall Oncotype score is 20, with a 13% chance of mets in within 10 years. It will be reduced 3% with Chemo. She also clarified that this is only for 5 years of Tamoxifen and she plans on giving me 5 years Tam and 5 years of an AI, so those percentages should be lower anyway. (another reason she's against chemo)
3) She said because I'm considered 98% ER, she thinks the Tamox would help the most. My mitosis level is still at a 1, so again she doesn't think Chemo would help.
4) She supports the idea of getting Adjuvant Bisphosphonate like Zometa because in some studies its shows to help Tamoxifen and she added it's used in a wide range of osteocases with little SE, so even if it doesn't help, it really couldn't hurt.
5) She additionally said if the mammaprint comes back as aggressive, she'll do the TCX4 and completely supports my decision to use Penguin cold caps if needed.
6) She's doing the blood work to see what my CYP2D6 – determines if you are a slow or fast metabolizer of Tamoxifen and will dose accordingly.
what do you all think? I HATE the idea of mets and stage IV, but I love the idea that she's so willing to do all the tests first to make the right choice... This is Kaiser, I'm amazed at her willingness. -
Lisey - your MO sounds amazing. That's about all I have to add.
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Hi Lisey:
Sounds like you are working towards a plan.
Re: "She also doubts I'm luminal B but says the mammaprint will tell us for sure."
FYI only, MammaPrint only calculates High Risk or Low Risk. However, Agendia offers additional tests as part of a group or "suite", one of which uses the same type of microarray technology to determine subtype. The following tests are part of a "test suite" (set of three tests) offered by Agendia:
(1) "MammaPrint" (different versions rely on tumor tissue prepared in different manners)
(a) "Mammaprint" (done with fresh frozen tumor tissue); OR
(b) "MammaPrint FFPE" (done with Formalin-Fixed Paraffin-Embedded tissue)
(2) "BluePrint" (for molecular subtype (Luminal-type; HER2 type; Basal type) (I believe Luminal A-type would be BluePrint Luminal-type/MammaPrint Low Risk)
(3) "TargetPrint" (re how active the ER, PR and HER2 genes are);
Please make sure your team obtains pre-approval from the payor of all such testing. Call the office and confirm that they will do so.
Re the proposed addition of zometa with tamoxifen: "even if it doesn't help, it really couldn't hurt." Your MO is balancing the risk/benefit here, but I note that the drug is not devoid of adverse effects (though relatively rare and some may be more pre-disposed to them than others). You may wish to inquire further about the nature and magnitude of the benefit(s) seen in patients of your menopausal status receiving the same endocrine therapeutic, with the same bone status/risk, and inquire about the incidence of serious adverse effects, as you weigh this aspect of your treatment plan.
Best,
BarredOwl
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Anti-osteoporosis drugs are not to be undertaken lightly, especially if taking a SERM like Tamox. that actually has some osteo-conserving effect. Because of the side effects (fierce GERD that might turn erosive in oral versions, severe bone pain for the first few days after administration of Zometa; and rare SE’s like osteonecrosis of the jaw and paradoxical horizontal femoral fractures) they are usually reserved for women already osteopenic and for those on AIs, which do seriously weaken bones. Recently, however, there have been studies that Zometa and Prolia can actually protect against bone mets (bone is usually the first place ER+ bc spreads). My MO says Zometa definitely; when I brought up studies that show Prolia is superior in that regard, she conceded that once the studies have been completed that may prove true, but she’s waiting till the next ASCO conf. to confirm it. Prolia has the fewest and mildest SE’s, but it is a biologic, hideously expensive, and not all Medicare Part D plans cover it (some Part B plans consider it a drug and therefore kick it over to Part D, some consider it a treatment like Prolia and do cover it.
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how do you determine if luminal a or b ? No one ever discussed with me. I fell like I have so many bad charecteristics they all told me not to focus on.
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