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Topic: Abemaciclib Verzenio for Stage IV

Forum: Stage IV/Metastatic Breast Cancer ONLY —

Please respect that this forum is for members with stage IV/metastatic breast cancer only. There is a separate forum for caregivers and friends: Caring for Someone with Stage 4 or Mets.

Posted on: Jan 1, 2018 02:03AM - edited Jun 17, 2018 09:19PM by zarovka

zarovka wrote:

Luckylegs and friends on Abemaciclib - I am bumping the Verzenio discussion in the hopes that more people have started abemaciclib. We need to get a community going. I have not started abemaciclib but it is on my short list. Like many I am very interested in how people do on this treatment do, both as a monotherapy and in combination with hormone suppression and other treatment. I am hoping that this thread can capture the experience of everyone on Abemaciclib in whatever combination. This is a very important treatment option that we all need to be evaluating.

I would expect more people on the drug given the significant advantages of abemaciclib over the first generation CDK 4/6 inhibitors. However, the FDA has approved abemaciclib for only limited indications. We have not established its use as a first line treatment nor as something to switch to from Ibrance. At the same time, they haven't made it clear that the drug can and should be used after Ibrance. As a result, the setting for using abemaciclib is supremely unclear.

I believe abemaciclib can be used either instead of or after palbo/ribo depending on whether you view abemiciclib as another class of drug or the same class of drug with significant improvement. One can make arguments for either strategy. If you've already done palbo/ribo, it is certainly worth trying abemaciclib. If you haven't done palbo/ribo, the current guideline that you start with the first generation CDK 4/6 is reasonable, but not necessary IMO. A lot depends on the side effect profile you can tolerate the best as the drugs have significant differences in side effects and also whether you are at risk of brain mets. Abemaciclib is better at crossing the blood brain barrier.

The following summary of abemaciclib data taken from a thread started by Constantine on Inspire. I moved his entire discussion from three posts because it's that good. Thank you Constantine.

ABEMACICLIB (VERZENIO)
Preliminary data from a phase I study of abemaciclib [SABCS 2014] in patients with five different tumor types including HR-positive metastatic breast cancer, with I note a median of seven prior systemic therapies (outliers out to 11 lines) found an objective response rate of 19% and a disease control rate (including stable disease (SD) under RECIST definition of >24 weeks of ) of 81% for HR-positive MBC patients. This Phase I study was expanded to evaluate abemaciclib plus fulvestrant in HR-positive MBC [ASCO 2014.] with patients having a median of four prior systemic therapies (and outliers out to the eight line), finding an objective response rate of 62% confirmed PRs.

A subsequent Phase I study [Tolaney et al, J Clin Oncol 2015;33(Suppl 1).] of abemaciclib in combination with different endocrine therapies for HR-positive MBC (median lines of treatment = 3, with outliers out to 8) demonstrated a disease control rate (CR + PR + SD) was 67% for those on abemaciclib + AI therapy, and 75% for those on abemaciclib + tamoxifen.

The phase II MONARCH-1 trial evaluated abemaciclib MONOTHERAPY in HR-positive, HER2-negative MBC patients with a median of 3 lines of prior therapy for advanced disease, including a median of 2 lines of chemotherapy (as opposed to endocrine or biological therapy) for advanced disease, yielding an objective response rate (ORR) of 17.4% and a clinical benefit rate (CBR) of 42.4%.

What's important to remember about MONARCH-1 is that many women in the study had already received multiple lines of endocrine treatment (median 3 - 5 previous lines in the metastatic setting, with outliers beyond that), developed resistance and were refractory to all of these treatments, AND progressed, many of whom also received chemotherapy, and these results were for MONOTHERAPY in a heavily pretreated population, which as I determined through examination of historical controls with any other agent achieves at best only 10 to 20% clinical benefit rates - half of that achieved by single-agent abemaciclib, and with responses of short duration.

Hence, the collective results of these trial, including MONARCH 1 (MONARCH-2 (with letrozole) and MONARCH-3 (with fulvestrant) are exceptionally exciting breakthrough in breast cancer therapeutics.

BREAKTHROUGH SURVIVAL
In addition, for me, the overall survival (OS) of these heavily pretreated MBC patients was 17 months, and that compares to historical control I review from all clinical trials to date, as significantly better than other survival results, which are usually are at best 13 months. Thus, consider that for the current champ, eribulin chemotherapy in this setting, the EMBRACE trial achieved a median overall survival (OS) was 13 months, we clearly have here a major advance and improvement in overall survival in the highly challenging later-line settings (past at least 3 lines of therapy).

HIGH TOLERABILITY
The major limiting constraint with all CDK4/6 inhibitors to date, like palbociclib (Ibrance), is their most common adverse effect, that of myelotoxicity via neutropenia (low WBC neutrophils), with palbociclib (Ibrance inducing some degree of neutropenia in over half of women on it, with associated dose interruptions and sometimes dose reductions, a toxicity that so fat from the available data seems to also afflict ribociclib.
But abemaciclib (Verzenio) evades a good deal of this because although strictly a CDK4/6 inhibitor, it is more specific in inhibiting CDK4, that is it is CDK4-selective, and myelotoxicity including neutropenia is primarily associated with CDK6, making the incidence of neutropenia on abemaciclib significantly lower and more manageable.

