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08-14-2007, 05:48 AM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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her2 and ER and PR status are age-related--triple positive bc occurs ~5 yrs earlier
Breast Cancer Res Treat. 2007 Aug 9; [Epub ahead of print]
Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer.
Neven P, Van Calster B, Van den Bempt I, Van Huffel S, Van Belle V, Hendrickx W, Decock J, Wildiers H, Paridaens R, Amant F, Leunen K, Berteloot P, Timmerman D, Van Limbergen E, Weltens C, Van den Bogaert W, Smeets A, Vergote I, Christiaens MR, Drijkoningen M.
Department of Obstetrics and Gynaecology, Multidisciplinary Breast Centre, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium, Patrick.neven@uz.kuleuven.ac.be.
BACKGROUND: : The negative association between the oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER-2) in breast cancer travels in both directions. ER(+) tumours are less likely HER-2(+) and HER-2(+) tumours are less likely ER(+). METHODS: : We studied the age-related immunohistochemical (IHC) expression of ER, progesterone receptor (PR) and HER-2 in 2,227 tumours using age as a continuous variable. Steroid receptors were considered positive for any nuclear staining of invasive cancer cells and for HER-2, either for strong expression by IHC (score 3(+)) or gene amplification by fluorescence in situ hybridisation (FISH). Based on nonparametric regression, the age-related association between steroid receptors and HER-2 was presented as likelihood curves. RESULTS: : The association between ER or PR and HER-2 is age-related. The age-related expression of ER and PR is HER-2 dependent. In HER-2(-) cases, the odds ratio (OR) for being ER(+) was 2.594 (95% CI = 1.874-3.591) up to age 50 and age-independent thereafter; for PR-expression the OR was 2.687 (95% CI = 1.780-4.057) up to age 45 and 0.847 (95% CI = 0.761-0.942) thereafter. In HER-2(+) cases, the OR was 0.806 (95% CI = 0.656-0.991) to be ER(+) and 0.722 (95% CI = 0.589-0.886) to be PR(+). The age-related OR for breast cancers to be HER-2(+) is steroid receptor dependent. Taking together, ER(+)PR(+)HER-2(+) breast cancers appear on average 5.4 years earlier than breast cancers of any other ER/PR/HER-2 phenotype (95% CI = 3.3-7.5; P < 0.0001). CONCLUSION: : There is a qualitative interaction between age and expression of steroid and HER-2 receptors. Our findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER(+)PR(+)HER-2(+) subgroup.
PMID: 17687649 [PubMed - as supplied by publisher]
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08-14-2007, 08:38 AM
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#2
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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Lani,
Thank you VERY much for posting this abstract.
Hopeful
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08-14-2007, 09:21 AM
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#3
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Senior Member
Join Date: Oct 2005
Posts: 3,519
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Normally I can sort of decipher these, but not this one. Can anyone put it in layman's terms for me?
__________________
Brenda
NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)
Nov'03~ dX stage 2B
Dec'03~ Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~ Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~ micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~ micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg
Apr'07~ MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~ Started Tykerb/Xeloda, no WBR for now
June'07~ MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~ MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~ PET/CT & MRI show NED
Apr'08~ scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~ MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~ dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~ Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~ new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~ new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~ 25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.
"I would rather be anecdotally alive than statistically dead."
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08-14-2007, 09:48 AM
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#4
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Senior Member
Join Date: Aug 2006
Posts: 492
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I think they are saying on average triple + bc is seen in younger women. 5 years younger than average age of other types bc.
Ding, ding, ding.... I am a winner. Triple + at 38 years young.
"Our findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER(+)PR(+)HER-2(+) subgroup."
Now what exactly is the growth advantage? I have always wondered if oral contraceptive use combined with delayed or no childbirth is an inconvenient combo.
__________________
Are we there yet?
Dx 10/05 IDC, multi-focal, triple +, 5 nodes+
MRM, 4 DD A/C, 12 weekly taxol + herceptin
rads concurrent with taxol/herceptin
finished herceptin 01/08
ooph, Arimidex, bilateral DIEP reconstruction
NED
Univ. of WA, Seattle vaccine trial '07
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08-14-2007, 10:56 AM
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#5
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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selective growth advantage assumes that
there are various cells that become cancerous but those that are triple + win out in younger patients perhaps because of the hormonal enviroment or other external force which causes them to outgrow the others (think of weeds in a garden), perhaps because of other reasons. But I don't think they really know enough to be sure that is the model ie, that a potential tumor or tumor is made of of heterogeneous cells and which set wins out in the out-of-control growth game is determined by outside environment /hormonal environment/etc. is really operative.
Equally plausible is a stem cell theory where either the stem cell or any one(or several) of its pluripotential daughter cells has a certain set of characteristics--and it is the daughter cells which make up 99% OF THE tumor cells and which the pathologists look at, whereas the culprits, and the ones capable of causing recurrence after sitting dormant, are perhaps cells with a different set of ER,PR and her2 characteristics altogether.
Sorry to confuse you more!
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08-14-2007, 12:08 PM
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#6
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Senior Member
Join Date: Sep 2005
Location: Stockton, NJ
Posts: 4,179
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__________________
Kind regards
Becky
Found lump via BSE
Diagnosed 8/04 at age 45
1.9cm tumor, ER+PR-, Her2 3+(rt side)
2 micromets to sentinel node
Stage 2A
left 3mm DCIS - low grade ER+PR+Her2 neg
lumpectomies 9/7/04
4DD AC followed by 4 DD taxol
Used Leukine instead of Neulasta
35 rads on right side only
4/05 started Tamoxifen
Started Herceptin 4 months after last Taxol due to
trial results and 2005 ASCO meeting & recommendations
Oophorectomy 8/05
Started Arimidex 9/05
Finished Herceptin (16 months) 9/06
Arimidex Only
Prolia every 6 months for osteopenia
NED 18 years!
