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11-28-2010, 12:45 AM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herceptin
Mod Pathol. 2010 Nov 19. [Epub ahead of print]
Semiquantitative hormone receptor level influences response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer.
Bhargava R, Dabbs DJ, Beriwal S, Yildiz IA, Badve P, Soran A, Johnson RR, Brufsky AM, Lembersky BC, McGuire KP, Ahrendt GM.
Department of Pathology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.
Abstract
Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in hormone receptor-negative/HER2+ tumors is seen in 27-45% of cases. In contrast, estrogen receptor (ER)+/HER2+ tumors demonstrate pathologic complete response in ∼8% of cases and is generally limited to weak-to-moderate ER+/HER2+ tumors. It is speculated that addition of trastuzumab to neoadjuvant chemotherapy regimen will increase the pathologic complete response rates in all HER2+ tumors. A list of HER2+ patients who received neoadjuvant chemotherapy (with trastuzumab) in the years 2007-2010 was obtained from our hospital database. The 104 HER2+ tumors were classified into three groups based on semiquantitative hormone receptor and HER2 results as follows: ERBB2 (ER-/PR-[H-score ≤10]/HER2+), Luminal B-HER2 Hybrid (LBHH; weak to moderate ER+ [H-score 11-199]/HER2+), and Luminal A-HER2 Hybrid (LAHH; strong ER+[H-score ≥200]/HER2+). Pathologic complete response was defined as absence of invasive carcinoma in the resection specimen and in the lymph nodes. Percentage tumor volume reduction was also calculated based on pretherapy size and detailed evaluation of the resection specimen. In all, 52% (25 of 48 cases) of ERBB2 tumors showed pathologic complete response, which was significantly higher than the pathologic complete response rate in LBHH (33%; 10 of 30) and LAHH (8%; 2 of 26) tumors. Average percentage tumor volume reduction was also highest in ERBB2 tumors (86%), followed by LBHH (74%) and LAHH (64%) tumors. We conclude that addition of trastuzumab to neoadjuvant chemotherapy regimen significantly increases the pathologic complete response rates in all HER2+ tumors. However, the benefit of trastuzumab is highest in ER-negative tumors and progressively decreases with increase in tumor ER expression. This information can be utilized to counsel patients considered for neoadjuvant chemotherapy and the same principle could be applied in the adjuvant setting.Modern Pathology advance online publication, 19 November 2010; doi:10.1038/modpathol.2010.209.
PMID: 21102420 [
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11-28-2010, 02:05 AM
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#2
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Senior Member
Join Date: Feb 2007
Location: Paris, France
Posts: 858
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Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
Hi Lani. Thank you once more for sharing such interesting findings.
I had neo adjuvant chemo. My tumor diminished during the 2 first FEC cycles and then stopped. I had imagery then before starting the 12 weeks of Taxol Herceptin. Imagery again after these cycles showed no benefit. I am 90% ER+ which is LAHH from what I understand. My onc fought to get me Lapatinib for a year a year of Herceptin hoping it would work better for me than herceptin. At the time we did not know that a combination of Herceptin and Lapatinib together may have been better. (may not be true for LAHH)
As you see 4 years later I have a liver met. What options are left for LAHH? Hormonotherapy alone is not enough. I figure it has to be combined with something. But what?
Thank you again Lani. I'll show this article to my onc.
Michka
__________________
08.2006 3 cm IDC Stage 2-3, HER2 3+ ER+90% PR 20%
FEC, Taxol+ Herceptin, Mastectomy, Radiation, Herceptin 1 year followed by Tykerb 1 year,Aromasin /Faslodex
12.2010 Mets to liver,Herceptin+Tykerb
03.2011 Liver resection ER+70% PR-
04.2011 Herceptin+Navelbine+750mg Tykerb
06.2011 Liver ned, Met to sternum. Added Zometa 09.2011 Cyberknife for sternum
11.2011 Pet clear. Stop Navelbine, continuing on Hercpetin+Tykerb+Aromasin
02.2012 Mets to lungs, nodes, liver
04.2012 TDM1, Ned in 07.2012
04.2015 Stop TDM1/Kadcyla, still Ned, liver problems
04.2016 Liver mets. Back on Kadcyla
08.2016 Kadcyla stopped working. mets to liver lungs bones
09.2016 Biopsy to liver. no more HER2, still ER+
09.2016 CMF Afinitor/Aromasin/ Xgeva.Met to eye muscle Cyberknife
01.2017 Gemzar/Carboplatin/ Ibrance/Faslodex then Taxotere
02.2017 30 micro mets to brain breathing getting worse and worse
04.2017 Liquid biopsy/CTC indicates HER2 again. Start Herceptin with Halaven
06.2017 all tumors shrunk 60% . more micro mets to brain (1mm mets) no symptoms
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11-29-2010, 12:14 AM
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#3
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Senior Member
Join Date: May 2010
Location: Melbourne, Australia
Posts: 434
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Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
Thanks again Lani-as ever your posts extremely useful. Does this suggest that herceptin with an anti hormonal agent would have a better chance of effectiveness? My onc reluctant to add one in while I am on Abraxane as apparently there is some data about taxanes being less effective when taken with Tamoxifen.She is open to persuasion though.