CLINICAL LESSONS ON ABEMACICLIB (VERZENIO)
And unlike palbociclib (Ibrance):

1. abemaciclib has strong single-agent activity in HR–positive MBC,
2. has durable response in later line settings,
3. a good tolerability profile with reduced neutropenia, and
4. to date the highest OS in these challenging heavily pretreated settings of any oncotherapeutic agent, whether endocrine therapy, chemotherapy, or biological therapy.

SOME NUANCES
1. The ESMO-reported MONARCH 3 Trial found an response rate of 48.2% for all patients, BUT for the subgroup of patients with measurable disease, a response rate (ORR) of 59.2%, these being the highest ever response rates achieved to date for ANY endocrine therapy in breast cancer.
2. And although data needs to mature further for survival outcomes, it is anticipated based on exploratory analyses that PFS will weigh in at an improvement of close to 12 months, again an extraordinary gain.
3. In addition, Verzenio was most effective in challenging populations like those with visceral metastases (especially liver) and those with rapidly recurrent (short disease-free-interval (DFS)) patients.
4. Finally, 16 patients across two of the three MONARCH trials were NED (complete response (CR)), likely to increase once the MONARCH-3 data matures, more still I anticipate when results are reported from the MONARCH PLUS and other trials.

DIARRHEA AND ITS MANAGEMENT
To put the adverse events into a bit of perspective, although it is true that with Verzenio, all-grade diarrhea was between 86 - 90%, yet serious (Grade 3+) incidence was 13 - 20% but this is aggregated across the trials, and note further that diarrhea incidence is concentrated during the first month, and more narrowly the MTO (median time to onset) of the first diarrhea event was 6 days, lasting a median duration of just 6 days for Grade 3. Furthermore, for the most recent MONARCH-3 RCT, grade 4 diarrhea was zero, and grade 3 diarrhea was just 9.5%.

An aggressive proactive regimen of:

- high-dose loperamide/Imodium (4 mg but NOT ever de-escalated down to 2mg (and up to 16 -32 mg daily);
- "Big Pink" (Petpto Bismol Extra Strength) used in "priming" mode (started on day 4 and also used for immediate relief during loperamide dosing;
- budesonide (Symbicort) for recalcitrant cases;
PLUS "adjunct interventions:
- high-dose probiotic (28 billion microorganism count in two divided doses), and
- electrolyte powder (most of the refractory diarrhea was analyzed to be secondary to disturbed microflora and electrolyte imbalances)
- at least 12 8 oz glasses of fluid daily, 8 of which should be electrolyte-enhanced

brought the rate of diarrhea-related drug omission or dose reduction down from 22% (MONARCH 1 and 2) to under 1 - 2% in the cohorts run by my research teams in India and the Middle East.
NOTE: We found that the adjunct interventions of Big Pink, high-dose probiotic, electrolyte rebalancing, and assured fluid intake were at least important as the conventional agents, and in cases that seem intractable, converted to success, given that therapy-driven diarrhea inevitably causes GI tract flora, and electrolyte, imbalances, aggravated by inadequate hydration. Also critical was "through-and-through" loperamide dosing: 4 mg at each episode, but NOT de-escalating - as current protocols do - down to 2 mg after first (that de-escalation regimen we found indifferently effective, with large numbers of failures.

And although not reported to date, I note that in the MONARCH 3 trials the incidence of ANY grade diarrhea dropped to just 2% (courtesy of data provided by Levi Garraway at Lilly).

ACTIVITY IN LOBULAR CARCINOMA
The trials largely fail to report to date differential invasive-type stats, but the impression from conversations with some principals is that lobular breast cancer subjects are unlikely to experience significant decrement, and I also extrapolate from some hints surrounding the PELOPS (Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study) Trial another CDK4/6 inhibitor palbociclib (Ibrance), as well as from some molecular considerations (the p27 gene is a key regulator of certain types of progression (G1 to S-phase) and it appears that lobular carcinomas tend to have higher p27 which in a complex way under contextual effects can have either positive or negative effects on phase progression), but we have to await sub-group analysis to report on this issue explicitly. I am cautiously confidant of little differential outcome, which I think may be confirmed across the general class of CDK inhibitors. In addition, both the lobular and the ductal groups appear to have benefited from the addition of palbociclib (Ibrance) in the PALOMA-/TRIO-18 Trial, but I note that the difference observed in PFS in that trial is likely to be an artificial artifact of the small patient in the subgroup with lobular carcinoma arm (n = 18/19) compared to n = 117 in the ductal subgroup, so this is a small sample size effect not a robust finding, an impression in agreement with that of the principal investigators (Richard Finn and UCLA and colleagues). As we learn more about lobular BC and abemaciclib in particular, I will offer further clarifications.

DEGREE OF DIFFERENCE - IBRANCE v VERZENIO
Given the dramatic 14-fold (!) greater CDK4 activity in abemaciclib (Verzenio) compared to palbociclib (Ibrance) and ribociclib (Kisqali), as MONARCH 3 lead author Angelo Di Leo has established and noted in interview, and other consequent fundamental molecular pathway differences, I view these as only shared-class (CDK), but therapeutically distinct, agents, more like the difference between third-generation capecitabine (Xeloda) versus first-generation 5-FU although these are both fluoropyrimidines.

