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Old 01-01-2008, 10:15 AM   #1
tdonnelly
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Excessive Coughing/Herceptin ???

I started excessive coughing with my 8th Herceptin treatment. By the time I got my 9th treatment (3 weeks later) I had developed a serious upper respiratory infection, coughing is now worse. I was given antibiotics (Z pack) for the infection; but cough is still bad when I lay down. No fever, just coughing to the point I had lost my voice for several days. I am concerned about continuing Herceptin for the year as was my original treatment plan. Are there other patients who have had to stop Herceptin? How are you doing? I also just finished 28 Rad. treatments when all this started. I am having a chest xray tomorrow. Anyone else familar with this side effect, any suggestions. Thanks
Tamara
Invasive Ductal Carcinoma 11/2006
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Old 01-01-2008, 10:41 AM   #2
Lani
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from a previous post of mine ( I added others too)

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LOPSIDED
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Sick & Tired Ofcoughing Everyday
I Was Really Starting To Worry About Mets To The Lungs. I Can't Quit Coughing. When I'm Talking, I Don't Sound Like I Have A Cold But Everyday I Am Having Coughing Spells. My Cough Sounds Terrible. I Went For A Chest X-ray And It Came Back Normal. Now My Doc Is Sending Me For A Ct Scan To Be On Safe Side. I Know Its That Time Of Year For Flu's & Cold But This Coughing Is Exausting. Any Cough Remedies.......anyone?

12-05-2007, 05:39 PM #2
Grace

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Sheila,

I had a similar cough last year (twice) where I simply couldn't stop coughing. It lasted for many weeks, but it did finally get better. I was on herceptin at the time. I know that others have had something similar, and I understand it's a particular type of flu that's going around. I used Tylenol for coughs and it helped some but not a whole lot. Have you tried honey before going to bed? I didn't but I read an article yesterday that honey is now being recommended for children in lieu of cough medicine. Hope you're better soon.

12-05-2007, 06:28 PM #3
Lolly
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Sheila, my husband had pneumonia this spring and to get some relief from the terrible coughing at night so he could sleep, his doctor prescribed codeine cough syrup, but only to take at night. It really worked, but it's strong stuff.
I don't think raw honey is recommended for chemo patients, if you're still on chemo, so talk that over with your doctor if you want to try it, or make sure you get pasturized honey.

<3 Lolly

12-05-2007, 06:44 PM #4
Lani
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from an old post of mine
For those complaining of nasal/sinus symptoms/coughing which they relate to Herceptin, I submit the following two articles. The nose, like the more distant airways/bronchiols have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) . These articles raise questions which may help explain symptoms while on Herceptin--showing that her2 is necessary not just in embryogenesis, but also in adulthood for repair of these kinds of cells. They may help explain your nasal complaints, the reports of rare pulmonary problems in patients on Herceptin and perhaps the dry-eye problem I posted on before. The more they look into what her2 does, the more they find!:


Am J Physiol Lung Cell Mol Physiol. 2006 Feb 17; [Epub ahead of print]
Related Articles, Links
*
Differentiation of Human Airway Epithelia Is Dependent on ErbB2.

Vermeer PD, Panko L, Karp P, Lee JH, Zabner J.

Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.

A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab, an anti-erbB2 antibody. This prompted the investigation into whether blocking the erbB2 receptor alters differentiation of the airway epithelium. If so, blocking or exogenously stimulating the receptor would lead to consequences on differentiation. To test this hypothesis, an in vitro model of well-differentiated human airway epithelia was treated with trastuzumab or heregulin-alpha, an erbB ligand. In addition, co-culturing with human lung fibroblasts tested whether in vivo subepithelial fibroblasts function as an endogenous source of ligands able to activate erbB receptors expressed by the overlying epithelial cells. Epithelia were stained with hematoxylin and eosin and used for morphometric analysis. Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%. Heregulin-alpha treatment increased epithelial height, decreased the number of metaplastic and non-ciliated columnar cells while it increased the goblet cell number. We found that normal human lung fibroblasts express transforming growth factor-alpha, heparin binding-epidermal-like growth factor, epiregulin, heregulin-alpha, and amphiregulin, all of which are erbB ligands. Co-cultures of airway epithelia with primary fibroblasts increased epithelial height comparable to that achieved following heregulin-alpha treatment. These data show that erbB2 stimulation is required for maintaining epithelial differentiation. Furthermore, the mesenchyme underlying the airway epithelium secretes a variety of erbB ligands that might direct various pathways of epithelial differentiation.