Trish
__________________
5/2004 (R) 30mm bre gr3 infiltrating ductal ca 16/18nodes er (2+) pr (3+) HER2 (3+)
6/2004 6 cycles(FEC), Oct 40 rads, Tamoxifen
5/2006 oopherectomy, Arimedex
12/2006 liver mets largest 9cm
1/2007 Herceptin,
3/2007 Taxol + Herc
1/2008 Herc alone
4/2008 Multiple bone mets,Zometa
7/2008 Herc + Gemcitabine
8/2008 Herc+Navelbine/vinoralbine
10/2008 Herc+Carboplatin+Taxol
12/2008 Tykerb+Xeloda
2/2010 Herceptin + trial drug
5/2010 Herceptin+Tykerb
8/2010 Tykerb+Abraxane
9/2010 Abraxane
12/2010 Abraxane+Tyk+Herc
4/2011 Tyk+Herc+Femara
6/2011 Liver and bone mets prog.Abraxane continue Herceptin,Tykerb,Femara and Zometa
8/2011 Probable liver progression and increased neuropathy. Xeloda with Tyk+Herc. Zometa 6 weekly.
9/2011 Liver progression,TM +++. Cyclophosphamide and Methotrexate metro Herc Zometa
10/2011 liver mets prog.Herc, 3 Tykerb +2mg decodron daily,Zometa
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12-01-2010, 08:59 AM
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#4
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Senior Member
Join Date: Aug 2009
Location: Owasso, OK
Posts: 185
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Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
Thanks, Lani. Great article.
__________________
Hayley
Oklahoma
3/35/2009 - Diagnosed, age 39
5/7/09 - Mastectomy and reconstruction started. Two tumors found. Tumors were side by side. DCIS tumor was 2.8 cm, ER-, PR-, grade 2. Invasive tumor was 1.1 cm, poorly differentiated, grade 3, ER+90%, PR+95%, HER2+3. Thankfully, no node involvement.
5/29/09 - Second surgery resulting from difficulty healing from mastectomy.
6/2/09 - Began Herceptin treatments
6/23/09 - Began Taxotere and Carboplatin treatments along with Herception every 3 weeks.
10/06/09 - Completed Taxotere and Carboplatin - Yeah!!!
10/27/2009 - Herceptin maintenance and began Femara
12/10/2009 - 2nd stage reconstruction surgery
2/2010 - Body rejected saline implant
3/18/2010 - Second stage reconstruction using silicone implant
5/4/10 - Completed Herceptin - YEE-HAA!
May '10 - Body rejects silicone implant...taking a break.
11/29/10 - Hysterectomy
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12-01-2010, 10:59 AM
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#5
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Senior Member
Join Date: Dec 2009
Posts: 56
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Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
I am assuming these study results can also be valuable to adjuvant chemo/herceptin?
__________________
Diagnosed 7/09 with 7mm IDC ER weakly +, PR -, Her2+
TCH chemo 8/09-12/09
Ooph/hysterectomy 4/10
Started Femara 6/10
Completed year of herceptin 10/11
Zometa 1/11 (2X/yr for 2yrs)
Hopefully nothing else!!!!
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12-01-2010, 07:02 PM
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#6
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Senior Member
Join Date: May 2008
Location: Hershey, PA. Live The Sweet Life!
Posts: 2,005
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Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
Sucky news for us triple positives.
__________________
Smile On!
Laurel
Dx'd w/multifocal DCIS/IDS 3/08
7mm invasive component
Partial mast. 5/08
Stage 1b, ER 80%, PR 90%, HER-2 6.9 on FISH
0/5 nodes
4 AC, 4 TH finished 9/08
Herceptin every 3 weeks. Finished 7/09
Tamoxifen 10/08. Switched to Femara 8/09
Bilat SPM w/reconstruction 10/08
Clinical Trial w/Clondronate 12/08
Stopped Clondronate--too hard on my gizzard!
Switched back to Tamoxifen due to tendon pain from Femara
15 Years NED
I think I just might hang around awhile....
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12-02-2010, 07:45 AM
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#7
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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Re: her2+ tumors with high ER level respond differently2treatmnt-chemo or chemo+herce
What I take from this is just substantiation of the previously demonstrated effect that chemotherapy is not the most effective treatment for hormone positive patients, and that adding Herceptin to it doesn't change that. A more revealing test of the efficacy of Herceptin in this population, IMO, would be treating highly hormone positive, Her2+ ("luminal A Her2+") patients with neoadjuvant endocrine therapy, with our without Herceptin.
Hopeful
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