So: More different than same as witness also the high degree of relative invariance of efficacy and durable response in later-line treatments for Verzenio compared to that of Ibrance (see my original posting, above). These differences are sufficient warrant for me to classify palbociclib (Ibrance) as a first-generation CDK inhibitor, and abemaciclib (Verzenio) as a second-generation CDK inhibitor. The devil - as always - is in the details.

CNS (BRAIN) ACTIVITY
We have preclinical data [Raub et al. Drug Metab Dispos. 2015] of the cross-BBB (blood-brain barrier) capability of Verzenio, as witness the remarkable benefit in GBM (glioblastoma, being even non-inferior to temozolomide (TMZ), the standard of care in cross-BBB activity, and this although not a human clinical, was an in vivo, not just in vitro, study. And the Dana-Farber JPBO human clinical trial (I3Y-MC-JPBO) under Sara Tolaney is investigating single-agent abemaciclib in patients with ER+/HER2+ brain metastases, where I fully expect clinically relevant CNS benefit to be confirmed, with first phase interim results reported in June at ASCO 2017 showing 2 patients (8.7%) out of 23 having confirmed partial response (PR).

I should point out that there has been some provisional data on palbociclib (Ibrance) having potential cross-BBB activity in brain metastasis, but I hasten to note that strong in vivo data show a 10-fold greater cross-BBB activity for abemaciclib than palbociclib, with abemaciclib brain levels being more efficient at substantially lower doses than palbociclib and also active for longer duration, and finally abemaciclib was active as monotherapy, palbociclib was not.

Finally, as to leptomeningeal metastases, no explicit data bears on this question directly, but as to date all agents active in brain metastases have also been active in leptomeningeal metastases, activity would be expected.

THE ISSUE OF SWITCHING
It remains an open question whether patients who have progressed on or after another CDK inhibitor like palbociclib (Ibrance) may derive significant benefit from continuance of CDK4/6 inhibition by using a following CDK inhibitor like abemaciclib (Verzenio), with many in-progress trials like TRINITI-120 (and NCT0185719319 and NCT0263204521, among others) exploring the issue. But there is some plausible extrapolation from some preclinical data which has suggested non–cross-resistance among CDK4/6 inhibitors. A Barts Cancer Institute study reported at SABCS 2016 found that some palbociclib(Ibrance)- and ribociclib(Kisqali)-resistant cell clones were sensitive to abemaciclib (Verzenio).

For patients now on Ibrance (or Kisqali) but who have NOT PROGRESSED , is it motivated to switch to abemaciclib (Verzenio)? This is an issue that needs to be thrashed about candidly with your oncology team and is a highly individual decision, but my own sense at this time is that it may be more optimal in the long run to stay the course, and consider abemaciclib (Verzenio) for recourse upon progression either off-label until the FDA expands its approval, or on one of the many abemaciclib (Verzenio) clinical trials available.

I would however entertain some specialized exceptions in which a switch now, off of Ibrance or Kisqali, onto abemaciclib (Verzenio), might be motivated; for example:

1. If a patient is experiencing repeated difficult-to-manage neutropenia, occasioning multiple drug interruptions or reductions (neutropenia being dramatically less with abemaciclib (Verzenio)), but the patient must weigh the associated countervailing issue of higher incidence - but still manageable I would argue - diarrhea on abemaciclib (Verzenio).
2. If a patient is in advanced later-line setting (say, more than 5 to 7 lines or so of treatment in the metastatic setting already completed), where it is suspected that abemaciclib (Verzenio) may be somewhat more consistent and durable in response and benefit in such challenging contexts. This is a difficult one to judgment-call, and I would tend to want to weigh each patient's circumstance and their complex treatment history and individual pathology to assist in the decision, since we have no hard data to be dispositive on this decision.

Yes, these are arguable and have to be intensively debated (as in a tumor board setting), but they are not wholly unreasonable. Outside of these exceptions, however, I do not see sufficient motivation to prematurely abandon Ibrance or Kisqali, as these have strong track records of efficacy and should be push to progression.

FDA APPROVAL

Abemaciclib is currently approved ...
1. as combination therapy with fulvestrant (Faslodex) for the treatment of women with HR+/HER2- advanced or metastatic breast cancer who experience disease progression AFTER ENDOCRINE therapy.

2. as monotherapy for the treatment of women with HR+/HER2- advanced or metastatic breast cancer who experience disease progression AFTER ENDOCRINE therapy AND prior CHEMOTHERAPY in the metastatic setting.

(Z) MO's have latitude to prescribe outside of these indications and there are strong arguments for doing so. My MO appears to have wide latitude to prescribe Abemaciclib and get insurance approval in other settings.

EXPANDED ACCESS:
Abemaciclib continues to be available through Lilly's attractive Expanded Access Program (EAP):
https://clinicaltrials.gov/ct2/show/NCT02792725?term=abemaciclib&rank=24
which is active and recruiting currently in several US locations (California, Florida, Minnesota, Missouri, Texas, and West Virginia), more being added. However that is for patients who have not as yet progressed on a previous CDK inhibitor like palbociclib (Ibrance), that is, for "switchers" who may want to explore the improved benefits of abemaciclib (Verzenio) over Ibrance (assuming the patient meet the other trial criteria); but not for patients who have already progressed on Ibrance.