PMID: 16489114 [PubMed - as supplied by publisher]


1: FASEB J. 2005 Aug;19(10):1374-6. Epub 2005 May 27.
Related Articles, Links
*
ErbB2 activity is required for airway epithelial repair following neutrophil elastase exposure.

Fischer BM, Cuellar JG, Byrd AS, Rice AB, Bonner JC, Martin LD, Voynow JA.

Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.

In cystic fibrosis and chronic bronchitis, airways are chronically injured by exposure to neutrophil elastase (NE). We sought to identify factors required for epithelial repair following NE exposure. Normal human bronchial epithelial cells were treated with NE (50 nM, 22 h) or control vehicle. Following NE treatment, we found a marked and sustained decrease in epithelial proliferation as detected by Ki67 immunostaining. 3H-thymidine incorporation was also initially depressed but increased over 72 h in NE-treated cells, which suggests that DNA synthesis constitutes an early repair process following NE exposure. We hypothesized that ErbB2 receptor tyrosine kinase, a regulator of cancer cell proliferation, was required for epithelial DNA synthesis following NE exposure. Immediately following NE treatment, by flow cytometry analysis, we found a decrease in ErbB2 surface expression. Protein levels of the full-length 185 kD ErbB2 receptor significantly decreased following NE treatment and smaller ErbB2-positive bands, ranging in size from 23 to 40 kD, appeared, which suggests that NE caused ErbB2 degradation. By real-time RT-PCR analysis, we found no change in ErbB2 mRNA expression following NE treatment, which suggests that changes in ErbB2 protein levels were regulated at the post-translational level. Following NE treatment, full-length 185 kD ErbB2 levels increased to pretreatment levels, correlating with the increase in thymidine incorporation during the same time period. Importantly, inhibition of ErbB2 activity with AG825 (5 microM) or Herceptin (3.1 microM), an ErbB2-neutralizing antibody, blocked thymidine incorporation only in NE-treated cells. These results suggest ErbB2 is a critical factor for epithelial recovery following NE exposure.

PMID: 15923396 [PubMed - in process]



I started the post with my summary:
"For those complaining of nasal/sinus symptoms which they relate to Herceptin, the following two articles may hold clues as to what may be going on. The nose/airways have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) and other specialized cells (including further down the "airways" in the bronchi and bronchioles). These articles raise questions which may help explain symptoms while on Herceptin--showing that her2 is necessary not just in embryogenesis, but also in adulthood for repair of these kinds of cells. They may help explain your nasal complaints, the reports of rare pulmonary problems in patients on Herceptin and perhaps the dry-eye problem I posted on before. The more they look into what her2 does, the more they find!:"

A “translation” of the “Greek” of the two articles:

Because of a case of a patient whose airways changed when Herceptin treatment was started and when Herceptin was stopped in terms of which types of specialized cells were present/absent they tried in a petri dish to see what happens to airway cells and found:

Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%.

Thus the cells necessary to fight infection were more than halved and the cells with little specialized function, which do not secrete or trap bacteria, mold or particles went up by more than 6 fold.

In the other article, after bronchitis or other diseases where a white blood cell enzyme injures airway (bronchial) lining tissue her2 is necessary to repair the damage caused by this enzyme in an adult. The "Greek" is just describing how they proved the mechanism of how this occurs, at what step it occurs and whether the changes were on a gene or protein level.

Both articles emphasize that her2 fulfills physiologic functions in an adult and Herceptin can potentially adversely affect those functions. Epithelial cells are numberous throught the body--thhey line organs facing the "outside world"(which is sometimes inside as in the stomach and intestines) they function to keep infectious and dangerous particles out, secrete substances to lubricate and or digest, etc. Her2 seems to be necessary to keep these cells specializiing to serve different necessary functions and to repair/replace damaged cells.

Thus it seems it is not just the heart that Herceptin affects.
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Old 01-01-2008, 10:43 AM   #3
Lani
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another thread I posted to on the same subject

#1
Caroline UK
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Herceptin cough
I've had a little, wheezy cough for the last 8 weeks or so, nothing too troublesome but always just there. Had a chest x-ray last week and it's fine, thank goodness. My oncologist said about 20% of people on Herceptin experience this cough. Not exactly allergic, sort of hyper-sensitive to it. Has anyone else experienced this? Have you noticed if anything helps or makes it worse?

