Endocrine Response Enhanced in ER+/PR+ Tumors

[Hopeful]

The best response to adjuvant endocrine therapy is seen in early-stage breast cancer patients with tumors that stain positive for both estrogen and progesterone receptors (ER+/PR+), research findings suggest.

"Our data suggest that lack of PR expression and human epidermal growth factor receptor (HER)-2 overexpression are both associated with aggressive tumor features, but the prognostic information of PR status on the risk of recurrence in endocrine-treated breast cancer patients is stronger," says the team.

Previous evidence has suggested that the effectiveness of endocrine therapy is reduced in patients with ER+ but PR- breast cancer with or without HER-2 overexpression.

To investigate further, R Ponzone (Institute for Cancer Research and Treatment, Turin, Italy) and colleagues examined retrospective data for 972 patients who received adjuvant endocrine therapy, including tamoxifen alone, tamoxifen combined with a gonadotropin-releasing hormone agonist, and aromatase inhibitors. The patients were treated between 1998 and 2005.

The researchers found that, compared with ER+/PR+ tumors, their ER+/PR- counterparts were larger, of higher grade, and expressed more Ki-67 and, on average, less ER and HER-2. All of these differences were statistically significant.

On univariate analysis, a lack of PR expression was also associated with a shorter disease-free survival (DFS; hazard ratio [HR]=2.1), as was HER-2 overexpression (HR=1.9), nodal status, tumor diameter, tumor grade, and Ki-67 expression, the researchers report in the Annals of Oncology.

The lack of PR expression along with nodal status and tumor diameter retained their significance on multivariate analysis, the team adds, whereas HER-2 overexpression was associated with a trend towards shorter DFS of only borderline significance.

"Our study confirms that PR status defines a subset of tumors with distinctive pathological characteristics and may help select those patients who derive the greatest benefit from endocrine treatment, particularly within the first few years of follow-up," the researchers conclude.


Ann Oncol 2006; 17: 1631-1636


http://www.breastcancersource.com/br...41_0_0_0.aspx?

Link to abstract: http://annonc.oxfordjournals.org/cgi...act/17/11/1631

Hopeful

[AlaskaAngel]

It is exasperating that compared to research on estrogen there is so little known about the purpose and effect of natural forms of progesterone... Thanks for one more piece of helpful info.

AlaskaAngel

[Hopeful]

AlaskaAngel,

It was surprising to see PR be a more important prognostic indicator than Her2. I agree, this is a stunningly overlooked factor for research.

Hopeful

[Becky]

So, do you think this is why Her2 positive cancers that are also ER/PR negative are more aggressive than those that are hormone positive?


I am always looking for information in regard to ER+ but PR neg bc because it is not very common and it is my pathology (as well as being Her2+).

From my investigations (and there is limited info out there), any work done on ER+ but PR neg usually also has a Her2 negative status as well. If the Her2 status is positive, this is looked upon as at least a known result (as researchers feel that the downregulation of PR is directly related to the upregulation of the Her pathway). So... if they find that an ER+ PR- tumor is also Her2+, they have an answer (as many of the Her2+ ones of this pathology tend to have a lesser (not a nonexistant) chance of also being Her1+ as well). However, if an ER+PR- tumor is also Her2 neg, it stands a GREAT chance of being Her1+ (and there's no "Herceptin" type drug for that except there are Her1 drugs out there).

Also, if ER+(but PR-) and Her2+, it has been shown that Herceptin and an aromatase inhibitor work very, very well together, better than if also PR+. The 2 researchers I spoke to at ASCO (who investigated this pathology), said that with adjuvant Herceptin in combination with an AI, it is really a triple punch for this pathology.

Any thoughts out there?

Kind regards

Becky

[Hopeful]

Becky,

I have done a lot of reading on the effect of PR status combined with Her2 status, and the conclusion I have seen drawn many times is that the ER+/PR- Her2+ pheonotype is more aggressive than PR+/ER- (rare, but it occurs) and ER+/PR+ Her2+ bc. I have copies of these articles but not where I am writing from at the moment and dashed if I can find the references when I want them. I will go through my other files and pull them for you if you are interested.

From your post, I gather you have read some of the research on PR- and Tamoxifen resistance, which is not the research I am referring to, but has a lot of info about the effects of ER+/PR- and Her2+.
I can provide a link to a recent abstract that concludes that ER+PR- breast cancer is growth factor dependent and constitutes a unique subgroup of ER+ patients which may be more likely to benefit from EGFR inhibition: http://meeting.jco.org/cgi/content/a...4/18_suppl/514; are the authors any of the people you spoke to at ASCO?

I would also like to thank you for the insightful comments you always provide and the terrific gift you have for translating complex techinical information into language that a lay person can understand.

Hopeful

[Becky]

A few of these names are ones I recognize but have to check when I get home. I do know all about PR- and tamoxifen resistance (and this was instrumental in deciding to get my ovaries removed to use Arimidex. The Herceptin/Arimidex combo data helped me convince my onc to give me 5 extra (every 3 week) Herceptin treatments so I could be on the combination one year (hence about 16 months of Herceptin versus one year). Everyone I have ever talked to about the ER+/PR- pathology say it is worse if you are not Her2+ as well. Data indicates that ER+/PR-/Her2- strongly indicateds Her1+ (aka EGFR) whereas with Her2+ it may well not be Her1+ as well. All have indicated that it is better for either hormone receptor to be positive rather than both be negative (as it is a pathway that has treatment options).


Thanks for your kind words and knowledge.

Becky

[Hopeful]

Here is the link: http://jcp.bmj.com/cgi/content/full/58/6/611 The title is "Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer."

The authors evaluated 1362 women from 2000-2003 in a single hospital in Belgium. The statistics they generated are very interesting. They concluded : "In women with ER+ tumours, the expression of PR affects the likelihood of HER-2/neu overexpression, and it may be that women with ER+ PR– tumours should be targeted with more aggressive treatment than those with ER+ PR+ tumours."

Hope this helps,

Hopeful

[Hopeful]

After a bit of digging, it surfaced. From May, 2003, titled: Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases.

Here is the link: http://www.jco.org/cgi/content/full/21/10/1973

Hope this is helpful.

Hopeful

[Becky]

Dear Hopeful


Thank you so much as I did not read that article. Of course it is best to be hormone positive on both fronts but at least being ER+ (even if PR-) is better than nothing.

I really appreciate your help.

Have a wonderful Thanksgiving (assuming you are from the USA)