RECHALLENGE

In several cases I have known, I counseled that although someone progressed on Ibrance, to reintroduce it after a hiatus of 3 - 6 months, and in many cases this washout appeared to resensitize the tumor cells to Ibrance, which upon re-introduction was newly effective. It is a variant of a trick I have counseled and seen working not infrequently with other agents like capecitabine (Xeloda) where after progression on it, I advised a trial on a new metronomic schedule (low-dose, continuous, daily, capecitabine) and seen again it newly effective despite previous progression, just by this shift I schedule (there is some provisional data for this, but not decisive). But these are beyond convention and reserved for highly special circumstances.

MARKERS THAT PREDICT RESPONSE TO CDK 4/6 INHIBITION
I am not convinced that there is any biomarker - protein or otherwise - that reliably identifies responsivity to CDK inhibitors, and Fabrice Andre of the Institut Gustave Roussy and colleagues, as reported in their presentation at ASCO 2017, were unable to identify any such biomarkers of response: neither Rb levels, p16 protein levels, Ki-67 cell proliferation, CDKN2A, CCND1, nor even ESR1 gene expression, all the usual suspects, and others, had any response-predictive value whatsoever. To date the only established biomarker for response to CDK4/6 inhibitors, remain hormone receptor positivity (HR+). Of course not everyone responds, but response rates remain historical high - and higher than any other treatment to date - and as long as one is HR+, one has the potential to benefit from a CDK inhibitor.

Constantine Kaniklidis
Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)
Oncology Reviewer, Current Oncology [journal]
Society for Integrative Oncology (SIO)
Member, European Association for Cancer Research (EACR)

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 18, 2018 12:13PM zarovka wrote:

Letrozol was hard on me, so I do understand. However, the various therapies are different in their effects. I am willing to try faslodex which many women say is easier. Faslodex with abemaciclib could potentially be more effective abemaciclib.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 18, 2018 12:40PM luce wrote:

zarovka: thanks. i hope faslodex works for you! i am just too attached to my estrogen to suppress it in any way. it is unfortunate that it happens to also fuel my cancer, sure, but the rest of my body needs it. i fully understand that i will die much sooner as a consequence.

Dx 12/12/2016, ILC/IDC, Left, Stage IV, metastasized to bone/lungs/other, Grade 2, 0/3 nodes, ER+/PR+, HER2-
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Jan 18, 2018 12:45PM JFL wrote:

Luce, I totally understand the attachment to estrogen. It is definitely the "feel good" hormone for me too. I continue to mourn that. If you ever do take the plunge in the future for hormone therapy, Cymbalta (the antidepressant) is a miracle drug for eliminating joint pain. I asked my MO what could help me with joint pain that wasn't an opiod and he prescribed it. It also helped with my bone pain.

Chart your own course. Dx at 30. Dx with mets at 38 while pregnant - extensive liver & bone involvement. Currently on Enhertu & XGeva. ER+/PR+, HER2-low (IHC equivocal, +2/FISH negative). Y90 liver radioembolization in 2018. Dx 9/2006, IDC, Right, 1cm, Stage IIB, Grade 3, 1/16 nodes, ER+/PR+, HER2- (FISH) Surgery 9/22/2006 Mastectomy: Left, Right Chemotherapy 11/6/2006 Adriamycin (doxorubicin), Cytoxan (cyclophosphamide), Taxotere (docetaxel) Hormonal Therapy 3/15/2007 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Dx 12/2014, IDC, Stage IV, metastasized to bone/liver/other, Grade 3, ER+/PR-, HER2- Surgery 12/26/2014 Prophylactic ovary removal Hormonal Therapy 12/26/2014 Aromasin (exemestane), Faslodex (fulvestrant) Targeted Therapy 6/18/2015 Ibrance (palbociclib) Chemotherapy 3/10/2016 Xeloda (capecitabine) Hormonal Therapy 5/14/2017 Aromasin (exemestane) Targeted Therapy 5/14/2017 Afinitor (everolimus) Chemotherapy 8/18/2017 Abraxane (albumin-bound or nab-paclitaxel) Chemotherapy 3/23/2018 Doxil (doxorubicin) Chemotherapy 4/26/2019 Navelbine (vinorelbine) Hormonal Therapy 4/26/2019 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Chemotherapy 11/27/2019 Gemzar (gemcitabine) Hormonal Therapy 8/25/2020 Faslodex (fulvestrant) Targeted Therapy 8/25/2020 Piqray (alpelisib) Targeted Therapy 10/2/2020 Enhertu (fam-trastuzumab deruxtecan-nxki)
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Jan 18, 2018 02:05PM NettaGER wrote:

JFL: Even though not being on Abemaciclib but on Ibrance, may I ask you how you tolerated the side effects of Cymbalta wrt diarrhea? I just tried Venlafaxine (Effexor, which is the same class of antidepressants) last week and had to stop it, because of extensive side effect. I am afraid that Duloxetine/Cymbalta would have the same side effect. On the other side, I was already able to tolerate the side effects of the antihormonal therapy much better during those few days on Venlafaxine.