05-10-2007, 11:26 PM #2
Roz
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Hi, Yes I have had the same cough! Feel as if I am asthmatic with the little wheeze. It is a shame for me as I also have tended to get my "cancer return" in my right upper lobe, so I tend to panic if I get too much wheezing. All part of the rich tapestry etc.. I suppose.

05-11-2007, 09:11 AM #3
tousled1
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Caroline,

I had the cough almost the entire year I was on Herceptin. Had my last Herceptin April 20th and my cough is almost gone.

05-11-2007, 09:50 AM #4
Jeanette
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cough
I also had the cough all the time i was on Herceptin. Sucked on a lot of hard candy to control it. It is gone now, thankfully, very annoying.

05-12-2007, 08:02 AM #5
Caroline UK
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Location: London, England
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Ok, thanks everyone, always seems to help when I hear from others who've had the same thing, even if it wasn't anything too serious. Sometimes I just feel a bit alone with all these little niggly things, and I feel reluctant to wear friends down by 'moaning' about them.

05-12-2007, 09:00 PM #6
Adriana Mangus
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Me too
Hi Caroline:

I have been coughing for at least 8 months, I have scratchy throat wheezing,a lot of phlegm, also. I feel like am producing excesive saliva. Do you have phlegm, too?

I went to see my personal physician, she said the lungs are clear, -thanks to God-, since my mets are in the upper lobe rt lung- so based on that the diagnosis is chronic rhinitis, but I really doubt it very much. I did not know that herceptin may be the cause. I feel good about knowing this information, but it's annoying to deal with this cough. The doc recommended Benadryl which it seems to help, I also take cough medicine like Robitusin. I have had many sleepless nights due to this, no FUN!..

How is it for you ladies? I can rest on my back, walk; but sometimes when I talk or want to eat, sip on water; then I feel like urgency to cough, like I said it's annoying!!!!!

Thanks all for sharing!!!!! I FEEL MUCH BETTER!!!!

05-13-2007, 03:38 PM #7
Lani
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Join Date: Mar 2006
Posts: 1,947
I posted this before---role of her2 in maintenance of upper airways explains cough
as well as nasal symptoms

For those complaining of nasal/sinus symptoms which they relate to Herceptin, I submit the following two articles. The nose, like the more distant airways/bronchioles have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) . These articles raise questions which may help explain symptoms while on Herceptin--showing that her2 is necessary not just in embryogenesis, but also in adulthood for repair of these kinds of cells. They may help explain your nasal complaints, the cough and the reports of rare pulmonary problems in patients on Herceptin and perhaps the dry-eye problem I posted on before. The more they look into what her2 does, the more they find!:


Am J Physiol Lung Cell Mol Physiol. 2006 Feb 17; [Epub ahead of print]
Related Articles, Links
*
Differentiation of Human Airway Epithelia Is Dependent on ErbB2.

Vermeer PD, Panko L, Karp P, Lee JH, Zabner J.

Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.

A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab, an anti-erbB2 antibody. This prompted the investigation into whether blocking the erbB2 receptor alters differentiation of the airway epithelium. If so, blocking or exogenously stimulating the receptor would lead to consequences on differentiation. To test this hypothesis, an in vitro model of well-differentiated human airway epithelia was treated with trastuzumab or heregulin-alpha, an erbB ligand. In addition, co-culturing with human lung fibroblasts tested whether in vivo subepithelial fibroblasts function as an endogenous source of ligands able to activate erbB receptors expressed by the overlying epithelial cells. Epithelia were stained with hematoxylin and eosin and used for morphometric analysis. Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%. Heregulin-alpha treatment increased epithelial height, decreased the number of metaplastic and non-ciliated columnar cells while it increased the goblet cell number. We found that normal human lung fibroblasts express transforming growth factor-alpha, heparin binding-epidermal-like growth factor, epiregulin, heregulin-alpha, and amphiregulin, all of which are erbB ligands. Co-cultures of airway epithelia with primary fibroblasts increased epithelial height comparable to that achieved following heregulin-alpha treatment. These data show that erbB2 stimulation is required for maintaining epithelial differentiation. Furthermore, the mesenchyme underlying the airway epithelium secretes a variety of erbB ligands that might direct various pathways of epithelial differentiation.

PMID: 16489114 [PubMed - as supplied by publisher]


1: FASEB J. 2005 Aug;19(10):1374-6. Epub 2005 May 27.
Related Articles, Links
*
ErbB2 activity is required for airway epithelial repair following neutrophil elastase exposure.

