Roll call for premenopausal Her+ and some hormonal positivity

[Janelle]

I decided I wanted more information about my path report so I called the pathologist directly. My path report gives wide ranges for ER and PR positivity.

For example, my path report states I am 2+ Er positive which corresponds to a range of 26-75% positivity. My path report also states I am 1+ PR positive which corresponds to the range of 5-25% of PR positivity.

I see, though, that many girls get an exact percentage of their ER/PR positivity. Why didn't I get this? Well....apparently, my path was just eyeballed by the pathologist which is a rather crude way of determining the percentages in my layman's opinion. He informed me that you can have a computerized image analysis done which results in more precise numbers. Also, Oncotype DX has started to test for ER/PR percentages. He thinks this is the most accurage way to determine how ER/PR positive you are. He said he would be happy to send my slides out to be tested but insurance probably would not cover the $3000 test. Now if I knew the test results might change my treatment protocol I would seriously consider the test but I don't get the idea that anyone knows definitively how to best treat me. The pathologist actually suggested I get a 3rd opinion for a tie breaker on my pressing issue which is SHOULD I BE TAKING TAMOXIFEN or other hormonal therapies? Do hormonals work on HER2 cancers if they are ER positive and either PR positive or negative. Does tamoxifen have a negative impact on PR negative tumors?

My primary onc wants me to take tamoxifen.
Dr. Slamon, the HER2 guru, tells me hormonals do not work particularly well in ER/PR positive cancers if you are also HER2 positive and it might not work at all. Oddly enough I metabolize tamoxifen normally but I don't have side effects....Does metabolization matter in the Her2 setting?

The pathologist told me he doesn't think the ER/PR percentage is the determining factor for how well Her2 tumors respond to hormonals and that in his opinion it seems that hormonals just don't work as well on any of us ER/PR positive girls no matter how high or low the percentages are. If this is true my new "nearly negative PR status" should not change my treatment protocol, right?

Anyway, the nice pathologist agreed to review my slides again so he could narrow the ranges that are indicated on my path report. He said it looks like I am about 60% ER positive (at the high end of the moderate range) and only 5-10% PR positive (at the low end of the PR positive range- and "close to negative").

Also, my path report indicated that I had a 30% Ki-67 proliferation index. He revised that and told me it was closer to 40%- but the good news is that chemo works best on fast growing tumors so this isn't all bad news. I admit I am a bit shaken up by my nearly negative PR result and the increased KI-67 number.

Now I am wondering if I should have my slides sent out to another institution for a second review of my pathology. I can't believe how imprecise my path report is....

So how may Her2 positive girls are out there with ER positivity and either low or negative PR positivity? And are you taking hormonals???

Thanks!
Janelle

[tricia keegan]

Janelle, I don't think I fit your description as highly triple positive but have taken arimidex for eighteen months now and so far still ned coming up to my three years out.
I'd consider any % wothwhile in taking these drugs despite the side effects as I'm sure taking it has a lot to do with so far keeping the cancer away.
Good luck and sorry I can't help more.

[Janelle]

Thanks, Tricia. I actually just listened to a pod cast by Dr. Sledge that I found on this board. In the last 2 minutes of the 30 minute podcast, he stated that he thinks it is possible that hormonals don't work as well in Luminal B cancers (which we are) but studies have not been done to conclusively show this so we may be in an "overtreated" group. He said he did not expect the standard of care (hormonal therapy) to change anytime soon.

[Becky]

Hi Janelle

I fit your description almost exactly although I got my ovaries removed so I am now postmenopausal (but I was premenopausal prior to and my menses returned). I am 50% ER and "less than 5% PR" which is considered negative.

With a negative PR, I worried that Tamoxifen just wouldn't work for me (especially since I am only moderately ER+). In 2004/2005, current research pointed to aromatase inhibitors as being better so I had my ovaries removed, went on Arimidex and continued Herceptin for a year from that point. Currently, I am doing well.

I didn't catch your age. I was 46 when I got my ovaries removed. I was at least starting to near the natural menopause age.

