Lani

and encourage him to read the FULL article -- which states that there is even one study showing that tamoxifen alone may ENCOURAGE growth of her2+ tumors rather than inhibit their growth or just be ineffective! Here is the abstract:

1: Ann Oncol. 2006 Feb 23; [Epub ahead of print] Related Articles, Links

Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status.

Dowsett M, Houghton J, Iden C, Salter J, Farndon J, A'hern R, Sainsbury R, Baum M.

Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.

BACKGROUND: Most women with oestrogen receptor (ER) positive primary breast cancer receive adjuvant tamoxifen after surgery. The measurement of tumour biomarkers should allow better selection of patients for such treatment or for therapies such as aromatase inhibitors. PATIENTS AND METHODS: Histopathological blocks of primary breast cancer patients who had been randomized to receive 2-years tamoxifen or no adjuvant therapy in two mature randomised clinical trials were retrieved. Immunohistochemical staining for ER, progesterone receptor (PgR), HER2 and epidermal growth factor receptor (EGFR) was undertaken. The primary endpoint was relapse free survival. RESULTS: 813 patients were included in the study. Benefit from tamoxifen was seen in ER-positive patients [Relative risk (rr) 0.77, ci 0.63 - 0.93]. ER-negative patients also showed a strong trend to benefit from tamoxifen (rr 0.73, ci 0.52-1.02) which was largely confined to the PgR-positive group. Amongst the ER-positive group, PgR-positive and PgR-negative patients showed similar benefit (rr 0.81; ci 0.65-1.02 and 0.70; ci 0.49-0.99, respectively). Patients positive for HER2 did not benefit significantly (rr 1.14; ci 0.75-1.73) but this group was small. CONCLUSIONS: Measurement of PgR status in ER-negative patients defines a group of patients that benefit from tamoxifen but would be excluded from tamoxifen therapy on the basis of ER status alone. The data are consistent with HER2 positive tumours being resistant to tamoxifen.

PMID: 16497822 [PubMed - as supplied by publisher]



Noone knows if Herceptin REALLY negates the resistance to tamoxifen therapy
or even if herceptin negates the resistance to aromatase inhibitor therapy (I have a fresh off-the-press article on her2neu resistance to ai treatment as well) Neither does anyone know if fulvestrant is the answer (its effect seems to depend on the ambient estradiol concentration)

Clinical trials to answer these questions have just begun and no results are available as yet.

There are papers out of Yale (I posted them earlier) on adding Herceptin to tamoxifen (preclinical studies done in a petri dish and/or mice, not in people) and an early study by Matthew Ellis on letrozole with Herceptin, I believe.

I believe the doctor you were consulting used the old ADJUVANT online computer program to estimate improvement of odds based on OLD PROGRAM which does not include her2 status. Those who are her2+ have a much higher rate of recurrence. They are relatively chemo- and hormonal-therapy resistant.

But the hormonally positive her2neu tumors are the ones they understand the least about as the 2 her2neu cell lines they study in most research labs are both hormonal receptor negative.

The oncoDx test gives very little additional information according to Dr. Dennis Slamon than ER, PR, her2 by FISH, and Ki67( a measurement of proliferation) If your insurance pays for it, you may consider it, of course

If you have a high Ki67 your tumor is multiplying rapidly and chemo MAY be more likely to help. At the San Antonio Breast Cancer Conference, the feeling was that all her2 positive invasive breast cancer (ie, not DCIS) should be treated with herceptin but Dr. Slamon suggested that to decrease cardiotoxicity the tumor's level of topoII should be tested, as only topoII positive tumors should require an anthracycline and other tumors could be spared the increased cardiotoxicity of an anthracycline. This is still cutting-edge and not generally readily available. His recommendation going forward was that
If someone offers you chemo and herceptin,
to see if it is worth risking your cardiac function by combining an anthracyline (like doxyrubicin) with herceptin have Topo II--which is available from Targeted Molecular Diagnostics (see Robin P's postings)

There is to date no foolproof way to determine if chemo is necessary for
your tumor or for anyone's individual tumor. Hopefully with time microgene arrays will be able to determine not only if chemo will be helpful, but WHICH chemo will be helpful.

Size used to be considered one of the most important prognosticators with respect to breast cancer. The tumor's molecular makeup is superceding that. There are several people posting at this site who started with microinvasion with DCIS only and then developed distant metastases--so I do not know if there is any "size" of her2neu that needs only surgery and radiation.

I gleaned the following not too nice statistics from a talk by Dr. Dennis Slamon:
Her2 positive tumors which receive no systemic treatment are more than twice as likely to recur than her2negative tumors and, once they recur, usually kill patients within one year vs within two years for her2negative

The good news is that those statistics have been superceded by the utilization of Herceptin which has cut the rate of recurrence in half (WHEN utilized WITH chemo) and there are a host of members of this board who can attest to 6,7, and 8 years survivals beyond metastasis!!

Does your oncologist treat more than breast cancer? It is hard to keep up with all the new findings, even for those who specialize in it. Having attended the San Antonio meeting and four other breast cancer meetings this year I saw few old faces (except some illustrious lecturers and they were not near retirement age) among the audience. Cutting-edge knowledge is discussed at these meetings.

Perhaps if you say where you live, members of the board could suggest oncologists for a second opinion or being presented at a tumor board (at specialized institutions oncologists, surgeons, radiation therapists, radiologists, nuclear medicine specialists and pathologists ALL GET TOGETHER and discuss a patient's case especially if the treatment is controversial. As noone knows the best way to treat hormone receptor positive her2neu + early breast cancer perhaps your case might interest them.

Inform yourself! Ask questions! Only you can DO THE HOMEWORK(noone cares about it as much as you do) and only you can decide how to weight the risks and benefits of different treatment options in YOUR particular case

Good luck!