Interesting data on PR- ( but ER+) and Tamox?

Rhiannon78

Hi everyone:  I came across something interesting regarding the effacy of Tamox for ladies with PR negative status.  I know that most of the research in this area has focused on the benefit of Tamox ER positive cancers, but this study seems to imply that the PR status may be an more impostant factor?  I have emailed my MO to get her opinions on this. http://www.ncbi.nlm.nih.gov/pubmed/16899609

I, like many others, am really struggling with whether to take it for risk reduction.  Since I "only" had DCIS in one breast and ADH in the other and not an invasive cancer, my choice to take this drug really hinges on whether or not I worry more about  future recurrances of DCIS or IBC (which are fairly low and have been estimated at about 5% higher than the "average") or the potential SE's.

Does anyone have any thoghts on this or talked to their MO about this?

thanks!

Beesie

Rhiannon, this isn't the only study that's found that women who are PR- get less benefit from Tamoxifen. I was diagnosed prior to the release of this study, but my PR- status was one of the reasons why my oncologist recommended against Tamoxifen for me. For me, he felt that the risk vs. benefit equation just didn't support taking Tamoxifen.

My situation was different than yours, however. There are three benefits from Tamoxifen and I would only have had one of the benefits, and it would have been quite small. 

The first benefit is approx. a 45% reduction in local recurrence risk. I had a single mastectomy so my local recurrence risk is only 1% - 2%.  A 45% reduction of such a low risk isn't much!  For someone who has a lumpectomy and who therefore may face a higher local recurrence risk, this benefit will be greater. Remember too that 50% of DCIS recurrences are not found until they are invasive cancer, so this benefit can be significant. 

The second benefit is a reduction in the risk of mets.  This is the most important benefit for those who have invasive cancer but it doesn't factor in for those who have DCIS or a high risk condition.  In my case, I had a microinvasion of IDC so I do have a very small - 1% or less - risk of mets.  But here again, with such a low risk, the benefit from Tamoxifen would be negligible. 

The third benefit is approx. a 45% reduction in the risk of a new primary breast cancer diagnosis. Because a new diagnosis can hit either breast, this provides protection for both breasts. But in my case, since I had the UMX, I had only one breast left to protect. As for my risk, my oncologist told me that my risk to be diagnosed with BC again, having been diagnosed once already, was about double that of the average woman my age. I was 49 at the time; the average 49 year old has an 11% remaining lifetime risk, so my risk was ~22%. The key thing to keep in mind here is that this is lifetime risk, spread over about 40 years. Back when I was diagnosed, Tamoxifen was only given for 5 years. 5 years of Tamoxifen provides about 10 years of risk reduction benefit; after that the effect is worn off. So I wouldn't have been protected for all of my remaining lifetime, only the next 10 years. This means that my risk reduction wouldn't have been a 45% reduction of my 22% risk; it would have been a 45% reduction of 10 years of my 40-year 22% risk. For me that worked out to less than a 3% risk reduction. 

And that's why I made the decision to not take Tamoxifen. However, if my situation had been different - if I had a greater local recurrence risk or if I had a larger amount of invasive cancer and therefore a greater risk of mets - my risk vs. benefit equation would have been very different and I likely would have given Tamoxifen a try. 

What you need to do is look at each of the benefits of Tamoxifen and determine for yourself what your risk reductions will be, and whether that makes it worthwhile for you to try Tamoxifen. 

Hope that helps!

MameMe

I also turned down tamoxifen, but it was when I had ER and PR + status, and both low grade and early stage features. I figured that the percentage of actual risk reduction was not worth taking a pill every day that reminded me of having had cancer. I wanted to let the whole thing go and just get out of cancer land. Ten years later, I am dealing with another tumor, and cannot know whether tamoxifen would have prevented it. I sure did have a great ten years, though! Its funny, I just posted a question about ER+ PR- tumors a minute or two after you did. Let's see what emerges.

Mame

Rhiannon78

OK, I will cut and paste the response that I got from my MO.  Bottom line, it doesn't add much.  Basically, there is a lot of interest in knowing more about all the combos of ER/PR status and how they respond to various endocrine therapies, but no clear answers.  Bottomline for me, there isn't enough evidence to sway my decision to take Tamox as a preventative. Also, the studies were done on IBC and not DCIS, which may well "behave" or respond differently.

As Beesie points out, I'm still left with weighing my own risk aversion to either a future "breast event" or the SE's of the medication.  And since I didn't have rads (my RO felt that it would only cut my already low risk of recurrance-about 5%-to 2.5%, he didn't recommend doing it), the decsion is even more complicated in some way.  I think if I'd have had rads, NOT taking the Tamox would be an easier decsion.  Now I feel that even though the benefit of Tamoxmight be pretty small, in some ways I feel it is my "only line of defense" (other than healthy living, which I already do) against a recurrance or preventing the ADH in my left breast from evolving to DCIS or IBC. Perhaps this info will be helpful to some of you. If anyone has other studies or info to share on this topic, please post. Thanks!