However, Tamoxifen while still on Herceptin is a very good therapy. I cannot comment on Tamoxifen alone but most research points to that it might not work well if you are not both ER and PR positive.

Contact me anytime. There aren't many of us ER+ PRneg gals out there.

Send your slide to a large cancer center for another opinion (I did) - somewhere like Sloan Kettering, Dana Farber, MD Anderson, Fox Chase, Johns Hopkins etc. They read so many slides that their opinion is objective versus subjective.

Hugs to you.

[kcherub]

Hi, Janelle!

I was HER2+, 90% ER, 90% PR. I am currently taking Tamoxifen. Eck.

Take care,

[Susan66]

Hi Janelle,

Another triple positive here...95% ER/90% PR and 5.7% HER2. Also taking tamox while still on herceptin. I'm 42 now, 41 at diagnosis and A/C has put me into chemopause for 1 year. I can't talk my my onc or gyn into removing my ovaries but will take the shots to shut down ovaries should periods return.

Susan

[Janelle]

Thanks, Becky. Yes our pathologies are extremely similiar. I was diagnosed when I was 37.5 and I just turned 39 last month. My period returned 6 weeks after chemo ended so I didn't stay in chemopause very long which probably isn't so good.

The research that made you decide to get your ovaries removed is exactly what I have on my mind....I, too, believe that many oncologists believe that tamoxifen does not work as well on the ER+ but PR - population. But I get the idea they really have no idea sometimes and I am not really near menopause at my age.

On the other hand....after listening to the Sledge podcast and talking to Slamon I get the idea that there is a possibilty that hormones are not driving our HER2 cancers especially if we are highly HER2 positive and moderate to low hormone positive. I would hate to "overtreat" (i.e., ovary removal and ai at my age) as much as I would hate to undertreat by only taking tamoxifen given my close to negative PR status. I just wish we had better information.

Thanks for the advice on institutions to send my slides to for further review.

Best,
Janelle

[Janelle]

Krista & Susan,
Thank you also for your replies. Frankly, if I were highly triple positve I would not have so much concern with only taking tamoxifen as hormonal therapy. I am primarily concerned that tamoxifen may be useless for me due to my negative PR status.

I need to update my signature to indicate that I am apparently now a "double positive"....but I'm not doing that until my path is re-reviewed by an outside institution.

Krista- one more thing...I don't love tamox either but it is better than chemopause for me. In a perfect world I would love for someone to tell us that hormonal therapy of any sort is useless and we can quit taking all these drugs. Not fun.

Cheers! (I'll have a glasss of red wine now and chill).

Janelle

[caya]

This is a very interesting thread Janelle.

I was diagnosed at age 48, with ER+ (90%), PR+ (50%) and of course HER2+. I was still premenopausal at dx, and because of my ostopenia (precursor of osteoporosis, which my mother and her 2 sisters all have), my onc. does not want to take out my ovaries.

I am on Tamoxifen, which I know is metabolizing well due to major hot flashes (which basically vanished after I started taking Effexor XR). I started Herceptin in June 2007, and then Tamoxifen in July 2007. So I was on both of these concurrently for almost a year. The plan is for me to be on Tamox. for a couple of years, then switch to an AI. I've been on Tamox. for one year now.

It is confusing, it's a crap shoot, let's hope it will all work out.

all the best
caya

[Janelle]

Hi Caya,
I, too, know that I metabolize tamoxifen because I had a test done (blood test) that determined I metabolize it properly. But still I wonder if it matters in a Her positve but Pr negative population. If I were as PR positive as you I would not be nearly so concerned. A study from the ASCO 2007 (Dec 2007) pointed out that true triple positives have a better prognosis than the ER positve/Pr negative cohort. So if I were you....I would not be so concerned.

I also agree with you that this is a total crap shoot. Thank goodness Herceptin is out big gun no matter our hormonal status.

Cheers!
Janelle

[carykim]

Hi Janelle--

I've been lurking for months, and your post made me dig up my login/password because I remember well being exactly where you are a year ago.