Dx 8/31/2017, IDC, Right, 6cm+, Stage IV, metastasized to bone, Grade 2, ER+/PR+, HER2- (FISH) Targeted Therapy 9/15/2017 Ibrance (palbociclib) Hormonal Therapy 9/15/2017 Femara (letrozole), Zoladex (goserelin)
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Jan 18, 2018 02:13PM zarovka wrote:

Right now I am only doing lupron which suppresses my estrogen to non-detect levels and I feel pretty good. It is clear now it was the letrozol and ibrance that made me stupid, tired and gave me joint pain and neuropathy. My point is that, for me, the lack of estrogen alone isn't bad.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 18, 2018 02:39PM ShetlandPony wrote:

Luce, Faslodex typically has the fewest side effects of the endocrine therapies and it is more targeted than aromatase inhibitors. so it might be worth considering at some point. I agree with you that it is barbaric to deplete our whole body of estrogen with aromatase inhibitors. But I was able to put up with letrozole while it was working. Z, my first mbc treatment, Taxol. made me post-menopausal. so presumably fairly low estrogen, but I definitely feel better in many ways being off that letrozole. I feel like being allowed to have whatever small amount of estrogen my body still makes, makes a difference. Yes, I just said I prefer these chemo pills to I+L.

Z, regarding the info you copied from Constantine at the top of this thread -- How do you interpret his comments on abemaciclib's efficacy for ILC? What is he saying? That he suspects lobular histology will not make a difference? I am willing to put this drug on my short list of what's next, with a plan to do everything possible to prevent diarrhea, if it makes sense for ILC.

2011 Stage I ITCs sn, premenopausal, Oncotype 16. 2014 Stage IV mets breast,liver. TaxolNEAD. Ibrance+letrozole 2yrs. Fas+afinitor nope. XelodaNEAD 2yrs. Eribulin,Doxil nope. SUMMIT FaslodexHerceptinNeratinib for Her2mut NEAD 1 1/2yrs. GI/perit mets Dx 2011, ILC, 1cm, Stage IA, Grade 1, 0/1 nodes, ER+/PR+, HER2- Dx 2014, ILC, 2cm, Stage IV, metastasized to liver/other, Grade 2, ER+/PR+, HER2- Hormonal Therapy Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Radiation Therapy Whole-breast: Breast Surgery Lumpectomy
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Jan 18, 2018 03:18PM zarovka wrote:

Shetland - Constantine is extrapolating from Ibrance trial data and from abemaciclib trial data that doesn't adequately segregate ILC for IDC type MBC. He hedges and falls into using big words unnecessarily, which people do when they are worried whether what they are saying is solid. However, the limited data available suggests that ILC and IDC will respond to abemaciclib about the same and there isn't any reason to expect otherwise. Keep it on your list, watch for more data.

I am very glad that you prefer xeloda to I+L. Xeloda is chemo and Xeloda is awesome. Very effective. Xeloda is on my short list, but probably after abemaciclib and/or faslodex. I have some concerns because I took a low dose of a Xeloda like drug (TS-1) in japan. After 3 doses, I broke out in a scary scary rash. I am still going to try Xeloda. I am starting at very low dose when I do.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 18, 2018 03:25PM ShetlandPony wrote:

"Keep it on your list, watch for more data" is just about exactly what my onc said!

Agree with putting X on your short list, and starting low.

2011 Stage I ITCs sn, premenopausal, Oncotype 16. 2014 Stage IV mets breast,liver. TaxolNEAD. Ibrance+letrozole 2yrs. Fas+afinitor nope. XelodaNEAD 2yrs. Eribulin,Doxil nope. SUMMIT FaslodexHerceptinNeratinib for Her2mut NEAD 1 1/2yrs. GI/perit mets Dx 2011, ILC, 1cm, Stage IA, Grade 1, 0/1 nodes, ER+/PR+, HER2- Dx 2014, ILC, 2cm, Stage IV, metastasized to liver/other, Grade 2, ER+/PR+, HER2- Hormonal Therapy Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Radiation Therapy Whole-breast: Breast Surgery Lumpectomy
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Jan 18, 2018 04:24PM - edited Jan 18, 2018 04:26PM by luce

shetland: i asked my oncologist about lobular and abemaciclib last week, and he agrees with constamtine and zarovka, although of course there is ALWASY way less data for lobular. i had both lobular and ductal (both invasive, and both in situ also) on my oriiginal diagnosis, and my oncologist and i suspect my recurrence is lobular. lobular has always felt like such a wild card to me. i even read a paper once that said that while lobular usually responds to anti-endocrine therapy, sometimes (if rarely) it responds the opposite way and gets fueled by it.

as for endocrine therapy. i just have no interest in it. after decades of eating disorders and not wanting to be a woman (or even have breasts at all), i only came to embrace my femininity and be comfortable with my body and being a woman a year or two before being diagnosed. the irony, of suddenly having the option of having my breasts removed, and effectively be put into extreme (since your body of course still produces estrogen in natural menopause) menopause (i am premenopausal. not even peri-menopausal), just as i wasn't interested in either anymore!

Dx 12/12/2016, ILC/IDC, Left, Stage IV, metastasized to bone/lungs/other, Grade 2, 0/3 nodes, ER+/PR+, HER2-
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Jan 18, 2018 06:09PM amarantha wrote:

After reading the opening post I am wondering if abemaciclib can still be a possibility after a bout with Halaven ?