Fischer BM, Cuellar JG, Byrd AS, Rice AB, Bonner JC, Martin LD, Voynow JA.

Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.

In cystic fibrosis and chronic bronchitis, airways are chronically injured by exposure to neutrophil elastase (NE). We sought to identify factors required for epithelial repair following NE exposure. Normal human bronchial epithelial cells were treated with NE (50 nM, 22 h) or control vehicle. Following NE treatment, we found a marked and sustained decrease in epithelial proliferation as detected by Ki67 immunostaining. 3H-thymidine incorporation was also initially depressed but increased over 72 h in NE-treated cells, which suggests that DNA synthesis constitutes an early repair process following NE exposure. We hypothesized that ErbB2 receptor tyrosine kinase, a regulator of cancer cell proliferation, was required for epithelial DNA synthesis following NE exposure. Immediately following NE treatment, by flow cytometry analysis, we found a decrease in ErbB2 surface expression. Protein levels of the full-length 185 kD ErbB2 receptor significantly decreased following NE treatment and smaller ErbB2-positive bands, ranging in size from 23 to 40 kD, appeared, which suggests that NE caused ErbB2 degradation. By real-time RT-PCR analysis, we found no change in ErbB2 mRNA expression following NE treatment, which suggests that changes in ErbB2 protein levels were regulated at the post-translational level. Following NE treatment, full-length 185 kD ErbB2 levels increased to pretreatment levels, correlating with the increase in thymidine incorporation during the same time period. Importantly, inhibition of ErbB2 activity with AG825 (5 microM) or Herceptin (3.1 microM), an ErbB2-neutralizing antibody, blocked thymidine incorporation only in NE-treated cells. These results suggest ErbB2 is a critical factor for epithelial recovery following NE exposure.

PMID: 15923396 [PubMed - in process]



A “translation” of the “Greek” of the two articles:

Because of a case of a patient who developed a chronic cought on herceptin (which disappeared when herceptin was stopped) whose airways changed when Herceptin treatment was started and when Herceptin was stopped in terms of which types of specialized cells were present/absent, they tried in a petri dish to see what happens to airway cells and found:

Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%.

Thus the cells necessary to fight infection were more than halved and the cells with little specialized function, which do not secrete or trap bacteria, mold or particles went up by more than 6 fold.

In the other article, after bronchitis or other diseases where a white blood cell enzyme injures airway (bronchial) lining tissue her2 is necessary to repair the damage caused by this enzyme in an adult. The "Greek" is just describing how they proved the mechanism of how this occurs, at what step it occurs and whether the changes were on a gene or protein level.

Both articles emphasize that her2 fulfills physiologic functions in an adult and Herceptin can potentially adversely affect those functions. Epithelial cells are numerous throught the body--they line organs facing the "outside world"(which is sometimes inside as in the stomach and intestines) they function to keep infectious and dangerous particles out, secrete substances to lubricate and or digest, etc. Her2 seems to be necessary to keep these cells specializiing to serve different necessary functions and to repair/replace damaged cells.

Thus it seems it is not just the heart that Herceptin affects.
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Old 01-01-2008, 01:38 PM   #4
MJo
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Gee, Lani. Ya think coughing might be a side effect of Herceptin? Ya think?
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Lumpectomy 11/04/05 Clear Margins
3 Dose dense AC (Couldn't tolerate 4)
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36 weeks Herceptin (Could not complete one year due to decrease in MUGA score)
2 years of Arimidex, then three years of Femara
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Old 01-01-2008, 03:03 PM   #5
Andrea Barnett Budin
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Wink Coughing...

SINCE I'VE BEEN ON HERCEPTIN FOREVER, IT IS HARD TO DISTINGUISH SOME SYMPTOMS. I have a little cough tat is not wheezy or phlegmy. Just a dry thing that has a need to come up here and there and throughout the day. I can live with it...

HOWEVER, a few wks ago I had a hacking cough and an upper respiratory flu that made my ribs hurt. It was exhausting coughing nonstop! I was given a prescription expectorant and that helped right off. Anything with codeine in it helps a cough. Just watch taking it during the day. It is strong. It'll give you the best night sleep ever, but not recommended for daytime, unless you're confined to the house...

My chest scans are all clear and stable. Hope all yours are too!!

Andi
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'95 post-meno dx Invasive LOBULAR w/9cm tumor! YIKES + 2/21 nodes. Clear mammo 10 mnths earlier. Mastec/tram flap reconst/PORT/8 mnths chemo (4Adria/8CMF). Borderline ER/PR. Tamoxifen 2 yrs. Felt BLESSED. I could walk and talk, feed and bathe myself! I KNEW I would survive...