I've read all those same reports that forecast the bleak prognosis of the ER+ PR- pathology. It's not a fun place to be when doctors don't agree and the research just isn't there yet.

Listen to Becky. Her advice is always sound. She was my beacon of hope when I first came to this site--she is doing great, further out from treatment than me. It's so hard to find that +-+ pathology!

As you can see from my sig (I hope it shows up under this post) that a year ago, the decision was made in my case to go with the ooph + AI. I was 35. I'm only 50% ER+ (my pathology report was vague like yours and I considered sending the slides for a 2nd read but didn't). I started Femara the day after my ooph/hyst and never looked back. I felt like I had to attack from every direction and at the time believed those estrogen receptors needed to be starved. Hearing that a year later the new thinking is that this might have been treatment overkill -- for some reason it doesn't affect me the way you'd think. I would have always been wondering if the Tamoxifen was working. In your case you have the metabolism test to ease your mind.

I wish I had the crystal ball. I just wanted you to know I'm thinking of you, sending you clarity to decide on the right treatment for you.

xo
cary

[Ursula]

I'm borderline HR-positive and don't get any Tamoxifen as adjuvant treatment. I asked several opinions of different Finnish oncologists but all were from that point of view that Tamoxifen would do me more harm than profit. My receptor status was ER 15%, PR 15,5%. I am strongly HER2-positive and was diagnosed at age 42. I still get my periods regularly and it seems that I will be on this way for many, many years.

[Janelle]

Cary,
Thank you for your post. I'm glad to here that you have never looked back on your treatment decisions. Do you suffer from side effects from the ooph/hyst now? I am concerned that menopause will sink me into the black hole depression that I experienced during chemopause. My mood is fine on Tamoxifen but it sure wasn't during chemopause and I'm not a baseline depressed person. Also, I am worried about bone loss. That said, I do think the approach that you and Becky took is one that has no chance of feeding cancer despite whatever other side effects you have.

Best,
Janelle

[Janelle]

Hi Ursula,
Thanks for your response too. I am at the high range of moderate (60%) for ER status so some sort of hormonal treatment would probably be recommended to me despite negative PR status. I almost wish I were both nearly ER and PR negative (like you) so I would not have to make decisions about hormonals.

Cheers!
Janelle

[jones7676]

It never hurts to have your pathology report double checked (per a pathologist I know). You might want to check out the NIH website. I believe they do it for free. They should be able to tell you exactly what they require in order to accomplish the task.

[Janelle]

Barb,
I spoke to my oncologist and she agreed to order a re-review at an outside institution. That said, she said her treatment protocol (tamoxifen for me) would not change even if I turned out to be PR negative. For peace of mind I think it is prudent to have accurate pathology. Thanks for your response and making me feel like I am not going overboard with my initial instinct to seek a second opinion.

Cheers!
Janelle

[carykim]

Janelle--

Not sure whether to post here or at YSC. I read Katie's response to you, and she laid out the reasons why I ended up with an ooph + AI. I took Tamoxifen for a few months during radiation and had no issues with it as a drug.

My life on an AI has been much the same--no major issues. No joint pain, minor hot flashes, some bone loss that is to be expected because of the loss of estrogen's protective effects. I've been in a study for the last ten months that is testing whether weight-bearing exercise has any effect on bone loss. I'll go on Zometa as soon as I finish in August because of the new findings that came out of the ASCO conference a few weeks back saying Zometa in the adjuvant setting can help prevent mets. Hopefully it will also prevent further bone loss.

I have dryness but no atrophy. Sex is different but by no means impossible.

Mood? I didn't realize an AI could cause depression. So I guess that hasn't been a problem.

