for all you ER+ her2+s--some GOOD news

[Lani]

don't know if it holds for Stage I-IIIs, but it seems to hold for Stage IVs (they may have just been HR+her2-s whose tumors upregulated her2 in order to survive)

ABSTRACT: Hormone Receptor Expression Is Associated With a Unique Pattern of Metastatic Spread and Increased Survival Among HER2-Overexpressing Breast Cancer Patients
[American Journal of Clinical Oncology]
Objectives: HER2/neu (HER2) overexpression occurs in approximately 20% of breast cancers and is associated with aggressive disease. Although a significant number of HER2-positive tumors also express hormone receptors (HR), the effects HR expression has on clinical characteristics, including response to trastuzumab among HER2-positive breast cancer, has not been elucidated yet.
Methods: A retrospective analysis of consecutive metastatic HER2-positive breast cancer patients was conducted in 2 medical centers. Associations between hormone receptors expression and clinical variables, and metastatic spread pattern and survival were studied.
Results: The study population included 137 metastatic HER2-positive breast cancer patients, 56 of them were HR-positive and 81 were HR-negative. No significant differences between the 2 groups were found for demographic and clinical characteristics, including age, stage at diagnosis, tumor histology, and grade. Similar response rate to trastuzumab was observed in both study groups. Significantly, longer, median, disease-free, and overall survival was noted among the HR-positive patients. Patients in the HR-negative group had significantly more liver metastases, a trend for more brain metastases, and less bone metastases. There was a strong trend for more visceral metastases in the HR-negative group.
Conclusions: Our results suggest an important role for HR expression in modulating metastases predilection and disease progression in HER2-positive breast cancer.

[margiermc]

thanks - now I can sleep better, great news

Lani, any way to get the full article without paying for it?

Thanks,

Jill

[bejuce]

What was considered ER+ in this study? Anything above 0? The reason I ask is that I'm only 5% ER+ so I'm wondering if the study looked at any statistically different significance that depended on the amount of ER expression in the cells.

Either way, thanks for posting this!

[Jackie07]

I think mine is also just 5% and is considered ER +.

Lani, I could not locate the article you posted above. Do you happen to have a 'citation' (volume, page, publication date...etc) available?

The only citation kept turning up is the Fact sheet in 2007-2008. My computer is too slow to show the whole 87 pages:

Breast Cancer Facts & Figures 2007-2008 (American Cancer Society) - PDF
... Waterbor JW, Brown D, Weiss H, Frost AR. Hormone receptors and proliferation in ... at: Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. ...

www.cancer.org/downloads/STT/BCFF-Final.pdf

[Laurel]

Finally! A bit of good news for us triple pos. folks!

[hutchibk]

It's also interesting that Herceptin is in trials being used to switch ER- to ER+, even if someone is not HER2+... this is potentially good news for triple negative breast cancer.

http://clinicaltrials.gov/ct2/show/NCT00726180

It's because of this theory that my onc and I decided to add Aromasin back into my regimen ~

[Rich66]

"Significantly, longer, median, disease-free, and overall survival was noted among the HR-positive patients."

Hope so. Although..mom discovered recurrence with pretty visceral mets. Always exceptional.

[CLTann]

Laurel, Your picture sketch is marvelous. I wanted to compliment you on this but always forgot to say it. I got up near middle of the night and didn't want to slip by again.

Ann

[Lani]

American Journal of Clinical Oncology:
October 2009 - Volume 32 - Issue 5 - pp 504-508
doi: 10.1097/COC.0b013e3181967d72
Original Article: Breast
Hormone Receptor Expression Is Associated With a Unique Pattern of Metastatic Spread and Increased Survival Among HER2-Overexpressing Breast Cancer Patients
Paluch-Shimon, Shani MBBS; Ben-Baruch, Noa MD; Wolf, Ido MD; Zach, Lior MD; Kopolovic, Juri MD; Kruglikova, Anna MD; Modiano, Tami RN; Yosepovich, Ady MD; Catane, Raphael MD; Kaufman, Bella MD

[Lani]

I just read the whole article

None of the patients got herceptin adjuvantly, as herceptin was only given for Stage IVs in Israel.

[TSund]

Lani,

Was any distinction made between ER+/PR- and ER?PR+?

THX

TRS

[Lani]

no they just said there were too few ER-PR+s to comment about but didn't comment on ER+s being either PR+ or PR-

[Laurel]

Ann,

Thanks so much! That was nice of you to get out of bed to say! It was sketched at a company Christmas party a few years ago. It provides a bit of anonymity, but gives me a presence, so to speak. I am a Realtor with a fairly substantial web presence. Although I want to be an honest, forthright participant on the site, I felt the need to be a bit "cloaked" initially. Of course, with time and familiarity with everyone I no longer care, but the sketch has become my moniker, so I'll keep it for now. One of these days I'll pop on the real me!