IBC metastasic, ER+. Tx: Gezmar, Decadron. Past txx : Xeloda, Halaven, Cisplatin, Afinitor/Aromasine, Ibrance/Faslodex, Tamoxifen, mastectomy x 2, chemo-radiation with Cisplatin x 2, CEF, Taxotere, Carboplatin, + the kitchen sink
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Jan 18, 2018 06:43PM zarovka wrote:

luce - you make a lot sense, as always.

amarantha - the phase I trial of abemaciclib was on a group of women who had had multiple lines of traditional chemo. they had a surprisingly good response on a population where you are almost not expected to get a response. so, yes. abemaciclib may be your best option after a bout with Halaven.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 18, 2018 07:19PM - edited Jan 18, 2018 07:23PM by ShetlandPony

That is such encouraging news, Zarovka. I am glad that abemaciclib can be used as a monotherapy, since endocrine therapies have not been very good in my case. It sounds like we are in the same boat, amarantha, with cancer no longer "functionally ER positive" as my onc puts it. It is great to have treatments on our lists that are not full-on chemo.

Yes, luce, I have seen many articles about tamoxifen promoting tumor growth under certain genetic circumstances, and also that a subset of ILC does not respond. In my case, I think the cancer was de novo resistant and even fueled by tamoxifen, and/or I did not metabolize it properly; while at the same time the drug raised the estrogen level very high in my premenopausal body by stimulating my ovaries, as evidenced by blood tests and uterine fibroid growth. Epic fail. (I'll say here that for many women Tamoxifen does work well.) It sounds like you have a very good sense of what you are and are not willing to do, luce. You are in charge of you.


2011 Stage I ITCs sn, premenopausal, Oncotype 16. 2014 Stage IV mets breast,liver. TaxolNEAD. Ibrance+letrozole 2yrs. Fas+afinitor nope. XelodaNEAD 2yrs. Eribulin,Doxil nope. SUMMIT FaslodexHerceptinNeratinib for Her2mut NEAD 1 1/2yrs. GI/perit mets Dx 2011, ILC, 1cm, Stage IA, Grade 1, 0/1 nodes, ER+/PR+, HER2- Dx 2014, ILC, 2cm, Stage IV, metastasized to liver/other, Grade 2, ER+/PR+, HER2- Hormonal Therapy Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Radiation Therapy Whole-breast: Breast Surgery Lumpectomy
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Jan 19, 2018 03:01PM booboo1 wrote:

Z,

So glad you are in this thread. I appreciate very much your knowledge and for being so good to pass along what you know. Thank you.

I hope you are doing better (I think I read that you were in some pain)

Laurie (aka Booboo) #metastaticbreastcancer Dx 3/1/2013, IDC, Left, 1cm, Stage IIA, Grade 2, 1/4 nodes, ER+/PR+, HER2- (FISH) Surgery 5/15/2013 Lumpectomy: Left; Lymph node removal: Sentinel Dx 1/2017, DCIS, Left, 1cm, Stage 0, metastasized to bone/liver, Grade 2, 1/4 nodes, ER+/PR+, HER2- (FISH) Chemotherapy Xeloda (capecitabine) Hormonal Therapy Faslodex (fulvestrant) Hormonal Therapy Femara (letrozole) Targeted Therapy Ibrance (palbociclib) Chemotherapy AC + T (Taxol) Radiation Therapy 3DCRT: Breast
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Jan 20, 2018 07:05PM Mostcapable wrote:

Hello all:

I have just completed 6 days on abemaciclib/letrozole and wanted to report my experience. So far (knock on wood) I have been tolerating these drugs well. A few little stomach rumbles but that's it. I do experience a weird taste in my mouth. Not sure what that's about. And, I think the letrozole is keeping me up throughout the night - going to switch that pill to the morning to see if that helps. Hoping I keep tolerating this combo well and that it works.

Last year was quite a year for me. I was on the Gedatolisib trial and had to stop after a few treatments because of a terrible rash that was potentially life threatening. Only took the palbo part for a short time too. I decided I wanted to only take faslodex. I feel the Gedatolisib and the resulting issues caused me to be hypercalcemic which then led to needing zometa. I think I the zometa led to the fracture in my vertebrae. These are my theories of course - for what they are worth. Long story short, I was on Faslodex for a little while and that caused some very loose stools. As a result, i feel that the combo of Faslodex with abemaciclib will result and more stomach disturbances than the letrozole/abemaciclib combo. Just a theory.

Maybe when the faslodex pill is introduced (my MO told me it's in clinical trials) that will lessen the stomach issues. I don't get to research as much as you guy but thought I'd share my experience and thoughts since I'm taking this drug.



Dx 10/8/2013, IDC, Right, Stage IV, metastasized to bone/liver, ER+/PR+, HER2- Hormonal Therapy 10/31/2013 Zoladex (goserelin) Hormonal Therapy 11/1/2013 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Hormonal Therapy 7/31/2015 Arimidex (anastrozole) Hormonal Therapy 1/8/2017 Faslodex (fulvestrant) Targeted Therapy 1/8/2017 Ibrance (palbociclib) Targeted Therapy 1/8/2017 Targeted Therapy 1/13/2018 Hormonal Therapy 1/14/2018 Femara (letrozole) Hormonal Therapy Aromasin (exemestane) Targeted Therapy Afinitor (everolimus)
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Jan 20, 2018 07:45PM zarovka wrote:

Mostcapable - Thank you so much for sharing your experience. Keep it coming. Your experience and theories are more useful than any paper ... I hope this protocol gives you a long easy run.