I worried a lot about my skin looking old and losing suppleness and that hasn't happened yet. I haven't gained weight and turned into a post-menopausal pear. It's been a pretty uneventful post=ooph year, but of course I wish I hadn't had to lose those body parts.

xo
cary

[Unregistered]

Janelle and all,

I recently found this site and saw this thread. I am confused after reading Janelle's original post. You say that you are on Tamoxifen but also consulted with Dr. Slamon and he told you anti-hormonals don't work in HER2+ patients. Did your oncologist convince you to stay on Tamoxifen? I know that Dr. Slamon is a leader in this field and wondered why you wouldn't go with his recommendation. I noticed that some of the responses were from women who had their ovaries removed just so they could take an AI. Are AIs considered anti-hormonal therapy? Sorry to have so many questions but I'm concerned because I am HER2+, moderately ER+ and weakly PR+ and am taking an AI. Is this doing me any good?

You ladies are wonderful. I am learning so much, but have a long way to go.

Suzie

[Janelle]

Suzie,
AI's are anti-hormonal therapy but they can only be used in post-menopausal women. If I were to have my ovaries removed or if I had gone into menopause naturally or from chemo, then an AI would probably be recommended to me. But I am pre-menopausal which is why I am on tamoxifen. My body is still producing alot of estrogen and tamoxifen helps the breast cells from absorbing it. An Ai (alone) is not a strong enough anti-hormonal therapy for a premenopausal woman.

As for Slamon's advice....He didn't actually tell me not to take tamoxifen. He didn't think it would hurt but he just wasn't so convinced it would help a lot (or at all). Basically, the gist was in his opinion if I had terrible side effects from tamoxifen then I would not be crazy (or killing myself) if I decided to stop taking it.

My primary onc did convince me to give it a try so I did....and much to my surprise I didn't have any terrible side effects so I stayed on it. She is still not recommending that I have more aggressive hormonal therapy (ovary removal, etc) even if I turn out to be PR negative. She still thinks I should stay on tamoxifen alone until more data comes out.

After listening to the George Sledge podcast, I get the idea that the medical community really doesn't know how much anti-hormonal therapy helps us HER2 positive ladies (especially those of us who are low-moderate Er/Pr positive or ER positive/PR negative). BUT since there aren't any answers yet doctors will continue to recommend the "standard of care" for anyone with any ER or PR positive breast cancers- which is some sort of hormonal therapy.

I hope this helps and did not confuse more....

Best,
Janelle

[Janelle]

Suzie,
The below is from the Mayo Clinic website:

HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor-2 (HER2), which promotes the growth of cancer cells. In about one of every three breast cancers, the cancer cells make an excess of HER2 due to a gene mutation. This gene mutation can occur in many types of cancer — not only breast cancer.

HER2-positive breast cancers tend to be more aggressive than other types of breast cancer.

They're also less responsive to hormone treatment. However, new treatments that specifically target HER2 are proving to be very effective:
<LI class=doublespace>Trastuzumab (Herceptin). Herceptin, which specifically targets HER2, kills these cancer cells and decreases the risk of recurrence. Herceptin is often used with chemotherapy. But it may also be used alone or in combination with hormone-blocking medications, such as an aromatase inhibitor or tamoxifen. A study published in 2005 found that Herceptin can reduce breast cancer recurrence by as much as 50 percent. Herceptin is usually well tolerated, but it does have some potential side effects, such as congestive heart failure and allergic reaction. This drug is also very expensive. <LI class=doublespace>Lapatinib (Tykerb). Like Herceptin, Tykerb is a HER2-specific drug. Approved by the Food and Drug Administration in 2007, Tykerb may be effective for HER2-positive breast cancer that doesn't respond to Herceptin. Tykerb is used in combination with the chemotherapy drug capecitabine (Xeloda).
Certain chemotherapy regimens, such as combinations of anthracycline drugs — doxorubicin (Adriamycin), epirubicin (Ellence).
Breast tissue can be tested for HER2, and routine testing is recommended for most women with breast cancer because the results may affect treatment recommendations and decisions. Whenever breast cancer recurs or spreads, the cancer cells should be tested for HER2.
http://www.mayoclinic.com/images/clear.gif

[Unregistered]

Hi Janelle,

Thanks so much for taking the time to respond to my questions. Your explanations make perfect sense and I feel so much better. I really appreciate what you copied and pasted from the Mayo Clinic website. It looks like there is a lot of info there, I will have to check it out.

Thanks again for your reply.

Suzie