Dear Al and all,
There are quite a few small studies out there regarding herceptin, her2, and brain mets. As with anything you can find positive conclusions, as well as negative and, oftentimes, neutral. I work in a clinical medical library and these things cross my desk everyday...
Here's a paper from 2003 re: herceptin and brain mets. This one has an unquestionably positive conclusion for those on herceptin:
Clin Breast Cancer. 2003 Jun;4(2):114-9. Related Articles, Links
Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival.
Lower EE, Drosick DR, Blau R, Brennan L, Danneman W, Hawley DK.
University of Cincinnati Medical Center, Department of Internal Medicine, OH, USA.
lowere@uc.edu
Trastuzumab is important for treatment of metastatic breast cancer patients with tumors that overexpress HER2/neu, but its penetration to the brain is poor. The aims of this study are to determine the prevalence of bone and brain metastasis during therapy, to compare the survival of breast cancer patients with brain metastasis who received trastuzumab to those patients not receiving trastuzumab, and to assess the impact of brain metastasis on the overall survival of trastuzumab patients. Of 103 patients treated with trastuzumab, 16 had brain metastasis and 43 had bone metastasis at the beginning of trastuzumab. The control group consisted of 196 patients with metastatic breast cancer who had never received trastuzumab. Six had brain metastasis and 75 had bone metastasis at the beginning of therapy. During therapy, only 9 of 60 trastuzumab patients (15%) developed bone metastasis, while 170 of 186 control patients (91%; c2 = 129.8, P < 0.0001) developed bone metastasis. In addition, 22 of 87 trastuzumab patients (25%) and 58 of 190 control patients (31%) subsequently developed brain metastasis. Control patients without brain metastasis experienced significantly better survival (median survival = 928 days) than those with brain metastasis (median survival = 639 days, c2 = 8.34, P < 0.005). There was no difference in survival for trastuzumab-treated patients if they acquired brain metastasis (median survival = 1400 days) or no brain metastasis (median survival > 2000 days, c2 = 0.12, P > 0.05). Patients receiving trastuzumab were unlikely to develop new bone metastasis but were as likely as control patients to develop brain metastasis. However, patients who developed brain metastasis experienced better survival compared with those patients with brain metastasis who never received trastuzumab.
PMID: 12864939 [PubMed - indexed for MEDLINE]
and this one from the Feb 1/05 issue of the journal "Cancer":
Increased Risk of Brain Metastases in Patients with HER-2/neu-Positive Breast Carcinoma
Ramin Altaha, M.D.
Edward Crowell, M.D.
Gerry Hobbs, Ph.D.
Gerry Higa, Pharm.D.
Jame Abraham, M.D.
Section of Hematology/Oncology, Mary Babb Randolph Cancer Center, West Virginia University,
Morgantown, West Virginia
Preliminary data have indicated that overexpression of HER-2/neu is correlated with more aggressive disease, an increasedmetastatic potential, and a poorer prognosis in patients with breast carcinoma.
(1–3) Trastuzumab, a humanized anti-HER-2 antibody, reportedly
is unable to penetrate the blood–brain-barrier and to our knowledge
its efficacy in patients with brain metastases remains unclear.(4–6) We
conducted a retrospective study to evaluate whether patients with
HER-2/neu-positive breast carcinoma have an increased risk of developing
brain metastases.
After approval from the institutional review board of West Virginia
University, the pathology reports of 703 breast carcinoma patients
who were diagnosed between April 1998 and January 2003 were
reviewed. Based on immunohistochemistry or fluorescence in situ
hybridization positivity, all patients who were positive for HER-2/neu
were identified and their medical charts reviewed with regard to their
course of disease and sites of metastases.
Of the 703 patients studied, 164 (23%) were found to be positive
for HER-2/neu; a sufficient oncologic history was available for
102 patients. Thirty-one patients (30%) developed distant metastases
(95% confidence interval [95% CI], 0.223– 0.399) during follow-
up lasting a median of 57 months. Brain metastases were
reported to have developed in 15 of these 31 patients (48%)(95% CI,
0.320 – 0.652). A proportional hazards model was fit to the data to
explore the association between patient age and time to the development
of metastases. A significantly positive association (P
0.01) was found to exist between the two variables. Other models
for censored data (Weibul, log-normal, and exponential models)
were fitted and were found to produce nearly identical P values
(Fig. 1).
The results of this small retrospective study demonstrate that
younger women with HER-2/neu-positive breast carcinoma may have
a higher risk of developing brain metastases than previously reported
for the general metastatic breast carcinoma patient population. This
442
© 2004 American Cancer Society
And, the conclusion of a 2004 article from the same journal...
CONCLUSIONS: Despite the impression of many oncologists, the results of this study did not support an association between trastuzumab therapy and an increased risk of CNS metastases. Copyright 2004 American Cancer Society.
I visit the board infrequently, but will try and be better in the future about posting anything that passes my way...
Kind regards,
/Christine