Luminal A vs. Luminal B stage 1 BC

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.

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.

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

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.

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

I know my chances are better if I go back on AI, but I feel so good off the medication.

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.

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.

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.

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

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.