Lani, thanks for the post. I was beginning to feel like a bit of a pariah in the BC-world! LOL!

[sassy]

No Pariah Laurel. There just doesn't seem to be a lot of us Triple+'s!

Glad to see this good news.

[caya]

Triple + here too - I think we are about 2.5 - 3% of the total BC population.

Thanks for the good news Lani.

And Laurel I love your sketch too. One of these days I should change my avatar, my hair is longer now.

xo
caya

[Cal-Gal]

Lani,

Thanks for this--

I am ER/PR negative--as negative as you can get
--complete obliterated big fat 0's---

I am happy for my HR+ sisters--

My question is this: Is this due to the fact that HR+ BC patients can have and respond very well to hormonal therapy?

Sounds plausible to me---

[Lani]

The study population included all consecutive women with HER2 overexpressing breast cancer who were treated at two Israeli hospitals,between January 2001 and July 2005.Herceptin had only been approved to be used for metastatic disease, so none of the patients got herceptin as part of their adjuvant treatment. This study only looked at those who became (or were originally at the time of diagnosis) Stage IV, ie, only those patients who were entitled to be treated with herceptin. The diagnosis of metastatic breast cancer was confirmed histologically in all patients, either from the primary tumor (in the event that the patient was stage I-III at diagnosis) or from metastatic sites (among those with stage IV disease at diagnosis). HER2 status was confirmed by either 3+ on immuno- histochemical (IHC) analysis (range 0–3+), ), or a positive result of greater than 2.0 on FISH for HER2 amplification . FISH studies were performed on IHC 2+ cases.
HR status was determined by IHC staining. HR-positive status was defined by presence of either (or both) >10% positive cells for estrogen receptors or progesterone receptors.

Patients’ charts were reviewed and clinical data, including age,ethnicity, and menopausal status, were documented. Stage was defined according to the 2002 American Joint Committee on Cancer Staging System for Breast Cancer. Distribution of metastatic disease was documented at the time of first recurrence, or at diagnosis for those who presented with metastatic disease, and also throughout the course of disease. All pathology reports were reviewed for tumor histology, size, lymph nodes involvement, grade, and ER, PR, and HER-2 status. Histologic grading was determined only for biopsies taken from the primary tumor and not from metastatic sites.

Information regarding therapy, including type of surgery, radiation therapy, hormonotherapy, chemotherapy, and herceptin therapy, was obtained from the patients’ charts, and response to herceptin therapy and its duration were documented. Response to herceptin was determined by RECIST criteria, and time-to-disease progression was determined from date of commencement of herceptin to date of documented disease progression. Disease-free survival (DFS) was defined from the date of surgery for removal of the primary tumor until the date of a definite clinical or radiologic evidence of recurrence. Overall survival (OS) was defined from the date of diagnosis to the date of death.

During the study period, 137 HER2-positive metastatic breast cancer patients were treated in both medical centers. Fifty-six (41%) of them had HR-positive disease and 81 (59%) had HR-negative disease. Interestingly, similar age, menopausal status, and ethnicity were noted for both study groups. Notably, no differences were noted for disease stage at presentation: size, nodal involvement, and metastatic disease; or for biologic characteristics of the tumors: histology and grade. Of the HR-positive cancers, 38 (68%) expressed both the ER and the PR, 11 (20%) and 7 (12%) expressed either the ER or the PR, respectively.

Herceptin was administered to most of the patients in both study groups and was administered predominantly in combination with chemotherapy (in 92% of cases in both groups); in the HR-positive group one patient received the herceptin in combination with hormonotherapy; the remaining patients received herceptin monotherapy (6% in the HR-positive group and 8% in the HR-negative group). Israeli Health ministry regulations mandated use of herceptin strictly for metastatic disease with strict monthly monitoring of treatment and response, mandating immediate cessation of treatment on evidence of disease progression. As such, strict and detailed documentation of treatment responses was available. The objective response rates to herceptin, and time to progression was similar in both study groups.

Adjuvant treatment for patients presented with early breast cancer was analyzed. Although similar proportions of patients received adjuvant chemotherapy (81% of the HR-positive and 87% of the HR-negative), significantly less of the HR-positive patients received anthracycline based chemotherapy, compared with HR-negative patients (74% vs. 95% respectively, P = 0.025). Eighty-four percent of the HR- positive patients and only 11% of the HR-negative patients received adjuvant hormonal therapy. In the HR-positive group among those that received adjuvant chemotherapy, 84% proceeded to receive adjuvant hormonal therapy.

Hope this answers your questions

[TSund]

hmm...would love to know which chemo those that did not receive anthracyclines received. Wonder if it was TCH or similar.

[Cal-Gal]

Thanks Lani for all this info---
I willl read this over tomorrow--can't see straight right now--
Good night-