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NEW RESEARCH: HER-2/neu overexpression in UPSC, and promising treatment with Herceptin

lindaprocopio's picture
lindaprocopio
Posts: 2022
Joined: Oct 2008

My chemo-oncologist said today that, with HERCEPTIN, HER-2neu overexpression is no longer the 'poor prognosis indicator' it used to be for endometrial cancers, and that he was confident he could get insurance approval to cover Herceptin for any UPSC patient who had assay pathology that showed HER-2neu overexpression. So, UPSC Sisters, GET THOSE ASSAYS if you can, because this article makes me believe that you NEED Herceptin if you are +2 or +3:

Overexpression of HER-2/Neu in Uterine Serous Papillary Cancer

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology [A. S., S. B., M. P., D. D., T. O., G. P.], Departments of Pathology [M. G.], Medicine [J. A., L. H.], and Microbiology and Immunology [M. J. C.], University of Arkansas, Little Rock, Arkansas 72205-7199, and Division of Gynecologic Oncology, University of Brescia, 25123 Brescia, Italy [A. S., S. B., M. P., S. P.]

Purpose: Uterine serous papillary carcinoma (USPC) is a highly aggressive variant of endometrial cancer and histologically similar to high-grade ovarian cancer. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistology in ∼25% of ovarian cancers. In this study, we have evaluated the expression of HER-2/neu in several fresh, established, paraffin-embedded, fixed USPCs. In addition, we have tested the sensitivity of USPC cells to Herceptin treatment.

Experimental Design: Ten consecutive USPC specimens were assessed by immunohistochemistry for the intensity of expression of HER-2/neu. In addition, three USPC cell lines were analyzed for expression of HER-2/neu by flow cytometry as well as for sensitivity to Herceptin-mediated, complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), and inhibition of cell proliferation.

Results: Eight of 10 (80%) of the USPCs assessed immunohistochemically for the intensity of expression of HER-2/neu stained heavily for HER-2/neu (2+ to 3+). Fresh and established primary USPC cell lines were found to express significantly more HER-2/neu receptor by flow cytometry (on the average, 10-fold greater) when compared with HER-2/neu-positive primary or established breast and ovarian cancer cell lines (P < 0.001). Importantly, although these USPC cell lines were resistant to chemotherapy in vivo and to natural killer- and complement-mediated cytotoxicity in vitro, they were found to be highly sensitive to Herceptin-mediated ADCC. USPC cell proliferation was also inhibited by Herceptin. A significant enhancement of ADCC was demonstrated when effector cells were exposed to low doses of IL-2 in vitro. Physiological concentrations of human serum IgG did not inhibit Herceptin-mediated ADCC against USPC.

Conclusions: On the basis of these findings and previous reports showing a positive in vivo correlation between efficacy of Herceptin therapy and the level of HER-2/neu overexpression by tumor cells, we propose that Herceptin might be a novel and attractive therapeutic strategy in patients harboring chemotherapy-resistant, recurrent, or metastatic USPC.
In the clinical setting, high levels of HER-2/neu in tumor tissue have been associated with shorter patient survival (13, 14, 15) , resistance to antiestrogens (27) and chemotherapeutic drugs (13, 14, 15) , and resistance to tumor necrosis factor-α, activated macrophages, and lymphokine-activated killer cells (28) .

In conclusion, we show that HER-2/neu is highly expressed by USPCs, and we further demonstrate that USPC cells are exquisitely sensitive to Herceptin-mediated ADCC. On the basis of these findings and previous evidence showing a correlation between efficacy of Herceptin therapy in direct proportion to the HER-2/neu overexpression on tumor cells, we postulate that Herceptin might be a novel and attractive therapeutic strategy in USPC patients either for the prevention of recurrence after surgical treatment or for the treatment of metastatic disease. The future design and implementation of clinical trials in this regard will ultimately determine the validity of this approach.

for full article & references:
http://clincancerres.aacrjournals.org/content/8/5/1271.full

A1pena's picture
A1pena
Posts: 93
Joined: Jan 2010

Hi Linda!

When we got a second opionion for my mom, her doctor had mentioned Herceptin as a viable option for UPSC as well! His exact words were "60% of UPSC cases are found to overexpress the protein HER2/neu. This same protein is overexpressed in some breast cancers and these breast cancer drugs like herceptin are very effective." He then goes on to recommend getting into a clinical trial that involves herceptin if she is HER+. But he also said "Given that the tumor is already P53 positive, which is common in breast cancers who respond to herceptin, it may well be that her tumor would be an ideal candidate for this newer modality." He mentioned that it may be difficult to get unless you are in a clinical trial but it sounds promising that your doctor is confident he can get it cleared. If I remember correctly, your tumor is P53+ correct? Maybe that could be another option to get your insurance to cover it?

After I got this news back in April, I did some research as well, and remember coming across an article titled "HER2/neu overexpression: has the Achilles' heel of uterine serous papillary carcinoma been exposed?" but am having a hard time finding the full article :(

I would be very interested to hear if you end up chosing this route. Best of luck to you!!!!

Kind Regards,

Amanda

california_artist's picture
california_artist
Posts: 865
Joined: Jan 2009

There is something called the compassionate use doctorine. It's for people who are in dire need of a treatment that is not the standard for the particlar disease but might allow someone to live longer. I don't feel these are the exact words, but someone out there should have an idea of what I am referring to.

Thanks

Kaleena's picture
Kaleena
Posts: 2036
Joined: Nov 2009

You are right. It is called compassionate use programs. It is when there are no other options and a drug, which has not yet been approved, may be used to help a terminal patient, who does not have any other options, to help save their lives before a drug can be approved, because the chance of the patient surviving outweighs the risk. See www.wisegeek.com.

sleem
Posts: 92
Joined: Feb 2010

USPC Survior: Surgery 9-2008--- 1A Grade 3 found in endometrial polyp, no cancer in omental biopsy, para-aortic lymph nodes, right or left lymph nodes , nomyometrial or lymphovascular invasion, or in fibroids, adenomyois, ovaries or tubes.

I had a D&C prior surgery to the Sept. surgery. The biopsy stains for p53 & Ki67 showed moderate nuclear staining in approximately 25% of cells of concern. Endometirum & endometrial from one polyp taken had fewer than 5% nuclei staning at time of D&C.

I have not had any further info provided on current p53 nor info on HER-2/neu. I know there are indicators that have a predictability for return rate. Has your research demonstrated how to learn about those?
Is anyone out there in HERCEPTIN treatment? How & why did you select it?

What questions do I need to ask to learn this information presently?

Does anyone know what Ki67 has to do with future survival?

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