"There is a lot of interest in trying to refine which patient will better respond to hormone therapy but in reality, factors predicting response is complicated.This is up to date info onPredictive value of PR refers to how like the PR is going to predict response to hormone therapy.


Contribution of PR expression — The independent contribution of PR expression has been debated [11]. Initial reports, which have been validated through the years, indicated that patients with ER-positive but PR-negative breast cancers have a worse prognosis than do those with ER-positive and PR-positive tumors [12,13]. (See 'Prognostic value of hormone receptor expression' below.)

However, the predictive value of PR expression remains controversial, as evidenced by the following data:


The early suggestion that absent PR expression would serve to further refine the predictive utility of ER expression for benefit from tamoxifen or aromatase inhibitors has not been borne out [14-17]. There is persistent controversy on this point, however [13].
On the other hand, for individuals with ER-negative tumors, the observation that the gene encoding for PR is estrogen-dependent led to the hypothesis that PR expression might serve as an indication of an intact estrogen-ER-estrogen response pathway, and therefore, responsiveness to endocrine therapy [18]. Although some studies suggest that the predictive value of PR is less important clinically as compared to ER [19-22], others have shown that PR status provides additional predictive value independent of ER values [23-25], especially among premenopausal women [9,26].

Like ER, PR was initially measured by forms of a ligand binding assay (LBA), and most of the data underlying our knowledge of the relationship between PR expression and response to endocrine therapy were generated using this assay. Like ER, PR is now measured almost exclusively by immunohistochemistry (IHC). There are some published reports that IHC for ER may be more predictive than LBA in identifying patients who will derive benefit from endocrine therapy, but there are no data addressing this issue for PR. (See 'Antibody-based assays (IHC)' below.)

In addition, as with ER, PR protein exists as two receptor isoforms (in this case, called A and but these forms are the products of the same gene. These isoforms of PR (A is a slightly truncated form of bind with one another to create homo- and heterodimers. There has been little work on the relative significance of these isoforms in clinical tissue specimens and their relevance to clinical decision making, although this is an active area of research.

Despite these issues, PR positivity may be helpful in selecting patients with ER-negative breast cancer who might benefit from endocrine therapy [27]. ER-negative/PR-positive tumors are uncommon, but endocrine therapy is usually recommended in this setting, in order to avoid undertreatment with such a highly effective and relatively low toxicity treatment strategy [16]. In this situation it is believed that the ER may be falsely negative.

On the other hand, lack of PR expression should not contribute to decision making regarding endocrine treatment in women with ER-positive breast cancer.

Guidelines from ASCO and the CAP recommend that both ER and PR analysis should be performed routinely in all invasive breast cancers, and the information used to select patients for endocrine therapy since there is evidence of potential benefit of PR testing to predict response of ER-negative, PR positive patients [1,2,11]. "

edited for typos only

Rhiannon78

And MameMe, I am so sorry to hear that you were diagnosed again.  And your are right-there is really no way to know if taking Tamox might have prevented this new primary.  However, the research on this is not overwhelmingly clear, as in" taking Tamoxifen reduces the risk of a new or recurrent cancer by 75%".  Numbers like that would be compelling and pretty much eeryone would have no trouble taking it, regardless of SE's..  As it has been explained to me, the actual percentages are quite low.   Best of luck to you as you move through the treatments process.

Rhiannon

MameMe

Thank you for your kind words! I love your signature, I want to make a sign with that quote, to remind me to use my strengths. : )

michellej1980

I worry about my negative PR status but have yet to ask my onc her opinion. There are so many unknowns in this game that it is driving me crazy rationalising everything and for every 'positive' aspect of my cancer there is a negative. 

I will be taking anastrozole after chemo anyway, but hope that it still benefits me despite my pr status. Are most people who are ER+/PR - post-menopausal?

NancyHB

I was diagnosed at 48, not post-menopausal.  My biopsy diagnosis was ER+ and barely PR+; my Oncotype test gives me barely ER+ (6.6, where 6.5 is the cutoff for negative), and PR-.  My MO and I have gone around and around about whether I'm actually PR+ or PR-; I tend to believe the latter, he insists it's the former.  Now I'm going to have to read this article and see if it makes sense.  :-)  Thanks for sharing!

pebee

I was pre-menopausal and I am PR-.  There was a paper that indicated that PR- is associated with insulin issues so that may be a factor. 

Pessa

Pebee,

Do you know where i can find that paper?