Please check back soon with updates.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 20, 2018 08:05PM PatgMc wrote:

Z, I'm happy to find you here tonight. I've missed your posts on the Ibrance thread and I hope you're doing well. I haven't read through all the posts to see.

My oncologist is enthusiastic about Verzenio and has been considering a switch for me. I've had a 6 week Ibrance break while ill with flu/pneumonia. I was planning on a one-month break anyway due to side effects after 15 cycles on 100mg. > mind-numbing fatigue, heartburn and increasing nausea. Anyway, after considering everything, the oncologist recommended that I remain on Ibrance since it has worked so well for me from the beginning....widespread bone mets and one soft tissue tumor which all appeared to be increasingly inactive at a 3-month PET/CT and now have almost zero uptake. I will begin 75mg. Ibrance tomorrow.

The other thing he's doing is sending off tissue to test for the biomarker indicating potential response to Keytruda. Looks like we will scan in 4 months to see if the Ibrance has kept things under control and if not, switch to Verzenio. I'm happy you've started this thread! Thank you.

PatGMc Dx 2/1994, IDC, Left, 4cm, Stage IIB, Grade 3, 0/15 nodes, ER-/PR- Dx 3/2002, IDC, Right, <1cm, Stage IA, Grade 1, 0/3 nodes, ER+/PR+, HER2+ (FISH) Dx 3/2012, IDC, Right, 4cm, Grade 3, ER+/PR+, HER2- Dx 9/2016, IDC, 0/16 nodes, ER+/PR+, HER2- Targeted Therapy 10/1/2016 Ibrance (palbociclib) Surgery Lymph node removal; Mastectomy; Reconstruction (left): Pedicled TRAM flap Chemotherapy Carboplatin (Paraplatin), Taxol (paclitaxel) Surgery Lymph node removal; Mastectomy; Reconstruction (right): Tissue expander placement Chemotherapy FAC
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Jan 20, 2018 08:59PM artistatheart wrote:

Shetland and Z,

I too am happy to hear that this drug could benefit ILC. I feel like ILC is a bit of the "orphan" subtype which is scary and confusing. More research!

Dx 7/22/2015, ILC, Left, 4cm, Stage IV, Grade 3, ER+/PR+, HER2- Hormonal Therapy 8/10/2015 Femara (letrozole) Targeted Therapy 8/25/2015 Ibrance (palbociclib) Hormonal Therapy Faslodex (fulvestrant)
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Jan 21, 2018 05:06AM Mostcapable wrote:

Thank you Z! I will keep up the updates! Thank you for sharing your knowledge and experience as well!

Dx 10/8/2013, IDC, Right, Stage IV, metastasized to bone/liver, ER+/PR+, HER2- Hormonal Therapy 10/31/2013 Zoladex (goserelin) Hormonal Therapy 11/1/2013 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Hormonal Therapy 7/31/2015 Arimidex (anastrozole) Hormonal Therapy 1/8/2017 Faslodex (fulvestrant) Targeted Therapy 1/8/2017 Ibrance (palbociclib) Targeted Therapy 1/8/2017 Targeted Therapy 1/13/2018 Hormonal Therapy 1/14/2018 Femara (letrozole) Hormonal Therapy Aromasin (exemestane) Targeted Therapy Afinitor (everolimus)
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Jan 22, 2018 03:20PM - edited Jan 22, 2018 03:28PM by thria157

Hello everyone

Do you see better results with your RBC on verzenio than on ibrance


Any idea what this will come to Europe

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Jan 22, 2018 04:04PM zarovka wrote:

In the trials Abemaciclib, was harder on the gut but easier on the blood counts generally.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 23, 2018 02:22AM thria157 wrote:

thanks a lot Z.

Does anyone knows when this will be approved by the EU

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Jan 23, 2018 05:26AM zarovka wrote:

I don't know but talk to your doctor. These companies have compassionate use programs. They like to get the buzz in advance of approval. It helps build market share. The point being it's not entirely altruistic, they have a reason for doing this that works for you.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 23, 2018 12:33PM warriorprincess2006 wrote:

Hello everyone!

While I am new to this forum, I am NOT new to breast cancer. I was diagnosed with Stage 2 ER+/PR+ Invasive Lobular BC with impact to nodes in 2006, at the age of 37. Lumpectomy & 13 nodes removed, plus 4.5 months of Taxotere/Adriamycin/Cytoxan chemo & 33 rounds of breast/node radiation. Started Tamoxifen post-treatment and didn't tolerate well, so took my chances and stopped after 1 month. 4 years later, in 2010, mets were found on my ribs and spine, and ascites in my peritoneum (for which I had 2 separate paracentesis procedures) ...started Tamoxifen back up (along with monthly infusions of Zometa for 1 year before switching to Xgeva injections), but due to SEVERE emotional mood swings was terribly inconsistent about taking it.

Needless to say, after 4 years (2014), my cancer, which had been mostly stable, started to progress. I switched to monthly Zoladex injections (while continuing the Xgeva) and started on aromatase inhibitors (first Femara, then Arimidex, then Aromasin). I had incapacitating bone & joint pain on the first two drugs, and while the Aromisin didn't cause as many side effects, it also wasn't as effective. By this point (2017), my bone scan lit up like a Christmas tree... I had multiple lesions throughout my spine & several on my ribs, hip joints, femur & skull, recurring ascites in my peritoneum and my tumor markers were slowly climbing month by month. It was time to bring in the big guns – so I started on 150 mg daily Ibrance with monthly Faslodex (fulvestrant) injections.

