?reason to look for androgen-receptors on ER-PR- breast cancers?

[Lani]

Am J Surg. 2006 May;191(5):576-80. Related Articles, Links

Transgenic introduction of androgen receptor into estrogen-receptor-, progesterone-receptor-, and androgen-receptor-negative breast cancer cells renders them responsive to hormonal manipulation.

Garreau JR, Muller P, Pommier R, Pommier S.

Division of Surgical Oncology, Department of Surgery, Oregon Health and Sciences University, 3181 S. W. Sam Jackson Park Rd., L223A, Portland, OR 97201, USA.

BACKGROUND: Estrogen-receptor (ER)-, progesterone-receptor (PR)-, and androgen-receptor (AR)-negative breast cancer cells are unaffected by treatment with dehydroepiandrosterone-sulfate (DHEAS) and an aromatase inhibitor (AI). We hypothesized that cell growth would be inhibited with DHEAS/AI treatment after successful transfection of an AR expression vector. METHODS: ER/PR/AR-negative breast cancer cells were transfected with an AR expression vector and treated with DHEAS/AI for 2 days. Growth inhibition of these cells was compared with that of transfected cells treated with only AI or with nontransfected cells treated with DHEAS/AI. Mann-Whitney U test was used to determine statistical significance. RESULTS: Cell death rates of 53.5% (P = .001) and 40.1% (P = .006) were seen in transfected cells treated with DHEAS/AI compared with controls for days 1 and 2, respectively. Nontransfected cells were unaffected by treatment. COMMENTS: ER/PR/AR-negative cells transfected with AR were killed by DHEAS/AI treatment, providing evidence that AR is responsible for this effect. This provides the first AR-targeted hormonal therapy for ER breast cancer.

PMID: 16647340 [PubMed - in process]

[StephN]

Does this article mean that they have been able to change hormone neg/neg cells to positive and then treat them?

I am neg/neg, but have been successfully maintained on Herceptin alone for 4 years after my liver/bone mets.

Was also post-menopausal when diagnosed. So wonder if the above first question is possible, would it work for post meno patients?

Lots of food for thought if this study means what I think it says.

[Lani]

Some breast cancer tumors are Androgen receptor positive. In this case, to make a cell line to test their hypothesis, they took a cell line negative for ER, PR and AR and did gene therapy to introduce AR into that cell line. Then they were able to utilize antihormonal therapy directed against the androgen receptor.

Having an androgen receptor or not should not depend on whether one is postmenopausal or not. But having an AI work should.

This article is not advocating gene therapy to introduce androgen receptor into your breast cancer, rather advocating looking for androgen receptors on your breast cancer against which antihormonal (in this case anti-androgen) therapy could be directed.

At least that is my take on it... Will try to see if I can get/read the original article and see if I can add more

[Lani]

excepted from paper:
vival rate of patients with ER

[Lani]

more from paper:
vival rate of patients with ER

[Lani]

Survival rate of patients with er+pr+ tumors is 15% greater than those who are er-pr---advantage attribuated to antihormone therapy.

Approx. 33% of breast cancers are hormone insensitive lacking both er and pr. Androgen receptor is the most common receptor present in breast cancers--present in 66% to 80% of tumors. AR status is easily determined by IHC, but is neither routinely assayed nor used for treatment planning.
Their results indicated 42% of er-pr-tumors are A+. SEVERAL STUDIES FOUND ASSOCIATION BETWEEN AR EXPRESSION AND SURVIVAL IN PTS WITH ER- TUMORS.
HE SUGGESTS TREATMENTS WHICH EXPLOIT THE USE OF AR OR CONFER INCREASED AR SENSITIVITY TO DRUGS TO IMPROVE THE PROGNOSIS OF PTS WITH ER-PR- BREAST CANCER. EVEN IF AR IS ONLY WEAKLY EXPRESSED GROWTH INHIBITION SEEMS TO BE POSSIBLE WITH DHEA AND AIS. THE COMBINATION LED TO CELL DEATH IN ER-PR- TUMORS AS LONG AS THERE WAS A THRESHOLD LEVEL OF AR

THIRD GENERATION AIS PREVENTED DHEA BEING CONVERTED TO ESTRONE AND THUS LED TO EVEN MORE DHEA BEING AVAILABLE TO INHIBIT THE ANDROGEN RECEPTOR