Said Christopher Robin to Pooh: "You must remember this: You're braver than you believe and stronger than you seem and smarter than you think"
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08-14-2007, 12:08 PM
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#7
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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I sprang and bought the full article
Understanding their findings is compounded because the article was either written (or translated into) English by someone for whom English is not the native language.
The authors sought to expand on earlier work detailed in a paper (which was an easier read!) where they determined that the ER+/PR- HER2+ phenotype was age dependant and was strongly associated with middle age. That study was questioned because of the small numbers of patients involved, so they sought to do a larger study with more patients.
What they found in the study population was that triple positives (ER+/PR+/Her2+) are the only group where the likelihood of Her2 positivity declines with age, i.e., the older you are and ER+/PR+, the less likely you are to be Her2+. Other Her2+ partially hormone positive phenotypes (ER-/PR+ or ER+/PR-) showed a constant probability that was not age related.
They consider their work hypothesis generating and not conclusive. Their theory is that hormone positive, Her2+ bc in younger women is regulated more by endocrines than growth factor signaling, and that these tumors are more sensitive to endocrine maniputlation, and that menopausal tumors that are hormone positive and Her2+ are more endocrine independent and less responsive to endocrine therapy. The reasoning this is based upon is the higher levels of circulating estrongen in the bloodstream of pre-meno women. They stress that testing must be done to prove or disprove this theory. If this turns out to be accurate, I think it is also a statement about the difference between ER+ bc driven by estrogen and ER+ bc driven by aromatase, which seems trickier to control with estrogen manipulation in the Her2+ context.
The issue I have is how they define "young". I thought the "young" vs. "old" categories referred to pre and post menopause, but then they say, "In conclusion, our believe that HER-2 expression is estrogen driven in young women with an ER<SUP>+</SUP> breast cancers is reflected by a mean younger age of diagnosis (52.4 years) of ER<SUP>+</SUP>PR<SUP>+</SUP>HER-2<SUP>+</SUP> breast cancers, on average 5.4 years younger than lesions with another ER/PR/HER-2 receptor status (95% CI = 3.3–7.5; P < 0.0001)."
Again, my math skills aren't my strong suit, but I am guessing this means that the larger number of pre-meno triple positives offsets the much lower number of post-meno triple positives and thus brings down the mean age for the entire group to where it is lower than that of any other phenotype.
Hope this helps.
Hopeful
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08-15-2007, 10:48 AM
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#8
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Senior Member
Join Date: May 2006
Location: California
Posts: 668
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Her2+ Er,Pr, Positive
Dear Margie:
I was too dx at 38 y/o, foward to 2003 and the cancer has mutated, now am ER,PR negative. Dx. with mets to rt lung, sternum July 16, 2003.
When I asked the onc, that's the simple explanation I was provided with...
"your cancer has mutated" I was post-menopausal at the time of recurrence, young @ menopause, due to chemo drugs.
I really do not know what to believe....?
__________________
1994 - rt brst, .lump, underarm node dissection,chemo+rad 1.2 cms, Grade 3.
28 nodes neg
Er,Pr, Positive HER2 status unknown
2003- Recur to rt lung.July 16 ( B-Day!)
Her2+++ Er,Pr, Negative
2003 - Aug04--Navelbine + Herceptin
2004- 2007--NED - Herceptin, only
2007 Feb-April Xeloda added to hereceptin
2007-May Back on Navelbine+Herceptin
2008-Feb-Mar 15 Ses Rad to Rt. Lung
2008- Oc 17 Add Tykerb to Herceptin
2009- June-- Discont Tykerb
2009 July 7--Current Taxol + Herceptin
2009 Dec--Discontinued treatment due to progression. Looking into cyberknife.
2010-Aug Accepted to TDM1, no SE, except liver count went up.
2010-2011 September got kicked out of the trial, due to a small spot found on lung.
2011- 2012 September thru early 2013 on Herceptin
2013- March Bone density shows small spot on 5th rib.
2013 - April 4th appt with onc. will post after discussing course of treatment.
2013-March-April Cyber knife to brain and radiation to rib. Chest --base line before chemo-CT-Scan stable for lung issue. CA2729 Normal.
2013 April Herceptin- TDMI
2013 Sept Herceptin + Perjeta . CA2729 within normal range. Brain and Pet scans October 31st. will post results.
2013 October Brain MRI- mixed response. Will see Onc/rad on Halloween.
2013 October/November Brain-MRI nothing new. Repeat MRI next year in May.
2013 December Continue Herceptin and Perjeta. Stable at the moment.
2014 February Brain MRI -clear!
2014 January Added Taxotere to Perjeta+Herceptin.
2014 March Stopped chemo-chest ct-scan next.
2014- March Scans shows tumor's larger, CA2729 higher. Discontinue Herceptin.
2014 April Perjeta+ Halaven
2014 April CA2729 went down 60 points after one cycle. Cough does not want to go away.
2014 June Continue on Perjeta + Halaven-- no more cough. Stable
2014 June Back on Herceptin + abraxane
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08-15-2007, 11:15 AM
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#9
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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Margerie,
I am in the group of women who used oral contraceptives for a long time and am childless. I question its relationship to my bc, also.
Hopeful
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08-15-2007, 04:05 PM
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#10
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Member
Join Date: Oct 2005
Posts: 23
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BC Pills
I used Birth Control Pills for probably 30 years and did not have a child until mid 30's. I am ER and PR strongly positive and HER2+++. Diagnosed at age 50 in 2004.
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