The first month, I was exhausted beyond belief…I barely left my bed and when I would climb just a single flight of stairs, my breathing was so labored and my heart rate so elevated, I would nearly pass out. In addition, my blood counts were completely wiped, almost to the point of requiring a blood transfusion. So, I took a break for a couple of weeks, and we titrated down to 100 mg tabs of Ibrance (again, taking 3 weeks on & 1 week off). Resulted in very minimal, if any, change to my blood counts, fatigue & anemia; so, after a short break, we tried another round at the lowest dose (75mg). Symptoms did not improve, and I made the decision to stop.

Around the same time, I had decided to change oncologists (for a multitude of personal reasons, but mainly because I had been doing research on immunotherapy clinical trials for a year and found the perfect onc in my area). The first set of baseline bone & CT scans ordered by my new M.O. showed marked improvement of my mets (ironically credited to the Ibrance, but not enough of a motivator to continue taking & living such a poor quality of life), so I decided to stay the course of continuing Xgeva, Zoladex and Faslodex for a while. 1st and 2nd months with my new doc showed increasingly elevated tumor markers, and by month 3 it was scan time. My scans were worse than ever and my ascites was starting to impact my breathing & made eating/drinking uncomfortable.

Enter Verzenio (I am the very first patient my onc has prescribed this to, and the clinical pharmacist & triage/oral chemo nurse are also all new to this drug – so, we are learning together). Started on 150mg twice daily yesterday…had terrible rumbling in my tummy last night and quite a bit of fatigue yesterday and today; but, I am hopeful this drug will be tolerable and effective.

Keep in mind that I have been living with MBC for nearly 8 years now (12 years since initial diagnosis); and, while it's been a physical & emotional rollercoaster, and I have been a less than medically compliant patient, I am extremely thankful that my organs are all still clear.

I look forward to following along with all of your journeys and learning more about the research and positive effects of this new medication.

Love to all of you!!!

Jamie

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Jan 23, 2018 01:10PM Moderators wrote:

warriorprincess2006, wow, thank you for sharing your experiences with us here. It is always really inspiring to hear your story, and we send you love as well!


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To send a Private Message to the Mods: community.breastcancer.org/mem...
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Jan 23, 2018 02:28PM zarovka wrote:

Jamie - welcome, we're hoping for the best possible outcome and waiting for your next report. it's new to many people so these experiences are of great interest.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 24, 2018 10:18AM letmywifelive wrote:

Joining this group formally. My wife will be starting on Verzenio + Faslodex combo from tomorrow. She previously progressed on Ibrance + Letrozole combo about a year back and since then on been on chemo. Let's see how this works out.

Dx 10/2013, ILC/IDC, Left, Stage IIB, 2/2 nodes, ER+/PR+, HER2- Dx 2/2016, Stage IV, metastasized to bone, ER+/PR+, HER2- Dx 1/2017, Stage IV, metastasized to liver, ER+/PR-, HER2- Radiation Therapy Whole-breast: Breast, Lymph nodes Radiation Therapy External: Bone Chemotherapy AC + T (Taxol) Hormonal Therapy Femara (letrozole) Targeted Therapy Ibrance (palbociclib) Hormonal Therapy Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Chemotherapy Xeloda (capecitabine) Chemotherapy Halaven (eribulin)
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Jan 24, 2018 10:22AM zarovka wrote:

Welcome. Good to see you again, but also not. Wish this was over for all of us.

>Z<

Ibrance/Letrozol Feb '16 -Sep '17. Adoptive Cell Therapy Oct 2017. Jan 2018 SBRT to sternum met and liver mets. Jan 2018 start Faslodex. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/16/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jan 24, 2018 06:15PM Moissy wrote:

LMWL - I hope your wife has a great response on this treatment! If you don't mind my asking, did you encounter any pushback from insurance since there was previously progression on Ibrance? I'm hoping to go on Verzenio in the future and my onc said not all insurances are approving this sequence right now.

Dx 2004, IDC, 6cm+, Grade 2, 0/1 nodes, ER+, HER2- Dx 2015, Stage IV, ER+/PR+, HER2-
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Jan 24, 2018 06:28PM letmywifelive wrote:

Hi Moissy, no we did not get any push back from insurance.

Dx 10/2013, ILC/IDC, Left, Stage IIB, 2/2 nodes, ER+/PR+, HER2- Dx 2/2016, Stage IV, metastasized to bone, ER+/PR+, HER2- Dx 1/2017, Stage IV, metastasized to liver, ER+/PR-, HER2- Radiation Therapy Whole-breast: Breast, Lymph nodes Radiation Therapy External: Bone Chemotherapy AC + T (Taxol) Hormonal Therapy Femara (letrozole) Targeted Therapy Ibrance (palbociclib) Hormonal Therapy Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Chemotherapy Xeloda (capecitabine) Chemotherapy Halaven (eribulin)
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Jan 24, 2018 06:44PM Moissy wrote:

That's great to hear. Wishing your wife well on this

Dx 2004, IDC, 6cm+, Grade 2, 0/1 nodes, ER+, HER2- Dx 2015, Stage IV, ER+/PR+, HER2-

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