'98 -- multiple mets to liver. HER2+ 80%. ER/PR- Raging, highly aggressive tumors spreading fast. New PORT. 9 mnths Taxotere Fought fire w/fire! Pronounced in cautious remission 5/99. Taxotere weekly for 6 wks, 2 wks off -- for 9 mnths. TALK ABOUT GRUELING! (I believe they've altered that protocol since those days -- sure hope so!!)
+ good old Vit H wkly for 1st 3 yrs, then triple dosage ev 3 wks for 7 yrs more... The "easy" chemo, right?! Not a walk in the park, but not a freight train coming at 'ya either...

Added Herceptin Nov '98 (6 wks after FDA fast-tracked it for met bc). Stayed w/Vit H till July '08! Now I AM FREE! Humbly and eternally grateful for this life-saving drug! NED since '99 and planning on keeping it that way. To hell w/poor prognosis and nasty stats! STOPPED VIT H JULY '08...! REMAIN STABLE... Eternally grateful...Yes is a world & in this world of yes live (skillfully curled) all worlds ... (e e cummings) EVERY DAY I BEAT MY PREVIOUS RECORD FOR # OF CONSECUTIVE DAYS I'VE STAYED ALIVE. Smile KNOWING you too can be a miracle. Up to me and God now...
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Old 01-01-2008, 08:52 PM   #6
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Herceptin Cough

I had a non-productive cough about 1/3 way through Herceptin treatments that were administered every three weeks. The coughing was interfering with meetings at work and keeping me and my husband awake at night.

After seeing a cardiologist with several tests and a pulmonologist, the oncologist felt that the coughing and corresponding high pulse were from the Herceptin. I took a month off of treatments and the coughing stopped. I am now back on Herceptin every week and tolerating it very well. The coughing was a symptom of cardiomyopathy and my EJ was about 45-50%. You might want to discuss weekly treatments with your oncologist.
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Old 01-14-2008, 09:16 AM   #7
Harmy
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Herceptin cough

I have decided to stop my herceptin after developing a cough. It started around Sept 07 and has just got worse and worse. More recently my voice has stared to be affected. I decided Dec 07 was my last dose of herceptin as no one could tell why the cough had developed and more importantly how to make it stop. It has made life very difficult. I have been prescribed loads of things but nothing work. I would welcom any suggestions / advice?????
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Old 01-14-2008, 09:44 AM   #8
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Have you had your heart function tested either via MUGA or Echo?
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Diagnosed 11/06; IDC
Stage 1, Grade 2
MRM 12/06; 19 nodes removed, all negative
ER/PR-, HER2+++
  • 4 rounds AC - every 3 weeks
  • 3 rounds Taxol + Herceptin - every 3 weeks (developed allergy to Taxol so stopped treatment)
  • Weekly Herceptin after Herceptin-induced cardiomyopathy from treatments every 3 weeks
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Old 01-14-2008, 09:51 AM   #9
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Herceptin Cough

Yes I have been having echos every three months. In fact had one on 3rd Jan 08 and was told everything is fine. Also had CT scan in October and everything was clear. Have undertaken a number of tests re: lung functioning and the consultant reports everything as being fine. In the meantime, this cough is driving me potty!
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Old 01-14-2008, 12:07 PM   #10
Rendi69CA
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My doctor give me benadryl before he give me herceptin. That help me from coughing.
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04/97- breast bx. diagnosis breast cancer.
05/97- radical mastectomy; 5cm tumor & 11 lymph nodes.
10/97- City of Hope, high dose chemotherapy.
11/97- 36 radiation therapy.
01/98- NED; tamoxifen.
02/02- breast reconstruction.
08/04- recurrence; mets to rt lung; thoracentesis; femara.
09/04- thoracentesis; ER/PR +, Her2+++.
10/04- total abdominal hysterectomy.
02/06- mets to 9th rib; monthly zometa; arimidex.
06/06- medi port insert; weekly herceptin.
10/06- 3 weeks herceptin treatment.
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11/07-liver clear
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12/08-taxol not working
01/09-navelbine/herceptin weelky
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04/09-xeloda/tykerb
09/09-30 radation to neck; xeloda/tykerb not working
11/09-Gemzar/herceptin weekly
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06/10-cancer spread to left lung;stop treatment; tap
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